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21 pages, 1557 KiB

Open AccessReview

Physiopathology of the Brain Renin-Angiotensin System

by Cristina Cueto-Ureña, María Jesús Ramírez-Expósito, María Pilar Carrera-González and José Manuel Martínez-Martos

Life 2025, 15(8), 1333; https://doi.org/10.3390/life15081333 - 21 Aug 2025

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Abstract

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the [...] Read more.

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article

(This article belongs to the Section Physiology and Pathology)

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17 pages, 1631 KiB

Open AccessArticle

Biological Potential of Hypericum L. Sect. Drosocarpium Species

by Nebojša Kladar, Branislava Srđenović Čonić, Goran Anačkov, Maja Hitl, Bojana Bokić, Boris Radak and Milica Rat

Life 2025, 15(8), 1332; https://doi.org/10.3390/life15081332 - 21 Aug 2025

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Abstract

The limited data on biological potential of the genus Hypericum sect. Drosocarpium species initiated the current research aimed at the chemical characterization of samples of six selected taxa (H. barbatum, H. montbretii, H. richerii subsp. grisebachii, H. rochelii, [...] Read more.

The limited data on biological potential of the genus Hypericum sect. Drosocarpium species initiated the current research aimed at the chemical characterization of samples of six selected taxa (H. barbatum, H. montbretii, H. richerii subsp. grisebachii, H. rochelii, H. rumeliacum, and H. spruneri) and the evaluation of their biological potential (antioxidant and antihyperglycaemic potential, acetylcholinesterase and monoamine oxidases inhibition). The obtained results suggest greater abundance of biologically active compounds, hypericin (H. rochelii, H. barbatum, and H. richerii subsp. grisebachii), amentoflavone (H. richerii subsp. grisebachii), quercetin and rutin (H. richerii subsp. grisebachii), and chlorogenic acid (H. richerii subsp. grisebachii, H. barbatum, H. rumeliacum), when compared to H. perforatum. Also, the scavenging potential of DPPH (median RSC₅₀ = 3.34 µg/mL), NO (median RSC₅₀ = 26.47 µg/mL) and OH radicals (median RSC₅₀ = 76.87 µg/mL) of evaluated species was higher, or at least comparable to H. perforatum, while the same trend was noticed in the case of anti-MAO-A (median IC₅₀ = 19.41 µg/mL) and antihyperglycaemic potential (inhibition of α-amylase and α-glucosidase (median IC₅₀ = 29.47 µg/mL)). The study results highlight sect. Drosocarpium species as a valuable source of biologically active secondary metabolites and suggest a wide spectrum of possible applications in the food and medicine industries. Full article

(This article belongs to the Special Issue Plant-Derived Natural Products and Their Biomedical Properties: 2nd Edition)

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16 pages, 2491 KiB

Open AccessArticle

Gut Microbiota Modulation and Anti-Obesity Potential of Epigallocatechin-3-Gallate-Quercetin-Rutin Against High-Fat Diet-Induced Obesity in Rats

by Yu-Jou Chien, Ching-Chang Cho, Yu-Ting Hung, Li-You Chen, Yue-Ching Wong, Shiuan-Chih Chen and Chin-Lin Hsu

Life 2025, 15(8), 1331; https://doi.org/10.3390/life15081331 - 21 Aug 2025

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Abstract

Polyphenols have been widely recognized for their potential anti-obesity effects. This study aimed to evaluate the impact of a polyphenol compound-epigallocatechin-3-gallate, quercetin, and rutin (EQR) on obesity-related parameters and gut microbiota composition. After four weeks of high-fat diet (HFD) induction, the obese Wistar [...] Read more.

Polyphenols have been widely recognized for their potential anti-obesity effects. This study aimed to evaluate the impact of a polyphenol compound-epigallocatechin-3-gallate, quercetin, and rutin (EQR) on obesity-related parameters and gut microbiota composition. After four weeks of high-fat diet (HFD) induction, the obese Wistar male rats received EQR treatment for an additional four weeks. EQR supplementation significantly reduced body weight gain, feed efficiency, adipose tissue accumulation, and liver lipid content in obese rats. Additionally, it enhanced fecal short-chain fatty acid (SCFA) levels and modulated gut microbiota composition. Specifically, EQR treatment significantly induced Fusobacteria, Fusobacteriaceae, Christensenellaceae, Christensenellaceae R-7 group, Lachnoclostridium, Enterorhabdus, and Parvibacter levels and reduced Deferribacteres and Mucispirillum levels. Gene expression analysis in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) revealed that EQR upregulated the expression of liver PPAR-α, WAT SIRT-1, and BAT PGC-1α, while downregulating liver PPAR-γ, liver FATP-1, and WAT FAS, indicating its role in promoting fatty acid oxidation and thermogenesis, as well as suppressing lipid synthesis and transport. In conclusion, EQR demonstrated significant anti-obesity effects by modulating gut microbiota and lipid metabolism, suggesting its potential as a functional ingredient for obesity management. Full article

(This article belongs to the Special Issue Natural Products and Modern Drug Discovery: Emerging Strategies Targeting Cancer- and Disease-Related Molecular Mechanisms)

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12 pages, 1255 KiB

Open AccessArticle

Proteomics Analysis of Plasma Biomarker of Cognitive Frailty in Elders Who Locally Reside in Chiang Mai Province of Thailand

by Paitoon Aobchey, Parunya Chaiyawat, Mathuramat Seesen and Jetsada Ruangsuriya

Life 2025, 15(8), 1330; https://doi.org/10.3390/life15081330 - 21 Aug 2025

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Abstract

Cognitive frailty in elders has become very common in Thailand society and is extremely difficult to manage in clinical practice due to poor detection and diagnosis. Plasma proteomic studies may be able to provide promising protein markers specific to this condition in order [...] Read more.

Cognitive frailty in elders has become very common in Thailand society and is extremely difficult to manage in clinical practice due to poor detection and diagnosis. Plasma proteomic studies may be able to provide promising protein markers specific to this condition in order to improve the quality of life in the elderly. The purpose of this study was to differentiate and identify a potential protein marker of cognitive frailty in plasma samples by proteomic approaches. Nine plasma samples from elders with cognitive frailty or non-frailty were pooled and subjected to 2D gel separation. Conventional analysis was performed with the stained gel, and the selected protein spot was identified by liquid chromatography–tandem mass spectrometry coupled to a SCIEX TripleTOF 6600+. It was found that fibrinogen gamma (FGG) chain protein was suggested. FGG was further validated with a commercial ELISA kit using both pooled and individual plasma samples. It was found that both pooled and individual samples showed a significant reduction in FGG levels in elders with cognitive frailty. The results from this study suggest that FGG chain may be a potentially useful plasma biomarker for early detection, diagnosis, and therapeutic applications of cognitive frailty in elders in order to achieve sustainable health in an aging society. Full article

(This article belongs to the Section Proteins and Proteomics)

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13 pages, 253 KiB

Open AccessArticle

Evaluation of Total Homocysteine Levels in Relation to Abdominal Fat Mass and Traditional Cardiovascular Risk Factors in Overweight and Obese Adolescents

by Małgorzata Rumińska, Ewelina Witkowska-Sędek, Maria Krajewska, Anna Stelmaszczyk-Emmel, Maria Sobol and Beata Pyrżak

Life 2025, 15(8), 1329; https://doi.org/10.3390/life15081329 - 21 Aug 2025

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Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide, with multiple risk factors contributing to their development. Among these, obesity and hyperhomocysteinemia have been recognized as significant contributors to endothelial dysfunction, a key early event in the pathogenesis of atherosclerosis. Our study aimed [...] Read more.

