Search Results (29,086)

In sepsis, a balanced pro-inflammatory and anti-inflammatory response results in the bacterial clearance and resolution of inflammation, promoting clinical recovery and survival. Semaphorins, a large family of secreted and membrane-bound glycoproteins, are newly recognized biomarkers and therapeutic targets in immunological and neoplastic disorders. Although semaphorins might also be a crucial part of host defense responses to infection, their role in sepsis is yet to be determined. This study aimed to analyze the association of serum semaphorin concentrations with sepsis severity and outcomes. Serum semaphorin concentrations (SEMA3A, SEMA3C, SEMA3F, SEMA4D, and SEMA7A) were measured in 115 adult patients with community-acquired sepsis and 50 healthy controls. While SEMA3A was decreased, SEMA3C, SEMA3F, SEMA4D, and SEMA7A were increased in sepsis patients. All analyzed SEMA showed good accuracy in identifying patients with sepsis. SEMA kinetics were related to sepsis complications; SEMA3A, SEMA3C, SEMA3F, and SEMA4D with respiratory failure; SEMA3C and SEMA7A with acute kidney injury; and SEMA3C and SEMA3F were related to septic shock. Importantly, SEMA3A, SEMA3C, SEMA4D, and SEMA7A were associated with 28-day mortality. In conclusion, we provide evidence that semaphorins are associated with sepsis course and outcomes. Full article

The 2007 Horse NRC reduced cobalt (Co) requirements from 0.1 ppm to 0.05 ppm in dietary dry matter, though preliminary research suggested increasing dietary-Co enhanced fiber digestion in horses. This study aimed to evaluate fiber digestion with varying dietary Co amounts, as well as to compare serum Co concentrations with dietary Co content. Four geldings (mean body weight [BW] 503 ± 37 kg) were studied in a 4 × 4 Latin square design consisting of four 5-week periods, each comprising a 2-week washout phase followed by a 3-week treatment phase. Supplementing 0.0, 5.6, 16.8, or 28.0 mg of Co daily resulted in total Co dietary concentrations of 0.06, 0.7, 2.0, and 3.0 ppm, respectively. Feces and urine were collected to evaluate fiber digestibility and Co balance. Co supplementation did not affect neutral detergent fiber, acid detergent fiber, or lignin digestibility. Co balance was negative for the control diet but positive for the other three treatments (p = 0.04). Serum cobalamin concentrations slightly decreased (6%) with increasing dietary Co intake (p = 0.003), while folate concentrations were unaffected. Serum Co concentration differed (p < 0.01) with a mean of 4.7 μg/mL for the high treatment and 0.8 μg/mL for the control. Results suggest that serum Co concentrations above regulatory limits are likely due not to higher levels of Co in fortified feeds, but rather to parenteral administration of Co solutions. Full article

Historically, oxidants have been considered mechanisms of glomerulonephritis, but a direct cause–effect correlation has never been demonstrated. Several findings in the experimental model of autoimmune conditions with renal manifestations point to the up-regulation of an oxidant/anti-oxidant system after the initial deposition of autoantibodies in glomeruli. Traces of oxidants in glomeruli cannot be directly measured for their rapid metabolism, while indirect proof of their implications is derived from the observation that Superoxide Oxidase 2 (SOD2) is generated by podocytes after autoimmune stress. The up-regulation of other anti-oxidant systems takes place as well. Here, we discuss the concept that a second wave of antibodies targeting SOD2 is generated in autoimmune glomerulonephritis and may negatively influence the clinical outcome. Circulating and renal deposits of anti-SOD2 antibodies have been detected in patients with membranous nephropathy and lupus nephritis, two main examples of autoimmune disease of the kidney, which correlate with the clinical outcome. The presence of anti-SOD2 antibodies in circulation and in the kidney has been interpreted as a mechanism which modifies the normal tissue response to oxidative stress. Overall, these findings repropose the role of the oxidant/anti-oxidant balance in autoimmune glomerulonephritis. The same conclusion on the oxidant/anti-oxidant balance may be proposed in renal transplant. Patients receiving a renal graft may develop antibodies specific for Glutathione Synthetase (GST), which modulates the amount of GST disposable for rapid scavenging of reactive oxygen species (ROS). The presence of anti-GST antibodies in serum is a major cause of rejection. The perspective is to utilize molecules with known anti-oxidant effects to modulate the anti-oxidative response in autoimmune pathology of the kidney. A lot of molecules with known anti-oxidant effects can be utilized, many of which have already been proven effective in animal models of autoimmune glomerulonephritis. Many molecules with anti-oxidant activity are natural products; in some cases, they are constituents of diets. Owing to the simplicity of these drugs and the absence of important adverse effects, many anti-oxidants could be directly utilized in human beings. Full article

