Liver Function Indices Research Articles

Clinical Efficacy of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Patients with Refractory Cirrhotic Ascites

Objective: To analyze the efficacy of autologous bone marrow mesenchymal stem cell (BMSC) transplantation for the treatment of cirrhotic ascites (refractory). Methods: 64 patients with cirrhosis ascites (refractory) who were admitted to the hospital between May 2022 and April 2024 were selected and divided equally by random number table, the observation group was treated with BMSC autologous transplantation, and the reference group was treated with conventional medication, and the total effective rate, therapeutic indexes, liver and renal function indexes, and the change of urine volume were compared. Results: The total effective rate of the observation group was higher than that of the reference group (P < 0.05). Before treatment, there was no difference between the two groups in terms of therapeutic indexes such as depth of ascites, liver and kidney function indexes and 24-hour urine volume (P > 0.05). After treatment, the observation group’s ascites depth and other indicators were better than that of the reference group, liver and kidney function indicators were better than that of the reference group, and 24h urine volume was more than that of the reference group (P < 0.05). Conclusion: BMSC autotransplantation can improve the clinical efficacy of patients with cirrhosis ascites (refractory), accelerate the absorption of ascites, reduce the values of body mass and abdominal circumference, and protect the liver and kidney functions and increase the amount of urination.

B-034 Performance Evaluation of the Total Bile Acids (TBA) Assay on Mindray BS-2800M Analyzer

Abstract Background Bile acids (BA) are synthesized in the liver and secreted into bile. The function of BA is to promote absorption of lipids including fat-soluble vitamins. During liver diseases such as viral hepatitis and liver injury by hepatotoxic drugs, and cholestasis condition, BA secretion to bile is impaired, causing serum BA level to rise. Therefore, the determination of serum BA can be used as a sensitive indicator of liver function. TBA reagent contains NADH that requires pH ≥ 9 to be stable that is usually difficult to be maintained during reagent opened and stored on the analyzer. Meanwhile, 3α-Hydroxysteroid Dehydrogenase (3α-HSD) is required for the reaction. 3α-HSD is sensitive to pH condition. Minor changes in pH results in significant changes of enzyme activity. We formulated our TBA reagent with prolonged stability when reagent is onboard on the analyzer. This study evaluated the performance of the new Mindray TBA assay on Mindray BS-2800M. Methods TBA assay was based on the method with coupled Thio-NAD and NADH reaction for BA. The R1 contains Thio-NAD. The R2 contains NADH and 3α-HSD. R1 is incubated with serum sample containing BA for 5 min at 37°C and R2 is then added. During further incubation in the presence of Thio-NAD, 3α-HSD converts BA to 3-ketosteroids and Thio-NADH. The reaction is reversible, and 3α-HSD can convert 3-keto steroids and Thio-NADH to BA and Thio-NAD. In the presence of excess NADH, enzyme cycling occurs efficiently and the rate of formation of Thio-NADH is determined by measuring specific change of absorbance at 412 nm. Two-point-line calibration is used by this assay. The TBA concentrations for the test samples are obtained by the absorbances of test samples from the calibration line. The performances of precision, linearity, onboard stability, interference (hemolysis, lipid and bilirubin), correlation are evaluated following CLSI protocols. Results The precision study was run according to EP05A3 with two commercial controls (about 21 and 36μmol/L) and two serum sample pools(about 9.9 and 24.2 μmol/L)on the Mindray BS-2800M system. The repeatability and within-lab CVs ranged from 0.74% to 1.97%, respectively. The linearity of the assay was determined as from 2.0 μmol/L to 180 μmol/L. The reagent onboard stability is for 28 days without recalibration that is superior to TBA reagents from other manufacturers. The interference of hemolysis, lipid and bilirubin are with less than ±10% impact with hemolysate Hemoglobin up to 500 mg/dL, Intralipids up to 500 mg/dL, and Conjugated bilirubin up to 30 mg/dL, Unconjugated bilirubin up to 30mg/dL. This assay (Y) also correlated well with SEKISUI TBA assay (x), (Y = 0.9965X + 0.2694, r= 0.9993). Conclusions From this evaluation, we concluded that Mindray TBA assay can measure serum TBA precisely and accurately with good performances, especially for onboard stability. It is suitable for use in routine clinical laboratories.