Cardiovascular diseases remain the leading cause of mortality worldwide, with multiple risk factors contributing to their development. Among these, obesity and hyperhomocysteinemia have been recognized as significant contributors to endothelial dysfunction, a key early event in the pathogenesis of atherosclerosis. Our study aimed to evaluate the relationship between total homocysteine (tHcy) levels and traditional cardiovascular risk factors in overweight and obese adolescents. We enrolled 42 obese, 14 overweight, and 25 non-obese children. No significant differences in tHcy levels were observed between overweight, obese, and non-obese adolescents. Homocysteine positively correlated with age (r = 0.433, p < 0.011) and creatinine concentrations (r = 0.363, p = 0.001) in the overall group of overweight, obese, and non-obese children, as well as in the combined group of overweight and obese children (for age: r = 0.275, p = 0.025; for creatinine: r = 0.278, p = 0.025). We did not find any association between homocysteine and atherogenic lipid profile, insulin-resistance status, blood pressure, and inflammatory parameters in overweight and obese patients. Age emerged as the strongest independent predictor of homocysteine levels. The observed association with creatine suggests a potential renal contribution to homocysteine metabolism. Full article

(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions—2nd Edition)

7 pages, 855 KiB

Open AccessCase Report

Diagnosis and Management of Struma Ovarii in Pregnancy: A Case Report

by Isidoro Narbona Arias, Lucia Castaño Frías, María Marfil Gonzalez, Laura Baños Cárdenas and Jesús S. Jimenez Lopez

Life 2025, 15(8), 1328; https://doi.org/10.3390/life15081328 - 21 Aug 2025

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Abstract

Adnexal tumors during pregnancy are rare, with a prevalence ranging from 0.05% to 3%, and in most cases, they are benign. Struma ovarii, a monodermal teratoma, consists of over 50% thyroid tissue and accounts for 2.7% of ovarian teratomas. It typically affects women [...] Read more.

Adnexal tumors during pregnancy are rare, with a prevalence ranging from 0.05% to 3%, and in most cases, they are benign. Struma ovarii, a monodermal teratoma, consists of over 50% thyroid tissue and accounts for 2.7% of ovarian teratomas. It typically affects women aged 40–60 and is exceptionally rare during pregnancy. Diagnosis is often only established after surgical intervention and histological examination. We present the case of a 39-year-old pregnant woman (gravida 2, para 1) at 19 weeks of gestation who presented with acute lower abdominal pain. At her first visit at 11 weeks, ultrasound revealed a 12 cm multilocular left adnexal mass. Initial conservative management was followed by emergency laparoscopy due to suspected ovarian torsion, resulting in a left oophorectomy. Histopathology confirmed struma ovarii. Thyroid function tests (TSH, FT4) remained within normal limits throughout pregnancy. The pregnancy continued without further complications, culminating in a spontaneous vaginal delivery at 40 + 4 weeks of a healthy female infant weighing 3800 g. Due to the rarity of this condition, treatment guidelines remain undefined, with management decisions relying on limited case reports and clinical judgment. This report highlights the importance of detailed evaluation and individualized management in such uncommon presentations during pregnancy. Full article

(This article belongs to the Special Issue Prevention, Diagnosis, and Treatment of Gestational Diseases)

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19 pages, 2270 KiB

Open AccessArticle

Integrated Proteomic and Molecular Identification of Thermophilic Geobacillus Strains from Algerian Desert Sands and Their Enzymatic Potential

by Amaria Ilhem Hammadi, Mohamed Merzoug, Marwa Aireche, Zohra Yasmine Zater, Keltoum Bendida, Chaimaa Naila Brakna, Slimane Choubane, Svetoslav Dimitrov Todorov and Djamal Saidi

Life 2025, 15(8), 1327; https://doi.org/10.3390/life15081327 - 21 Aug 2025

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Abstract

Thermophilic microorganisms are among the key natural sources of thermostable enzymes, found not only in geothermal areas but also in arid environments. In this study, eight Geobacillus strains were isolated from the arid sands of Aïn Sefra (Naâma, Algeria) and characterized both phenotypically [...] Read more.

Thermophilic microorganisms are among the key natural sources of thermostable enzymes, found not only in geothermal areas but also in arid environments. In this study, eight Geobacillus strains were isolated from the arid sands of Aïn Sefra (Naâma, Algeria) and characterized both phenotypically and genetically. All strains exhibited an optimal growth temperature of 70 °C, with most showing alkaliphilic pH preferences. Proteomic and molecular analyses (MALDI-TOF MS, 16S rRNA) identified Geobacillus kaustophilus as predominant, with BOX-PCR and RAPD-PCR revealing notable intraspecies diversity. All strains synthesized at least one thermostable enzyme (protease, amylase, laccase, or DNase) at their optimal temperature (70 °C), positioning them as promising candidates for biotechnological processes requiring extreme thermal conditions. Full article

(This article belongs to the Section Proteins and Proteomics)

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12 pages, 3493 KiB

Open AccessArticle

Beta-Blocker Use and Risk of Hip Arthroplasty in Osteoarthritis: A Retrospective Electronic Health Record Study

by Ping-Hao Chiang, Yang-Chi Lin, Jing-Yang Huang and Yun-Che Wu

Life 2025, 15(8), 1326; https://doi.org/10.3390/life15081326 - 20 Aug 2025

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Abstract

Objectives: This study aimed to determine whether prior use of a beta blocker (BB) is associated with the three-year risk of total hip arthroplasty after being diagnosed with osteoarthritis of the hip and compare risks across BB subtypes. Methods: Through the TriNetX database, [...] Read more.

Objectives: This study aimed to determine whether prior use of a beta blocker (BB) is associated with the three-year risk of total hip arthroplasty after being diagnosed with osteoarthritis of the hip and compare risks across BB subtypes. Methods: Through the TriNetX database, patients with hip OA were included and further divided into the with- and without-BB cohorts. BB users were defined as patients with prescriptions between 1 day and 1 year before hip OA diagnosis and at least one refill afterward. The index date was defined as the diagnosis date of hip OA. Moreover, the BB cohorts were split to evaluate the difference between different types of beta-blocking agents. After propensity score matching, a three-year risk of undergoing THA was calculated. Results: A total of 313,430 patients were involved in this study, including 23,580 with BB usage, and 289,850 without. After propensity score matching, 23,096 patients remained in each cohort. For the with- and without-BB cohort, the average ages were 69 ± 11.9 and 63.3 ± 11.4, with a majority being female (52.4% vs. 56%). After the three-year follow-up, the use of BBs (2333 vs. 1539, HR = 1.494; 95% C.I. = 1.4–1.593) was associated with a higher risk of undergoing THA. Furthermore, among the three types of BBs, the use of alpha-BBs showed the highest hazard ratio when compared to the without-BB cohort (788 vs. 470, HR = 1.639; 95% C.I. = 1.462–1.837). Conclusions: These findings suggest a potential association between BB use and hip arthroplasty in OA patients, warranting further investigation rather than immediate changes in clinical practice. Exploration into the detailed mechanisms is warranted and merits investigation in future studies. Full article

(This article belongs to the Section Medical Research)

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11 pages, 2475 KiB

Open AccessArticle

Comparing Performance of NAF and NT-2013 to SGA as Nutritional Assessment Tools in Systemic Sclerosis Patients

by Kittipadh Boonyavarakul, Chingching Foocharoen, Orathai Wantha and Veeradej Pisprasert

Life 2025, 15(8), 1325; https://doi.org/10.3390/life15081325 - 20 Aug 2025

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Abstract

Malnutrition is one of the common complications of patients with systemic sclerosis (SSc). However, several nutritional assessment tools are implemented in Thailand. The study aimed to compare the performance of nutritional assessment tools including Nutritional Assessment Form (NAF) and Nutritional Triage 2013 (NT-2013) [...] Read more.

