Search Results (35,874)

Organophosphorus pesticides (OPs) are widely used in agriculture, but prospective studies on their chronic exposure and risk of type 2 diabetes (T2D) and glucose metabolism disorders are scarce. Most previous studies focused on agricultural workers and relied on questionnaires or urinary metabolites for exposure assessment. We conducted a nested case–control study with 1006 pairs of participants based on the Dongfeng–Tongji cohort to investigate the association between serum OP levels, T2D risk, and fasting blood glucose (FBG) changes over a 5-year follow-up. Serum OP concentrations were measured by gas chromatography–triple quadrupole mass spectrometry. Among the 29 types of OPs detected, Chlorpyrifos and Fenitrothion had detection rates of 99.9% and 87.9%, respectively. Etrimfos and Parathion were detected in 75.8% and 64.5% of participants. Four types of OPs—Ethoprophos, Phorate, Diazinon, and Malathion, categorized into ≤LOD and >LOD groups—had detection rates ranging from 20% to 60%. OP exposure was not associated with T2D risk in the overall population. Among participants with baseline FBG ≥ 6.1 mmol/L, OP exposure showed a positive association with incident T2D and with increases in FBG during a 5-year follow-up. In contrast, OP exposure was associated with decreased FBG in the overall population. Moreover, significant interactions were observed between OP exposure and baseline FBG levels (P_interaction < 0.05), suggesting that baseline glucose levels may modify the metabolic effects of chronic OP exposure. These findings highlight the importance of considering basal glucose status when evaluating the long-term metabolic effects of OP exposure. Full article

Background/Objectives: CLEC-2 (C-type lectin-like receptor 2), the newest discovered platelet receptor, is involved in platelet activation and aggregation, the inflammatory response, tumor growth, metastasis, and angiogenesis. These unique features make CLEC-2 a promising candidate for a new biomarker and therapeutic target. The aim of our study was to evaluate the diagnostic value of CLEC-2 in patients with colorectal cancer (CRC). Methods: The serum CLEC-2 concentration was determined using ELISA methods in 64 CRC patients and 25 healthy subjects. Results: Our results indicate that the concentration of the serum CLEC-2 was significantly higher in CRC patients than in healthy subjects. Furthermore, the CLEC-2 levels were significantly higher in G3- than G2-grade CRC, and in patients with more advanced CRC, such as those with lymph node and distant metastases, than in patients without any metastases. CLEC-2 showed a positive correlation with platelet indices (PLT and MPV). The area under the ROC curve confirmed CLEC-2’s excellent diagnostic power in distinguishing between patients with CRC. Conclusions: Our results indicate that CLEC-2 may be associated with CRC development and suggest that the identification of this biomarker could be useful for determining CRC progression. Full article

Background/Objectives: Spotty liver disease (SLD), caused by Campylobacter hepaticus, is an emerging disease that leads to substantial production losses in the egg industry. The shift toward antibiotic-free and cage-free production systems has further intensified the impact of SLD. The current control measures largely rely on autogenous killed vaccines; however, their use is constrained by the slow and fastidious growth of C. hepaticus and inconsistent efficacy. To overcome these limitations, this study aimed to identify immunogenic mimotopes as vaccine candidates and express them on the surface of an avian pathogenic Escherichia coli (APEC) vector. Methods: To identify immunogenic mimotopes, Ph.D.-12 phage display peptide library was screened using the hyperimmune serum raised against killed whole-cell C. hepaticus in specific pathogen-free chickens. Subsequently, the outer membrane protein C (OmpC) of E. coli was used as a scaffold for constructing a surface display library. A single restriction site, PstI, located in the seventh external loop of OmpC, was strategically utilized to insert each 12-amino-acid mimotope with a six-histidine (6xHis) tag sequence at its N-terminus, generating ompC + mimotope fusion constructs. These constructs were cloned into the inducible expression vector pTrc and electroporated into an E. coli DH5α ∆ompC strain, which lacked ompC. The surface expression of the mimotopes was confirmed in vitro. The verified ompC + mimotope constructs were subsequently subcloned into the pYA3422 constitutive expression vector and electroporated into the APEC PSUO78 ∆aroA ∆asd vaccine vector strain. A chicken vaccination–challenge trial was conducted using nine groups of chickens, including an unvaccinated challenged control and an unvaccinated–unchallenged negative control. Each experimental group received a mixture of two recombinant E. coli strains carrying different mimotopes at a dose of 1 × 10⁹ CFU, which were administered orally twice at 16 and 18 weeks of age. Results: Fourteen immunogenic mimotopes corresponding to 13 different C. hepaticus proteins were identified as potential vaccine candidates. The expression of these mimotopes on the surface of the E. coli was successfully demonstrated using the OmpC-mediated surface display system. Of the 14 mimotopes tested, two flagellar-related peptides and one major outer membrane protein (MOMP)-derived peptide elicited significant immune responses and conferred protection against the C. hepaticus challenge. Conclusions: We successfully developed a functional E. coli surface display system that was capable of expressing 12-amino-acid mimotopes of C. hepaticus, providing a robust platform for evaluating vaccine candidates against SLD. Immunogenicity and efficacy studies in chickens demonstrated that three identified mimotopes conferred protection against C. hepaticus colonization of the bile and liver. Future in vivo investigations are necessary to develop and evaluate the immunogenicity and protective efficacy of a multivalent mimotope vaccine consisting of three identified mimotopes against both C. hepaticus and APEC, utilizing the ΔaroA Δasd APEC PSU078 strain as the vaccine vector. Full article

