Glutamic Pyruvic Transaminase Research Articles

Nonalcoholic Fatty Liver Disease: Changes in Gut Microbiota and Blood Lipids.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing. Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity-occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis. Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1. Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Mulberry leaf and konjac flour compound dietary fiber improves digestion and metabolism in elderly mice with high-fish-protein diet by regulating gut microbiota structure and intestinal tissue repair

Ensuring sufficient protein intake, efficient digestion, and optimal absorption are crucial for the elderly. This study aims to investigate the potential of a compound dietary fiber, consisting of mulberry leaf and konjac flour (CMK), to enhance the digestion and absorption of a high-fish-protein diet in elderly mice. Results showed that CMK effectively reduced the number of unique peptide segments, generated short-chain fatty acids (SCFA) in feces, improved the content of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), amino acid, and urea nitrogen in serum, activated the contents of pepsin, trypsin, and erepsin, and enhanced the expression of glutamate dehydrogenase (GDH), peptide transporter 1 (PepT1), and aminopeptidase N (APN). Furthermore, CMK demonstrated its ability to decrease the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP), while increase the abundance of beneficial bacteria, such as Lactobacillus and Blautia. In conclusion, CMK proved effective in enhancing the digestion and metabolism of protein in elderly mice through the regulation of gut microbiota structure and intestinal tissue repair.

Promising role of traditional Indian Ayurvedic medicine in treatment, management and better clinical outcomes of COVID-19 patients: a retrospective study

IntroductionThe Coronavirus disease (COVID-19) has negatively impacted the lives of people globally. To date, no specific treatment has emerged to combat the disease. Hence, there is an urge for immediate therapy against infections like COVID-19 through the inclusion of various traditional medicines including Ayurveda. MethodsThis retrospective study was performed on 300 patients who were treated using the Holistic Ayurveda protocol at the COVID Health Care (CHC) centre. Out of 300 patients, 258 who took the AYURAKSHA Kit regularly along with the other Ayurvedic medicines for treatment were selected for this study. Demographic distribution, viral clearance, and haematological parameters of COVID-19 patients were analysed. ResultsThe maximum number of COVID-19 positive cases (31.4%) were found in the age group 20–29 years whereas the age group 40–49 years (11.52 days) and ≥ 60 years (11.5 days) took the maximum time (P = 0.035) for viral clearance. The haematological investigations showed that the Ayurveda treatment maintained the admitted patients' blood profile and coagulation profile. Strikingly, liver and kidney profiles improved post-treatment as Serum Glutamic-Oxaloacetic Transaminase (P = 0.000), Serum Glutamic Pyruvic Transaminase (P = 0.000), Urea (P = 0.000), and Creatinine (P = 0.002) levels were significantly reduced. Likewise, a significant reduction in inflammation markers like C-reactive Protein (P = 0.000), Erythrocyte Sedimentation Rate (P = 0.003), and serum Ferritin (P = 0.000) was also observed. No adverse treatment effects were observed during follow-up of the patients. ConclusionThe above outcomes showed that the Holistic Ayurveda Protocol in treating COVID-19 patients is safe, acceptable and effective. Thus, suggesting the possible integration of Ayurvedic treatment in combating such deadly diseases.

Hypoxia leads to gill endoplasmic reticulum stress and disruption of mitochondrial homeostasis in grass carp (Ctenopharyngodon idella): Mitigation effect of thiamine

Hypoxia in water environment is one of the important problems faced by intensive aquaculture. Under hypoxia stress, the effects of dietary thiamine were investigated on grass carp gill tissue damage and their mechanisms. Six thiamine diets with different thiamine levels (0.22, 0.43, 0.73, 1.03, 1.33 and 1.63 mg/kg) were fed grass carp (Ctenopharyngodon idella) for 63 days. Then, 96-hour hypoxia stress test was conducted. This study described that thiamine enhanced the growth performance of adult grass carp and ameliorated nutritional status of thiamine (pyruvic acid, glucose, lactic acid and transketolase). Additionally, thiamine alleviated the deterioration of blood parameters [glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), glucose, cortisol, lactic dehydrogenase (LDH), erythrocyte fragility, and red blood cell count (RBC count)] caused by hypoxia stress, and reduced reactive oxygen species (ROS) content and oxidative damage to the gills. In addition, thiamine alleviated endoplasmic reticulum stress in the gills, which may be related to its inhibition of RNA-dependent protein kinase-like ER kinase (PERK)/eukaryotic translation initiation factor-2α (eIF2α)/activating transcription factor4 (ATF4), inositol-requiring enzyme 1 (IRE1)/X-Box binding protein 1 (XBP1) and activating transcription factor 6 (ATF6) pathways. Furthermore, thiamine maintaining mitochondrial dynamics balance was probably related to promoting mitochondrial fusion and inhibiting mitochondrial fission, and inhibiting mitophagy may involve PTEN induced putative kinase 1 (PINK1)/Parkin-dependent pathway and hypoxia-inducible factor (HIF)-Bcl-2 adenovirus E1B 19 kDa interacting protein 3 (BNIP3) pathway. In summary, thiamine alleviated hypoxia stress in fish gills, which may be related to reducing endoplasmic reticulum stress, regulating mitochondrial dynamics balance and reducing mitophagy. The thiamine requirement for optimum growth [percent weight gain (PWG)] of adult grass carp was estimated to be 0.81 mg/kg diet. Based on the index of anti-hypoxia stress (ROS content in gill), the thiamine requirement for adult grass carp was estimated to be 1.32 mg/kg diet.

