Search Results (718)

Major depressive disorder (MDD) is one of the most common diseases, affecting millions of people worldwide. Existing antidepressants do not allow sustainable remission to be achieved in many cases, probably due to insufficient understanding of the etiopathogenesis of MDD. The aim of this study was to identify the key genes, pathways, and master regulators associated with MDD based on a combination of genomic and transcriptomic data analyses. We performed a transcriptome-wide association study (TWAS) to identify the increase and decrease in transcription of particular genes that can be associated with MDD risk, the results of which were used to perform a pathway enrichment analysis that elucidated the pathways and processes associated with MDD. Besides changes in the metabolism of neurotransmitters, the association of some other processes with MDD was revealed, including changes in phospholipid and glycan metabolism, chromatin remodeling, RNA processing and splicing, and cell–extracellular matrix interaction. The transcriptomic analysis performed for brain regions mostly confirmed genome-level findings. The gene expression changes in the brain related to MDD were mostly sex-specific, and the transcription of many genes was changed in the opposite direction in males and females. Finally, master regulators were found, which are the proteins responsible for the transcriptional regulation of the revealed genes and represent the most important proteins contributing to MDD development. Full article

Background: Childhood obesity is a growing public health challenge, with altered taste perception potentially influencing food choices and contributing to weight gain. Objective: To determine detection thresholds for linoleic acid (fat taste) and sucrose (sweet taste) in children aged 6–12 years, and to explore associations with obesity, dietary intake, and food preferences. Methods: In this cross-sectional study, 100 Tunisian children (mean age: 8.05 ± 1.44 years; 54% girls; 45 obese, 55 non-obese) were recruited from an educational support center in Nabeul. Taste sensitivity was evaluated using the 3-alternative forced choice (3-AFC) method with ascending concentrations of linoleic acid (0.018–12.0 mM) for fat taste and sucrose (0.00125–0.32 mol/L) for sweet taste. Participants were categorized as tasters or non-tasters based on detection thresholds. Anthropometric measurements, 24 h dietary recalls, food frequency questionnaires, and food preference assessments were also conducted. Results: Low taste sensitivity was common (93% for sweet, 49% for fat). Girls were more often fat tasters than boys (68.6% vs. 31.4%, p = 0.003). Children with obesity had higher fat taste thresholds (median 3.00 mM, range 0.37–12.0) than non-obese peers (median 1.50 mM, range 0.018–6.0; p = 0.012), indicating reduced fat taste sensitivity. Linear regression showed a significant positive association between fat taste threshold and BMI (p = 0.001), meaning higher detection thresholds corresponded to higher BMI. Sweet taste thresholds did not differ significantly between children with and without obesity (p = 0.731). Sweet non-tasters consumed more sucrose (85.9 ± 64.9 g/d vs. 70.3 ± 62.3 g/d; p = 0.033) and reported more frequent table sugar use (p = 0.047). Fat non-tasters consumed more magnesium (425 ± 414 mg/d vs. 287 ± 60.8 mg/d; p = 0.026) and fiber (22.9 ± 7.51 g/d vs. 20.3 ± 5.32 g/d; p = 0.048) and reported higher intake frequencies of cheese (p = 0.039), sour cream (p = 0.004), and fast food (p = 0.012). Food preferences reflected similar patterns, with non-tasters generally rating high-fat or high-sugar foods more favorably. While most children demonstrated high detection thresholds, girls showed significantly higher fat taste sensitivity compared to boys (p = 0.03). Children with obesity exhibited significantly higher fat taste detection thresholds compared to non-obese children (p = 0.012), with thresholds ranging from 0.37 to 12.0 mM versus 0.018 to 6.0 mM, respectively. No significant difference was observed for sweet taste perception between weight groups (p = 0.731). Conclusions: Nearly half of the children exhibited reduced fat taste sensitivity, which was moderately associated with obesity and positively linked to BMI. Full article