The aim of this study is to determine the effects of a high-concentrate diet on growth performance, serum biochemical indexes, and rumen microbiota in house-fed yaks. Sixteen male yaks (body weight, 151.73 ± 14.11 kg; 18 months) were randomly allocated into two dietary treatments: a group with a low level of concentrate (n = 8, LC, concentrate–forage = 40:60) and a group with a high level of concentrate (n = 8, HC, concentrate–forage = 60:40). We found that compared with the LC group, the average daily feed intake (ADFI), the average daily gain (ADG), and the serum albumin (ALB) concentration in the HC group were significantly increased (p < 0.05). The rumen bacterial compositions also differed significantly between the groups, as indicated by principal coordinate analysis (p < 0.05). Firmicutes and Bacteroidota were the main dominant phyla of rumen bacteria in yaks. Compared with the LC group, the relative abundance of Firmicutes in the HC group was significantly increased (p < 0.05) and the relative abundance of Bacteroidota was significantly decreased (p < 0.05). At the genus level, Rikenellaceae_RC9_gut_group, Succiniclasticum, Prevotella, Christensenellaceae_R-7_group, and NK4A214_group had the highest relative abundance. The relative abundance of Christensenellaceae_R-7_group in the HC group was significantly higher than that in the LC group (p < 0.05). The PICRUSt 2 results showed a significant enrichment in glycosaminoglycan degradation, apoptosis, and ECM–receptor interaction in HC relative to LC (p < 0.05). In conclusion, high-concentrate diets can enhance growth performance and alter the compositions and functions of ruminal bacterial communities in yaks. Full article

This investigation aimed to study the effects of varying light exposure durations on ram sperm. A total of 25 rams were randomly divided into five groups. The control group was exposed to light durations of 12 h, while the experimental groups were exposed to light durations of 14, 16, 18, and 20 h. After three months of rearing, semen was collected from each ram four times using the artificial vagina method. The sperm motility parameters, sperm abnormality, sperm concentration, acrosome integrity, membrane integrity, semen volume, and total sperm number were measured. Thereafter, the metabolome, amino acid level, testosterone content, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and sperm antioxidant capacity were measured. The results showed that the sperm motility, sperm concentration, ejaculation volume, total sperm number, acrosome integrity, and membrane integrity in the 16 h light group were significantly improved compared to the control (p < 0.05), meanwhile the sperm abnormality was decreased. Moreover, we found 345 different metabolites between the control and 16 h light group. Among these, 273 were upregulated and 72 were downregulated. Furthermore, the amino acid content of the seminal plasma in the 16 h light group was significantly increased (p < 0.05) compared to the control. Interestingly, the seminal plasma testosterone content and the levels of FSH and LH in the serum in the 16 h light group were significantly increased (p < 0.05) compared to the control. In terms of the sperm antioxidant capacity, it was observed that the CAT activity was the highest in the group exposed to 16 h of light and decreased at 18 h of light exposure when compared to the control group; however, the CAT activity at 20 h was not different from the control. Additionally, within the 14 to 18 h light exposure range, prolonged light exposure increased the GSH content (p < 0.05), whereas 20 h of light exposure reduced the GSH content. The MDA levels decreased with prolonged light exposure, reaching the lowest point at 16 h (p < 0.05), but increased again at 20 h of light exposure. KEGG analysis indicated that the differential metabolites were mainly involved in metabolic and synthetic activities. Based on the results of this study, we can conclude that the artificial extension of the light duration for 16 h has a positive effect on ram sperm quality. Full article

