Search Results (34,593)

Background: This systematic review aims to evaluate the effectiveness of various treatments and strategies for managing infections caused by Vibrio parahaemolyticus and Vibrio alginolyticus in whiteleg shrimp (Penaeus vannamei). Shrimp aquaculture faces significant challenges from these pathogens, resulting in substantial economic losses. Vibrio species are known for their ability to form biofilms, enhancing their resistance to conventional treatments. Methods: The review follows the PRISMA guidelines, searching Scopus and PubMed databases for relevant studies on antibiotics and plant extracts used against these pathogens. Data were extracted and analysed to assess the effectiveness of different treatments, including antibiotics, plant extracts, and combined therapies. Results: The review found that while antibiotics remain widely used, the emergence of antibiotic-resistant strains necessitates alternative strategies. Plant extracts, rich in bioactive compounds such as flavonoids, showed promising antimicrobial activity. Combined therapies involving antibiotics and plant extracts were also explored for their potential to enhance treatment efficacy and reduce resistance. Conclusions: The findings underscore the importance of addressing biofilm formation in managing Vibrio-related infections and highlight the need for further research to develop sustainable and effective treatment protocols for shrimp aquaculture. Full article

Background: Staphylococcus aureus is a major zoonotic and foodborne pathogen with substantial One Health implications, yet its prevalence, resistance, and virulence potential within the aquaculture sector in Nigeria remains poorly characterized. Objectives: To supplement existing information, this current study investigated the prevalence, clonal distribution, antimicrobial resistance, and virulence gene profiles of S. aureus isolates from fish, fish water, and occupationally exposed fish handlers in Anambra State, Southeast Nigeria. Methods: A total of 607 samples—comprising 465 surface swabs from raw and processed fish, 36 fish water samples, and 106 nasal swabs from fish handlers—were processed using selective culture, biochemical tests, antimicrobial susceptibility testing, DNA microarray analysis, spa typing, and SCCmec typing. Results: S. aureus was recovered from 16.5% (100/607) of the samples. Fourteen (14%) isolates were methicillin-resistant (MRSA), harboring mecA and SCCmec types IV and V, with a combined MRSA prevalence of 2.3%. Multidrug resistance was observed in 52.2% of isolates (mean Multiple Antimicrobial Resistance index: 0.23), with 19 resistance genes spanning nine antimicrobial classes—including heavy metal and biocide resistance. Twenty-eight spa types across 13 clonal complexes (CCs) were identified, with CC1, CC5, and CC8 predominating. The detection of shared spa types between fish and handlers indicates potential cross-contamination. Detected virulence genes included those for accessory gene regulators (agrI-IV), Pantone–Valentine leucocidin (lukFS-PV), toxic shock syndrome (tsst-1), hemolysins (hla, hlb, hld/hlIII, hlgA), biofilm formation (icaA, icaD), immune evasion (chp, scn, sak), enterotoxins (sea, seb, sec, sed, egc, and others), exfoliative toxins (etA, etB), epidermal cells differentiation (edinA, edinB), and capsular types (cap5, cap8). Conclusions: This study reveals that the aquaculture sector in Southeast Nigeria serves as a significant reservoir of genetically diverse, multidrug-resistant S. aureus strains with robust virulence profiles. These findings highlight the necessity of integrated One Health surveillance and targeted interventions addressing antimicrobial use and hygiene practices within aquatic food systems. Full article

The gut microbiota plays an essential role in human health, influencing gut–brain communication. Imbalances in this microbial ecosystem, termed dysbiosis, have been associated with increased gut permeability and gastrointestinal symptoms commonly reported in autism spectrum disorder (ASD), without implying a direct causal role in ASD itself. This study aimed to determine whether alterations in gut microbiota exist in individuals with Fragile X Syndrome (FXS), with or without ASD, compared to ASD patients and neurotypical controls, and to identify microbiota biomarkers associated with these disorders. Stool samples from Caucasian individuals aged 3–18 years belonging to four groups (ASD, FXS, FXS + ASD, and controls) were analysed by amplifying the V3–V4 region of the bacterial 16S rRNA gene to characterize microbiota composition. Significant differences were found among patient groups compared to neurotypical controls, with notable similarities between the ASD and FXS + ASD groups. Additionally, specific microbiota biomarkers were identified for each patient group. These findings suggest that distinct microbiota alterations are associated with FXS and ASD, which may contribute to a more accurate characterization of symptoms in these disorders and could serve as potential biomarkers for assessing neurodevelopmental risk. Full article