Background: Sarcopenia is a critical complication in hemodialysis patients, associated with poor clinical outcomes, increased morbidity, and reduced quality of life. Despite this, its significance, prevalence, and risk factor data in developing countries remain limited. Objective: This study aimed to determine the prevalence of sarcopenia and identify its independent risk factors in patients undergoing maintenance hemodialysis, while evaluating its impact on physical performance, nutritional intake, and quality of life. Methods: A multicenter cross-sectional study was conducted across three hemodialysis units in Tunisia. Sarcopenia was diagnosed using EWGSOP2 (European Working Group on Sarcopenia in Older People 2) criteria based on muscle strength, muscle mass, and physical performance. Handgrip dynamometry, mid-arm and calf circumferences, gait speed, Short Physical Performance Battery (SPPB), and Timed Up and Go (TUG) test were employed. Nutritional intake was assessed using a 7-day food history. Quality of life and functional status were evaluated using the SF-36 and Barthel Index, respectively. Logistic regression was used to identify independent predictors of sarcopenia. Results: Among 118 patients (mean age 56.74 ± 14.44 years), the prevalence of sarcopenia was 42.4% (n = 50). Sarcopenic individuals exhibited significantly poorer physical performance than their non-sarcopenic counterparts. Marked reductions were observed in handgrip strength (p < 0.001, d = −1.60, very large), SPPB scores (p < 0.001, d = −1.55, very large), and increased TUG time (p < 0.001, d = 1.46, very large), indicating substantial functional impairment. Limb circumferences were also significantly lower in the sarcopenic group, including calf circumference (p = 0.002, d = −1.39, large) and mid-arm circumference (p = 0.013, d = −0.87, large). Gait speed was slower (p = 0.010, d = −0.40, small to moderate). Health-related quality of life was significantly compromised in sarcopenic individuals, with lower SF-36 total scores (p = 0.001, d = −1.96, very large) and reduced functional independence as measured by the Barthel Index (p = 0.010, d = −0.97, large). Hemoglobin levels were also significantly lower in the sarcopenic group (p = 0.048, d = −0.96, large). Dietary assessment revealed lower fiber intake (p = 0.006, d = 1.80, very large) and reduced magnesium consumption (p = 0.020, d = 0.94, large) among individuals with sarcopenia. In the multivariate logistic regression analysis, diabetes mellitus (OR = 2.14, 95% CI: 1.30–3.67, p < 0.001) and longer duration of hemodialysis (OR = 1.56, 95% CI: 1.20–2.71, p = 0.028) were identified as independent predictors of sarcopenia. A lower SPPB score (OR = 0.48, 95% CI: 0.35–0.65, p < 0.001) was associated with sarcopenia. Conclusion: Sarcopenia is highly common among hemodialysis patients and is independently linked to diabetes, treatment duration, and reduced physical performance. It significantly affects the quality of life and ability to perform daily activities. Routine screening with simple functional tests is crucial, especially in high-risk patients. Early intervention should include physical rehabilitation, nutritional support, and strict blood sugar management to decrease sarcopenia-related complications. Full article

Background: Despite the identification of various environmental factors that increase the risk of multiple sclerosis (MS), the effects of many factors on the etiology of MS remain to be elucidated. In this study, we aimed to investigate the effects of radon, a factor previously studied in relation to various other neurodegenerative diseases, on the epidemiology of MS. Methods: A door-to-door field study was conducted in residential areas with relatively high and low radon gas concentrations to determine the prevalence of MS. The study area comprises the Bolvadin and İhsaniye regions, which have different geological characteristics, such as seismic activity, active faults, and distributions of volcanic rocks. CR-39 detectors, with an accepted limit of 300 Bq/m³, were utilized to measure radon gas concentrations. During the screening field, the patients diagnosed with multiple sclerosis were confirmed with their hospital records. Mc Donald’s revised diagnostic criteria were used for multiple sclerosis diagnosis. Results: The regions were grouped into higher radon areas and lower radon areas. The İhsaniye city center, Kayıhan, Kemerkaya, Döğer, and Bolvadin city center were classified as higher radon regions, whereas Dişli, Yaylabağı, Gazlıgöl, and Özburun were identified as lower radon regions. A total of 40,841 individuals were surveyed in the field. The crude MS prevalence was 41.8/100,000 in settlements with high radon gas concentrations and 20.5/100,000 in settlements with low radon gas concentrations. Conclusions: In this study, we revealed that the prevalence of MS was greater in settlements with high radon gas concentrations than in settlements with low radon gas concentrations. These results demonstrated that radon gas is an important environmental risk factor in the etiopathogenesis of MS. Full article

