Aspartate Aminotransferase Research Articles

Gut microbiota of miR-30a-5p-deleted mice aggravate high-fat diet-induced hepatic steatosis by regulating arachidonic acid metabolic pathway.

Patients with non-alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA-30a-5p (miR-30a-5p) against atherosclerosis. In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR-30a-5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high-fat diet (HFD)-induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD-fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild-type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD-treated KO and WT mice showed that the loss of miR-30a-5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX-related (PGF2a, 8-iso-PGF2a and PGF2) and LOX-related (LTB4, LTD4, 12S-HETE and 15S-HETE) factors in HFD-treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR-30a-5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR-30a-5p in HFD-treated KO mice. This study reveals the pivotal mechanism by which miR-30a-5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics. MiR-30a-5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR-30a-5p. Gut microbiota metabolism-related arachidonic acid metabolic pathway contributed to miR-30a-5p-regulated hepatic steatosis and lipid disorder. Reintroducing miR-30a-5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR-30a-5p deletion.

Association of Monocyte Chemoattractant Protein-1 (MCP-1) 2518 A/G Polymorphism with Obesity in Korean Type 2 Diabetes Mellitus.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family, and the MCP-1 2518 A/G gene polymorphism is reported to be correlated with chronic inflammatory diseases, including insulin resistance and metabolic syndrome. However, few studies have investigated the association between MCP-1 gene polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective case-control study and evaluated the association between the MCP-1 2518 A/G polymorphism and obesity in Korean patients with T2DM. This single-center, retrospective, case-control study enrolled 526 Korean patients with T2DM. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze MCP-1 2518 A/G polymorphism; the genotypes was presented as GG, AG, or AA. We compared the MCP-1 2518 A/G polymorphism with the prevalence of diabetic complications, as well as clinical and biochemical characteristics. The obese group had a higher number of females and higher C-peptide, insulin, triglycerides, aspartate transaminase (AST), and alanine transaminase (ALT) levels. The obese group also had a higher prevalence of cardiovascular disease than the non-obese group. The obese group had a higher frequency of the MCP-1 2518 AA genotype and the A allele than the non-obese group. The results of multiple logistic regression analysis showed that the non-G allele of MCP-1 was significantly associated with obesity (odds ratio (OR), 1.888; P=0.016). This study demonstrates that the MCP-1 2518 A/G polymorphism is associated with obesity in Korean patients with T2DM. Further studies involving various ethnic groups are required to validate our results.

Impact of Rumex nepalensis on Performance, Blood Markers, Immunity, Intestinal Microbiology and Histomorphology in Broiler Chicken.

The study investigated the impact of utilizing Rumex nepalensis leaf powder (RNL) as a phytogenic feed additive on performance, blood markers, intestinal microbiology and histomorphology in broiler chicken. One hundred eighty day-old Cobb broiler chicks were randomly divided into four treatment groups having three replicates with fifteen birds each. Four iso-caloric and iso-nitrogenous diets primarily based on maize-soybean were formulated, viz., CN (Control)-fed basal diet only; RNL2.5 (basal diet + 2.5 g/kg RNL); RNL5 (basal diet + 5 g/kg RNL); and RNL10 (basal diet + 10 g/kg RNL). The results revealed a significant (p < 0.05) increase in body weight gain and feed conversion ratio in dietary treatments compared to CN with best values in RNL10 followed by RNL5. The blood markers like glucose, total protein, creatinine, alanine transaminase (ALT) and aspartate transaminase (AST) showed no significance (p > 0.05) among all the treatments, however total cholesterol significantly (p < 0.05) decreased in RNL5 and RNL10 as against CN. Regarding immune parameters, immunoglobulin G (IgG) and immunoglobulin M (IgM) levels significantly (p < 0.05) enhanced in RNL5 and RNL10. Antioxidant enzyme status showed that superoxide dismutase (SOD) increased and malondialdehyde (MDA) decreased significantly (p < 0.05) in RNL10 compared to CN. Gut health in terms of cecal microbiology and histomorphology of duodenum and jejunum were altered by inclusion of RNL in the broiler diet. A significant decrease (p < 0.05) in coliform count was recorded by incorporation of dietary treatments with highest reduction in RNL10. Lactobacillus count and total viable count did not vary significantly (p > 0.05) among dietary treatments and CN. Duodenal and jejunal villus height and villus height/crypt depth ratio were significantly (p < 0.05) increased in RNL5 and RNL10 compared to RNL2.5 and CN. Thus, it could be concluded that inclusion of Rumex nepalensis leaf powder in the diet resulted in improved performance and better immuno-antioxidant status of broilers. Further, an improvement in the gut health was observed in terms of positive effects on cecal microbiota and intestinal histomorphology of broiler chickens.