Semen parameters, including sperm counts, have rapidly declined in men across the globe over the last five decades. Although this decline remains unexplained, lifestyle factors may affect male fertility. Recently, several studies highlighted a potential link between non-steroidal anti-inflammatory drug (NSAID) usage, such as naproxen and ibuprofen, and declining male fertility. However, the mechanisms by which these common analgesics affect male fertility, including their effects on the blood–testis barrier (BTB), remain poorly characterized. Utilizing an in vitro rhesus macaque non-human primate (NHP) BTB model, we demonstrate that serum levels of naproxen and ibuprofen alter the function of BTB. Following short-term naproxen and ibuprofen treatment of NHP primary Sertoli cells, we show that these NSAIDs increase the transepithelial electrical resistance, indicating an overall strengthening of the Sertoli cell junctions. Furthermore, naproxen and ibuprofen treatment alter the expression of genes involved in maintaining the BTB. Specifically, the genes that were significantly expressed in response to ibuprofen exposure were enriched for human phenotypic abnormalities linked to male factor infertility. Together, these results suggest that short-term naproxen and ibuprofen treatment disrupt the function of the BTB by altering the integrity of the Sertoli cell junctions, proposing a potential role of NSAIDs in male factor infertility. Full article

Jellyfish, as representatives of the phylum Cnidaria, possess venoms characterized by structurally diverse and functionally complex toxins, rendering them a central focus in cnidarian toxin research. This article presents a systematic review of the physicochemical properties of jellyfish toxins, examines their mechanisms of action from a molecular biology perspective, investigates the patterns of toxin transformation in organisms, elucidates the structure–activity relationships between structure and toxicity, introduces advancements in research on novel jellyfish toxins, and offers an outlook on future developments in this field. By integrating modern proteomic techniques, such as liquid chromatography-tandem mass spectrometry, this review provides comprehensive theoretical support for the foundational research and application development of jellyfish toxins, as well as a scientific basis for practical applications, including antivenom serum development and novel marine drug design. Full article

This study evaluated the effects of different environmental enrichment tools on broiler chickens from 1 to 21 days of age. A total of 120,000 one-day-old broiler chicks were randomly assigned to five treatments, each consisting of four replicates with 6000 birds per replicate. Replicates were housed in pens measuring approximately 362 m². The treatments included: T1, green balls (approximately 40 balls per pen); T2, hanging toys (8–10 toys per pen); T3, hanging strings (8–10 string bundles per pen); T4, rotational use of green balls, hanging toys, and strings at equivalent densities; and T5, a control group without enrichment. Data were collected on growth performance, foot health, behavioral activity, serum biochemical parameters, and carcass and meat quality traits. Birds provided with hanging enrichment tools showed significantly improved growth performance (p ≤ 0.05) compared with the control group. Among enriched treatments, T2 yielded the highest body weight and weight gain, as well as the lowest feed conversion ratio. Enrichment treatments also resulted in significant improvements (p ≤ 0.05) in carcass characteristics and selected meat quality parameters, including lightness (L*) and pH stability. Behavioral observations indicated substantially higher activity levels in enriched groups relative to the control. Toe damage scores differed significantly among treatments (p = 0.004), with the lowest scores observed in T1 and the highest in T4; however, no significant differences were detected in footpad dermatitis or hock burn scores (p > 0.05). In conclusion, hanging environmental enrichment tools, particularly hanging toys, can effectively enhance growth performance, behavioral activity, and selected carcass and meat quality traits in broiler production systems, while their effects on footpad health appear limited under the conditions of this study. Full article