Systemic sclerosis (SSc) is a complex connective tissue disease that affects the skin and internal organs and is characterized by immune dysregulation, progressive fibrosis, and microvascular dysfunction. Chronic tissue ischemia, accompanied by impaired angiogenesis, leads to the gradual loss of small vessels, resulting in clinical complications, such as Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and renal crisis. Emerging evidence highlights the crucial regulatory role of microRNAs (miRNAs) in vascular homeostasis through the modulation of key signaling pathways and endothelial cell activity. Dysregulated miRNAs influence fibroblast proliferation, inflammatory responses, and immune cell activity in SSc, contributing to disease progression. Current knowledge is still limited, highlighting the need for further research to elucidate the miRNAs network involved in the etiopathogenesis of SSc. The use of miRNA-based biomarkers is gaining tremendous attention for early diagnosis, risk stratification, classification, and the prediction of therapeutic responses. This review provides insights into angiogenesis-related miRNAs involved in SSc pathogenesis, discusses their relevance as biomarkers, and explores their promise as therapeutic targets. Advancing our knowledge of miRNAs-mediated regulatory networks may open new possibilities for personalized approaches to SSc management. Full article

Alopecia areata is a persistent autoimmune-mediated disease with a complicated pathophysiology and a prevalence of approximately 2%. The exact pathogenesis is yet to be identified; nevertheless, environmental factors, autoimmune mechanisms and genetic factors among others all contribute to the multifactorial etiopathogenesis of the disease. Even though alopecia areata is frequently self-limiting and recovery can occur on its own, it can cause esthetic challenges that might precipitate psychosocial disorders. This article aims to provide a clinical update on alopecia areata comparing the most important international guidelines, with particular emphasis on current treatment options and comorbidities. Full article

Background: The etiopathogenesis of IBD is not fully known; however, both genetic and environmental risk factors, including diet, are contributors to the disease. The present study aimed to determine the effect of dietary inflammatory potential, assessed using the Dietary Inflammatory Index (DII), on disease activity and inflammatory markers, such as IL-6, IL-1β, and IL-10, in patients with IBD. Methods: The study enrolled 90 patients with IBD. Dietary intake was assessed based on a 24 h questionnaire interview conducted in each subject three times. Based on these data, the DII for each subject was calculated. The serum levels of IL-6, IL-1 β, and IL-10 were determined with the quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The mean DII value was −0.39 ± 0.52 and did not differ significantly between the groups with CD and UC (−0.42 ± 0.47 vs. −0.37 ± 0.54, p = 0.6452, respectively); however, it was remarkably lower among patients in remission and with mild disease compared to those in the active phase of the disease (−0.45 ± 0.61 vs. −0.23 ± 0.65, p = 0.0217). Considering the DII tertiles, the subjects differed significantly in terms of age and disease activity. Logistic regression analysis of disease severity and DII in the crude model revealed that the probability of severe disease in IBD patients increased with higher DII scores. Conclusions: The results of the present study revealed a significant association between pro-inflammatory diet and IBD severity, which indicates a need to formulate an anti-inflammatory diet to reduce disease severity in patients with CD and UC. Full article