Aquamimicry feeding system improved growth, physiological status, muscle and intestine histomorphology, and flesh quality of keeled mullet, Liza carinata

The aquamimicry feeding system (AMFS) is one of the modern aquaculture systems that aim to reduce feed costs and water exchange rates to improve the sustainability of aquaculture projects. In AMFS, the aquatic environment is simulated to produce natural food by adding probiotics to carbon sources. Therefore, a 108-day field study was conducted to evaluate the efficiency of AMFS as a solo feed or in combination with a commercial diet for the rearing of keeled mullet, Liza carinata. The L. carinata fingerlings with an initial body weight of 30.0 ± 3.25 g were randomly distributed into three experimental treatments in triplicate rectangular polyethylene ponds (measured 7 × 3 × 1 m) at an initial stocking density of 105 fish per pond. The fish were fed one of the following regimes: the 1st is a commercial floating diet (CFD, 30 % crude protein; T1), the 2nd is a combination of 50 % CFD: 50 % AMFS (T2), the 3rd is a solo of AMFS (T3). Water quality parameters did not differ significantly among different treatments except for a significant reduction in total ammonia nitrogen and a higher zooplankton count in the water of the AMFS group. The fish reared with AMFS as a solo feed (T3) experienced a significant growth performance, somatic indexes, and digestive enzyme activities compared to the fish reared in other treatments. Fish fed AMFS alone (T3) or in combination with CFD (T2) had an improved hematological profile, liver and kidney function indicators, serum lipid, and protein profiles than those fed CFD (T1). Histological and histometric analysis of the intestine showed an improved architecture with AMFS feeding. Furthermore, AMFS feeding increased the diameter of muscle bundles and the protein content of the dorsal muscles. The flesh quality parameters, including water holding capacity, stored loss, drip loss, and frozen leakage rate were improved in fish fed on AMFS alone or in combination with CFD. Therefore, from the above-mentioned beneficial effects of AMFS, it could be used as a promising, economical, and sustainable technology for rearing L. carinata.

Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder marked by hepatic fat accumulation and inflammatory infiltrates which may evolve to cirrhosis. Clinical studies have demonstrated the higher risk of MASH development after tamoxifen (TAM) therapy, especially in obese patients. Therefore, we aimed to evaluate MASH induction by TAM combined with high fat diet (HFD) and the potential interference of memantine (MEMA) with MASH progression via modulation of SIRT6 and its related signaling pathways. MASH was induced in female Wistar rats by co-administration of TAM (25 mg/kg/day, p.o.) and HFD for 5 weeks. Liver function biomarkers, tissue triglyceride and cholesterol, MASH scoring, SIRT6 with its related signals, and lipid synthesis/oxidation markers were estimated. By comparison to MASH group, MEMA improved liver function indices (ALT, AST, ALP, albumin) and reduced the progression of MASH, evidenced by decreased accumulation of lipids in hepatic tissue, improved histological features, and reduced MASH scoring. MEMA enhanced hepatic SIRT6 and downregulated p-AKT/mTOR signaling, that subsequently reduced expressions of the lipid synthesis biomarkers (SREBP1c, SCD), while elevating the lipid oxidation markers (PPAR-α, CPT1). Moreover, MEMA enhanced NRF2/HO-1 signaling, with subsequently improved antioxidant defense and pro-inflammatory/anti-inflammatory cytokines balance. Analysis of SIRT6 correlations with p-AKT/mTOR, NRF2/HO-1, SREBP1c, and PPAR-α further confirmed our results. Consequently, we conclude that MEMA could interfere with MASH progression, at least in part, via enhanced SIRT6 expression and modulation of its related p-AKT/mTOR and NRF2/HO-1 signaling pathways, eventually reducing liver steatosis and inflammation. That could be a promising therapeutic modality for curbing MASH progression.