Malnutrition is one of the common complications of patients with systemic sclerosis (SSc). However, several nutritional assessment tools are implemented in Thailand. The study aimed to compare the performance of nutritional assessment tools including Nutritional Assessment Form (NAF) and Nutritional Triage 2013 (NT-2013) to Subjective Global Assessment (SGA) in SSc patients. A cross-sectional diagnostic study was conducted in adult SSc patients at Srinagarind Hospital, Thailand. To elucidate the efficacy and correlations of these tools, descriptive statistics, Pearson correlation analyses, and kappa coefficient of agreement were employed. A total of 208 SSc patients were included, of which 70.7% were females. The respective mean age and body mass index was 59.3 years and 21.1 kg/m². Nearly half (45.7%) were malnourished based on SGA. Malnutrition diagnosis using the NAF and NT-2013 criteria were found in 80.3% and 34.6%, respectively. The respective sensitivity and specificity of NAF for diagnosis of malnutrition was 93.7% and 31.9%, while NT-2013 was 60.0% and 90.3%. Both NAF and NT-2013 had slight agreement with SGA with a kappa of 0.149 for NAF and 0.131 for NT-2013. Adjusting the cut-off points of NAF and NT-2013 could enhance sensitivity, specificity, and improve agreement for diagnosis with SGA. Full article

(This article belongs to the Special Issue Clinical Manifestations and Treatment of Autoimmune Diseases: 2nd Edition)

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17 pages, 2121 KiB

Open AccessArticle

Olfactory Network Functional Connectivity as a Marker for Parkinson’s Disease Severity

by Senal Peiris, Anupa Ekanayake, Jiaming Lu, Rommy Elyan, Katie Geesey, Ross Cottrill, Paul Eslinger, Xuemei Huang and Prasanna Karunanayaka

Life 2025, 15(8), 1324; https://doi.org/10.3390/life15081324 - 20 Aug 2025

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Abstract

Olfactory impairment was assessed in akinetic-rigid (PD_AR) and tremor-predominant (PD_T) subtypes of Parkinson’s disease (PD), classified based on motor symptoms. Seventeen PD_AR, fifteen PD_T, and twenty-four cognitively normal (CN) participants completed the University of Pennsylvania [...] Read more.

Olfactory impairment was assessed in akinetic-rigid (PD_AR) and tremor-predominant (PD_T) subtypes of Parkinson’s disease (PD), classified based on motor symptoms. Seventeen PD_AR, fifteen PD_T, and twenty-four cognitively normal (CN) participants completed the University of Pennsylvania Smell Identification Test (UPSIT). Groups were well-matched for age and demographic variables, with cognitive performance statistically controlled. Resting-state fMRI (rs-fMRI) and seed-based functional connectivity (FC) analyses were conducted to characterize olfactory network (ON) connectivity across groups. UPSIT scores were significantly lower in PD_AR compared to PD_T. Consistently, ON FC values were reduced in PD_AR relative to both PD_T and CN. FC of the primary olfactory cortex (POC) significantly differed between CN and the PD subtypes. Furthermore, connectivity in the orbitofrontal cortex and insula showed significant differences between PD_AR and PD_T, as well as between PD_AR and CN. Notably, ON FC between the left hippocampus and the posterior cingulate cortex (PCC) also differed significantly between PD_AR and PD_T. These findings reveal distinct ON FC patterns across PD_AR and PD_T subtypes. Variations in UPSIT scores suggest that motor symptom subtype is associated with olfactory performance. Moreover, ON connectivity closely paralleled the UPSIT scores, reinforcing a neural basis for olfactory deficits in PD. Given the accelerated motor and cognitive decline often observed in the PD_AR, these results support the potential of olfactory impairment as a clinical marker for disease severity. Full article

(This article belongs to the Special Issue New Insights into Parkinson’s Disease: From Molecular Basis to Therapy)

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14 pages, 997 KiB

Open AccessArticle

Differential Performance of Children and Adults in a Vision-Deprived Maze Spatial Navigation Task and Exploration of the Impact of tDCS over the Right Posterior Parietal Cortex on Performance in Adults

by G. Nathzidy Rivera-Urbina, Noah M. Kemp, Michael A. Nitsche and Andrés Molero-Chamizo

Life 2025, 15(8), 1323; https://doi.org/10.3390/life15081323 - 20 Aug 2025

Viewed by 331

Abstract

Spatial navigation involves the use of external (allocentric) and internal (egocentric) processing. These processes interact differentially depending on age. In order to explore the effectiveness of these interactions in different age groups (study 1), we compared the performance of children and adults in [...] Read more.

Spatial navigation involves the use of external (allocentric) and internal (egocentric) processing. These processes interact differentially depending on age. In order to explore the effectiveness of these interactions in different age groups (study 1), we compared the performance of children and adults in a two-session spatial maze task. This task was performed under deprived vision, thus preventing visual cues critical for allocentric processing. Number of correct performances and performance time were recorded as outcome measures. We recruited thirty healthy participants for the children (mean age 10.97 ± 0.55) and the adult (mean age 21.16 ± 1.76) groups, respectively. The results revealed a significantly higher number of correct actions and shorter performance times during maze solving in children compared to adults. These differences between children and adults might be due to developmental and cortical reorganization factors influencing egocentric processing. Assuming that activation of the posterior parietal cortex (PPC) facilitates egocentric spatial processing, we applied excitatory anodal tDCS over the right PPC in a second study with a different healthy adult group (N = 30, mean age 21.23 ± 2.01). Using the same spatial navigation task as in study 1, we evaluated possible performance improvements in adults associated with this neuromodulation method. Compared to a sham stimulation group, anodal tDCS over the right PPC did not significantly improve spatial task performance. Full article

(This article belongs to the Section Physiology and Pathology)

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20 pages, 495 KiB

Open AccessReview

Comorbidities Across Functional Neurological Disorder Subtypes: A Comprehensive Narrative Synthesis

by Ioannis Mavroudis, Katerina Franekova, Foivos Petridis, Alin Ciobîca, Dăscălescu Gabriel, Emil Anton, Ciprian Ilea, Sotirios Papagiannopoulos and Dimitrios Kazis

Life 2025, 15(8), 1322; https://doi.org/10.3390/life15081322 - 20 Aug 2025

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Abstract

Background: Functional Neurological Disorder (FND) encompasses a spectrum of symptoms—including motor, cognitive, and seizure-like manifestations—that are not fully explained by structural neurological disease. Accumulating evidence suggests that comorbid psychiatric and somatic conditions significantly influence the clinical course, diagnostic complexity, and treatment response in [...] Read more.