A metabolome-derived score predicts metabolic dysfunction-associated steatohepatitis and mortality from liver disease

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts. MethodsThe MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 plasma metabolites measured by proton nuclear magnetic resonance (1H-NMR) in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n=305). We investigated association of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng Study (n=5,893) and the UK Biobank (n=111,673). ResultsA total of 24 clinical parameters and 194 1H-NMR metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included body mass index, aspartate transaminase, tyrosine, and the phospholipids-to-total lipids ratio in very-low density lipoprotein. The score identified patients with MASH with AUROCs of 0.87 (95% CI, 0.83-0.91) and 0.81 (95% CI, 0.75-0.87) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (HR, 23.19; 95%CI, 4.80-111.97) and European individuals (HR, 27.80; 95%CI, 15.08-51.26) after 7.4 and 12.6 years of follow-up. The MASH prediction score was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related mortality. ConclusionThe metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals. Impact and implicationsMetabolic dysfunction-associated steatohepatitis (MASH) is associated with more than a 10-fold increase in liver-related death. However, biomarkers predicting not only MASH, but also death due to liver disease, are missing. We established a MASH prediction score based on 44 clinical parameters and 250 plasma metabolites using a machine learning strategy. This metabolome-derived MASH prediction score could accurately identify patients with MASH among both Chinese and Finnish individuals, and it was superior to the FIB-4 index and the NAFLD Fibrosis Score in predicting MASLD-related death in the general population. Thus, the new MASH prediction score is a useful tool for identifying individuals with a markedly increased risk of serious liver-related outcomes among at-risk and general populations.

Impact of Silver Nanoparticles (Ag-NPs) as a Dietary Supplement on Growth Performance, Carcass Traits, Blood Metabolites, Digestive Enzymes, and Cecal Microbiota of Growing Rabbits

Abstract The present study investigated the impact of silver nanoparticles (Ag-NPs) on growth performance, carcass traits, liver and kidney functions, immunity and antioxidant indicators, digestive enzymes, and cecum bacteriology of growing rabbits. One hundred 5-week-old New Zealand White (NZW) male rabbits were randomly divided into 5 equal groups and fed for 8 weeks on the basal diet only or on the basal diet supplemented with different levels of Ag-NPs (0.25, 0.50, 0.75, or 1.00 mg/kg diet). Animals in each group were randomly distributed in 10 cages (replicates), with two rabbits each. Different dietary concentrations of Ag-NPs significantly increased live body weight (LBW) and feed conversion ratio (FCR). Also, body weight gain (BWG) increased dramatically during all experimental periods except 11–13 weeks of age. Levels of 0.25 and 1 mg of Ag-NPs/kg diet showed the highest increase in LBW, BWG, and FCR. All studied carcass traits, except liver %, were not affected by Ag-NPs levels. Rabbits fed diet supplemented with 1 mg Ag-NPs had the highest liver %. Serum total protein, albumin, and globulin levels were increased (P&lt;0.05) in groups treated with 0.25 and 0.75 mg Ag-NPs. In contrast, serum values of aspartate transaminase (AST) and alanine transaminase (ALT), urea and creatinine were significantly reduced with the supplementation of Ag-NPs up to 0.75 mg/kg diet. The immunoglobulins M, G, and A (IgM, IgG, and IgA), complement 3 (C3) and lysozyme activity were improved with the inclusion of nano-silver in the rabbit feeds, particularly at the level of 0.25 mg Ag-NPs/kg feed. The inclusion of Ag-NPs in rabbit diets at different concentrations increased the total antioxidant capacity and the activities of superoxide dismutase, catalase, and glutathione peroxidase. Growing rabbits fed on diets supplemented with Ag-NPs had higher levels of digestive enzymes than the control group. The addition of Ag-NPs reduced the load of E. coli, Salmonella spp. and coliform in the rabbit cecum. Overall, the inclusion of 0.25–1 mg Ag-NPs/kg to NZW rabbit diets has shown beneficial effects on health and performance.