Rujifang inhibits triple-negative breast cancer growth via the PI3K/AKT pathway

Ethnopharmacological relevanceRujifang (RJF) constitutes a traditional Chinese medicinal compound extensively employed in the management of triple-negative breast cancer (TNBC). However, information regarding its potential active ingredients, antitumor effects, safety, and mechanism of action remains unreported. Aim of the studyTo investigate the efficacy and safety of RJF in the context of TNBC. Materials and methodsWe employed the ultra high-performance liquid chromatography-electrospray four-pole time-of-flight mass spectrometry technique (UPLC/Q-TOF-MS/MS) to scrutinize the chemical constituents of RJF. Subcutaneously transplanted tumor models were utilized to assess the impact of RJF on TNBC in vivo. Thirty female BLAB/c mice were randomly divided into five groups: the model group, cyclophosphamide group, and RJF high-dose, medium-dose, and low-dose groups. A total of 1 × 106 4T1 cells were subcutaneously injected into the right shoulder of mice, and they were administered treatments for a span of 28 days. We conducted evaluations on blood parameters, encompassing white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), neutrophils, lymphocytes, and monocytes, as well as hepatorenal indicators including alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin, and creatinine (CRE) to gauge the safety of RJF. Ki67 and TUNEL were detected via immunohistochemistry and immunofluorescence, respectively. We prepared RJF drug-containing serum for TNBC cell lines and assessed the in vitro inhibitory effect of RJF on tumor cell growth through the CCK8 assay and cell cycle analysis. RT-PCR was employed to detect the mRNA expression of cyclin-dependent kinase and cyclin-dependent kinase inhibitors in tumor tissues, and Western blot was carried out to ascertain the expression of cyclin and pathway-related proteins. Results100 compounds were identified in RJF, which consisted of 3 flavonoids, 24 glycosides, 18 alkaloids, 3 amino acids, 8 phenylpropanoids, 6 terpenes, 20 organic acids, and 18 other compounds. In animal experiments, both CTX and RJF exhibited substantial antitumor effects. RJF led to an increase in the number of neutrophils in peripheral blood, with no significant impact on other hematological indices. In contrast, CTX reduced red blood cell count, hemoglobin levels, and white blood cell count, while increasing platelet count. RJF exhibited no discernible influence on hepatorenal function, whereas Cyclophosphamide (CTX) decreased ALP, GOT, and GPT levels. Both CTX and RJF reduced the expression of Ki67 and heightened the occurrence of apoptosis in tumor tissue. RJF drug-containing serum hindered the viability of 4T1 and MD-MBA-231 cells in a time and concentration-dependent manner. In cell cycle experiments, RJF diminished the proportion of G2 phase cells and arrested the cell cycle at the S phase. RT-PCR analysis indicated that RJF down-regulated the mRNA expression of CDK2 and CDK4, while up-regulating that of P21 and P27 in tumor tissue. The trends in CDKs and CDKIs protein expression mirrored those of mRNA expression. Moreover, the PI3K/AKT pathway displayed downregulation in the tumor tissue of mice treated with RJF. ConclusionRJF demonstrates effectiveness and safety in the context of TNBC. It exerts anti-tumor effects by arresting the cell cycle at the S phase through the PI3K-AKT pathway.