Background: Functional Neurological Disorder (FND) encompasses a spectrum of symptoms—including motor, cognitive, and seizure-like manifestations—that are not fully explained by structural neurological disease. Accumulating evidence suggests that comorbid psychiatric and somatic conditions significantly influence the clinical course, diagnostic complexity, and treatment response in FND. Objective: This study systematically explores psychiatric and medical comorbidities across major FND subtypes—Functional Cognitive Disorder (FCD), Functional Movement Disorder (FMD), and Psychogenic Non-Epileptic Seizures (PNES)—with an emphasis on subtype-specific patterns and shared vulnerabilities. Methods: We conducted a narrative review of the published literature, guided by systematic principles for transparency, covering both foundational and contemporary sources to examine comorbid conditions in patients with FCD, FMD, PNES, PPPD and general (mixed) FND populations. Relevant studies were identified through structured research and included based on methodological rigor and detailed reporting of comorbidities (PRISMA). Extracted data were organized by subtype and comorbidity type (psychiatric or medical/somatic). Results: Across all FND subtypes, high rates of psychiatric comorbidities were observed, particularly depression, anxiety, PTSD, and dissociative symptoms. FCD was predominantly associated with internalizing symptoms, affective misattribution, and heightened cognitive self-monitoring. FMD demonstrated strong links with trauma, emotional dysregulation, and personality vulnerabilities. PNES was characterized by the highest burden of psychiatric illness, with complex trauma histories and dissociation frequently reported. Somatic comorbidities—such as fibromyalgia, chronic pain, irritable bowel syndrome, and fatigue—were also prevalent across all subtypes, reflecting overlapping mechanisms involving interoception, central sensitization, and functional symptom migration. Conclusions: Comorbid psychiatric and medical conditions are integral to understanding the presentation and management of FND. Subtype-specific patterns underscore the need for individualized diagnostic and therapeutic approaches, while the shared biopsychosocial mechanisms suggest benefits of integrated care models across the FND spectrum. Full article

(This article belongs to the Section Medical Research)

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13 pages, 2445 KiB

Open AccessArticle

A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation

by Wenjing Yan, Yongwang Zhong and Shengyun Fang

Life 2025, 15(8), 1321; https://doi.org/10.3390/life15081321 - 20 Aug 2025

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Abstract

The endoplasmic reticulum (ER) maintains protein homeostasis through chaperone-mediated folding and ER-associated degradation (ERAD). Disruption of this quality control, particularly involving the ER chaperone GRP94, contributes to diseases such as hypercholesterolemia, cancer, and immune disorders, where defective GRP94-dependent folding and the trafficking of [...] Read more.

The endoplasmic reticulum (ER) maintains protein homeostasis through chaperone-mediated folding and ER-associated degradation (ERAD). Disruption of this quality control, particularly involving the ER chaperone GRP94, contributes to diseases such as hypercholesterolemia, cancer, and immune disorders, where defective GRP94-dependent folding and the trafficking of client proteins like PCSK9, integrins, and Toll-like receptors drive pathology. Here, we characterize NSC637153 (cp153), a small molecule identified in a drGFP-based ERAD dislocation screen, as a selective probe of GRP94-dependent processes. cp153 inhibits the dislocation of ERAD substrates, preferentially affecting luminal clients, increases PCSK9 secretion, and promotes LDLR degradation. Unlike ATP-competitive HSP90 inhibitors, cp153 does not induce HSP70 or destabilize AKT, suggesting that it perturbs GRP94 function by interfering with client interaction or folding. The identification of cp153 provides a useful tool to for probing GRP94’s role in protein folding, trafficking, ER quality control, and disease-relevant signaling pathways, and supports the development of client-selective GRP94-targeted therapies. Full article

(This article belongs to the Section Physiology and Pathology)

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25 pages, 2778 KiB

Open AccessArticle

Non-Variceal Upper Gastrointestinal Bleeding: A Retrospective Cohort of 364 Cases, Historical Comparison, and Updated Management Algorithm

by Laurențiu Augustus Barbu, Liviu Vasile, Liliana Cercelaru, Valeriu Șurlin, Stelian-Stefaniță Mogoantă, Gabriel Florin Răzvan Mogoș, Tiberiu Stefăniță Țenea Cojan, Nicolae-Dragoș Mărgăritescu and Anca Buliman

Life 2025, 15(8), 1320; https://doi.org/10.3390/life15081320 - 20 Aug 2025

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Abstract

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective [...] Read more.

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective observational study analyzed 364 consecutive adult patients diagnosed with NVUGIB and hospitalized at the First Surgical Clinic of the County Emergency Clinical Hospital Craiova between January 2009 and December 2014. Inclusion criteria required a confirmed diagnosis based on clinical presentation, laboratory findings, and upper gastrointestinal endoscopy (UGIE). Demographic variables, etiology, comorbidities, drug-induced triggers, laboratory parameters, onset-to-admission and onset-to-surgery intervals, endoscopic findings, therapeutic interventions (medical, endoscopic, surgical), rebleeding rates, and mortality were recorded and analyzed. Results were descriptively compared with historical data from the national and international literature. Due to the retrospective and aggregate nature of the data, survival analysis (Kaplan–Meier) was not applicable. Results: Peptic ulcers, erosive gastritis, Mallory–Weiss syndrome, and gastric neoplasms were the predominant etiologies. NSAID use, oral anticoagulation, and alcohol consumption emerged as major risk factors. Endoscopic hemostasis was achieved in the majority of cases; surgical intervention was required in 11.5% of patients, mainly for refractory or recurrent bleeding. The overall mortality rate was 10.9%, consistent with historical benchmarks. Comparative analysis revealed trends in etiology and management reflecting evolving clinical practice standards. Conclusions: NVUGIB remains a significant clinical challenge with persistent mortality and rebleeding risks. This cohort highlights the need for timely diagnosis, risk stratification, and an evidence-based therapeutic strategy integrating modern endoscopic and surgical options. An updated diagnostic and management algorithm is proposed to guide practical decision-making and optimize outcomes in similar tertiary care settings. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations)

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10 pages, 227 KiB

Open AccessArticle

Balance Assessment Under Different Conditions in Patients with Surgically Treated Pilon Fracture Compared to Healthy Controls: A Pilot Study

by Andrei-Daniel Bolovan, Gheorghe-Bogdan Hogea, Elena-Constanta Amaricai, Alexandra-Roxana Tapardea, Alina-Daniela Totorean, Anca-Raluca Dinu, Adrian-Emil Lazarescu, Mihai-Alexandru Sandesc and Jenel-Marian Patrascu, Jr.

Life 2025, 15(8), 1319; https://doi.org/10.3390/life15081319 - 20 Aug 2025

Viewed by 195

Abstract

Background: Tibial pilon fractures are usually high-energy fractures that are linked to higher rates of complications and poor clinical outcomes, particularly concerning pain and walking impairments. However, few studies have evaluated postural stability among patients surgically treated for pilon fractures. Objective: This pilot [...] Read more.