Diosgenin Alleviates Obesity-Induced Insulin Resistance by Modulating PI3K/Akt Signaling Pathway in Mice Fed a High-Fat Diet.

Obesity is a global medical issue that can be effectively treated by relieving adipose inflammation and subsequent insulin resistance. Diosgenin (DIOS) has various effects as a steroidal saponin in inflammatory disorders. This study explored the effects and mechanism of DIOS on adipose inflammation and insulin sensitivity, both in silico and in vivo. The high-fat diet-induced obesity model in C57BL/6 mice was divided into five groups: normal chow (NC), high-fat diet (HFD), HFD with atorvastatin 10 mg/kg (AT), HFD with DIOS 100 mg/kg (DIOS 100), and HFD with DIOS 200 mg/kg (DIOS 200). Each group underwent an oral intervention for seven weeks. DIOS significantly suppressed weight gain in the body, liver, and epididymal fat pads. Additionally, it significantly improved fasting glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance test results, and reduced the proportion of total and M1 adipose tissue macrophages. Significant changes were shown in mRNA expression of janus kinase 2 (JAK2), insulin receptor (INRS), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), all of which exhibited high binding affinity in the in silico. Safety indices, including aspartate aminotransferase (AST), alanine transaminase (ALT), and creatinine level indicated the preventive effects of DIOS. In conclusion, DIOS improves insulin resistance and obesity-associated inflammation via the PI3K/Akt signaling pathway.

Antioxidant and Immunological Properties of Dracocephalum moldavica Extract in Penaeus vannamei

Objectives: The effects of different concentrations of Dracocephalum moldavica extract (DME) supplement on growth, survival, antioxidants, some biochemical parameters and innate immunity of White leg shrimp (Penaeus vannamei) juveniles investigated. Methods: For 56 days, shrimp (4.5-5 g) received diets that were enhanced with 0 (control), 50, 100, 200 mg DME/kg feed to attain apparent satiety. Results: The results revealed that feeding shrimp with DME significantly improved Feed efficiency and Feed conversion ratio with an optimum level of 200 mg/kg diet. Dietary DME supplementation had no significant effects on their carcass composition. Total albumin and protein higher (P &gt; 0.05) in DME-fed particularly at 200 mg/kg treatment On the other hand, shrimp fed 200 mg DME/kg feed experienced significant decreases in aspartate and alanine aminotransferase levels. As dietary extract levels increased, there was a significant (P &lt; 0.05) increase in SOD and CAT activities, as well as LYZ and PO levels, so that treatments with 100 and 200 mg DME/kg feed had the highest values, and Significant (P &lt; 0.05) reductions in MDA and NO levels were observed at high dietary extract levels of 100 and 200 mg DME/kg. Conclusion: P. vannamei's growth, antioxidant capacity and innate immunity were boosted by diets that contained 200 mg DME/kg feed.

Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke

Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke

S219 Evaluation of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index Stabilization in the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis

S219 Evaluation of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index Stabilization in the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis

A novel predictive model for optimizing diabetes screening in older adults.

The fasting blood glucose test is widely used for diabetes screening. However, it may fail to detect early-stage diabetes characterized by elevated postprandial glucose levels. Hence, we developed and internally validated a nomogram to predict the diabetes risk in older adults with normal fasting glucose levels. This study enrolled 2,235 older adults, dividing them into a Training Set (n = 1,564) and a Validation Set (n = 671) based on a 7:3 ratio. We employed the least absolute shrinkage and selection operator regression to identify predictors for constructing the nomogram. Calibration and discrimination were employed to assess the nomogram's performance, while its clinical utility was evaluated through decision curve analysis. Nine key variables were identified as significant factors: age, gender, body mass index, fasting blood glucose, triglycerides, alanine aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, blood urea nitrogen, and hemoglobin. The nomogram demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.824 in the Training Set and 0.809 in the Validation Set. Calibration curves for both sets confirmed the model's accuracy in estimating the actual diabetes risk. Decision curve analysis highlighted the model's clinical utility. We provided a dynamic nomogram for identifying older adults at risk of diabetes, potentially enhancing the efficiency of diabetes screening in primary healthcare units.

A phase 2/3 study of romiplostim N01 in chemotherapy-induced thrombocytopenia (CIT).

217 Background: CIT causes dose reduction or delay of chemotherapy (chemo), bleeding, and platelet (PLT) transfusion. This phase 2/3 study aimed to assess the efficacy and safety of romiplostim N01 in CIT. Methods: This trial comprising Part A (open-label) and B (randomized double-blinded) recruited patients (pts) with solid tumors or lymphoma and with CIT. In Part A, pts with a PLT count ≤200×10 9 /L before the day of chemo were included. Romiplostim N01 was injected subcutaneously per week (QW) for a 3-week chemo cycle at 1 μg/kg (group 1) or 2 μg/kg (group 2) for pts with a PLT count 100~200×10 9 /L, and at 2 μg/kg (group 3) for pts with a PLT count &lt;100×10 9 /L. Primary endpoint was proportion of responders on the last day of chemo cycle, defined as pts who had an increase in PLT count of ≥30×10 9 /L from baseline for pts with a PLT count 100~200×10 9 /L, and an increase in PLT count of ≥30×10 9 /L or a PLT count ≥100×10 9 /L for pts with a PLT count &lt;100×10 9 /L. In Part B, pts with a PLT count 75~150×10 9 /L were included and randomized 2:1 to receive romiplostim N01 or placebo QW at 2 μg/kg on day 1, and at 1 μg/kg on day 8 and 15 for two chemo cycles. Primary endpoint was proportion of responders, defined as pts resuming two consecutive chemo cycles without thrombocytopenia-induced dose modification (dose reduction by ≥15% or delay by ≥4 days or discontinuation) and without a rescue therapy. Results: In Part A, 50 pts were included between Mar 12, 2021 and Jul 29, 2021. The proportions of responders were 66.7% (10/15) in group 1, 53.3% (8/15) in group 2, and 90.0% (18/20) in group 3. Between Nov 8, 2022 and Jan 15, 2024, 63 pts were randomized in Part B. The proportion of responders in the romiplostim N01 group was significantly higher than that in placebo group (68.3% vs 40.9%). The adjusted rate difference was 27.6% (95% confidence interval [CI]: 2.1%, 50.2%). Treatment-related adverse events (TRAEs) occurred in 17 (41.5%) and 12 (54.5%) pts in the romiplostim N01 and placebo groups, of whom 1 (2.4%) and 0 were ≥grade 3. The most frequent TRAEs were nausea (12.2% vs 0), vomiting (12.2% vs 0), and increased aspartate aminotransferase (9.8% vs 4.5%). No treatment-related hemorrhage or death occurred. In pool analysis, the proportion of responders was 73.3% and 40.9% in pts treated with romiplostim N01 and placebo, respectively. The rate difference was 32.4% (95% CI: 9.2%, 52.9%). Conclusions: Romiplostim N01 showed promising efficacy and manageable safety in patients with CIT. Clinical trial information: PartA:NCT05851027 ; PartB:NCT05554913 . Pool analysis of Part A (pts with PLT count ≥75×10 9 /L) and Part B (all pts). Romiplostim N01 Placebo Rate Difference Part A+B (n=75) Part B (n=22) Romiplostim N01 (Part A+B) vs Placebo Lowest PLT count in Cycle 1, ×10 9 /L 85±41 59±32 / Highest PLT count in Cycle 1, ×10 9 /L 226±101 132±45 / Proportion of responders who completed the first chemo cycle without rescue therapy and without thrombocytopenia-induced dose modification of the second chemo cycle 55 (73.3%) 9 (40.9%) 32.4% 95% CI 61.9~82.9% 20.7~63.6% 9.2~52.9%