Caffeoylquinic acids from Silphium perfoliatum L. show hepatoprotective effects on cholestatic mice by regulating enterohepatic circulation of bile acids

Ethnopharmacological relevanceThe incidence of cholestatic liver disease (CLD), which is primarily marked by abnormal bile acids (BAs) metabolism and can result in significant hepatic injury, is rising. Nevertheless, there remains a lack of effective treatments and drugs in clinical practice. Silphium perfoliatum L. (SP) is rich in various structural types of caffeoylquinic acid (CQA) compounds, and it is a traditional herb of North American Indians with hepatobiliary therapy effects. However, its therapeutic effect and mechanism of action on CLD have never been studied. Aim of the studyTo determine if SP-8, an extract rich in CQAs from SP, protects against cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) and to clarify its mechanism based on the farnesoid x receptor (FXR) signaling pathway and enterohepatic circulation of BAs. Materials and methodsThe therapeutic efficacy of SP-8 was evaluated by assessing the serum biochemical indices, inflammatory factors, and liver histopathology. Targeted metabolomics of the BAs was studied in the feces, liver, serum, and bile using UPLC-MS/MS. Additionally, a Western blot analysis was used to examine the expression levels of the peroxisome proliferator-activated receptor γ (PPARγ), the FXR, and proteins related to the synthesis and transport of BAs. 16S rRNA gene sequencing was performed to evaluate the gut microbiota (GM). Finally, molecular docking simulations were conducted to assess the interaction between seven types of CQAs from SP-8 with FXR and PPARγ. ResultsSP-8 significantly enhanced the health status of cholestatic mice induced by ANIT as evidenced by a notable reduction in the liver function indices and pro-inflammatory factors, restoration of liver pathological damage, and acceleration of BAs excretion through the feces. In addition, the levels of harmful secondary BAs in the liver and blood were significantly reduced by SP-8. Furthermore, the results of the study on the mechanism of action confirmed that SP-8 not only regulated FXR and PPARγ but also significantly ameliorated the GM structure, thereby promoting the enterohepatic circulation of BAs and achieving the homeostasis of the BAs in the blood and liver. In addition, SP-8 successfully reduced the inflammatory response by strongly suppressing the nuclear translocation of NF-κBp65. According to the molecular docking results, the extract's primary active ingredients could be the seven CQAs in SP-8, as they exhibited a strong affinity for both FXR and PPARγ. Finally, the Mantel test analysis revealed a significant correlation among cholestatic-associated parameters, the GM, and BAs. ConclusionIt was confirmed for the first time that the SP-8 extract of Silphium perfoliatum L. that is rich in seven CQAs had a strong therapeutic effect on ANIT-induced CLD. Its mechanism may involve the regulation of the FXR signaling pathway and the amelioration of the GM structure to promote the homeostasis of BAs enterohepatic circulation. This study provides a potential candidate medicinal herb and its components for the development of CLD therapeutic drugs.

HTLV1 infection and long term association with liver function and lipid indices; 10 years’ follow-up

BackgroundHuman T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term.MethodsThis data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated.ResultsMultivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039).ConclusionIndividuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus’s involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue.

Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway

BackgroundThe cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear.Materials and methodsA cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI.ResultsPGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1.ConclusionsPGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Comparison and Analysis of Clinical Characteristics of Common COVID-19 and NSIP Patients

Objective: To investigate the relationship between coronavirus disease 2019 (COVID-19) and non-specific interstitial pneumonia (NSIP), with a focus on the clinical features of COVID-19 and NSIP, and the key points of differential diagnosis. Methods: The clinical data of 20 patients with common-type COVID-19 and NSIP admitted to Linyi People’s Hospital from January 21, 2020, to June 21, 2022, were retrospectively analyzed. Gender, age, history of residence in Hubei province, underlying diseases, clinical manifestations, laboratory test results (including blood routine indexes, inflammatory markers, liver function indexes, and coagulation indexes), and computed tomography (CT) scan images were compared between the two groups. Results: COVID-19 patients were younger than NSIP patients (P &lt; 0.05). Nine COVID-19 patients had a travel history to Hubei province, while none of the NSIP patients did (P &lt; 0.05). Eight COVID-19 patients had underlying chronic conditions, fewer than the NSIP group (12 patients; P &lt; 0.05). Both groups experienced symptoms such as shortness of breath, expectoration, fatigue, and runny nose, but fever and cough were more severe and more frequent in the COVID-19 group. Compared to normal reference ranges, both groups exhibited normal white blood cell counts (WBC) and liver function indexes, but elevated lymphocyte counts (LYMP), inflammatory markers, and coagulation indexes, with reduced neutrophil counts (NE). WBC and LYMP were higher in the COVID-19 group compared to the NSIP group. Male patients in the COVID-19 group had higher erythrocyte sedimentation rates and C-reactive protein values than those in the NSIP group, while procalcitonin levels were lower in the COVID-19 group, although the differences were not statistically significant (all P &gt; 0.05). The NE count in the COVID-19 group was significantly lower than in the NSIP group (P &lt; 0.05). Alanine aminotransferase, total bilirubin, and indirect bilirubin were significantly higher in the COVID-19 group compared to the NSIP group (P &lt; 0.05). Chest CT scans of both groups showed bilateral patchy ground-glass opacities, but the lesions in COVID-19 patients were scattered. NSIP patients’ chest CTs showed diffuse lesions centered around the hilum or multiple lesions in both lungs, with pleural involvement being rare. Conclusion: While there are certain specific clinical, laboratory, and imaging findings in both COVID-19 and NSIP, the specificity of these features is not high. Differentiating the two requires careful consideration of epidemiological history, nucleic acid testing, and antigen-antibody levels.