Background: Tibial pilon fractures are usually high-energy fractures that are linked to higher rates of complications and poor clinical outcomes, particularly concerning pain and walking impairments. However, few studies have evaluated postural stability among patients surgically treated for pilon fractures. Objective: This pilot study aimed to evaluate static and dynamic balance in patients who have undergone unilateral pilon fracture fixation, compared to matched healthy controls. Methods: Ten adult patients, post-fixation for unilateral pilon fracture (with clinical and radiological evidence of fracture healing and ability to bear full weight on the affected lower limb), completed a series of balance tests on K-Force plates. Ten matched healthy controls performed the same tests. Outcomes included CoP path length, CoP mean velocity, time to stabilisation (TTS), and peak force normalized to body weight. Results: Patients showed significantly increased mediolateral sway during bipodal stance (mean CoP velocity of 33.7 vs. 22.4 mm/s, p < 0.01), especially under eyes-closed conditions. In single-leg stance, CoP velocity on the affected limb was more than double that of controls (118 vs. 54 mm/s, p = 0.036). Dynamic tests revealed longer TTS after landing (1563 vs. 501 ms, p = 0.048) and lower force output during squats. The unaffected limb performed nearly normally in static tasks but was slower during dynamic stabilization. Conclusions: Even after fracture healing, patients with tibial pilon fractures show persistent sensorimotor deficits and impaired balance. Full article

(This article belongs to the Section Physiology and Pathology)

13 pages, 245 KiB

Open AccessReview

A Narrative Review of Clinical and Molecular Criteria for the Selection of Poor Candidates for Optimal Cytoreduction in Epithelial Ovarian Cancer

by George Pariza, Carmen Mavrodin, Alina Potorac, Octavian Munteanu and Monica Mihaela Cîrstoiu

Life 2025, 15(8), 1318; https://doi.org/10.3390/life15081318 - 20 Aug 2025

Viewed by 193

Abstract

Objective: The objective of this paper is to define “poor candidates” and to conduct an analysis of preoperative selection criteria, considering factors related to the patient, tumor burden, and histopathological characteristics, in the case of patients with advanced epithelial ovarian cancer (EOC) FIGO [...] Read more.

Objective: The objective of this paper is to define “poor candidates” and to conduct an analysis of preoperative selection criteria, considering factors related to the patient, tumor burden, and histopathological characteristics, in the case of patients with advanced epithelial ovarian cancer (EOC) FIGO III-IV with a low probability of optimal cytoreduction. Methodology: The authors of this narrative review conducted an analysis of articles published over a 20-year period (2005–2025), with the following selection criteria for the topics of the papers: advanced epithelial ovarian cancer (FIGOIII-IV), surgical indications in advanced ovarian cancer, poor candidates for surgery, and dependence between surgery and histopathologic and molecular type of EOC. They used using PubMed, Science Direct, and Scopus as databases. The results of the analysis were organized into three large chapters that grouped patient-related factors, tumor burden-specific factors, and histopathological criteria. Results: The authors identify a series of criteria with a high risk of unfavorable postoperative evolution, which led to delayed chemotherapy treatment and suboptimal management. These criteria are related to the patient’s field (ECOG > 3, Charlson Comorbidity Index (CCI) > 2, BMI > 25–30, hypoalbuminemia, hypokalemia), imaging or intraoperative factors predictive for residual tumor, and histopathological or genetic factors (presence of BRCA mutation favors optimal cytoreduction even in cases with high tumor burden; in the case of low-grade serous ovarian carcinoma, surgical intervention is recommended even if there are suboptimal resection criteria, accepting resection > 1 cm due to the poor response to specific chemotherapy treatment). Conclusions: Considering all these aspects, patient selection for primary debulking surgery (PDS) or NACT (neoadjuvant chemotherapy) and interval debulking surgery (IDS) should be conducted in oncological surgery centers highly specialized in gynecological neoplasms, thus ensuring an optimal therapeutic pathway for patients with EOC. Full article

(This article belongs to the Special Issue Current Approaches and Future Directions in the Treatment of Gynecologic Tumors: Molecular Biology, Diagnostic Advancements and Targeted Therapeutic Strategies)

17 pages, 1446 KiB

Open AccessArticle

Real-World Outcomes and Prognostic Factors of Polymyxin B Hemoperfusion in Severe Sepsis and Septic Shock: A Seven-Year Single-Center Cohort Study from Taiwan

by Wei-Hung Chang, Ting-Yu Hu and Li-Kuo Kuo

Life 2025, 15(8), 1317; https://doi.org/10.3390/life15081317 - 20 Aug 2025

Viewed by 292

Abstract

Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. [...] Read more.

Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. Methods: This retrospective cohort study included 64 adult patients with severe sepsis or septic shock who received at least one session of PMX-HP in a 25-bed tertiary medical ICU in Taiwan between July 2013 and December 2019. Demographic, clinical, microbiological, and treatment data were extracted. The primary outcome was 28-day mortality. Prognostic factors were analyzed using logistic regression. Results: The mean age was 66.1 ± 12.3 years; 67.2% were male. Pneumonia (29.7%) and intra-abdominal infection (18.8%) were the most common sources of sepsis, with E. coli and K. pneumoniae as leading pathogens. Median APACHE II score at ICU admission was 26 (IQR 21–32), and 79.7% received two PMX-HP sessions. The 28-day mortality rate was 46.9%, with ICU and hospital mortality both 53.1%. Non-survivors were older, had higher APACHE II scores, and more frequent use of continuous renal replacement therapy (CRRT). Positive changes in vasoactive-inotropic score (VIS) after PMX-HP were also more common among non-survivors. Multivariate analysis identified advanced age, higher APACHE II score, and CRRT requirement as independent predictors of mortality. Conclusions: In this real-world Asian ICU cohort, PMX-HP was used mainly for severe cases with a high disease burden and Gram-negative predominance. Despite its frequent use, overall mortality remained high. Prognosis was primarily determined by underlying disease severity, organ dysfunction (especially renal failure), and persistent hemodynamic instability. In this high-severity cohort, mortality appeared to be primarily driven by baseline organ dysfunction and persistent hemodynamic instability; PMX-HP session number or sequencing showed no association with survival. Given the absence of a contemporaneous non-PMX-HP control group, mortality observations in this cohort cannot be causally attributed to PMX-HP and should be interpreted with caution as hypothesis-generating rather than definitive evidence of efficacy. Further multicenter studies are needed to clarify the optimal role of PMX-HP in modern sepsis management. Full article

(This article belongs to the Section Medical Research)

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13 pages, 4494 KiB

Open AccessArticle

Molecular Dynamics Simulation Analysis of JAK1 Initial Activation: Phosphorylation-Induced Conformational Dynamics and Domain Interactions

by Xinyu Peng, Kefu Liu, Guodong Chen and Shengjie Sun

Life 2025, 15(8), 1316; https://doi.org/10.3390/life15081316 - 19 Aug 2025

Viewed by 236

Abstract

Janus kinase is critical for cytokine-mediated signaling, and its hyperactivation due to mutations drives various diseases. The activation of Janus kinase 1 (JAK1) involves a conformational transition from a closed to an open state, but the underlying mechanism remains unclear. This study investigates [...] Read more.

Janus kinase is critical for cytokine-mediated signaling, and its hyperactivation due to mutations drives various diseases. The activation of Janus kinase 1 (JAK1) involves a conformational transition from a closed to an open state, but the underlying mechanism remains unclear. This study investigates the roles of two tyrosine residues, Y1034 and Y1035, within the activation loop of the tyrosine kinase domain. Molecular dynamics simulations reveal that phosphorylation, particularly bisphosphorylation at Y1034 and Y1035, promotes the transition to the open conformation, with pY1035 exerting a greater influence than pY1034. Phosphorylation increases the negative charge on the TK domain surface, facilitating its dissociation from the FERM domain, while also weakening TK-FERM interactions. However, the loop between the TK and PK domains formed stable hydrogen bonds with other domains, hindering the full activation process. Using 1 µs molecular dynamics simulations is not sufficient for full activation. These findings elucidate the molecular mechanisms governing the JAK1 initial activation and provide insights for targeting its regulation in disease contexts. Full article

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

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25 pages, 2042 KiB

Open AccessArticle

CFTR Modulators Counteract F508del CFTR Functional Defects in a Pancreatic Epithelial Model of Cystic Fibrosis

by Alessandra Ludovico and Debora Baroni

Life 2025, 15(8), 1315; https://doi.org/10.3390/life15081315 - 19 Aug 2025

Viewed by 225

Abstract

Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, [...] Read more.

Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, such as the pancreas, has been less explored. This study evaluated the effects of the CFTR modulators, VX770 (ivacaftor), VX661 (tezacaftor), and VX445 (elexacaftor), administered either individually or in combination, on CFPAC-1 cells, a pancreatic ductal epithelial cell line derived from a cystic fibrosis patient harboring the F508del CFTR mutation. The cells were cultured and differentiated onto porous supports, and a panel of functional parameters was assessed. These included transepithelial electrical conductance, fluid reabsorption, apical surface fluid pH, protein concentration, and microviscosity, the latter analyzed with multiple particle tracking. To simulate a pro-inflammatory micro-environment, the cells were preconditioned with lipopolysaccharide (LPS). Treatment with VX661 and VX445 resulted in significant improvement in epithelial function, with the triple combination producing the most pronounced rescue. Pro-inflammatory stimulation by LPS increased the production of cytokine IL6, IL-8, and IL-1β, as well as the protein content of the apical surface fluid. Despite the LPS pro-inflammatory stimulus, CFTR modulators preserved or slightly enhanced their efficacy in restoring CFTR-mediated ion and fluid transport. However, they did not reduce cytokine expression under pro-inflammatory conditions. Collectively, these findings show that CFTR modulators can restore critical aspects of cystic fibrosis pancreatic epithelial physiology in vitro, even under pro-inflammatory stress, supporting their potential relevance beyond the airway disease. Full article

(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)

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10 pages, 507 KiB

Open AccessReview

Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review

by Carmen-Elena Florea, Bianca Bălaș-Maftei, Alexandra Rotaru, Patricia Lorena Abudanii, Stefana Teodora Vieru, Maria Grigoriu, Adelina Stoian and Carmen Manciuc

Life 2025, 15(8), 1314; https://doi.org/10.3390/life15081314 - 19 Aug 2025

Viewed by 358

Abstract

Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent [...] Read more.

Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body’s immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver’s central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

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16 pages, 952 KiB

Open AccessArticle

Encephalitis: Predictive Role of Clinical and Diagnostic Data on Outcome—A Monocentric Study

by Deborah K. Erhart, Luisa T. Balz and Hayrettin Tumani

Life 2025, 15(8), 1313; https://doi.org/10.3390/life15081313 - 19 Aug 2025

Viewed by 211

Abstract

Encephalitis is a potentially life-threatening condition with long-term neurological sequelae. However, data on early clinical, demographic, and diagnostic predictors of functional outcomes remain limited. We performed a retrospective monocentric study including 98 patients diagnosed with infectious encephalitis of various etiologies treated in the [...] Read more.

Encephalitis is a potentially life-threatening condition with long-term neurological sequelae. However, data on early clinical, demographic, and diagnostic predictors of functional outcomes remain limited. We performed a retrospective monocentric study including 98 patients diagnosed with infectious encephalitis of various etiologies treated in the University Hospital Ulm between January 2014 and December 2024. Ordinal logistic regression models were applied to evaluate associations between admission characteristics and functional outcome at discharge, as measured by the modified Rankin Scale. Three multivariate models incorporating clinical, demographic, and MRI/EEG variables explained up to 53% of the variance in mRS at discharge (p < 0.001), outperforming models based solely on CSF parameters. Key predictors of poor functional outcome included ‘altered consciousness’ (OR 7.08, p < 0.001), higher ‘mRS at admission’ (OR 0.03–0.07 across categories, p < 0.001), ‘focal/generalized EEG slowing’ (OR 9.97, p < 0.001), ‘epileptiform EEG activity’ (OR 17.49, p < 0.001), ‘MRI: myelitis’ (OR 16.44, p = 0.004), and ‘intrathecal IgM synthesis’ (OR 8.93, p = 0.018). Conversely, ‘longer hospitalization’ (OR 0.13–0.17 for different intervals, p < 0.006) and ‘intrathecal IgG synthesis’ (OR 0.05, p = 0.03) were associated with more favorable outcomes. Despite the single-center and retrospective aspects of this study, our findings underscore a multifactorial pattern of outcome determinants in infectious encephalitis, highlighting the prognostic relevance of initial neurological status, electrophysiological abnormalities, and neuroimaging features. Full article

(This article belongs to the Special Issue Encephalitis: From Molecular Pathophysiology to Therapy)

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23 pages, 4724 KiB

Open AccessArticle

Exploring the Proteomic Signature of Diabetic Nephropathy: Implications for Early Diagnosis and Treatment

by Duygu Sari-Ak, Fatih Con, Nazli Helvaci, Hayriye Ecem Yelkenci, Alev Kural, Ozgur Can and Mustafa Caglar Beker

Life 2025, 15(8), 1312; https://doi.org/10.3390/life15081312 - 19 Aug 2025

Viewed by 308

Abstract

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, characterized by progressive kidney dysfunction. Early detection and targeted therapies remain key challenges in managing DN. This study aims to identify proteomic alterations in DN patients compared to healthy controls, focusing on [...] Read more.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, characterized by progressive kidney dysfunction. Early detection and targeted therapies remain key challenges in managing DN. This study aims to identify proteomic alterations in DN patients compared to healthy controls, focusing on proteins involved in inflammation, oxidative stress, immune response, and metabolic dysregulation. Using mass spectrometry and advanced bioinformatics, we identified significant upregulation of proteins associated with platelet activation, immune regulation, and extracellular matrix remodeling, as well as downregulation of proteins linked to lipid metabolism, immune regulation, and structural stability. These findings highlight the molecular complexity of DN and suggest that altered protein expression plays a critical role in the progression of kidney damage. The identified proteins may serve as potential biomarkers for early diagnosis and therapeutic targets for DN. Our results underline the importance of proteomic analyses in advancing the understanding of DN pathogenesis and in developing strategies for personalized treatment to improve patient outcomes. Future research should focus on further elucidating these molecular mechanisms and their implications for clinical management. Full article

(This article belongs to the Special Issue From Pathophysiology to Pathology—an Update on Diabetic Kidney Disease)

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17 pages, 5091 KiB

Open AccessArticle

Identification of Hyalomma Ticks on Migratory Birds in Poland During the 2023 and 2024 Spring Seasons

by Klaudia Bylińska, Jan Rapczyński, Paweł Górski, Oliwia Obuch-Woszczatyńska, Damian Pietrzak, Karol Korzekwa, Małgorzata Krzyżowska and Piotr Bąska

Life 2025, 15(8), 1311; https://doi.org/10.3390/life15081311 - 19 Aug 2025

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Abstract

Ticks from the Hyalomma genus have recently garnered public attention in countries in Northern and Central Europe, as they are transported by migratory birds and might have established stable populations due to climate warming. The main threat associated with Hyalomma ticks is their [...] Read more.