Evaluation of the presence and severity of spontaneous splenorenal or gastrorenal shunts via four-dimensional flow magnetic resonance imaging: a preliminary study.

Four-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) is a relatively new type of MRI acquisition technique that provides a unique and comprehensive set of information within a single acquisition, including hemodynamic and anatomical information. This study was designed to noninvasively evaluate the correlation between the presence and severity of spontaneous splenorenal shunt (SRS) or gastrorenal shunt (GRS) and 4D flow MRI-derived parameters. This retrospective case-control study enrolled 70 patients who were diagnosed with hepatocirrhosis portal hypertension and admitted to the Second Affiliated Hospital of Chongqing Medical University. Patients were divided into three groups according to the diameter of the SRS and GRS. 4D flow MRI-derived parameters, including the turbulent kinetic energy, total volume (TV), flow velocity, blood flow volume (BFV), maximum flow (MF), wall shear stress, and relative pressure, were obtained for eight cut planes: proximal to the splenomesenteric confluence and liver hilum of the portal vein (PV1/PV2); the left/right branch of the bifurcation of the PV (LPV/RPV), at the mesosplenic confluence of the splenic vein (SV1), at the splenic hilum of the SV (SV2); at the proximal to the splenomesenteric confluence of the superior mesenteric vein (SMV1), and 5 cm from the splenomesenteric confluence of the SMV (SMV2). Comparisons among the three groups were based on one-way analysis of variance (ANOVA). Logistic regression was used to identify the risk factors for small SRS/GRS (S-SRS/GRS) and for large SRS/GRS (L-SRS/GRS). Receiver operating characteristic curves were used to evaluate the diagnostic performance of the independent risk factors for SRS and GRS. The associations between the clinical data and the 4D flow MRI-derived parameters of GRS and SRS were assessed via Spearman correlation coefficient analysis. The presence of SRS or GRS was correlated with TVLPV (r=-0.302; P=0.035), TVPV1 (r=-0.385; P=0.001), TVPV2 (r=-0.301; P=0.013), BFVPV1 (r=-0.360; P=0.010), BFVSMV2 (r=0.371; P=0.008), MFPV1 (r=-0.341; P=0.004), and MFPV2 (r=-0.291; P=0.017). Meanwhile, the severity of the SRS or GRS was correlated with alanine aminotransferase level (r=-0.535; P<0.001), BFVLPV (r=-0.560; P=0.008), aspartate aminotransferase level (r=-0.321; P=0.038), and model for end-stage liver disease score (r=0.323; P=0.039). TVPV1, TVPV2, BFVPV1, BFVPV2, and MFSMV2 were found to be independent risk factors for L-SRS/GRS, with intermediate diagnostic efficacy, with the area under the curve (AUC)TV PV1=0.706 [95% confidence interval (CI): 0.519-0.853; sensitivity, 61.54%; specificity, 80.77%; P=0.018], AUCBFV PV1 =0.694 (95% CI: 0.507-0.844; sensitivity, 95.00%; specificity, 63.16%; P=0.035), AUCTV PV2 =0.729 (95% CI: 0.544-0.870; sensitivity, 77.78%; specificity, 66.67%; P=0.016), AUCBFV PV2 =0.718 (95% CI: 0.531-0.862; sensitivity, 60.00%; specificity, 82.35%; P=0.017), and AUCMF SMV2 =0.788 (95% CI: 0.608-0.912; sensitivity, 44.00%; specificity, 84.46%; P=0.005), respectively. As the TV of PV1 and PV2 and the BFV of PV1 and PV2 decreased, the risk of L-SRS/GRS increased. As the MF of SMV2 increased, the risk of the presence of L-SRS/GRS increased. 4D flow MRI-derived parameters correlated with the presence and severity of SRS or GRS. Meanwhile, the independent risk factors for the presence of L-SRS/GRS were the TV of LPV, PV1, and PV2; the BFV of PV1 and SMV2; and the MF of PV1 and PV2.