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are frequently associated with comorbid disorders, including coronary artery disease and osteoarthritis, in which ectopic calcification with basic calcium phosphate crystals commonly affects arteries and articular cartilage, respectively. Accepting the 2024 G-CAN Gold Medal, I review my research philosophy for translational etiopathogenesis investigation in gout and CPPD, atherosclerosis, responses to arterial injury, and osteoarthritis. Since molecular homeostasis points to pathophysiology and vice versa, I have followed selected molecular players and pathways to phenotypes. Typically, behind each disease target is another target. Illuminating passageways between etiopathogenic pathways is especially productive when using approaches beyond conventional “omics” to reveal the impact of specific post-translational protein modifications, and changes in protein conformation, complex assembly, and interactomes. Highlighting these concepts, I review my past studies on specific molecular pathways, and current perspectives for the following: (i) PP_i, NPP1, ANKH, and transglutaminase 2 (TG2); (ii) relationships between NPP1, ANKH, Vanin-1 Pantetheinase, and ectopic chondrogenesis; (iii) intersections between adenosine, AMPK, CXCL8 and its receptor CXCR2, the receptor for advanced glycation endproducts (RAGE) and chondrocyte hypertrophy; (iv) lubricin homeostasis and proteolysis; (v) receptor for advanced glycation endproducts (RAGE) and TG2-catalyzed post-translational calgranulin modification; (vi) complement activation and C5b-9 assembly, and the nucleotide-bound conformation of TG2. The inescapable conclusion is that these molecular pathways tightly knit crystal arthropathy with both arterial and osteoarthritis comorbidity. Full article

For nearly 30 years, a chronic disease causing severe chronic subcutaneous edema of unknown etiology has been affecting cattle in the Central–Northern and Central–Southern mesoregions of the State of Bahia, Brazil. In this research we investigated 15 outbreaks of the disease, from October 2023 to April 2025, to determine its etiopathogenesis, epidemiology, clinical signs, and pathology. The disease occurs during the dry season in areas of native forest. It is characterized by chronic subcutaneous edema, especially in the regions of the head, dewlap, chest, and thoracic limbs, and by hydropericardium, hydrothorax, ascites, and right ventricular dilation. Marked hypertrophy of smooth muscle cells in the tunica media of arteries and arterioles, sometimes with an eccentric, irregular, and asymmetric arrangement, were the main histologic lesions observed. The thicknesses of the media of pulmonary and heart arteries and arterioles of 10 affected cattle were significantly thicker than those from 10 control cattle. The tunica adventitia was thickened with increased deposition of collagen, and the intima was hyperplasic. The aorta and carotid arteries showed multifocal smooth muscle cell proliferation in the tunica media. It is concluded that the disease is due to right heart failure due to pulmonary arterial hypertension (chronic cor pulmonale). Epidemiological data and inspections of affected pastures suggest that the disease is caused by a toxic plant. Full article

Polycystic ovary syndrome (PCOS) is a hormonal disorder with complex, multifactorial and still not fully explained etiopathogenesis. It is believed that the cause is a combination of genetic and environmental factors. Background: With the aim to better understand PCOS etiology, the study examines body composition and compares the occurrence of lipid disorders and visceral adipose tissue depending on the adopted Rotterdam phenotypes. Methods: The study included 242 patients classified into four classic Rotterdam phenotypes. Clinical data from patients were collected and carefully analyzed to determine the relationship between the occurrence of lipid disorders and the visceral adiposity index (VAI). Results: The results obtained after assessing the differences between the Rotterdam phenotypes were not statistically significant. Differences in the levels of coefficients included in the VAI equation in the given phenotypes were also analyzed, as follows: waist circumference (p-value = 0.3415), BMI (p-value = 0.7112), TG [mmol/L] (p-value = 0.5341) and HDL [mmol/L] (p-value = 0.2302). None of the differences were statistically significant. Conclusions: Although the results did not show a clear association between VAI and the individual Rotterdam PCOS phenotypes, this coefficient can be used in the assessment of cardiometabolic risk in women with PCOS regardless of the adopted classification. Full article