Redefining the hepatoprotective potential of Javanese turmeric (Curcuma xanthorrhiza) Kombucha towards the diethylnitrosamine-induced hepatotoxicity of mice

PurposeThis research intended the utilization of Javanese turmeric (0.4% w/v) as a kombucha substrate and analysis of its hepatoprotective activity, in comparison against nonfermented Javanese turmeric beverage (JTB) and black tea kombucha.Design/methodology/approachForty-two healthy male Balb/c mice (two- to three-week-old, 20–30 g) were divided into six groups with seven replicates each. The treatments were normal diet, normal diet + Javanese turmeric kombucha (JTK), normal diet + diethylnitrosamine (DEN), DEN + JTB, DEN + JTK, DEN + black tea kombucha. Kombuchas and JTB were given at 0.3 mL/20 g BW/d. DEN was induced intraperitoneally at a dose of 100 mg/kg. Observed biomarkers were blood serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) activity, serum malonaldehyde (MDA), as well as liver histology. Data were analyzed using analysis of variance.FindingsAmong DEN-induced groups, JTK significantly (p < 0.05) diminished the level of blood SGPT, SGOT and serum MDA. JTK also had lower blood SGPT (8.604 ± 2.195 U/L) and serum MDA levels (2.884 ± 0.083 nM/mL) compared to the normal group (8.604 ± 2.195 U/L and 5.050 ± 0.998 nM/mL, respectively). JTK also produced the least damaged liver-cell numbers.Originality/valueJTK demonstrated better hepatoprotective activity compared to JTB.

Dietary supplementation of prebiotic yeast Saccharomyces cerevisiae cell wall promotes growth performance and intestinal health in broiler chickens challenged with Clostridium perfringens

ABSTRACT 1. This study evaluated the effectiveness of yeast (S accharomyces cerevisiae) cell wall (YCW) supplementation on the growth performance, carcase characteristics, serum biomarkers, liver function, ileal histology and microbiota of broiler chickens challenged with Clostridium perfringens (C. perfringens). 2. In a 35-d trial, 240 chicks aged 1-d-old were randomly assigned to one of four treatment groups, each with 10 replicates: control (CON) with no challenge or additives, challenged with C. perfringens (CHAL), CHAL and supplemented with YCW at either 0.25 g/kg (YCW0.25) or 0.5 g/kg (YCW0.5). 3. In comparison to CON, the CHAL birds had reduced growth performance, survival rate, dressing percentage, breast meat yield, levels of total protein (TP), globulin (GLO), glucose (GLU), total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD), as well as a decreased Lactobacillus population (P < 0.01). Additionally, this group showed elevated levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and C. perfringens count (P < 0.01). Compared to CHAL, the YCW0.25 or YCW0.5 groups had improved growth performance, survival rate, dressing percentage, breast meat yield, levels of TP, GLO, GLU, and T-AOC, as well as the activities of T-SOD, GOT, and GPT, villus height, villus surface area, villus height to crypt depth ratio, and the populations of both Lactobacillus and C. perfringens; (P < 0.01). 4. The data suggested that YCW supplementation at either 0.25 or 0.50 g/kg can restore the growth performance of broiler chickens during a C. perfringens challenge.

Exploring Therapeutic Potential of Pleurotus ostreatus and Agaricus bisporus Mushrooms against Hyperlipidemia and Oxidative Stress Using Animal Model.

The mushrooms oyster (Pleurotus ostreatus) and white button (Agaricus bisporus) contain bioactive compounds that have potential beneficial effects on hypercholesterolemia and cardiovascular diseases. In this study, hypolipidemic and antioxidative potential of these mushrooms' extract were explored using hypercholesterolemic (HC) rats as animal model. For the study, 56 adult rats were divided into seven groups, i.e., G1 (negative control), G2 (positive control group), G3 (HC rats with statin drug orally), G4 and G5 (HC rats @ 100 and 200 mg/kg body weight (BW) dose of oyster mushroom extracts), and G6 and G7 (HC rats @ 100 and 200 mg/kg BW dose of white button mushroom extracts). The hypercholesterolemia was induced experimentally in fasted rats through a high-fat diet along with injection of triton WR-1339. After 48 h, the treatment groups were given extract for 28 days along with standard diet. At the trial termination, we analyzed the blood sugar levels, antioxidant parameters, lipid profile, and renal function, as well as conducting liver function tests of the rats. The results indicated that positive control group rats exhibited increased levels of total cholesterol (TC), triglycerides (TG), low-density level (LDL), and very-low-density level (vLDL) by 19%, 37%, 52%, and 32%, respectively, and 53% decrease in HDL, whereas treatment groups that received 200 mg oyster and white button mushroom extracts reported 15%, 34%, 22% reduction in TC, TG, vLDL, respectively, and 22% improvement in HDL level. The enzyme profiles of different groups showed non-significant differences, although both mushroom extracts provision reduced glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels. Overall, the results indicated that mushroom extracts were helpful in maintaining oxidative stress and have the potential to improve dyslipidemia in the tested rat animal model.