Background: Immunotherapy has transformed cancer treatment; however, predicting treatment response remains challenging. Serum biomarkers can help identify patients who are most likely to benefit from immunotherapy. Objective: This study evaluates the relationship between serum growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) levels and treatment outcomes in cancer patients undergoing second-line immunotherapy. Methods: We conducted a prospective observational study involving 85 patients with non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or malignant melanoma treated with nivolumab. The baseline serum levels of GDF-15 and IL-6 were measured by using ELISA kits. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with cachexia as a secondary outcome. Results: Elevated GDF-15 levels were significantly associated with shorter PFS (HR: 0.55, 95% CI: 0.32–0.96, p = 0.032) and OS (HR: 0.47, 95% CI: 0.25–0.90, p = 0.020). Higher IL-6 levels correlated with shorter PFS, though statistical significance was not achieved. Additionally, high GDF-15 levels were linked to increased cachexia incidence (p = 0.037). Conclusion: Our findings indicate that GDF-15 could serve as a prognostic biomarker for immunotherapy response and may also be a target for cachexia management. Further studies should explore its potential to guide clinical decision making in oncology. Full article

Background: Osteoporosis (OP) is a chronic inflammatory bone disease characterized by reduced bone structure and strength, leading to increased fracture risk. Effective therapies targeting both bone and cartilage are limited. This study compared the therapeutic effects of extracorporeal shockwave therapy (ESWT), bisphosphonate (Aclasta), and human Wharton jelly-derived mesenchymal stem cells (WJMSCs) in a rat model of OP. Methods: Female rats were assigned to four groups: Sham (no surgery or treatment), OP (bilateral ovariectomy, OVX), ESWT (OVX + ESWT on both tibias at 0.25 mJ/mm², 1500 impulses per tibia), Aclasta (OVX + zoledronic acid 0.1 mg/kg via tail vein injection), and WJMSC (OVX + 2 × 10⁶ WJMSCs). Pathological changes, bone microarchitecture (by micro-CT), serum cytokines (by ELISA), and tissue-specific molecular markers (by immunohistochemistry) were evaluated. Results: All treatments improved bone density, preserved cartilage, and modulated cytokines (IL31, IL33, VEGF, and BMP2), with Aclasta showing the greatest improvements in bone parameters and cartilage preservation. ESWT and WJMSC also demonstrated significant effects, with ESWT highlighting non-invasive chondroprotective potential. Conclusions: Aclasta provided the best overall therapeutic response, particularly in bone regeneration. However, ESWT and WJMSC also showed comparable chondroprotective effects. ESWT emerges as a promising non-invasive alternative for OP management when pharmacological or cell-based therapies are not feasible. Full article

Introduction: Extracellular volume (ECV) analysis using computed tomography is recognized as a potential method for diagnostic application. It is currently the only noninvasive method for quantitatively evaluating myocardial fibrosis in dialysis patients for whom gadolinium contrast agents are contraindicated. In this study, we assessed the utility of ECV measurement via CT in the left ventricular (LV) myocardium (LVM) to predict major adverse cardiac events (MACEs) in dialysis patients. Materials and methods: We analyzed 57 dialysis patients who underwent cardiac CT and assessed the utility of LVM ECV (LV-ECV) for predicting MACEs. All the patients were followed for a median of 11 months, and MACEs occurred in 15 cases (26%). Results: LV-ECV and plasma brain natriuretic peptide levels were higher in subjects with MACEs than those without (40.29 ± 8.23% vs. 33.76 ± 4.60% and 1481 ± 997 vs. 807 ± 1109 pg/mL; both p < 0.05). Significant valvular disease was more frequently detected in patients with MACEs than those without (60% vs. 24%; p = 0.023). Serum hematocrit levels were significantly lower in patients with MACEs than those without (29 ± 5 vs. 34 ± 5; p < 0.001). The administration of statin was significantly lower in patients with MACEs than in those without (13% vs. 48%; p = 0.029). A receiver operating characteristic (ROC) curve analysis was performed using LV-ECV for predicting MACEs. The area under the curve was 0.80, and the best cut-off value of LV-ECV was 37.26% (p = 0.0003). In a Cox proportional hazards model, LV-ECV ≥ 37.26% was the only significant independent predictor of MACEs (p = 0.020). Conclusions: LV-ECV measured using CT is a useful predictor of MACEs in dialysis patients. Full article