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), dilated (DCM), and hypertrophic (HCM) cardiomyopathies. The Uniform Manifold Approximation and Projection (UMAP) clustering identified major cardiac cell types, revealing neuron-specific transcriptional programmes. Neuronal populations showed enriched expression of neurodevelopmental disorder-linked genes (NRXN3, CADM2, ZNF536) and synaptic signalling pathways. CHD cardiac neurons exhibited upregulated markers of cognitive dysfunction (APP, SNCA, BDNF) and neurodevelopment regulators (DNMT1, HCFC1) across subtypes. Cardiomyocyte troponin elevation correlated with neuronal exosome receptor expression (TLR2, LRP1), suggesting intercellular communication. Gene ontology analysis highlighted overlaps between cardiovascular disease pathways and neurodevelopmental disorder signatures in CHD neurons. These findings provide the first neuro-genomic map of cardiac neurons in CHD, linking cardiac pathology to neural outcomes through transcriptional dysregulation. Further, the systemic analysis of clinical findings in CHD further supports the risk of neurodevelopmental impacts. In summary, this study identifies transcriptional dysregulation within cardiac neurons in CHD and, together with a systemic analysis of clinical data, provides molecular evidence linking cardiac pathology to neurodevelopmental and cognitive impairments. Full article

Background/Objectives: Increased dehydroepiandrosterone sulfate (DHEAS) is used as a diagnostic marker of hyperandrogenism in women with polycystic ovary syndrome (PCOS). The mechanisms of adrenal hyperandrogenism in PCOS include hyperinsulinism as a potential stimulator, but results of studies associating insulinemia with DHEAS in PCOS are conflicting. The objective of this study was to evaluate the factors associated with DHEAS levels in PCOS, focusing on insulinemia. Methods: We performed a cross-sectional retrospective study in a total of 257 patients with PCOS (Rotterdam criteria) evaluated in our tertiary center of endocrinology. Clinical and biochemical parameters included body mass index (BMI), serum DHEAS, total testosterone and sex hormone-binding globulin (SHBG), insulin and glycaemia at fasting and 2 h during the oral glucose tolerance test (OGTT), and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. Results: The comparative analysis of PCOS divided into DHEAS tertiles revealed that patients in the upper tertile were younger (p < 0.05) and had higher 2 h insulin in the OGTT (p < 0.05) than the lower tertile, while fasting insulin and HOMA-IR were not different. DHEAS correlated negatively with age (r = −0.146, p < 0.05) and positively with 2 h insulinemia (r = 0.246, p < 0.001), while fasting insulin and HOMA-IR did not correlate with DHEAS in all PCOS. In stepwise linear regression models, 2 h insulin remained a positive independent predictor for DHEAS only in non-obese PCOS (p < 0.0001). Conclusions: Our data indicate a positive association between stimulated insulin and DHEAS in PCOS. Two-hour insulin in OGTT was an independent predictor of DHEAS in non-obese PCOS, suggesting that DHEAS might be a reliable marker for the stimulatory insulin effect on adrenal steroidogenesis in non-obese PCOS patients. Full article

Alpha-gal syndrome (AGS) is an IgE-mediated allergy, triggered by a carbohydrate—galactose-α-1,3-galactose (α-Gal). AGS is marked by a delayed onset of symptoms, typically occurring 3–8 h after the ingestion of red meat or other mammalian-derived products. The primary risk factor is believed to be tick bites, which sensitize individuals through the introduction of α-Gal via tick saliva. Diagnosis of AGS is based on a combination of anamnesis and detection of α-Gal-specific IgE antibodies. We evaluated 28 patients with a history of unexplained anaphylaxis, angioedema, and/or urticaria, in whom the diagnostic work-up included the assessment of serum IgE specific to alpha-gal. Elevated alpha-gal-specific IgE levels were detected in five patients. Among them, four reported anaphylactic episodes following meat consumption. In three cases, symptoms developed during the evening or nighttime, typically 3 to 6 h after the last meal. One patient experienced anaphylaxis within one hour after a meal. Another patient presented angioedema up to 24 h after meat consumption and was also tested positive for specific IgE against beef and pork allergens. The AGS case series showed variability in clinical picture and time to reaction. In patients presenting idiopathic anaphylaxis and nonspecific symptoms after red meat consumption, AGS should be considered as a differential diagnosis. Full article