Effect of Zinc Oxide Nanoparticles on Liver Functions in Albino Mice.

An alarming number of zinc oxide nanoparticles (ZnO-NPs) have leaked into the environment, endangering the tissues of many living creatures, due to the recent surge in their use in several items. Through intra-peritoneal injection, this research intends to examine the impact of ZnO-NPs on the hepatic and gastrointestinal structures of male albino mice. For seven and 14 days, animals were given 0.1 ml of 100 and 200 mg kg-1 of 50 nm-size ZnO-NPs, respectively. In contrast, those in the control group were given only water and food. The results demonstrated that the treated mice's livers underwent functional changes and histological damage. After seven and 14 days, there was a notable rise in the average levels of the glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase enzymes in comparison to the control group (p≤0.05). Concentration time determines the magnitude of this impact. When enzyme levels vary, it means the liver isn't working properly. Histological changes in the liver, such as necrosis, destruction of hepatocyte membranes, widening of sinusoidal spaces and vacuolation of their cytoplasm, vascular congestion, and an increased number of Kupffer cells, were induced in mice treated with ZnO-NPs at two studied concentrations (100 and 200 mg/kg) for seven and 14 days, respectively. These effects were time-dose-dependent, according to the results of hematoxylin-eosin staining of liver tissue images.

Hypoglycemic Activity and Safety Assessment of Pediococcus acidilactici Strain DNH16 in Experimental Type 2 Diabetes Mellitus Rats Induced with Streptozotocin

BACKGROUND: Type 2 diabetes mellitus (T2DM) cases tend to rise throughout the year in all parts of the world. The α-glucosidase inhibitors are frequently used to both prevent and treat T2DM. This α-glucosidase inhibitor activity is seen in some probiotic species, and a certain strain of Pediococcus acidilactici exhibits promising characteristics as an α-glucosidase inhibitor. This study was conducted to assess the hypoglycemic activity and safety of P. acidilactici strain DNH16 (PADNH16) in experimental rats with T2DM induced by streptozotocin.METHODS: The experiment was conducted in vivo using Wistar rats. Acarbose was employed as a positive control, and Lactobacillus casei was used as a comparative. For 24 days, post-prandial blood glucose levels were assessed every 3 days, followed by serum biochemical levels measurement of liver, kidney, and lipid profiles. The pancreas was histopathologically examined utilizing the Hematoxyline-Eosin staining procedure.RESULTS: Administration of PADNH16 to T2DM rats lowered post-prandial blood glucose levels and gave hypoglycemic benefits comparable to acarbose and commercial probiotics. PADNH16 dosing did not affect serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), urea, or creatinine levels, showing that PADNH16 was not hazardous to liver or kidney function. The lipid profile assessment revealed that the values, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, were comparable to the control group. The pancreatic histopathology revealed that injection of PADNH16 caused no alterations to pancreatic β cells.CONCLUSION: P. acidilactici isolate DNH16 has a hypoglycemic effect on T2DM rats, but does not affect liver function enzymes, kidneys, lipid profiles and does not provide significant changes in pancreatic β cells.KEYWORDS: diabetes mellitus, inhibitor α-glucosidase, Pediococcus acidilactici strain DNH16

Antidiabetic activity of methanolic extract of Hibiscus sabdariffa Linn. fruit in alloxan-induced Swiss albino diabetic mice

Abstract The majority of natural diabetic medications come from fruits and vegetables. These natural medications help protect humans from negative impacts of chemical antidiabetics by scavenging free radicals. The present study aimed to explore the antioxidant and antidiabetic properties of methanolic extract of fruits of Hibiscus sabdariffa Linn. (MEHSF) in alloxan-induced Swiss albino diabetic mice. The dried coarse powder of Hibiscus sabdariffa Linn. fruits was subjected to methanol extraction. The antidiabetic activity was determined by using alloxan-induced (80 mg/kg body weight) diabetic mice. Following a 15-day treatment period, serum biochemical parameters including total cholesterol (TC), triglyceride (TAG), LDL-cholesterol (LDL), HDL-cholesterol (HDL), serum glutamic pyruvic transaminase (SGPT), and serum glutamic-oxaloacetic transaminase (SGOT) enzymes were estimated. The antioxidant activity was evaluated through a DPPH and ABTS free radical scavenging assay. Total phenolic content and total flavonoid content were assessed using established methods. MESHF, containing polyphenolic and flavonoid compounds, exhibited antioxidant properties. A 100 and 200 mg/kg significantly (p &lt; 0.05) lowered the blood glucose levels and improved biochemical parameters such as TC, TAG, LDL, and HDL in diabetic mice. Further, MESHF significantly (p &lt; 0.05) reduced the activity of the SGPT and SGOT in diabetic mice compared to untreated diabetic mice. These results suggest that MEHSF with promising antioxidant and antidiabetic potentials can be considered to be a probable new resource of the antidiabetic agent.

