Serum Biochemical Markers Research Articles

Comparative Evaluation of Hemato-biochemical and Oxidative Parameters of Racing Horses

Racing horses are prone to alterations in hemato-biochemical and oxidative stress parameters. The aim of this study was to determine the effect of racing on hemato-biochemical, and oxidative stress parameters of racing horses. Blood samples were collected from 15 control and 15 racing horses at four intervals (before, immediately after, 30 minutes after, and 24 hours after) to assay for hematological, serum biochemical, and oxidative stress markers. The result revealed significant changes (P < 0.05) in vital parameters such as erythrocyte count, hematocrit index, hemoglobin concentration, leucocyte count, lymphocyte, neutrophil, neutrophil: lymphocyte ratio, total protein, albumin, urea, creatinine, cortisol, lactate, lactate dehydrogenase, creatinine kinase, aspartate aminotransferase, while glucose, cholesterol, triglyceride, gamma-glutamyl transferase, malondialdehyde, glutathione peroxidase, and catalase remained unaltered (P > 0.05). The alteration in hemato-biochemical parameters reported in this study only lasted for about 30 minutes after racing, with all values returning to the baseline range by 24 hours post-race. Interestingly, the comparable activities of antioxidant stress markers reported suggests that the horses have developed adaptive mechanisms that have conferred them with increased resistance to oxidative stress and reduced oxidative damage. This study demonstrates the importance of schematic monitoring of racing horses peri-racing to prevent racing-induced pathophysiological alterations and promote their general wellbeing.

Lasia spinosa Stem Aqueous Extract Potentiates Antidiabetic Effects Exhibiting Antioxidant Genes Upregulation and DNA-Damage Protection.

This research elucidated the hypoglycemic effect correlated with DNA-protective and antioxidative activity of Lasia spinosa stem aqueous extract (LSSAE) using streptozotocin-induced type 2 diabetic rat models. LSSAE, characterized by phytochemical screening, gas chromatography-mass spectroscopy (GC-MS), and FTIR analyses, was investigated for its DNA-protective activity by exposing PBR322 plasmid DNA to Fenton's reagents. Long Evans rats, treated by LSSAE, were found to be improved for body weight, fasting blood glucose level, and oral glucose load. A 30-day supplement of LSSAE significantly recovered serum biochemical markers, including hepatic (i.e., ALP, AST, ALT, and TB); renal (i.e., creatinine and uric acid); and lipid profiles (i.e., TC, TG, HDLc, LDLc, and VLDLc). An increased level of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH), and a decreased level of malondialdehyde (MDA) were observed in LSSAE-treated rat liver. Antioxidant enzyme activities were evaluated by mRNA expression level of antioxidant genes (CAT, SOD2, GPX1, PON1, PFK1, GAPDH, using the 2-ΔΔCT method, normalized with housekeeping gene, ß-ACTIN) using qRT-PCR. Additionally, histological examination confirmed the restoration of morphology, and function of pancreatic β-cell, kidney, liver, and spleen. Results reveal that LSSAE exerts an antidiabetic effect through upregulation of antioxidant genes, DNA protection and modulation of biochemical and histological parameters.

The gut microbiota-produced vitamin B6 mitigates alcohol-associated liver disease by attenuating hepatic oxidative stress damage.

Alcohol-associated liver disease (ALD) is a major clinical issue characterized by progressive stages, including hepatic steatosis, liver fibrosis, cirrhosis, and HCC. Patients with long-term chronic alcoholism often present with gut microbiota dysbiosis and reduced plasma levels of vitamin B6. This study aimed to verify that gut microbiota disruption in ALD significantly contributes to reduced in vivo production of vitamin B6 and to investigate the role of this reduction in the pathogenesis of ALD. The ALD was investigated utilizing the Gao-binge mouse model. Fecal microbial composition was analyzed in pair-fed mice and ALD mice to identify alcohol-induced functional changes in the microbiota. Additionally, liver protein expression profiles and liver and plasma metabolomic profiles were characterized to elucidate the role of vitamin B6 in ALD pathogenesis through integrated proteomic and metabolomic analyses. The findings were further validated using animal models and clinical patient samples. Alcohol consumption disrupted the gut microbiota in the mice, impairing the vitamin B6 synthesis by intestinal microorganisms. Vitamin B6 deficiency aggravated the disorder of amino acid metabolism in the liver and inhibited ornithine aminotransferase expression, thereby worsening oxidative stress damage. In patients with ALD, significant disturbances of gut microbiota were observed, along with decreased intestinal vitamin B6 levels, which were negatively correlated with serum biochemical markers. The imbalance of gut microbiota in ALD mice reduces vitamin B6 synthesis, which affects amino acid metabolism and glutathione synthesis in the liver, thereby exacerbating ALD. These findings suggest that vitamin B6 may play a critical protective role in ALD progression by regulating amino acid metabolism.