Enhancing Sensitivity in Detecting Severe Fever With Thrombocytopenia Syndrome Virus: Development of a Reverse Transcription-Droplet Digital Polymerase Chain Reaction.

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

HELLP syndrome and associated factors among pregnant women with preeclampsia/eclampsia at a referral hospital in southwestern Uganda: a cross-sectional study

BackgroundHemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, a complication of preeclampsia/eclampsia, is associated with severe maternal morbidity and mortality. In resource-limited settings, such as Uganda, gaps in routine laboratory assessments may lead to underdetection of HELLP syndrome. This study determined the prevalence and factors associated with HELLP syndrome among pregnant women with preeclampsia/eclampsia at Mbarara Regional Referral Hospital (MRRH), southwestern Uganda.MethodsA cross-sectional study was conducted at the high-risk ward of the MRRH from December 2022 to June 2023. Pregnant women diagnosed with preeclampsia or eclampsia were enrolled consecutively. Participants’ sociodemographic and clinical data were collected using an interviewer-administered questionnaire. The diagnosis of complete HELLP syndrome was made based on the Tennessee classification: aspartate aminotransferase enzyme ≥ 70 IU/L, platelet counts < 100,000 cells/µL, and serum lactate dehydrogenase enzyme ≥ 600 IU/L. We used multivariable modified Poisson regression analysis to determine factors associated with HELLP syndrome.ResultsA total of 129 participants with a mean age of 28 ± 6.6 years were enrolled in the study. The prevalence of HELLP syndrome was 18.6% (n = 24; 95% CI: 12.7–26.3%). Independent factors associated with HELLP syndrome were maternal age (adjusted prevalence ratio [aPR]: 4.96; 95% CI: 1.57–15.65; for mothers aged < 20 years compared to those aged 20–34 years), the presence of epigastric pain (aPR: 5.89; 95% CI: 1.41–14.63), and referral from other health facilities (aPR: 3.14; 95% CI: 1.27–7.72).ConclusionApproximately 2 of the 10 women who presented with preeclampsia or eclampsia had HELLP syndrome. It is more common among teenage mothers, those with a history of epigastric pain and those referred from lower health facilities. Incorporating routine laboratory testing for HELLP syndrome in the diagnostic protocol for preeclampsia or eclampsia, especially among adolescent mothers, those experiencing epigastric pain, and those referred from lower health facilities, could enhance timely detection and management of mothers with preeclampsia whose pregnancies are complicated by HELLP syndrome.

AcFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study

Background & AimsMetabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs). MethodsWe analyzed data from 3,004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and nine international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9,034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs. ResultsIn the pooled global cohort, the acMASH index identified MASH with an AUROC of 0.802 (95%CI 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI 0.693-0.800, P<0.01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted-hazard ratio: 11.23 95%CI 3.98-31.66). ConclusionsThis multi-ethnic study validates the acMASH index as a reliable, non-invasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

Growth-coupled production of L-isoleucine in Escherichia coli via metabolic engineering

L-isoleucine, an essential amino acid, is widely used in the pharmaceutical and food industries. However, the current production efficiency is insufficient to meet the increasing demands. In this study, we aimed to develop an efficient L-isoleucine-producing strain of Escherichia coli. First, accumulation of L-isoleucine was achieved by employing feedback-resistant enzymes. Next, a growth-coupled L-isoleucine synthetic pathway was established by introducing the metA-metB-based α-ketobutyrate-generating bypass, which significantly increased L-isoleucine production to 7.4 g/L. Upon employing an activity-improved cystathionine γ-synthase mutant obtained from adaptive laboratory evolution, L-isoleucine production further increased to 8.5 g/L. Subsequently, the redox flux was improved by bypassing the NADPH-dependent aspartate aminotransferase pathway and employing the NADH-dependent pathway and transhydrogenase. Finally, L-isoleucine efflux was enhanced by modifying the transport system. After fed-batch fermentation for 48 h, the resultant strain, ISO-12, reached an L-isoleucine production titer of 51.5 g/L and yield of 0.29 g/g glucose. The strains developed in this study achieved a higher L-isoleucine production efficiency than those reported previously. These strategies will aid in the development of cell factories that produce L-isoleucine and related products.

Effects of water immersion on immune, intestinal flora and metabolome of Chinese mitten crab (Eriocheir sinensis) after air exposure

Air exposure stress can induce stress response of Eriocheir sinensis and affect its normal life activities. The goal of this study was to investigate the effects of water immersion on the recovery of hepatopancreas immune-related enzyme activity, intestinal microbial diversity and metabolic level of Chinese mitten crabs after exposure to air. The results show that immersion can effectively alleviate the adverse effects of air exposure on the antioxidant capacity and immune capacity of Chinese mitten crabs, and the longer the time of immersion, the more obvious the recovery effect. Among them, the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acid phosphatase significantly increased after exposure to air (P < 0.05), reached a peak at 3 h, began to decline after immersion, and returned to a level close to the initial value at 24 h (P < 0.05). In addition, after exposure to air, the glucose and total cholesterol in haemolymph of Eriocheir sinensis were significantly different from the initial values (P < 0.05), gradually recovered to the initial level after re-immersion. However, changes in intestinal flora and hepatopancreas metabolism caused by air exposure did not fully recover after water exposure, and its negative effects did not completely disappear. The sequencing results showed that the species composition and diversity of intestinal microorganisms of Chinese mitten crab changed after air exposure and immersion treatment. The relative abundance of Actinomycetes increased significantly, while that of Proteobacteria and Firmicutes decreased significantly. Metabolomics analysis showed that air exposure and immersion destroyed the metabolic balance of amino acids and carnitine, reduced the level of carnitine metabolism, hindered the absorption of nutrients, and led to the accumulation of harmful substances.

Higher toll-like receptor 3 expression in umbilical cord blood B cells than in adult blood B cells

Background Umbilical cord blood (UCB), which is considered a rich source of stem cells, has been used for applications in different clinical settings. Therefore, it is crucial to examine the toll-like receptor (TLR) expression levels in UCB B cells as compared to adult blood cells. Aim To determine the phenotypes of B cells in UCB and to investigate their expression of TLR3 as compared to adult blood. Patients and methods Samples of UCB were collected (n=20) after delivery, and peripheral blood samples were collected from female healthy volunteers (n=10) in K2EDTA tubes. Cells were washed twice, then stained using anti-CD19 and anti-TLR3. The samples were acquired by flow cytometry to assess the phenotype of B cells and their expression of TLR3. Besides, the liver and kidney functions were assessed. Results The relative number of CD19+ cells showed lower numbers (5.35%) in UCB than adult blood (15.64%). Additionally, the absolute number of CD19+ cells showed lower numbers by two-fold in cord blood than in adult blood. The relative expression of TLR3 on CD19+ cells showed lower expression in UCB as compared to adult blood by 5.8-fold. However, the absolute number of TLR3+CD19+ was higher in UCB than in adult blood by two-fold. The liver and kidney function showed normal values as investigated the enzyme activity of aspartate aminotransferase, alanine aminotransferase, bilirubin, and creatinine in both cord and adult. Conclusion B cells express lower TLR3 in cord blood than in adult blood. The data from this study open new avenues for the manipulation of cord blood by TLR agonists for clinical application.