Immunization against Gonadotropin-Releasing Hormone (GnRH) has been successfully explored and developed for the parenteral inoculation of animals, aimed at controlling fertility, reducing male aggressiveness, and preventing boar taint. Although effective, these vaccines may cause adverse reactions at the injection site, including immunosuppression and inflammation, as well as the involvement of laborious and time-consuming procedures. Oral vaccines represent an advancement in antigen delivery technology in the vaccine industry. In this study, a Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant lacking the pathogenicity island 2 (S. Typhimurium ΔSPI2) was used as a vehicle and mucosal adjuvant to deliver two genetic constructs in an attempt to develop an oral immunological preparation against gonadotropin hormone-releasing hormone (GnRH). S. Typhimurium ΔSPI2 was transformed to carry two plasmids containing a modified GnRH gene repeated in tandem (GnRXG/Q), one under eukaryotic expression control (pDNA::GnRXG/Q) and another under prokaryotic expression control (pJexpress::GnRXG/Q). A group of three male BALB/c mice were orally immunized and vaccination-boosted 30 days later. The oral administration of S. Typhimurium ΔSPI2 transformed with both plasmids was effective in producing antibodies against GnRXG/Q, leading to a decrease in serum testosterone levels and testicular tissue atrophy, evidenced by a reduction in the transverse tubular diameter of the seminiferous tubules and a decrease in the number of layers of the seminiferous epithelium in the testes of the inoculated mice. These results suggest that S. Typhimurium ΔSPI2 can be used as a safe and simple system to produce an oral formulation against GnRH and that Salmonella-mediated oral antigen delivery is a novel, yet effective, alternative to induce an immune response against GnRH in a murine model, warranting further research in other animal species. Full article

The effect of sodium alginate on the denaturation and aggregation behavior of bovine serum albumin and hen egg-white lysozyme was studied. Large amounts of polysaccharide increase the thermal stability of albumin due to the weak binding interactions. At the same time, sodium alginate can reduce the quantity of amyloid fibrils formed by albumin under denaturing conditions, which is a consequence of the stabilization of the native protein form by glycan binding. In the case of lysozyme, the polysaccharide has no influence on the thermal stability of the protein in 2 M guanidinium hydrochloride. However, the inhibition of fibril formation with an increase in the lag time was observed, which is explained by the binding of sodium alginate to lysozyme fibrils, but not to the protein monomer. The molecular nature of the binding interactions between alginate and the studied proteins was elucidated using molecular docking and known experimental structures of glycan–protein complexes. Full article

Live fish transportation plays a crucial role in the commercial fish trade. Consequently, mitigating stress during transportation is essential for enhancing the survival rate of fish and reducing potential financial losses. In this study, the effectiveness was evaluated of exogenous tryptophan in reducing transport stress in hybrid grouper, Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂. Firstly, the groupers were divided into the following five experimental groups: 40 mg/L MS-222 group, 30 mg/L tryptophan, 50 mg/L tryptophan, 70 mg/L tryptophan, and the control group without additives. Followed by transportation simulation, the fish samples were collected before and after transportation for the determination of antioxidant enzyme activities, apoptosis gene, and inflammatory gene expressions. The results indicated that the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels in all groups were significantly increased, while they were lower in the 50 mg/L Trp treated group compared to the control group (p < 0.05). Compared with the control group in the 50 mg/L Trp, 70 mg/L Trp, and 40 mg/L MS-222-treated groups, serum cortisol and blood glucose levels were significantly increased (p < 0.05), and anti-inflammatory factor (IL-10) gene expression was upregulated and pro-inflammatory factor (IL-1β) gene expression was decreased (p < 0.05). In addition, it was found that the 30 mg/L Trp, 50 mg/L Trp, and 40 mg/L MS-222 treatment groups had less green fluorescence than the control group by measuring the mitochondrial membrane potential, and 50 mg/L Trp and MS-222 showed more red fluorescence in fluorescence images than the other samples at the same sampling time. Therefore, in this study, it was demonstrated that the tryptophan could be used as a new anti-stress agent for hybrid groupers during transport, and additional research is required to identify the specific conditions that yield the best outcomes. Full article

Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period. Full article

A novel approach to developing lateral flow assays (LFAs) for the detection of CYFRA 21-1 (cytokeratin 19 fragment, a molecular biomarker for epithelial-origin cancers) is proposed. Magnetic bioconjugates (MBCs) were employed in combination with advanced optical and magnetic tools to optimize assay conditions. The approach integrates such techniques as label-free spectral-phase interferometry, colorimetric detection, and ultrasensitive magnetometry using the magnetic particle quantification (MPQ) technique. For the first time in LFA applications, the MPQ-based and colorimetry-based detection methods were compared side by side, and superior analytical performance was demonstrated. The limit of detection (LOD) of 0.9 pg/mL was achieved using MPQ, and 2.9 pg/mL with optical detection. This study has demonstrated that MPQ provides elimination of signal saturation, higher sensitivity (slope of the calibration curve), and a 19-fold wider dynamic range of detected signals. Both optical and magnetic detection results are comparable to the best laboratory-based tests with the added benefits of a 20-min assay duration and the LFA format convenience. The assay effectiveness was validated in human serum and artificial saliva, and high recovery rates were observed. The proposed approach offers rapid and reliable detection of molecular biomarkers and holds significant potential for point-of-care diagnostics, particularly in resource-limited settings. Full article

Background/Objectives: Human β-defensin 2 (HBD2) is a protein that plays an important role in activating the immune system by modulating spinal pathways and the inflammatory response. According to previous research, HBD2 was proven to be important in chronic spontaneous urticaria (CSU) (their values were significantly elevated in CSU patients, with a significant correlation between HBD2 levels and the percentage of peripheral basophils, suggesting that elevated HBD2 levels may be a potential marker of basophil and mast cell activation), which led us to additional research on the HBD2 molecule in isolated chronic angioedema. The aim of this research is to examine HBD2 values in the saliva and serum of patients with isolated angioedema, as a potential biomarker of the disease. Methods: This cross-sectional study involved a total of 102 participants, involving three groups: 33 patients with isolated chronic non-hereditary angioedema (AE) (defined as sudden onset of localized edema without chronic urticaria), 33 patients with angioedema associated with chronic urticaria (CU+AE), and 35 healthy participants (controls, CTRL). They provided a saliva sample to determine HBD2 levels using an ELISA (Enzyme-Linked Immunosorbent Assay). Subsequently, a peripheral blood sample (serum) was taken from the participants to determine HBD2 levels using the same ELISA. Results: Salivary HBD2 levels were significantly higher in those with CU+AE than in the CTRL (p = 0.019). While salivary HBD2 values differed between those with angioedema and CTRL, the serum HBD2 values did not. Also, no correlation between the levels of HBD2 in saliva and serum was found. Conclusions: Since we found that salivary HBD2 values were significantly higher in those with CU+AE than in CTRL, this points to a possible role of the HBD2 molecule in pathogenesis of AE (namely, that it induces degranulation in mast cells and vascular permeability, and has antimicrobial properties) Therefore, more research is needed to determine how reliable salivary HBD2 measurement is, as well as its significance. Full article

Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO₂) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO₂ administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO₂ was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO₂ administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO₂ exerts protective effects in the myocardial IR model. Full article