Ticks from the Hyalomma genus have recently garnered public attention in countries in Northern and Central Europe, as they are transported by migratory birds and might have established stable populations due to climate warming. The main threat associated with Hyalomma ticks is their ability to transmit Crimean–Congo hemorrhagic fever virus (CCHFV), which can be fatal in up to 40% of cases. Here, we collected Hyalomma ticks from migratory birds during annual ringing actions in the spring seasons of 2023 and 2024. Four ticks were found on birds from the Acrocephalus genus and two on Hippolais icterina. The ticks were examined for the presence of Rickettsia spp., Babesia microti, Babesia divergens, Coxiella burnetii, Borreliella burgdorferi (s. l.), Anaplasma phagocytophilum, West Nile virus, and CCHF virus (CCHFV). The collected H. rufipes specimens were negative for tested pathogens, except for two ticks collected in 2024, which were positive for Rickettsia aeschlimannii. The data show that Hyalomma ticks are efficiently transported on birds preferring reedbeds or deciduous trees. The possibility of the occurrence of CCHF or rickettsiosis (induced by R. aeschlimannii) is currently assessed as low. Nevertheless, we have shown the transfer of Hyalomma ticks to Poland and indicated the need for careful future epidemiological monitoring of the presence of Hyalomma ticks. Full article

(This article belongs to the Section Animal Science)

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12 pages, 1482 KiB

Open AccessArticle

The Cortical Chlorenchyma Collaboration Gradient Dominates the Shoot Economics Space in Larix principis-rupprechtii

by Yang Yu, Huayong Zhang, Zhongyu Wang and Zhao Liu

Life 2025, 15(8), 1310; https://doi.org/10.3390/life15081310 - 19 Aug 2025

Viewed by 198

Abstract

Plant economics is based on carbon and nutrients rather than money. While leaf strategies aboveground are well characterized along an economic spectrum from “fast-growing and short-lived” to “slow and conservative,” economic models defined by aboveground shoot strategies remain unclear. Here, we offer a [...] Read more.

Plant economics is based on carbon and nutrients rather than money. While leaf strategies aboveground are well characterized along an economic spectrum from “fast-growing and short-lived” to “slow and conservative,” economic models defined by aboveground shoot strategies remain unclear. Here, we offer a comprehensive view of aboveground economics and show that collaboration between shoots and stem cortical chlorenchyma can break out of the one-dimensional economic spectrum, offering a full range of economic possibilities. Trait data from 1551 current-year shoots of a single species confirm the classical fast–slow “conservation” gradient but reveal that most variation is explained by an orthogonal “cooperation” gradient, ranging from self-reliant resource acquisition to outsourced nutrient synthesis via the stem cortical chlorenchyma. This expanded “shoot economics space” provides a solid foundation for predicting aboveground responses to environmental change. Full article

(This article belongs to the Section Plant Science)

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14 pages, 1656 KiB

Open AccessArticle

Correlations Between H. pylori Gastric Histopathology and NAFLD: A Retrospective Observational Study

by Ioana Alexandra Cardos, Cătălina Dănilă, Ovidiu Laurean Pop, Andrea Pop-Crisan, Ovidiu Pavel Burta, Andreea Camarasan, Felicia Marc and Simona Daniela Cavalu

Life 2025, 15(8), 1309; https://doi.org/10.3390/life15081309 - 18 Aug 2025

Viewed by 267

Abstract

The importance of H. pylori infection in the development of non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, insulin resistance, and non-alcoholic steatohepatitis has been shown in earlier studies. Our work aims to assess the risk of developing hepatic fibrosis in patients with or [...] Read more.

The importance of H. pylori infection in the development of non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, insulin resistance, and non-alcoholic steatohepatitis has been shown in earlier studies. Our work aims to assess the risk of developing hepatic fibrosis in patients with or without H. pylori, using noninvasive scores such as the APRI index, the BARD score, or the FIB-4 index, and to evaluate a possible association between the severity of fibrosis scores and histopathology evidence (such as chronic gastritis, gastric atrophy, gastric metaplasia, and gastric dysplasia). Moreover, the risk of preneoplastic stomach lesions was assessed in patients with hepatic fibrosis. The study enrolled a total of 110 patients: 65 were H. pylori-positive and 45 were negative. The differences in BARD, APRI, and FIB-4 indexes between H. pylori-positive and negative cases were assessed using the Mann–Whitney test. Noticeably higher BARD scores and APRI indexes were observed when comparing H. pylori-positive patients with NAFLD to H. pylori-negative ones. In terms of the FIB-4 index, an insignificant increase was observed in H. pylori-positive versus H. pylori-negative patients. Multiple linear regression was performed for the BARD scores and APRI indexes, revealing further significant associations with age and H. pylori status. A substantial correlation was demonstrated between H. pylori and elevated hepatic fibrosis scores in individuals with NAFLD and gastritis, suggested by the complexity features of infection and the intricacies of histology. Full article

(This article belongs to the Special Issue Helicobacter pylori: 2nd Edition)

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25 pages, 9525 KiB

Open AccessArticle

The Functional Ingredients of the Combined Extract of Mulberry Leaves and Butterfly Pea Flowers Improve Insomnia, Anxiolytic, Memory-Enhancing, and Antidepressant-like Activities in Stress-Exposed Rats

by Orraya Suna, Jintanaporn Wattanathorn, Supaporn Muchimapura, Wipawee Thukham-mee, Sitthichai Iamsaard and Nongnut Uabundit

Life 2025, 15(8), 1308; https://doi.org/10.3390/life15081308 - 18 Aug 2025

Viewed by 365

Abstract

At present, a novel herbal regimen targeting anti-insomnia, anti-anxiety, cognitive performance, and anti-depression effects is required due to the limitations of the current therapy. Based on the crucial role of oxidative stress in the pathophysiology of stress-related brain disorders, it was hypothesized that [...] Read more.

At present, a novel herbal regimen targeting anti-insomnia, anti-anxiety, cognitive performance, and anti-depression effects is required due to the limitations of the current therapy. Based on the crucial role of oxidative stress in the pathophysiology of stress-related brain disorders, it was hypothesized that the functional ingredient derived from mulberry leaves and butterfly pea flowers, which exhibits potent antioxidant activity, should protect against the disorders just mentioned. Male Wistar rats (180–200 g) were orally administered at doses of 125, 250, and 500 mg/kg BW once daily, 45 min before exposure to a 6-h immobilization stress for 14 days. Behavioral assessments, including sleep, anxiety, spatial memory, and depression, were assessed every 7 days. At the end of the study, corticosterone levels, oxidative stress markers, neurotransmitters, IL-6, BDNF, and neuron density in the prefrontal cortex and hippocampus were measured. The functional ingredients demonstrated anti-insomnia, anxiolytic, memory-enhancing, and antidepressant properties. It also increased neuron density and BDNF and activity of SOD and CAT enzymes, whereas corticosterone, GABA-T, AChE, MAO, IL-6, and MDA levels were reduced. A potential regimen targeting showed the benefits of anti-insomnia, anxiolytic, memory-enhancing, and antidepressant properties. However, further studies regarding the precise underlying mechanism and a clinical trial are essentially required. Full article

(This article belongs to the Section Physiology and Pathology)

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11 pages, 731 KiB

Open AccessArticle

Multimodal Assessment of Ocular Parameters in Patients with Severe Obstructive Sleep Apnea with Emphasis on Retinal Structural Changes

by Anita Pusic Sesar, Anja Cehajic, Antonela Geber, Mia Zoric Geber, Ivan Cavar and Antonio Sesar

Life 2025, 15(8), 1307; https://doi.org/10.3390/life15081307 - 18 Aug 2025

Viewed by 253

Abstract

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a potential risk factor for glaucoma due to its association with intermittent hypoxia and vascular dysregulation. The aim of this study was to investigate early glaucomatous changes in the eyes of patients with OSA. [...] Read more.