Intestinal disorders such as inflammatory bowel diseases (IBDs), Crohn’s disease, malabsorption syndromes, and gastrointestinal fistulae (GIFs) are often characterized by chronic inflammation, epithelial barrier disruption, impaired stromal remodeling, and defective angiogenesis. These multifactorial alterations hinder tissue repair and contribute to poor clinical outcomes, with limited efficacy from current therapeutic options. Despite recent advances in surgical and endoscopic techniques, current treatment options remain limited and are frequently accompanied by high morbidity and costs. In this context, regenerative medicine offers a promising avenue to support tissue repair and improve patient care Regenerative medicine offers a promising avenue to restore intestinal homeostasis using advanced biomaterials and cell-based therapies. In this study, we developed a 3D-bioprinted model based on patient-derived stromal vascular fraction (SVF) embedded in a GelMA hydrogel, designed to promote intestinal tissue regeneration. To identify the most suitable hydrogel for bioprinting, we initially evaluated the mechanical properties and biocompatibility of four distinct matrices using bone marrow-derived mesenchymal stromal cells (BM-MSCs). Among the tested formulations, GelMA demonstrated optimal support for cell viability, low oxidative stress, and structural stability in physiologically relevant conditions. Based on these results, GelMA was selected for subsequent bioprinting of freshly isolated SVF. The resulting bioprinted constructs enhanced key regenerative processes across multiple compartments. The SVF-laden constructs significantly enhanced intestinal epithelial cell viability and tight junction formation, as shown by increased trans-epithelial electrical resistance (TEER). Co-culture with fibroblasts accelerated wound closure, while endothelial cells exhibited increased tube formation in the presence of SVF. Together with VEGF secretion, indicating strong paracrine and angiogenic effects. By supporting epithelial, stromal, and vascular regeneration, this approach provides a versatile and translational platform for treating a broad spectrum of intestinal pathologies. Full article

Congenital ichthyoses, now grouped under the acronym EDD (Epidermal Differentiation Disorders), include nonsyndromic forms (nEDD) that may be caused by loss-of-function mutations in the CDSN gene encoding corneodesmosin (CDSN-nEDD, formerly Peeling skin syndrome type 1). It is characterized by skin peeling, inflammation, itching and food allergies, while no specific therapy is currently available. High levels of KLK5, the serine protease that initiates the desquamation cascade, are found in the epidermis of CDSN-nEDD patients. Thus, we hypothesized that KLK5 inhibition would alleviate the symptoms of CDSN-nEDD and could serve as a new pharmacological target. A human epidermal equivalent (HEE) model for CDSN-nEDD was developed using shRNA-mediated CDSN knockdown. This model was characterized and used to assess the role of KLK5 knockdown on CDSN-nEDD. Also, Klk5^−/− mice were crossed with Cdsn^epi−/− mice, the murine model of CDSN-nEDD, to examine in vivo the effect(s) of Klk5 deletion in CDSN-nEDD. Both models recapitulated the CDSN-nEDD desquamating phenotype. Elimination of KLK5 aggravated the CDSN-nEDD phenotype. Epidermal proteolysis was surprisingly elevated, while severe ultrastructural (corneo)desmosomal alterations increased epidermal barrier permeability and stratum corneum detachment was manifested. Based on these results, we concluded that targeting epidermal proteolysis with KLK5 ablation cannot compensate for the loss of corneodesmosin and rescue over-desquamation of the CDSN-nEDD. Possibly, in the absence of KLK5, other proteases take over which increases the severity of over-desquamation in CDSN-nEDD. The translational outcome is that over-desquamation may not always be rescued by eliminating epidermal proteolysis, but fine protease modulation is more likely required. Full article