Moringa oleifera fruit extract as a potential antioxidant against liver injury by 2-Nitropropane induction in obese male mice model: pre-clinical study

Background: Moringa oleifera fruit extract contains beneficial chemical compounds. This study was conducted to observed the power of antioxidant against liver injury by 2-Nitropropane induction in an obese male mice model. Methods: This research was in vivo laboratory experimental study with a post-test control design group only. The population was obese male mice models, Swiss strain, aged 6–8 weeks, weighing between 60–80 gr. The research sample was determined by Federer's formula for a complete randomized design experimental test, group N (control), O1 (induced by 2-Nitropropane intraperitoneal (i.p) once), O2 (induced by 2-Nitropropane i.p twice), P1 (induced by 2-Nitropropane i.p. once and gavage with M. oleifera fruit extract 500mg/kg bodyweight (BW) once a day), P2 (induced by 2-Nitropropane i.p. twice and gavage of M. oleifera fruit extract 500mg/kg BW once a day), and P3 (induced by 2-Nitropropane i.p. twice and gavage of vitamin C 500mg/kg BW once a day). Antioxidant potential parameters were measured by levels of malondialdehide (MDA), glutation (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), catalase activity, manganese superoxide dismutase (MnSOD), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT). This research was held at the Biochemistry laboratory of Medicine Faculty, UPN Veteran Jakarta in May–September 2020. Analysis was carried out using SPSS version 20.0. The parameters were tested using ANOVA. Results: MDA levels decreased, GSH increased, 8-OHdG decreased, catalase activity increased, MnSOD activity increased and SGOT, SGPT levels decreased. M. oleifera fruit extract was statistically proven to be a candidate for potential antioxidant against liver injury of 2-Nitropropane induction in obese male mice model. Conclusions: M. oleifera fruit extract was statistically evident as an antioxidant substance that reduces oxidative stress in acute liver injury caused by 2-Nitropropane induction.

Intervention effect of Cigu Xiaozhi prescription on ceramide lipoapoptosis in non-alcoholic fatty liver disease.

To explore the mechanism of the Chinese medicine Cigu Xiaozhi prescription (, CGXZ) in the treatment of the non-alcoholic fatty liver disease (NAFLD) by detoxification and phlegm-reducing, the effect of CGXZ prescription on ceramide-mediated lipid apoptosis in Hep G2 cells with NAFLD. The experiment was randomly divided into 6 groups: normal control group, model group, CGXZ prescription medicated serum high, medium, and low dose groups, and pioglitazone positive control group. Using 500 μmol/L free fatty acid (FFA) mixture to induce Hep G2 cells to establish NAFLD cell model, respectively, with 2%, 4%, and 6% concentration of CGXZ prescription medicated serum intervention for 24 h. The changes in organelles and lipid droplet accumulation were observed under the electron microscope. Furthermore, TdT-mediated dUTP Nick-End Labeling method was used to assay hepatocyte apoptosis; Biochemical determination of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, triglycerides, and FFA levels in Hep G2 cells; the content of ceramide was determined by high-performance thin-layer chromatography. Finally, Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the protein and gene expression levels, such as inducible nitric oxide synthase (iNOS), nuclear factor κB (NF-κB), B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). Under the electron microscope, the cells in the model group showed moderate-to-severe steatosis, and apoptotic bodies could be seen. The model group had greater improvements in the apoptosis rate (P < 0.01), and the levels of ceramide C2 and FFA in the cytoplasm (P < 0.01) than the normal control group. The protein expressions of NF-κB, iNOS, and Bax were significantly up-regulated (P < 0.05), while the Bcl-2 had no significant change (P > 0.05). Compared with the model group, the levels of ceramide C2 and FFA (P < 0.01), the protein expressions of NF-κB, iNOS, and Bax (P < 0.05) in the CGXZ prescription treatment group and pioglitazone positive control group were significantly decreased; Only the Bcl-2 protein was significantly up-regulated in the high-dose Chinese medicine group (P < 0.05). The down-regulation of Bax mRNA expression in each Chinese medicine treatment group was significantly better than in the pioglitazone positive control group (P < 0.01). The CGXZ prescription, formulated with the method of detoxification and phlegm, can inhibit lipoapoptosis in the NAFLD cell model by down-regulating the levels of ceramide C2 and FFA, which may be achieved by regulating ceramide/iNOS/NF-κB signaling pathway.