Antituberculosis drug-induced hepatotoxicity: Preclinical benefit of glutamine

Background: Rifampicin/isoniazid/pyrazinamide/ethambutol (RIPE) which is the corner stone for the treatment of tuberculosis may cause hepatotoxicity. Glutamine (Gtn) is an important amino acid with potential cell-regulative and cytoprotective capabilities. Objective: This study assessed the ability of Gtn to prevent RIPE-induced hepatotoxicity in rats. Materials and Methods: Thirty adult Wistar rats (both sexes) weighing 180-220 were used. The rats were randomized into 6 groups of n=5/group and orally administered with the experimental agents daily for 30 days as follows: Groups 1-3 were administered with ([Control] normal saline, 0.2mL), Gtn (80mg/kg) and RIPE (Rifampicin 150, isoniazid/75, pyrazinamide 400 and ethambutol 275 mg/kg), respectively. Groups 4-6 were supplemented with Gtn (20mg/kg, 40mg/kg, 80mg/kg) prior to the administration of RIPE, respectively. On day 31, the rats were weighed, anesthetized and blood samples were collected and assessed for serum biochemical markers. Liver samples were weighed and examined for histology and oxidative stress markers. Results: Body weight, liver superoxide dismutase, glutathione peroxidase, catalase and glutathione levels decreased significantly (p

Association between osteoarthritis-related serum biochemical markers over 10-13 years and knee symptoms in middle-aged adults.

To describe the associations between OA-related biochemical markers and knee symptoms in middle-aged adults followed up over 10-13 years. Blood samples were collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year: 2004-06) and 10-13 year follow-up at CDAH-3. Serum samples from baseline (n=156) and follow-up (n=167) were analyzed for three OA-related biomarkers [cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, and hyaluronan (HA)] using non-isotopic enzyme-linked immunosorbent assay (ELISA). Knee symptoms were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at follow-up. Univariable and multivariable (adjusted for age, sex, and body mass index (BMI)) zero-inflated Poisson (ZIP) regression models were used for analysis. In cross-sectional multivariable models, significant positive associations between COMP [ratio of means (RoM): 1.156; 95%CI: 0.989, 1.324], MMP-3 [RoM: 1.013; 95%CI: 1.001, 1.025], and HA [RoM: 1.008; 95%CI: 1.002, 1.015] with knee pain and WOMAC-total score were observed in middle-aged adults. Baseline serum MMP-3 [RoM: 1.013; 95%CI: 1.006, 1.020], sum of serum COMP [RoM: 1.022; 95%CI: 1.011, 1.033], and an increase in the serum HA [RoM: 1.014; 95%CI:1.007, 1.020] were significantly positively associated with knee pain assessed after 10-13 years. The cumulative COMP levels in young adulthood (baseline) and mid-adulthood (follow-up), MMP-3 levels in young adulthood (baseline), and change in HA levels over the follow-up period were positively associated with knee pain assessed after 10-13 years. These biochemical markers measured in middle-aged adults may be explored further as a predictor of future knee symptoms.

Activation of Ferroptosis and NF-κB/NLRP3/MAPK Pathways in Methylmercury-Induced Hepatotoxicity.

Methylmercury (MeHg) is a potent hepatotoxin with a complex mechanism of inducing liver injury. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is implicated in various toxicological responses, but its role in MeHg-induced liver damage remains under investigation. In this study, we established an acute liver injury (ALI) model in mice via gavage of MeHg (0, 40, 80, 160μmol/kg). Histopathological analysis revealed dose-dependent liver damage, corroborated by elevated serum biochemical markers, confirming MeHg-induced hepatotoxicity. MeHg exposure raised MDA levels, inhibited SOD and GSH activity, and downregulated CAT expression. Increased iron accumulation and elevated transferrin receptor expression were observed, alongside decreased GPX4 and SLC7A11 levels, indicating ferroptosis involvement. Additionally, inflammation in MeHg-exposed livers was markedly intensified, as evidenced by increased MPO activity, upregulation of pro-inflammatory cytokines, and activation of the NF-κB/NLRP3 signaling pathway. The Keap1/NRF2/HO-1 oxidative stress response pathway was significantly activated, and p38/ERK1/2 MAPK signaling was notably increased. These findings suggested that MeHg induced acute liver injury through the interplay of ferroptosis, oxidative stress, inflammation, and MAPK signaling pathways, providing a scientific basis for future exploration of the mechanisms underlying MeHg-induced hepatotoxicity and potential therapeutic strategies.