Background/Objectives: Acute high-intensity exercise may transiently alter circulating vitamin D metabolites. However, the effects of training status, supplementation dose, and vitamin D-binding protein (VDBP) on the exercise-induced redistribution and bioavailability of vitamin D remain unclear. This pilot study examined whether training status and vitamin D₃ supplementation dose modulate vitamin D status, anaerobic performance, and acute post-exercise changes in vitamin D metabolites and VDBP. Methods: Thirty-four healthy young men participated, comprising 22 mixed martial arts (MMA) athletes and 12 untrained controls. MMA athletes received either 3500 or 6000 IU/day of vitamin D₃ for four weeks, while untrained participants received 3500 IU/day or a placebo. Before and after the intervention, participants performed a supramaximal anaerobic exercise protocol (3 × 30 s Wingate tests). Blood samples were collected at rest and 30 min and 24 h post-exercise to assess vitamin D metabolites, VDBP, bioavailable and free 25(OH)D₃, interleukin-6, and lactate. Results: Supplementation with 3500 IU/day significantly increased serum 25(OH)D₃ in untrained men (p = 0.003) but not in MMA athletes. In contrast, 6000 IU/day increased 25(OH)D₃ in MMA athletes to a sufficient concentration (p = 0.001) and improved maximal power (+7.5%), mean power (+4.9%), and total work (+5.0%). Acute exercise increased circulating vitamin D metabolites in trained athletes but reduced them in untrained men supplemented with vitamin D. Conclusions: The efficacy of vitamin D₃ supplementation and the acute exercise-induced vitamin D responses appear to be training-dependent. A daily dose of 6000 IU is more effective in achieving vitamin D sufficiency and performance benefits in MMA athletes, whereas 3500 IU is sufficient for untrained men. Full article

Background: Despite its high vaccination coverage, pertussis remains a public health concern due to waning vaccine-induced immunity and the emergence of pertactin (Prn)-negative strains. Nevertheless, anti-Prn antibodies and memory B cells elicited by vaccinations may contribute to long-term immunity and protection against Prn-positive strains. While most vaccination studies focus on serum antibodies, data on memory B cells remain limited. Methods: In this study, we implemented a flow cytometry-based approach to characterize Prn-specific B-cell fluctuations following Tdap booster vaccination in five healthy adults. Total and Prn- and tetanus toxoid fragment C (TTC)-specific plasma cells and memory B cells were analyzed at baseline and at 7, 14, 21, and 90 days post-vaccination using Prn Klickmers^® and TTC tetramers. Following this, cellular responses were correlated with antigen-specific serum IgG and IgA levels. Results: Prn-specific and TTC-specific memory B cells increased on days 14 and 7 post-vaccination, respectively, accompanied by a phenotypic shift from IgMD+ to IgG+ cells. Clear expansions of total as well as Prn- and TTC-specific plasma cells occurred on day 7. These plasma cells primarily comprised IgG+, but an increase in Prn-specific IgA+ plasma cells was also observed. The numbers of Prn-specific IgG+ memory B cells on day 7 post-vaccination correlated weakly with serum anti-Prn IgG levels at later time points. Conclusion: To our knowledge, this is the first study to use flow cytometry to evaluate Prn-specific B-cell responses and report their fluctuations over time following vaccination. These findings support the potential of this method to complement serological assays and improve our understanding of vaccine-induced immunity. Full article

Background/Objectives: Vitamin D deficiency and malnutrition may lead to poor outcomes in colorectal cancer (CRC) patients. This study aims to perform an integrative analysis of serum vitamin D, nutritional status, anthropometric parameters and biochemical profiles in advanced CRC patients. Methods: The study included 58 advanced CRC patients. Serum vitamin D levels were measured by a chemiluminescence immunoassay. Nutritional status was evaluated with the Mini Nutritional Assessment (MNA). Body composition profiles were assessed using a bioelectrical impedance analyzer, and handgrip strength was measured with a handgrip dynamometer. Biochemical and clinical parameters were retrieved from an electronic database. Correlation, regression and receiver operating characteristic (ROC) analyses were performed. Results: Abnormal nutritional status and vitamin D deficiency were diagnosed in 55.17% and 50.00% of patients, respectively. Sarcopenia was diagnosed in 29.31%. Serum vitamin D concentrations were negatively correlated with absolute neutrophil counts (ANC). MNA scores showed significant negative correlations with ANC, platelet count, alkaline phosphatase and carcinoembryonic antigen. In multivariable regression models, albumin remained statistically associated with both serum vitamin D levels (β 7.049; 95% CI: 1.686–12.413; p = 0.011) and MNA score (β 6.951; 95% CI: 4.623–9.278; p < 0.001). Furthermore, albumin showed exploratory performance in ROC analyses for malnutrition and vitamin D deficiency (AUC^ROC 0.814 and 0.725, respectively), which should be interpreted cautiously given potential overlap with MNA-defined nutritional status and the limited sample size. Conclusions: Vitamin D deficiency, malnutrition and systemic inflammation commonly co-occur and are closely interrelated in patients with advanced CRC. A comprehensive assessment of nutritional status in a CRC supportive care setting is recommended. Full article