Toxic Impact of Dietary Cadmium on Bioaccumulation, Growth, Hematological Parameters, Plasma Components, and Antioxidant Responses in Starry Flounder (Platichthys stellatus)

Starry flounders (Platichthys stellatus) (average weight—114.69 ± 13 g, length—19.0 ± 0.21 cm) underwent a 4-week exposure to varying dietary cadmium (Cd) concentrations: 0, 10, 20, 40, 60, and 80 mg/kg. Bioaccumulation patterns were revealed in the intestine, kidney, liver, and gills in descending order of accumulation. Significant declines in growth indicators—body weight gain (BWG), specific growth rate (SGR), and feed efficiency ratio percentage (FER)—were evident at 80 mg Cd/kg for 2 weeks and beyond 60 mg Cd/kg for 4 weeks. Hematological parameters, including red blood cell (RBC) count, hematocrit (Ht), and hemoglobin (Hb), remarkably reduced at 80 mg Cd/kg for both 2 and 4 weeks. The total plasma protein reduced significantly after exposure to Cd for 2 and 4 weeks, alongside increased glucose levels, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvate transaminase (GPT). Considerable increases in antioxidant responses—superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione (GSH) levels—were observed after exposure to Cd for 2 and 4 weeks. P. stellatus exhibits a high accumulation of dietary Cd in specific tissues. Moreover, concentrations above 60 mg Cd/kg adversely affected the growth performance, hematological parameters, plasma components, and antioxidant responses.

Effects of Dietary Sodium Propionate on Growth Performance, Fillet Texture, Hematologic and Plasma Biochemical Parameter, Immune Responses, and Intestine Histology of Juvenile Trachinotus ovatus

Seven graded levels of sodium propionate (SP) diets with 0 (SP1), 0.2% (SP2), 0.4% (SP3), 0.6% (SP4), 0.8% (SP5), 1.0% (SP6), and 1.2% (SP7) were prepared to feed Trachinotus ovatus (initial body weight: 8.64 ± 0.08 g) for 56 days. The results showed that increasing dietary SP levels quadratically increased significantly final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) of T. ovatus but linearly and quadratically decreased significantly viscerosomatic index (VSI) and hepatosomatic index (HSI) of T. ovatus (P&lt;0.05). In the SP4 treatment, FBW, WGR, and SGR presented the highest values. Both positive linear and quadratic trends were detected between crude lipid content of whole fish, adhesiveness of dorsal muscle, white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), blood performance, high-density lipoprotein cholesterol (HDL-c), intestinal villus height, and dietary SP level, while negative linear and quadratic trends were found between firmness of dorsal muscle, triglyceride (TG), glucose (GLU), and dietary SP level (P&lt;0.05). The increasing SP led to quadratic increases in lymphocyte (Lym), complement 3 (C3), chymotrypsin, villus number, and muscle layer thickness, and a quadratic decrease in hepatic malondialdehyde (MDAP&lt;0.05). A significant negative linear trend was found between the content of glutamic-pyruvic transaminase (GPT) and dietary SP level, while significant positive linear trends were presented between C4, immunoglobulin M (IgM), α-amylase and dietary SP level (P&lt;0.05). The increasing SP resulted in linear and quadratic increases in superoxide dismutase (SOD), total antioxidant capacity (T-AOC) of livers and C3, C4, IgM of head kidney (P&lt;0.05). The expression levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) were linearly and quadratically decreased, while the mRNA levels of growth factor beta (TGF-β) were linearly and quadratically increased with the increasing SP level (P&lt;0.05). In conclusion, SP could be considered as a beneficial feed additive for enhancing growth and immunity of fish. And dietary SP level at 0.6% is optimal for the growth of Trachinotus ovatus based on a quadratic regression model of WGR.

Anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.