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disorder of the oral cavity, although its etiology is still unknown. The present study aimed to identify the proteomic profile associated with the RAS inflammatory process, thereby enhancing our understanding of its etiopathogenesis. We compared salivary protein profiles of RAS patients during an active episode of oral ulceration (30 patients, mean age 36.9) to those from healthy donors without a history of RAS (30 healthy subjects, mean age 37.9). Using 2D-electrophoresis and mass spectrometry (MALDI-TOF) analysis, we identified 17 proteins that were differentially expressed in the two groups. Notably, Cystatin SN (CST1) appeared to be significantly downregulated in RAS patients. These findings were validated by Western blot analysis: CST1 was detected in only 3 of the 30 RAS cases, while it was strongly expressed in all the healthy subjects. Although preliminary, our results suggest a potential role for CST1 in the etiopathogenesis of RAS. Interestingly, the relative absence of CST1 in RAS patients seems to align with some clinical and molecular features of this disease. Full article

Cystic fibrosis (CF) is a multisystemic genetic disorder caused by dysfunctional CF transmembrane conductance regulator (CFTR) protein, leading to impaired chloride and bicarbonate transport. Advances in care have increased patient lifetime, revealing chronic complications such as CF-related bone disease (CFBD), characterized by low bone mineral density and increased fracture risk. CFBD results from a complex interplay of factors including chronic inflammation, nutritional deficiencies, hormonal imbalances, and impaired glucose metabolism. Pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, and IL-8) promote osteoclastogenesis, disrupting bone remodeling via the RANK/RANKL/OPG pathway. In vivo murine and in vitro studies have elucidated the pathogenic mechanisms underlying CFBD, highlighting CFTR’s role in bone cell function. Diagnosis is based on clinical evaluation, bone densitometry, and laboratory assessments of bone metabolism markers. In this narrative review we highlight the recent scientific evidence on the etiopathogenesis and the current strategies for management of CFBD. Full article

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia characterized by progressive frontotemporal hairline recession, frequently accompanied by eyebrow and body hair loss. Once considered rare, FFA is now recognized as the most common form of scarring alopecia, predominantly affecting postmenopausal women. Although its pathogenesis remains unclear, hormonal, genetic, autoimmune, and environmental factors have been implicated. Among environmental contributors, the potential role of cosmeceuticals has received increasing attention, with particular emphasis on sunscreen and facial moisturizers. Patch testing has identified sensitization to allergens frequently found in these products. However, due to numerous limitations in the existing studies, the association between cosmeceuticals and FFA remains controversial. As the prevalence of FFA continues to rise alongside widespread cosmetic product use, understanding their potential role in disease pathogenesis is essential. Current findings highlight the need for further investigation into environmental triggers. Full article

Fibromyalgia has unclear etiopathogenesis, no curative treatment, and a severe impact on the quality of life. Gratitude practices have been shown to enhance the quality of life in chronic diseases. This systematic review, performed by searching five electronic databases, following the PRISMA guidelines, is the first aiming to evaluate the impact of gratitude in fibromyalgia. Data from eligible studies was extracted and a narrative synthesis was performed. Six articles (four observational studies and two randomized clinical trials) were included. Higher levels of gratitude are associated with reduced symptom severity, an enhanced quality of life, improved well-being, and the improvement of pain-related outcomes in fibromyalgia patients. Gratitude is related to reduced stress, anxiety, and depression; better sleep patterns; and less functional impairment in FM patients. Higher levels of gratitude contribute to a better quality of life, general well-being, and higher functioning capacity in fibromyalgia patients. Based on the results gathered in this systematic review, we propose that gratitude should be investigated as a therapeutic adjuvant in the management of fibromyalgia. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article