Hepatoprotective Effects of Rheum turkestanicum Janisch on High-fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice

Background: Consumption of a high-fat diet (HFD) is one of the main causes of nonalcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. background: Consumption of a high-fat diet (HFD) is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on which the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. Objective: This study aimed to evaluate the effect of Rheum turkestanicum Janisch extract (RTE) on HFD-induced NAFLD in BALB/c mice. Materials and Methods: The study was performed with two models of prevention and therapeutic effect of RTE. Serum biochemical markers, histopathology, oxidative stress indicators, and qRTPCR were measured to evaluate the effects of RTE on lipid metabolism disorders in mice feeding with HFD. Results: In the prevention model, compared to the HFD group, RTE treatment decreased the levels of glucose, triglyceride, and cholesterol and improved liver profile markers, oxidative stress, and expression of genes involved in lipid metabolism. Conclusion: The results of this study suggest that RTE has hepatoprotective effects against HFDinduced liver damage by reducing oxidative stress, lipogenesis, and increasing beta-oxidation of free fatty acids.

The clinical performance of fetal sex chromosome abnormalities in serum biochemical screening in the second trimester

This study aimed to investigate the serum biochemical markers’ propensity associated with sex chromosome abnormalities (SCAs) and assess the clinical efficacy of SCAs in serum biochemical screening during the second trimester. A retrospective case-control analysis was conducted on pregnant women who underwent serum biochemical screening during the second trimester. The study compared groups of women with SCAs to those with normal chromosome karyotypes to assess changes in biochemical markers. We analysed and compared the performance of serum biochemical screening in each SCA group. The results showed that the alterations in serum biochemical markers varied among the different SCA groups. Typically, the serum biochemical markers of fetal SCAs were either above the 95th percentile or below the 5th percentile. The proportions of high- and intermediate-risk findings for 45,X, 47,XXX, 47,XXY, 47,XYY, and mosaic sex chromosomal abnormalities were 43.48%, 78.95%, 63.89%, 70.59%, and 78.13%, respectively. Besides detecting fetal trisomy 21 and trisomy 18, the current contingent screening procedures may also accidentally identify various fetal SCAs at a rate of 69.18%.

Optimizing selenium-enriched yeast supplementation in laying hens: Enhancing egg quality, selenium concentration in eggs, antioxidant defense, and liver health

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

Shenling Baizhu San alleviates central fatigue through SIRT1-PGC-1α-Mediated mitochondrial biogenesis

Ethnopharmacological relevanceShenling Baizhu San (SLBZS) is a Traditional Chinese Medicine (TCM) formula composed of 10 medicinal herbs, historically used to strengthen the spleen, replenish qi, and alleviate fatigue-related symptoms. SLBZS originates from the 'Taiping Huimin Heji Ju Fang' of the Song Dynasty. Central fatigue (CF), a subtype of fatigue, is considered in TCM to be closely associated with spleen deficiency. However, there is currently a lack of research on SLBZS's therapeutic effects on CF and the pharmacological mechanisms underlying its potential benefits. Aim of the studyThis study aims to assess the effects of SLBZS on CF in rats induced by the Modified Multiple Platform Method (MMPM) and to elucidate the underlying mechanisms, focusing on mitochondrial biogenesis and SIRT1/PGC-1α pathway regulation. Materials and methodsCF was induced in male Wistar rats using MMPM, involving intermittent sleep deprivation over 21 days. SLBZS was administered at low(LSLBZS), medium(MSLBZS), and high doses(HSLBZS). Chemical components of SLBZS were identified and quantified using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS). Behavioral tests evaluated physical performance, emotional state, and cognitive function, while serum biochemical markers, mitochondrial morphology, and the protein and gene expression levels of the SIRT1/PGC-1α pathway were analyzed to explore underlying mechanisms. ResultsA total of 141 main compounds in SLBZS were identified, comprising various components such as flavonoids, phenylpropanoids, terpenoids, among others. SLBZS significantly improved physical performance, alleviated negative emotions, and enhanced cognitive function in CF rats. Biochemically, SLBZS increased serum ATP levels and reduced fatigue-related markers. Mitochondrial analysis demonstrated that SLBZS reversed mitochondrial degeneration, increased mitochondrial number, and increased mtDNA copy number in the hippocampus. Furthermore, SLBZS upregulated SIRT1/PGC-1α pathway expression at both the protein and gene levels in the hippocampus. Notably, the HSLBZS group demonstrated particularly pronounced effects. ConclusionSLBZS significantly alleviates CF symptoms enhances mitochondrial function via upregulating the SIRT1/PGC-1α pathway, positioning it as a promising alternative for CF management by addressing both its physiological and symptomatic aspects.