340 Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Aug 2023, a total of 23 patients were enrolled, 19 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 14 PR (73.7%), 2 SD (10.5%) and 3 NE (15.8%). Therefore, the preliminary ORR was 73.7% (95%CI: 48.8%-90.9%), DCR was 84.2% (95%CI: 60.4%-96.6%). Median PFS of the 19 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 23 patients with the incidence &gt;20% were leukopenia (30%) and anemia (30%). Common grade ≥3 treatment-emergent adverse events were leukopenia (9%), glutamic-pyruvic transaminase was elevated (4%), glutamic oxaloacetic transaminase increased (4%), hypertension (4%) and diarrhea (4%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. The conclusions needed to be confirmed in subsequent trials.

Inositol Inclusion Affects Growth, Body Composition, Antioxidant Performance, and Lipid Metabolism of Largemouth Bass (Micropterus salmoides).

The present study explored the effects of inositol on growth performance, body composition, antioxidant performance, and lipid metabolism of largemouth bass (Micropterus salmoides). Six isonitrogenous and isolipidic diets containing 0 mg/kg (G1, control), 125 mg/kg (G2), 250 mg/kg (G3), 375 mg/kg (G4), 500 mg/kg (G5), and 625 mg/kg (G6) inositol were prepared and fed to cultured fish (initial weight: 110 ± 1 g) for 8 weeks in recirculating the aquaculture systems. The results indicated that compared with G1 group, the weight gain rate (WGR), specific growth rate (SGR), and feed efficiency rate (FER) in the G3 group were significantly higher. The crude lipid content of the whole fish and the liver of cultured fish was significantly reduced with increasing dietary inositol inclusion. However, no significant effects on moisture, crude protein, and ash contents of fish were observed among the different groups. Dietary inositol supplementation significantly increased muscular crude protein. However, muscular total lipid contents were decreased when the inclusion level was higher than 250 mg/kg (G3-G6 groups). As dietary inositol supplemental level increased, serum triglyceride (TG), and cholesterol (TC) contents showed an increasing trend and reached the maximum value in the G3 group. Additionally, serum low-density lipoprotein cholesterol (LDL-C) in G2, G3, G4, and G5 groups was significantly upregulated by increasing inositol. While, there was no significant change in serum high-density lipoprotein cholesterol (HDL-C) among the treatments. Inositol inclusion also significantly reduced the serum alkaline phosphatase (AKP), glutamic-pyruvic transaminase (ALT), and glutamic-oxaloacetic transaminase (AST) activities as well as serum malondialdehyde (MDA) content but significantly increased serum catalase (CAT), superoxide dismutase (SOD) activities, and total antioxidant capacity (T-AOC). Compared with the control group, the activities of hepatic total lipase (TL) and lipoprotein lipase (LPL) were significantly elevated in the G3, G4, and G5 groups. Above all, dietary inositol supplementation could improve growth performance and antioxidant capacity, and reduce the liver fat content of largemouth bass, and the optimal supplementation level of inositol in feed is estimated to be 250.31-267.27 mg/kg.

Characteristics of Metformin Transporter Coding Gene (SLC22A1 rs628031 and SLC47A1 rs2289669) in Healthy Indonesian Subject

Background: Metformin might be a first therapy for Type 2 diabetes; however, it had a lot of variation in glycemic response. Objective: to analyze the frequency of minor alleles of the OCT1 coding gene (SLC22A1 rs628031) and MATE1 coding gene (SLC47A1 rs2289669) as well as the genotypic variation of the interaction of these two genetic polymorphisms in healthy subjects of Indonesia. Material and Methods: Through inclusion criteria, the study employed an observational descriptive technique with 70 Indonesian Javanese healthy individuals. Subject health information was obtained from the complete blood routine test, serum glutamic oxaloacetic transaminase/ serum glutamic-pyruvic transaminase (SGOT/SGPT), complete urine test, and serum creatinine tests. All data were compared to the normal range. Results: The finding shows that the minor allele frequency on SLC22A1 rs628031 A&gt;G and SLC47A1 rs2289669 G&gt;A respectively at 53% and 36%. There are four SLC22A1 rs628031 and SLC47A1 rs2289669 genetic polymorphism interactions; 16 Wt/Wt (16.75%), 24 Wt/M (25%), 32 M/Wt (33.3%) and 24 M/M (25%). The discovery demonstrates that such minor allele frequencies of the SLC22A1 rs628031 OCT1 and SLC47A1 rs2289669 MATE1 genes in healthy Indonesian subjects are relatively high. The SLC22A1 rs628031 A&gt;G and SLC47A1 rs2289669 G&gt;A respectively at 53% and 36%, almost the same as the minor allele frequencies found in several other Asian countries eg. India, Japan, and China. Conclusions: OCT1 coding genes (SLC22A1 rs628031 A&gt;G) were found more dominant than MATE1 coding genes (SLC47A1 rs2289669 G&gt;A) and both alleles are relatively high in healthy subjects of Indonesia, which can be used as information to explore the consequences of different genes' interactions on the Indonesian pharmacokinetic properties, and the efficacy variations of metformin in Type2 DM patients.