Malnutrition afflicts millions of the world’s children and predisposes to death from diarrhea and infectious diseases. Children with severe acute malnutrition (SAM) are at highest risk. Our review of the endocrinology and metabolomics of SAM implicates critical roles for white adipose tissue and its regulatory hormones and growth factors in the adaptation to nutritional deprivation and the restoration of metabolic homeostasis: white adipose provides substrates and energy for hepatic glucose production and cardiopulmonary and central nervous system function, and products of fat metabolism inhibit muscle glucose uptake and utilization and spare muscle protein. Collectively, these effects maintain glucose availability for the brain, red blood cells, and renal medulla and conserve muscle mass. White adipose tissue also secretes leptin, which facilitates the immune response and may protect against mortality from infection. Euglycemia and survival in SAM are thereby prioritized over linear growth, which is suppressed owing to inhibition of insulin-like growth factor 1 production and action. Diversion of energy from growth serves to maintain essential bodily functions in critically ill malnourished children, who have limited energy reserves. Thus, short-term reductions in growth rate have adaptive benefits in SAM. Under favorable conditions, clinical and metabolic recovery are accompanied by catch-up growth, which can mitigate, and in many cases reverse, the stunting of growth in childhood. Nevertheless, clinical recovery can be complicated by preferential accrual of central fat and a relative deficiency of lean/skeletal mass, with potential long-term complications including insulin resistance, glucose intolerance, and metabolic syndrome. Full article

Lignans are plant-derived biphenolic compounds with multiple hydroxyl groups, which, upon ingestion, are metabolized by gut microbiota into enterolignans—enterolactone and enterodiol. These mammalian metabolites exhibit structural similarity to estradiol, enabling lignans to modulate hormonal balance and exert estrogen-like effects. A growing body of evidence highlights their broad spectrum of health-promoting properties, including antioxidant, anti-inflammatory, and hormone-regulating effects. Lignans have shown potential in alleviating menopausal symptoms, preventing estrogen-dependent cancers, and mitigating conditions such as cardiovascular disease, diabetes, and metabolic syndrome. Additionally, their antimicrobial activity against bacteria, fungi, and viruses is being increasingly recognized. This review provides a comprehensive and up-to-date synthesis of current knowledge. It uniquely integrates the latest insights into lignan biosynthesis, gut microbiota-mediated metabolism, and clinically relevant outcomes. Importantly, this review incorporates recent findings from prospective cohort studies and meta-analyses and sheds light on emerging therapeutic applications, including antifungal activity—an area rarely covered in earlier literature. By presenting a holistic perspective, this review advances our understanding of lignans as multifaceted compounds with significant potential in preventive and therapeutic health strategies. Full article

Background: The coexistence of sickle cell disease (SCD), vascular Ehlers–Danlos syndrome (vEDS), primary ciliary dyskinesia (PCD), and Phelan–McDermid syndrome (PMS) in a single pediatric patient is extremely rare and poses substantial diagnostic and management challenges. Case presentation: We report an 8-year-old male from Jazan, Saudi Arabia, born to consanguineous parents, with early-onset SCD, followed by the identification of vEDS, PCD, and PMS through clinical presentation and whole exome sequencing. His disease course has been exceptionally severe, marked by monthly hospitalizations, multiple PICU admissions, and a wide spectrum of systemic complications. Conclusions: The coexistence of SCD, vEDS, PCD, and PMS may lead to synergistic vascular, pulmonary, and neurodevelopmental compromise, demanding multidisciplinary long-term management. This case underscores the need for a comprehensive targeted genetic assessment in patients with unusually aggressive or syndromic SCD phenotypes, particularly in regions with high levels of consanguineous marriages. Full article

The prevalence of hyperuricemia with elevated serum uric acid is increasing worldwide. However, the effects of high uric acid on diabetic patients with dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in male hamsters to evaluate the effects of high uric acid on glucolipid metabolism, renal injury and the gut microbiota. Twelve healthy hamsters were randomly divided into two groups and fed with a normal diet and high-fat/cholesterol diet (HFCD), respectively. Twenty-four diabetic hamsters were randomly divided into four groups receiving a normal diet; HFCD; potassium oxonate (PO) treatment (intragastric PO at doses of 350 mg/kg and adenine at doses of 150 mg/kg with 5% fructose water); and PO treatment with HFCD, respectively. After 4 weeks, all animals were dissected for determining serum biochemical indicators, tissue antioxidant parameters, renal pathological changes, target gene expressions, fecal short-chain fatty acids content, and the gut microbiota composition. The results showed that a hamster model with hyperuricemia and dyslipidemia was successively established by the combination of PO treatment and HFCD, in which serum uric acid, glucose, triglyceride and total cholesterol levels reached 499.5 ± 61.96 μmol/L, 16.88 ± 2.81 mmol/L, 119.88 ± 27.14 mmol/L and 72.92 ± 16.62 mmol/L, respectively. PO treatment and HFCD had synergistic effects on increasing uric acid, urea nitrogen, creatinine levels, liver xanthine oxidase activity, plasminogen activator inhibitor-1 and transforming growth factor-β expressions, and the relative abundance of Lleibacterium (p < 0.05); in addition, they caused glomerular mesangial cells and matrix proliferation, protein casts and urate deposition. High uric acid was closely related to decreased antioxidant capacity; decreased renal vascular endothelial growth factor expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes ratios (p < 0.05); and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. The findings indicate that high uric acid affects the glucolipid metabolism, accelerates renal damage, and disrupts the balance of intestinal flora in diabetic animals, which provides a scientific basis for metabolic syndrome prevention and control in diabetes. Full article