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Quantitative analysis of dried serum FTIR spectra based on correlation Analysis-Interval random Frog-Partial least squares

Serum biochemical markers are widely used in clinical practice but often require expensive, specific reagents, complex instruments, and prolonged result waiting times. Infrared spectroscopy offers multiple advantages for serum analysis, such as reagent-free testing and the ability to quickly and directly measure multiple parameters simultaneously. This study collected serum samples from 66 healthy subjects to explore the relationship between dried serum infrared spectra and biochemical parameters, and to investigate the feasibility of simultaneously quantifying nine major serum components using dried serum infrared spectra. Initially, correlation analysis was conducted between spectral data and biochemical parameters, and the correlation spectral bands of glucose, protein and lipid were determined according to the correlation results. Subsequently, the interval random frog (IRF) algorithm was utilized to select the optimal characteristic wavenumbers of the correlated spectral bands, extracting the most informative spectral variables and constructing partial least squares (PLS) quantitative models. This method successfully achieved rapid and accurate quantification of nine major components in serum, including glucose, total protein, albumin, apolipoprotein A1, apolipoprotein B, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The experimental results showed that the correlation coefficient (Rp) range in the test set was 0.8892–0.9941. Among them, the quantification of total cholesterol yielded the highest Rp, corresponding to a root mean square error (RMSEP) of 7.2425 mg/dL in the test set, while the quantification of glucose yielded the lowest Rp, with an associated RMSEP of 2.3683 mg/dL. The Correlation Analysis (CA)-IRF-PLS method developed in this study outperformed the conventional PLS method, the direct use of the successive projection algorithm (SPA)-PLS quantitative method and other reported quantitative techniques, providing a novel approach for the real-time determination of clinical parameters in serum.

Sensitive Detection of Gynecological Cancer Recurrence Using Circulating Tumor DNA and Digital PCR: A Comparative Study with Serum Biochemical Markers.

Early detection of recurrences in gynecological cancers is crucial for women's health. Circulating tumor DNA (ctDNA) analysis through liquid biopsy offers a promising approach for monitoring disease progression and identifying relapses. This study investigated the utility of digital Polymerase Chain Reaction (dPCR) for ctDNA detection in three gynecological cancer patients with clinically confirmed relapses during a two-year post-surgical follow-up. Patient-specific tumor mutations were identified through whole-exome sequencing (WES) and confirmed via Sanger sequencing. dPCR probes targeting these mutations were used to quantify the ctDNA levels in plasma samples collected throughout the follow-up period, and the findings were compared with standard serum biochemical markers. In two patients, persistent positive dPCR signals for the selected mutations were detected after tumor removal, with ctDNA levels progressively increasing even after post-surgical chemotherapy. Notably, dPCR identified elevated ctDNA levels before an increase in the cancer antigen 125 (CA125) biochemical marker was observed. In the third patient, no ctDNA signals from the two selected mutations were detected despite clinical evidence of recurrence, suggesting the emergence of new mutations. While this study highlights the promise of dPCR for early recurrence detection in gynecological cancers, it also underscores the critical need for comprehensive mutation panels to overcome the inherent challenges posed by tumor heterogeneity and the emergence of new mutations during disease progression.

A novel small molecule phagocytosis inhibitor, KB-208, ameliorates ITP in mouse models with similar efficacy as IVIG.