Efficacy and safety of dienogest on ovarian endometrioma

Objective: To observe the effects and safety of dienogest on the volume and symptoms of ovarian endometrioma (OMA). Methods: The clinical data of 75 patients with OMA who underwent treatment with dienogest (2 mg/day) at the First Affiliated Hospital of Nanjing Medical University from July 1st 2020 to March 31st 2024 were retrospectively analysed, mainly comparing the changes in the volume of OMA and the visual analogue scale (VAS) scores of endometriosis-related pain before and after the treatment, as well as observing the changes in the blood biological indicators, liver and kidney function, coagulation function and changes in breast. Results: The median cyst volumes of the OMA patients at 3, 6 and 12 months of dienogest treatment were 13.21 cm3 (volume reduction rate: 36.00%), 8.33 cm3 (volume reduction rate: 56.00%) and 4.10 cm3 (volume reduction rate: 77.62%), respectively, which were all significantly decreased from the pre-treatment period (all P<0.05). The VAS scores of pain of the OMA patients at 3, 6 and 12 months of dienogest treatment all were 0 mm. Blood cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) levels decreased progressively during treatment (all P<0.05). There were no statistical differences in the coagulation indexes, liver and kidney function indexes of the patients during dienogest treatment compared with those before treatment (all P>0.05). During the follow-up period, there were a few patients with changes in the growth sites or lesion category of the breast nodules, but there were no occurrence of breast cancer or precancerous lesions. Conclusion: Dienogest is effective in reducing OMA volume and alleviating endometriosis-related pain with few adverse effects.

Discrimination of Abrus cantoniensis Hance and Abrus mollis Hance using UPLC-Q/TOF-MS and assessment of their in vivo hepatoprotective effects

Ethnopharmacological relevanceIn Guangzhou and Guangxi, China, Abrus cantoniensis Hance (AH) is known for its liver-protective properties and is commonly used in herbal teas and soups. In the herbal market and pharmaceutical preparations, AH and Abrus mollis Hance (AMH) are often used interchangeable. Despite their morphological and usage similarities, distinguishing their differences is essential for scientific research and clinical practice. Aim of the studyThis study focuses on the morphological identification, chemical composition, and hepatoprotective effectiveness of AH and AMH. It aims to evaluate their interchangeable use and provide a rationale for this practice. This research helps regulate the market of AH medicinal materials, ensuring clinical safety and effectiveness. Materials and methodsSamples of AH and AMH roots, stems, leaves, and seeds were collected and photographed using a stereoscope and digital imaging system. The chemical components of AH and AMH were qualitatively analyzed using UPLC-Q/TOF-MS. Chemometric techniques, such as PCA and OPLS-DA, were employed to discern the componential differences between the two species. A CCl4-induced acute liver injury mouse model was developed to assess hepatoprotective effects. The hepatoprotective properties of AH and AMH were evaluated by analyzing the liver index, H&E staining, changes in serum liver function indicators (TBIL, ALT, AST), and concentrations of SOD, MDA in liver homogenate. ResultsThe root color, texture, stem diameter, cross-sectional characteristics, leaf shape, and seed morphology of the two plants were observed. Notable differences were identified, which can be used for accurate identification. The UPLC-Q/TOF-MS identified 50 compounds in both species, which were classified into 3 alkaloids, 22 flavonoids, 2 triterpenes, 10 triterpene saponins, 10 amides, and 3 others, and 20 different compounds between AH and AMH were screened by chemometrics. By improving serum biomarkers (ALT, AST, TBIL) and regulating oxidative stress markers (SOD, MDA), the alleviating effect of AH and AMH extracts on liver injury was confirmed. Notably, AH showed a stronger liver protective effect, significantly reducing ALT and AST levels more than AMH. ConclusionThis study enhances understanding of the morphological identification, chemical profiling, and hepatoprotective effects of AH and AMH. It provides a reference for future scientific research and the clinical application of AH in treating liver damage.