GDF-15 improves the predictive capacity of Steatotic liver disease non-invasive tests for incident morbidity and mortality risk for cardio-renal-metabolic diseases and malignancies

Background & aimsNoninvasive tools (NITs) are currently used to stratify the risk of having or developing hepatic steatosis or fibrosis. Their performance and a proteomic-enabled improvement in forecasting long-term cardio-renal-metabolic morbidity, malignancies, as well as cause-specific and all-cause mortality, are lacking. Therefore, the performance of established NITs needs to be investigated in identifying cardio-renal-metabolic morbidity, malignancies, cause-specific and overall mortality and improve their performance with novel, proteomic-enabled NITs, including growth differentiation factor 15 (GDF-15), allowing multipurpose utilization. Methods502,359 UK Biobank participants free of the study outcomes at baseline with a 14-year median follow-up were grouped into three categories: a) general population, b) potentially metabolic dysfunction-associated steatotic liver disease (MASLD) population, c) individuals with type 2 diabetes mellitus. The investigated NITs include Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis 4 Index (FIB-4), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and metabolic dysfunction–associated fibrosis (MAF-5) score. ResultsAdding GDF-15 to the existing NITs led to significantly increased prognostic performance compared to the traditional NITs in almost all instances, reaching substantially high C-indices, ranging between 0.601 and 0.808, with an overall >0.2 improvement in C-index. Overall, with the GDF-15 enhanced NITs, up to more than seven times fewer individuals need to be screened to identify more incident cases of adverse outcomes compared to the traditional NITs. The cumulative incidence of all outcomes, based on the continuous value percentiles of NITs, is increasing exponentially in the upper quintile of the GDF-15 enhanced NITs. ConclusionsThe herein-developed GDF-15 enhanced indices demonstrate higher screening effectiveness and significantly improved prognostic abilities, which are reduced to practice through an easy-to-use web-based calculator tool (https://clinicalpredictor.shinyapps.io/multimorbidity-mortality-risk/).

Protective effect of Zhizi Huangqi Shanzha formula on aflatoxin poisoning in mice and its effect on intestinal flora.

To evaluate the protective effect of Zhizi Huangqi Shanzha formula (, ZHSF) on aflatoxin-induced liver injury. The protective effect of ZHSF on the aflatoxin-induced liver injury was evaluated by histological observation, blood cell analysis, evaluation of liver function and immunity, and gut microbiota analysis. ZHSF can significantly up-regulate the percentage of lymphocytes and eosinophils in the blood of Aflatoxin B1-intoxicated mice, down-regulate the levels of serum aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, and recover the liver tissue structure. Aflatoxin poisoning induces a variation of the intestinal flora of mice, and ZHSF may recover the variation of intestinal flora induced by Aflatoxin B1. Cluster analysis showed that the intestinal flora of mice in the intervention group was more similar to that of the control group. Correlation analysis showed that Lachnospiraceae, Desulfovibrio, and Lactobacillus may be the key flora for the pharmacological effects of ZHSF. ZHSF may protect against aflatoxin-induced liver damage, improve immunity, and inhibit oxidative stress by regulating the composition and relative abundance of intestinal flora, which makes it a promising liver-protective candidate drug.