The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto- or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short-term usage along with alternative options. KB-208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB-208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60-day chronic administration of KB-208 by a biochemistry panel, gross necroscopy and histopathology. KB-208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000-2500 mg/kg. KB-208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found. KB-208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB-208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB-208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology.

Prospective evaluation of serum and peritoneal fluid markers as indicators of postoperative complications in patients with enteric anastomosis.

Postoperative complications of colorectal cancer surgery contribute to increased morbidity and mortality in patients. Investigate the role of biochemical markers in serum and peritoneal fluid in the development of postoperative complications in patients with enteral anastomosis. Prospective. University hospitals. The studied population consisted of patients who underwent surgical treatment with created anastomosis or Hartmann's resection from April 2022 to April 2024, conducted at the Clinical-Hospital Center Kosovska Mitrovica and the University Clinical Center Kragujevac. Spearman's correlation coefficient (rs) was used to test associations between categorical variables. Lactate, albumin, lactate dehydrogenase, and IgA antibodies were monitored as predictors of anastomotic dehiscence and general postoperative complications. 52. The concentration of lactate in the drain fluid on the third postoperative day was statistically significantly higher in patients who did not develop anastomotic dehiscence (P=.006). The concentration of IgA antibodies in the drain fluid on the third and fifth days post-surgery showed a moderate negative correlation with lactate concentration (rs=-.670, P=.012; rs=-.577, P=.039), repectively. There was a significantly higher concentration of albumin in the drain fluid on the third day post-surgery in patients who developed dehiscence (P=.040), and on the seventh day post-surgery in those who did not develop dehiscence (P=.001). The concentration of LDH on the third day in the drain fluid after surgery was statistically significantly higher in patients who did not develop dehiscence (P=.020). There was a statistically significant difference in lactate concentration in the drain fluid on the third (P<.001) and fifth days (P=.041) post-surgery, as well as in albumin concentration on the third day post-surgery (P=.024) with respect to the development of general postoperative complications. This study revealed significant differences in the concentrations of lactate, albumin, and LDH in the drain fluid on the third and fifth days post-surgery with respect to the development of complications. These results suggest that monitoring these markers may help in the early identification of patients at risk of complications such as dehiscence. Limited literature on specific aspects of this study, including the absence of a control group, small sample size, and two-center study.

Overexpression of SULT1E1 alleviates salt-processed Psoraleae Fructus-induced cholestatic liver damage

ObjectiveSalt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. MethodsBy utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. ResultsA total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the “estrogen signaling pathway” identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. ConclusionThe overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Therapeutic effects of Mudan granules on diabetic retinopathy: Mitigating fibrogenesis caused by FBN2 deficiency and inflammation associated with TNF-α elevation

Ethnopharmacological relevanceMudan granules (MuD), a time-honored traditional Chinese patent medicine (TCPM), are widely utilized in the clinical treatment of diabetic peripheral neuropathy (DPN). In the field of biomedical diagnostics, both diabetic retinopathy (DR) and DPN are recognized as critical microvascular complications associated with diabetes. According to the principles of traditional Chinese medicine (TCM), these conditions are primarily attributed to a deficiency in Qi and the obstruction of collaterals. Despite this, the protective effects of MuD on DR and the underlying mechanisms remain to be comprehensively elucidated. Aims of the studyThe purpose of this study was to investigate the effect of MuD on DR and to further explore the promising therapeutic targets. MethodsA diabetic mouse model was established by administering 60 mg/kg of streptozotocin (STZ) via intraperitoneal injection for five consecutive days. The therapeutic efficacy of MuD was evaluated using a comprehensive approach, which included electroretinogram (ERG) analysis, histopathological examination, and assessment of serum biochemical markers. Then, the pharmacodynamic mechanisms of MuD were systematically analyzed using Tandem Mass Tags-based proteomics. Meanwhile, the candidate compounds of MuD were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and molecular docking was applied to estimate the affinity of the active ingredient to their potential key targets. In addition, the functional mechanisms identified through bioinformatics analysis were confirmed by molecular biological methods. ResultsWe demonstrated that MuD provided significant protection to retinal function and effectively mitigated the reduction in retinal thickness observed in the animal model. Through proteomic analysis, we identified a substantial regulation by MuD of 70 biomarkers associated with diabetic retinal damage. These proteins were notably enriched in the tumor necrosis factor (TNF) signaling pathway, a critical mediator in inflammatory processes. A particularly intriguing finding was the significant downregulation of fibrillin-2 (FBN2) in the diabetic retina compared to the control group (0.36 times the level), and its most pronounced upregulation (3.26 times) in the MuD treatment group. This suggests that FBN2 may play a pivotal role in the protective effects of MuD. Molecular docking analyses have unveiled a robust interplay between the components of MuD and TNF-α. Further corroboration was provided by molecular biological methods, which confirmed that MuD could suppress TNF-mediated inflammation and prevent retinal neovascularization and fibrogenesis. ConclusionMuD have the potential to alleviate diabetic retinal dysfunction by effectively curbing the fibrogenesis-associated neoangiogenesis and mitigating the inflammatory response, thereby restoring retinal health and function.