Liver function assessment based on hepatobiliary contrast agent-enhanced magnetic resonance imaging

BACKGROUND: Liver function assessment is very important in clinical practice. The use of magnetic resonance imaging for the anatomical and functional evaluation of the liver is possible in actual clinical practice. AIM: To examine the possibility of using hepatobiliary contrast-enhanced magnetic resonance imaging for the evaluation of liver function. MATERIALS AND METHODS: Datasets of patients who underwent gadoxetic acid-enhanced magnetic resonance imaging were retrospectively reviewed. Patients were divided into two groups: group 1 included patients with impaired liver function, and group 2 included those with normal liver function. Based on magnetic resonance imaging in the hepatobiliary phase, the liver parenchyma signal intensity and its ratio to spleen signal intensity and portal vein signal intensity were estimated. Differences among these parameters were compared between groups. The correlation between liver parenchyma signal intensity and laboratory blood tests reflecting liver function (total bilirubin, albumen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, and prothrombin time) were analyzed. RESULTS: Datasets of 53 patients (25 men and 28 women, aged 24–84 years) were analyzed. Group 1 included 19 patients, whereas group 2 included 34. The median liver parenchyma signal intensity was 919.05 [669.65; 1258.35] in group 1 and 1525.13 [1460.5; 1631.4] in group 2 (p=0.0000001). The median ratio of liver parenchyma signal intensity to spleen signal intensity was 1.2 [1.04;1.7] in group 1 and 1.7 [1.46; 1.96] in group 2 (p=0.00076). The median ratio of liver parenchyma signal intensity to portal vein signal intensity was 1.44 [1.29; 1.83] in group 1 and 1.6 [1.43; 1.83] in group 2 (p=0.1). The estimated correlation values between liver parenchyma signal intensity and blood tests parameters were as follows: total bilirubin (r=–0.61; p=0.000001), albumen (r=0.13; p=0.61), aspartate aminotransferase (r=–0.57; p=0.000009), alanine aminotransferase (r=–0.44; p=0.001), alkaline phosphatase (r=–0.45; p=0.0007), gamma glutamyl transpeptidase (r=–0.5; p=0.0003), prothrombin time (r=–0.34; p=0.04). CONCLUSION: The study reflects the ability to assess liver function using indices (liver parenchyma signal intensity and its ratio to spleen signal intensity) derived from gadoxetic acid-enhanced magnetic resonance imaging. However, this study did not confirm the assumed effectiveness of using the liver parenchyma signal intensity to portal vein signal intensity ratio as an index of liver function. A significant inverse correlation was identified between liver parenchyma signal intensity and blood test parameters in reflecting liver function, except for albumin. The results indicate the possibility of using magnetic resonance imaging to assess liver function.

Ameliorative effects of HGF-overexpressed exosomes derived from ADMSCs on oxidative stress in hepatic fibrosis.