Background: Chronic low-grade inflammation plays a central role in the pathogenesis of type 2 diabetes (T2DM) and its complications. Neopterin, a marker of macrophage activation and Th1-mediated immune response, has been associated with cardiovascular disease and metabolic disorders. However, its relationship with diabetic autonomic neuropathy remains insufficiently investigated. Methods: We conducted a cross-sectional study including 129 participants (93 with T2DM and 36 with obesity without carbohydrate disturbances). Clinical, anthropometric, and biochemical assessments were performed. Cardiovascular autonomic neuropathy was evaluated using Ewing cardiovascular reflex tests and sudomotor dysfunction scoring. Neopterin concentrations were measured in serum. Correlation, ROC, and logistic regression analyses were performed. Results: Neopterin levels were not significantly different between T2DM and obesity groups. No differences were observed in patients with versus without peripheral neuropathy, nephropathy, or retinopathy. However, neopterin levels were significantly higher in individuals with cardiovascular autonomic neuropathy (p = 0.013). Neopterin correlated with cardiovascular autonomic neuropathy score, sudomotor dysfunction, fasting glucose, fasting insulin, and HOMA-IR. It showed a moderate negative monotonic correlation with eGFR (Spearman’s rho = −0.41, p< 0.001). In multivariable logistic regression adjusted for age, HbA1c, BMI, eGFR, and diabetes duration, each 1-SD increase in neopterin was associated with 2.67-fold higher odds of cardiovascular autonomic neuropathy (95% CI 1.21–5.89; p = 0.015). Conclusions: Circulating neopterin is independently associated with cardiovascular autonomic neuropathy in T2DM but not with classical microvascular complications. These findings suggest a potential role of immune-mediated mechanisms in the pathogenesis of diabetic cardiovascular autonomic neuropathy. Full article

Background: In recent years, the severity of COVID-19 has diminished. However, some patients progressed to respiratory failure, necessitating intubation and mechanical ventilation. This study investigated the impact of variants of concern and vaccination status on mortality in mechanically ventilated patients. Method: We conducted a retrospective analysis of the medical records of intubated COVID-19 patients from 1 January 2021, to 31 December 2023. Patients who received at least one dose of a vaccine were classified as vaccinated, and variant types were classified based on the dominant variant reported by the Taiwan Centers for Disease Control. The primary outcome measured was time from intubation to all-cause in-hospital death. Result: A total of 254 patients were analyzed, comprising 65 patients infected with the Alpha variant and 189 with the Omicron variant. Clinical data, including variant type, vaccination status, and SOFA score at the time of intubation, were meticulously recorded. The overall mortality rate was 40%, with two epidemic surges occurring in 2021 and 2022. Infection with the Alpha variant was associated with a significantly higher risk of mortality (adjusted hazard ratio = 5.42 (2.78–10.7); p < 0.01). Key prognostic factors identified included age, body mass index, SOFA score, and serum bicarbonate levels. Conclusions: The overall mortality rate remained notably high. The study identified several factors associated with increased mortality risk, including older age, higher SOFA scores, Alpha variant infection, decreased serum bicarbonate levels, and lower BMI. However, vaccination status was not a significant prognostic indicator. Full article