Carbenoxolone upregulates TRAIL\\TRAILR2 expression and enhances the anti-neoplastic effect of doxorubicin in experimentally induced hepatocellular carcinoma in rats

AimsThis study investigates the in vivo anticancer activity of carbenoxolone (CBX) and its role in fighting hepatocellular carcinoma (HCC) progression and alleviating resistance against doxorubicin (DOX). Moreover, the molecular mechanism of action of CBX is explored. MethodsHCC was induced in Sprague Dawley rats via biweekly administration of thioacetamide (TAA) (200 mg/kg) intraperitoneally (i.p.) for 16 weeks after administering a single dose of diethylnitrosamine (DEN) (200 mg/kg, i.p.). A prophylactic model was established by treating rats with i.p. CBX (20 mg/kg/day) for 4 weeks starting on week 13 post-TAA injection. A therapeutic model was established by treating rats with CBX, DOX, or their combination for 7 weeks following 16 weeks of TAA administration. Serum Alpha-fetoprotein (AFP) and biochemical markers of hepatic functions were assessed. Histopathological examinations of hepatic tissues were performed. Immunohistochemical and qRT-PCR analyses were applied to assess the differential expressions of TRAIL/TRAILR2, Bcl-2, TGF-β1, and caspases 3, 8, and 9. ResultsCBX markedly improved hepatic functions, reduced serum AFP levels, and alleviated TAA-induced hepatic histopathological alterations. CBX triggered apoptosis as evident by upregulating apoptotic markers: TRAIL/TRAILR2, caspases 3, 8, and 9, and downregulating the antiapoptotic protein Bcl-2. CBX downregulated TGF-β1. Interestingly, CBX/DOX combination mitigated hepatic damage and induced apoptosis in a way that surpassed DOX-only treatment. ConclusionThe current study proposes that CBX is a promising anti-tumor compound, which can work effectively under prophylactic and therapeutic modes. Interestingly, CBX enhanced the anti-tumor effect of DOX. CBX exerted these effects via, in part, stimulating TRAIL-induced apoptosis along with attenuating fibrosis.

Bacterial Cellulose Membrane Experimentally Implanted in the Peritoneum of Wistar Rats-Inflammatory Immunoreactivity and Oxidative Stress.

Bacterial cellulose (BC) has been used for various applications; however, studies investigating the immunohistochemical characteristics of the inflammatory and scarring component in BC implanted in the peritoneum in vivo have not yet been fully described. This study aimed to evaluate the systemic and organic safety of BC through oxidative stress, blood, and serum biochemical markers, as well as the late inflammatory response in rats, using histopathology and immunohistochemistry. Forty-three rats (26 males; 17 females) received BC in the peritoneal cavity (implanted group-IG), while twenty-seven rats (12 males; 15 females) served as the control (sham group-SG). Sixty days after surgery, oxidative stress in tissues, blood biochemical markers, and histopathological and immunohistochemical analyses for lymphocytes, macrophages, collagen, and vascular response around the BC were assessed. Only one oxidative stress marker, glutathione peroxidase, was elevated in the liver of IG rats. Creatine kinase MB and lactate dehydrogenase levels were significantly lower in IG animals. Histopathological analysis showed granulomatous inflammation in 93% of IG rats, with 74% of mild intensity. Immunohistochemistry revealed a significant macrophage presence (F4/80), with CD3, CD20, and F4/80 markers indicating differences favoring macrophages. In conclusion, BC implantation in the peritoneum induces a foreign body granulomatous response with prominent macrophage presence (F4/80). Type I and III collagen were observed around the membrane, and vascularization was intense 60 days post-implantation. From a biochemical and oxidative stress perspective, BC seems to be a safe material to be used in the peritoneal cavity.