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a potential risk factor for glaucoma due to its association with intermittent hypoxia and vascular dysregulation. The aim of this study was to investigate early glaucomatous changes in the eyes of patients with OSA. Methods: This case–control study included 25 patients with OSA and 25 age- and sex-matched healthy controls. According to the STOP-Bang Questionnaire, patients with an intermediate or severe risk of OSA underwent polysomnography. Based on the apnea-hypopnea index, only patients with severe OSA were included in the study group. All participants underwent a full ophthalmological examination, with measurements of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness performed using optical coherence tomography (OCT). Results: Statistical comparisons revealed that intraocular pressure (IOP) was slightly elevated, while central corneal thickness (CCT) was slightly reduced in patients with OSA compared to healthy controls. OCT measurements showed an overall reduction in both RNFL and GCL thicknesses in the OSA group. Among these findings, only the differences in average and minimum GCL thickness in the left eye reached statistical significance. Conclusions: The results of our study indicate significant thinning of the GCL in patients with OSA, suggesting possible early glaucomatous changes and a potential link between OSA and glaucoma. Given the increasing prevalence of OSA, further large-scale, long-term studies are needed to better understand this relationship and its clinical implications. Full article

(This article belongs to the Special Issue Sleep and Sleep Apnea: Impacts, Mechanisms, and Interventions)

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10 pages, 441 KiB

Open AccessReview

Resmetirom in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis

by Fares Jamal, Amani Elshaer, Nour B. Odeh, Mayar H. Alatout, Tala Shahin, Astin R. Worden, Hashem N. Albunni, Blanca C. Lizaola-Mayo, Channa R. Jayasekera, David M. H. Chascsa, Hugo E. Vargas and Bashar A. Aqel

Life 2025, 15(8), 1306; https://doi.org/10.3390/life15081306 - 18 Aug 2025

Viewed by 502

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are among the most prevalent causes of chronic liver disease worldwide, closely linked to the global rise in overweight and obesity, type 2 diabetes, and metabolic syndrome. Until recently, [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are among the most prevalent causes of chronic liver disease worldwide, closely linked to the global rise in overweight and obesity, type 2 diabetes, and metabolic syndrome. Until recently, treatment options were limited to lifestyle interventions, with no approved pharmacologic therapies. Resmetirom, a liver-directed, selective thyroid hormone receptor beta (THR-β) agonist, is a promising disease-modifying agent that targets hepatic lipid metabolism, inflammation, and fibrosis. Clinical trials, including the pivotal phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials, have demonstrated significant improvements in liver fat reduction, lipid profiles, histological endpoints, and health-related quality of life, with a favorable safety profile. In March 2024, the FDA granted accelerated approval of resmetirom for adults with MASH and moderate-to-advanced fibrosis, marking a significant milestone in MASLD treatment. This review discusses the mechanistic rationale, preclinical data, and pivotal clinical trial outcomes supporting resmetirom’s role in MASLD/MASH management, while outlining ongoing research needs, including long-term safety, pediatric evaluation, and biomarker development for optimized patient selection. Full article

(This article belongs to the Section Physiology and Pathology)

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15 pages, 308 KiB

Open AccessArticle

The Impact of Aging on Meniscal Tears and Chondral Lesions in Men: Insights from First-Time Arthroscopic Knee Evaluation

by Sorin Florescu, Cristian Zaharia, George Andrei Drăghici, Dragoş Vasile Nica and Cosmin Grațian Damian

Life 2025, 15(8), 1305; https://doi.org/10.3390/life15081305 - 17 Aug 2025

Viewed by 312

Abstract

(1) Background: This is the first study investigating the age-related distribution of meniscal and chondral lesions in an all-male cohort undergoing first-time knee arthroscopy. (2) Methods: The study population included 876 adult men stratified into five decade-based age groups. Lesions were confirmed arthroscopically [...] Read more.

(1) Background: This is the first study investigating the age-related distribution of meniscal and chondral lesions in an all-male cohort undergoing first-time knee arthroscopy. (2) Methods: The study population included 876 adult men stratified into five decade-based age groups. Lesions were confirmed arthroscopically after MRI evaluation, with chondral injuries being graded using the ICRS system. (3) Results: The frequency of medial meniscal tears differed significantly across age strata (p = 0.042), increasing with age. No differences were detected for lateral meniscal damage or patellar damage. Age was a significant predictor of medial meniscal damage (OR = 1.04; p = 0.003), but not for other types of knee injuries. Medial meniscal damage correlated with patellar damage (men < 30, 50–59) and inversely with lateral damage (30–39); other correlations were non-significant. Chondropathy severity increased significantly with age in the medial femoral condyle and medial tibial plateau (p < 0.001), with severe (ICRS grade IV) lesions showing a steep rise after 60 years. Cartilage lesions at the level of the lateral knee compartment were, by contrast, less prevalent and less severe, with no significant variation across age groups. (4) Conclusions: These findings demonstrate that intra-articular knee pathology in men shifts with age, with medial compartment degeneration becoming increasingly prominent. Full article

(This article belongs to the Section Medical Research)

11 pages, 1294 KiB

Open AccessArticle

Cerebral Resistance Artery Histological Remodeling After Training—Sex Differences

by Tobias Hainzl, György L. Nádasy, Emese Róza Márka, Kamilla Nagy, Réka Kollarics, Anna-Mária Tőkés, Attila Oláh, Tamás Radovits, Béla Merkely, Nándor Ács, Szabolcs Várbíró, Attila Jósvai and Marianna Török

Life 2025, 15(8), 1304; https://doi.org/10.3390/life15081304 - 17 Aug 2025

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Abstract

Background: Chronic exercise has been linked to positive effects on cognitive function and brain health. The aim of our study was to investigate how exercise affects cerebral resistance artery morphology, with an underlying focus on potential sex differences. Methods: Wistar rats [...] Read more.

Background: Chronic exercise has been linked to positive effects on cognitive function and brain health. The aim of our study was to investigate how exercise affects cerebral resistance artery morphology, with an underlying focus on potential sex differences. Methods: Wistar rats were divided into male exercising (M.Ex; n = 6), female exercising (F.Ex; n = 5), male sedentary (M.Sed; n = 5), and female sedentary (F.Sed; n = 5) groups. After a 12-week swimming program, histological examinations of the intracerebral and pial arterioles were performed. SMA-DAB (smooth muscle actin) and resorcin-fuchsin (elastica) stained brain coronal sections were used for quantitative colorimetric analysis. Results: Investigating the effect of exercise, we found that in both pial and intracerebral arterioles, the elastic fiber density increased in both female and male exercising animals compared to the sedentary groups (p < 0.05 (M.Sed vs. M.Ex); p < 0.0001 (F.Sed vs. F.Ex)). As sex differences, we found that in female animals’ pial arterioles, the density of elastic fiber was increased compared to the male exercising group (p < 0.001 (M.Ex vs. F.Ex)). In pial arterioles, the smooth muscle density was higher in the male sedentary animals (p < 0.01 (M.Sed vs. F.Sed)); in intracerebral arterioles, the smooth muscle density increased with exercise in the male animals as well (p < 0.0001 (M.Ex vs. F.Ex)). Conclusions: Our results demonstrate that the increase in vascular elasticity is more pronounced overall in female animals. Full article

(This article belongs to the Special Issue Regulation of Cerebrovascular Resistance in Health and Disease: From Molecules to Humans)

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Life, Volume 15, Issue 8 (August 2025) – 178 articles

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