Background and Aims: Egg-derived proteins and peptides have been investigated for various health outcomes, yet no comprehensive meta-analysis has synthesized this evidence to guide clinical practice. This study aimed to evaluate the efficacy of oral egg-derived protein and peptide supplementation on health outcomes, including serum albumin and phosphorus in dialysis patients, and visceral fat area, blood pressure, muscle protein synthesis, and cognitive function in adults. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched through January 2026 for RCTs. Random-effect meta-analyses, sensitivity analyses, and publication bias assessments were performed. Risk of bias was evaluated using the RoB 2 tool. Evidence certainty was evaluated using GRADE. Results: Thirty RCTs (n = 1938) were included. In dialysis patients, egg white supplementation significantly increased serum albumin (MD: +0.42 g/dL [95% CI: 0.12–0.72]; I² = 82.4%; four RCTs; GRADE: very low) and decreased serum phosphorus (MD: −2.04 mg/dL [−2.50, −1.58]; I² = 22%; two RCTs; GRADE: low). Leave-one-out sensitivity analysis showed consistency. Lactic-fermented egg white peptide reduced the visceral fat area (MD: −11.6 cm² [−18.5, −4.8]; two RCTs; GRADE: very low). NWT-03 egg protein hydrolysate showed no significant effect on blood pressure (MD: +0.5 mmHg [−1.8, +2.7]; two RCTs). Publication bias was not detected. Conclusions: Egg-derived protein supplementation provides clinical benefits in dialysis patients with hypoalbuminemia, but evidence is lacking supporting its routine use in healthy adults or other clinical populations. Full article

Background: Procalcitonin (PCT) is a biomarker of bacterial infection and sepsis severity, but its role in melioidosis remains unclear. This study aimed to synthesize available evidence on serum PCT levels in culture-confirmed melioidosis and explore associations with disease severity and mortality. Methods: We conducted a systematic review following PRISMA guidelines and registered the protocol with PROSPERO (CRD420251166979). PubMed, Embase, and Scopus were searched up to 30 October 2025. Observational studies reporting serum PCT levels in microbiologically confirmed melioidosis were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS) for observational studies. Random-effects models were used to calculate pooled mean PCT levels, with heterogeneity assessed by I². Sensitivity analyses were performed to explore the influence of historical and small-sample studies. Results: Seven studies comprising 284 patients with culture-confirmed melioidosis were included. The pooled mean PCT level was 14.46 ng/mL (95% CI: 4.59–24.33), with substantial heterogeneity (I² = 87.7%). Sensitivity analyses excluding the oldest study and the smallest sample size reduced heterogeneity but retained consistently elevated PCT levels across cohorts. Higher PCT concentrations were consistently observed among patients with septic shock, bacteremia, and fatal outcomes, although variability in definitions precluded quantitative synthesis of prognostic effect sizes. These findings were based on heterogeneous study-level comparisons and could not be synthesized quantitatively. Conclusions: PCT is markedly elevated in melioidosis and reflects the severity of systemic infection, supporting its potential role as an adjunctive biomarker for early risk stratification. However, substantial heterogeneity and limited sample sizes prevent the establishment of a melioidosis-specific prognostic threshold. Standardized, prospective, multicenter studies are required to clarify the independent prognostic value of PCT in melioidosis management. This study establishes a pooled estimate of serum PCT levels in melioidosis and demonstrates that these values are comparable to those observed in severe bacterial sepsis, supporting its interpretation as a marker of systemic inflammatory burden rather than a disease-specific biomarker. Full article

Nateglinide (Nat) is an oral antidiabetic agent of the meglitinide class that has been reported to exert protective effects beyond glycemic control, particularly against oxidative stress and inflammation. Since oxidative stress and inflammation play a key role in the pathogenesis of acute kidney injury (AKI), especially following ischemia/reperfusion (I/R), this study aimed to evaluate the potential renoprotective effects of Nat in a rat model of I/R-induced AKI. Forty male Sprague Dawley rats were randomly divided into four groups (n = 10): Control, I/R, I/R + Nat (50 mg/kg), and I/R + Nat (100 mg/kg). Bilateral renal ischemia was induced by clamping renal arteries for 45 min, followed by 24 h of reperfusion. Nat was administered orally 1 h before ischemia. Renal levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiobarbituric acid reactive substances (TBARSs) were assessed. Serum blood urea nitrogen (BUN), creatinine, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were also measured, and histopathological analyses were performed. Nat significantly increased renal antioxidant parameters and reduced TBARS levels. Moreover, Nat markedly decreased serum BUN, creatinine, TNF-α, and IL-1β levels compared with the I/R group (p < 0.05). Histopathology confirmed attenuated renal damage in Nat-treated groups (p < 0.0001). These results indicate that Nat confers significant renoprotection against renal I/R injury via suppression of oxidative stress and inflammation. Full article