Long-Term Effects of Microfiltered Seawater and Resistance Training with Elastic Bands on Hepatic Parameters, Inflammation, Oxidative Stress, and Blood Pressure of Older Women: A 32-Week, Double-Blinded, Randomized, Placebo-Controlled Trial.

The bulk of research on microfiltered seawater (SW) is based on its short-term effects. However, the long-term physiological adaptations to combining SW and resistance training (RT) are unknown. This study aimed to analyse the impact of an RT program using elastic bands combined with SW intake on hepatic biomarkers, inflammation, oxidative stress, and blood pressure in post-menopausal women. Ninety-three women voluntarily participated (age: 70 ± 6.26 years; body mass index: 22.05 ± 3.20 kg/m2; Up-and-Go Test: 6.66 ± 1.01 s). RT consisted of six exercises (32 weeks, 2 days/week). Nonsignificant differences were reported for hepatic biomarkers except for a reduction in glutamic-pyruvic transaminase (GPT) in both RT groups (RT + SW: p = 0.003, ES = 0.51; RT + Placebo: p = 0.012, ES = 0.36). Concerning oxidative stress, vitamin D increased significantly in RT + SW (p = 0.008, ES = 0.25). Regarding inflammation, interleukin 6 significantly decreased (p = 0.003, ES = 0.69) in RT + SW. Finally, systolic blood pressure significantly decreased in both RT groups (RT + placebo: p < 0.001, ES = 0.79; RT + SW: p < 0.001, ES = 0.71) as did diastolic blood pressure in both SW groups (RT + SW: p = 0.002, ES = 0.51; CON + SW: p = 0.028, ES = 0.50). Therefore, RT + SW or SW alone are safe strategies in the long term with no influences on hepatic and oxidative stress biomarkers. Additionally, SW in combination with RT positively influences vitamin D levels, inflammation, and blood pressure in older women.

Effects of Varying Dietary Protein Levels on Growth Performance, Survival, Body Composition, Haemato-Biochemical Profile, and Metabolic Responses of Hypselobarbus jerdoni (Day, 1870) Juveniles

A 60-day feeding trial has been carried out to access the optimal dietary crude protein (DCP) requirement of juvenile Jerdon’s carp, Hypselobarbus jerdoni. Six isoenergetic (around 400 Kcal DE/100 g), isolipidic (60.80 g/kg), and heteronitrogenous diets were prepared with graded levels of protein, viz., 200, 250, 300, 350, 400, and 450 g/kg (TCP 20-TCP 45 with 50 g/kg incremental level). A completely randomised design (CRD) was used to distribute 270 Jerdon’s carp juveniles (6.12–6.18 g) in six experimental groups in triplicates (15 fish/tank, 200 l water capacity). After 60 days, the fishes of the TCP30 group showed significantly higher weight gain, final body weight, and percentage weight gain (WG%). The fish of the TCP30 group exhibited a significantly higher feed efficiency ratio and specific growth rate. On the other hand, a significantly lower feed conversion ratio is recorded in the TCP30 and TCP35 groups. The protein efficiency ratio of fish was reduced significantly with the elevated DCP level. Whole-body moisture, lipid, and total ash contents of H. jerdoni were remain unaffected by DCP levels. However, DCP levels significantly influenced the whole-body protein of H. jerdoni juveniles, with significantly higher values noticed in the TCP30 and TCP35 groups. The TCP35, TCP40, and TCP45 groups exhibited significantly higher (p&lt;0.05) protease activity, and the amylase activity showed a decreasing trend in response to dietary protein levels. A significantly (p&lt;0.05) higher SOD and CAT activity were observed in the TCP20 and TCP25 groups. However, lower hepatic glutamate pyruvate transaminase and glutamic-oxaloacetic transaminase activity were observed in the TCP30 and TCP35 groups, respectively. Furthermore, based on broken-line linear and second-order polynomial regression with respect to WG%, the optimal dietary crude protein requirement of H. jerdoni cultured for 60 days was found to be 309.72 and 316.40 g/kg.