Background: Endometriosis is a chronic disease defined by the presence of endometrial-like tissue outside the uterine cavity. While typically confined to the pelvis, extrapelvic manifestations—including thoracic endometriosis—can occur. Although rare, thoracic endometriosis is the most common extragenital form. In clinical practice, this presentation is often described as thoracic endometriosis syndrome (TES), a constellation of cyclic thoracic symptoms temporally associated with menstruation but not always histologically confirmed. Its atypical symptoms and limited clinical awareness frequently lead to delayed diagnosis, mismanagement and increased patient burden. Methods: In accordance with the CARE guidelines, we present a case report of a female patient with thoracic endometriosis syndrome, emphasizing the prolonged interval between symptom onset and final diagnosis. Case Report: We describe a 42-year-old woman with a longstanding history of dysmenorrhea and menorrhagia, who developed cyclical chest pain and dyspnea in 2019. Despite multiple thoracoscopic procedures, her symptoms persisted and were repeatedly misattributed to anxiety or infection. Thoracic endometriosis syndrome (TES) was suspected in 2022, and although histopathological confirmation was lacking, intraoperative visualization revealed diaphragmatic fenestrations. In 2025, a second laparoscopic intervention targeting the abdominal surface of the diaphragm resulted in significant symptom relief. The patient is currently continuing hormonal therapy with Dienogest and has reported a marked improvement in quality of life. Nevertheless, the protracted diagnostic and therapeutic process—marked by chronic pain and repeated hospitalizations—had a profound psychosocial impact, culminating in a suicide attempt. Conclusions: This case illustrates the substantial burden associated with the delayed recognition of thoracic endometriosis syndrome and the consequences of fragmented care. The patient’s experience underscores the urgent need for coordinated, multidisciplinary management and psychological support, particularly for patients with extrapelvic manifestations. Early multidisciplinary evaluation, with readiness to consider surgical intervention alongside individualized hormonal therapy, may support improved outcomes, provided they are reinforced by increased clinical awareness and systemic improvement in diagnostic pathways. Full article

Takotsubo syndrome (TTS) is a condition marked by sudden and temporary dysfunction of the left ventricle, occurring without significant coronary artery disease. It was previously thought to be a benign and self-limiting condition, associated with a favorable long-term prognosis and minimal impact on survival. However, the most recent findings provide evidence that TTS is a heterogeneous condition with various presentation patterns. Using the most recent evidence regarding long-term prognosis in TTS, this review article aims to provide an overview of the long-term survival of patients with TTS, highlighting potential risk factors and comorbidities that may worsen prognosis. It also explores the risk of recurrence and the utility of advanced imaging modalities for prognosis assessment. Risk factors negatively impacting long-term outcomes include male sex, older age, reduced left ventricular ejection fraction (LVEF), physical triggers (especially pulmonary and neurological diseases), and comorbidities such as atrial fibrillation, chronic obstructive pulmonary disease, and active cancer. Recurrence, though relatively uncommon, can affect up to 11% of patients, with “super recurrence” linked to higher peak troponin levels, lower LVEF, and emotional triggers. Advanced imaging modalities—such as coronary angiography and ventriculography, which are considered the gold standard, along with serial echocardiographic assessment—combined with cardiac biomarkers, including relatively low peak troponin levels and markedly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as diagnostic ratios like copeptin/NT-proBNP, provide a robust framework for differentiating TTS from acute coronary syndromes. Key findings suggest that chronic therapeutic strategies in the long-term management of TTS patients should focus on improving long-term outcomes and reducing the risk of mortality and TTS recurrence. Methods: A comprehensive review was conducted using PubMed (U.S. National Library of Medicine and National Institutes of Health) and Google Scholar to identify relevant English-language publications addressing the long-term prognosis, biomarkers, imaging, risk of recurrence, and long-term management of TTS. Full article