Hepatic fibrosis, ultimately causing hepatic sclerosis, remains significant health concerns. Adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes (Exo) exhibit amelioration of liver injury. Hepatocyte growth factor (HGF) regulates hepatocyte growthn. However, its involvement during hepatic fibrosis remains unclear. Isolation of ADMSCs and Exo, transfection of HGF overexpression, and activation of hepatic stellate cells (HSCs) by Angiotensin II (AngII) were conducted. Cells were randomized into HSC, AngII-HSC, ADMSCs-Exo, ADMSCs<supblank</sup>-Exo, and ADMSCs<sup>HGF</sup-Exo, DPI, LY294002, and SB203580 groups. MTT for cell viability, cell migration, and flow cytometry for ROS were performed. BALB/c mice were treated with CCL4 for hepatic fibrosis models. The mice were randomized into Control, PBS, ADMSCs-Exo, ADMSCs^blank-Exo, and ADMSCs^HGF-Exo groups (n=6). HE, Sirius red, and Oil Red O staining, liver function indicators, and ELISA for oxidative stress were performed. ROS generation-related and PI3K/Akt/P38MAPK-related factors were detected by immunofluorescence, immunohistochemistry, and western blot. After identification of ADMSC-Exo and transfection, AngII increased cell viability, migration, Collagen I (CoLI), α-smooth muscle actin (α-SMA), ROS, NADPH oxidase 4 (NOX4), PI3K, p-Akt, p-P38MAPK, ras-related C3 botulinum toxin substrate 1 (RAC1), p47phox, and p22phox expression. However, ADMSCsHGF-Exo, DPI, LY294002, and SB203580 reversed the above effects. Moreover, ADMSCsHGF-Exo inhibited pathological damage, fibrosis, lipid accumulation, ALT, AST, TBIL, CoLI, α-SMA, NOX4, MDA, PI3K, p-Akt, and p-P38MAPK expression, and increased ALB, SOD, GPx, CAT, GSH, Mn-SOD, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase levels in hepatic fibrosis mice. ADMSCsHGF-Exo attenuated hepatic fibrosis by inhibiting oxidative stress through activating the PI3K/Akt/P38MAPK pathway, providing valuable insights for potential treatment of liver fibrosis.

Dendrobine Suppresses Tumor Growth by Regulating the PD-1/PD-L1 Checkpoint Pathway in Lung Cancer

Background: Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study. Methods: Bioinformatics was performed to screen the potential targets of dendrobine. The in-tersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was es-tablished to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the ex-pression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-β, and the changes of indicators of liver and renal function were measured. Results: Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed pro-tein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, den-drobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-β in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors. Conclusion: Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer. conclusion: Dendrobiine inhibited tumor immune escape by suppressing PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer. other: N/A

Catalpol ameliorates liver fibrosis via inhibiting aerobic glycolysis by EphA2/FAK/Src signaling pathway

BackgroundHepatic fibrosis is a pathological process in a variety of acute or chronic liver injuries. Catalpol (CAT), an iridoid glycoside found in Rehmannia glutinosa, has several pharmacological properties, including anti-inflammatory, antidiabetic and anti-fibrotic effects. Nevertheless, there is currently no report on whether CAT regulates the aerobic glycolysis of hepatic stellate cells (HSCs) to inhibit liver fibrosis. ObjectiveThis study aimed to investigate the protective effects of CAT on hepatic fibrosis and elucidate its underlying mechanisms. MethodsTo explore whether CAT improved liver fibrosis in vivo and in vitro, hepatic fibrosis was induced to mice by intraperitoneally injecting carbon tetrachloride (CCl4). Additionally, LX-2 cells were stimulated with transforming growth factor-β (TGF-β) to simulate fibrosis in vitro. Serum markers of liver injury were examined by using an automatic biochemical analyzer. Histopathological staining, Immunofluorescence (IF) staining, Western blot (WB) analysis, co-immunoprecipitation (Co-IP), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), etc. were employed to identify the targeting between CAT and EphA2 and detect the expression of aerobic glycolysis related proteins, fiber markers and signaling pathways that are responsible for CAT's anti-fibrotic effects of CAT. ResultsResults showed that CAT significantly inhibited hepatic injury, fibrogenesis and inflammation in mice treated with CCl4. This was demonstrated by the enhancement of fibrosis markers, liver function indices, and histopathology. In addition, CAT significantly inhibited the activation of HSCs in TGF-β-induced LX-2 cells, as indicated by decreased proliferation, migration, and expression of collagen I and a-SMA. The study results also suggested that CAT may exert anti-fibrotic effects by inhibiting glycolysis in activated HSCs and in CCl4-treated mice. Mechanistically, CAT directly targets Ephrin type-A receptor 2 (EphA2) to reduce binding with focal adhesion kinases (FAK) and significantly inhibits the FAK/Src pathway. In addition, the pharmacological inhibition of EphA2 cannot further increase the therapeutic effects of CAT on liver fibrosis in vivo and in vitro. ConclusionThe study findings generally demonstrated that CAT presented a novel therapeutic method to treat hepatic fibrosis; this method which inhibits the aerobic glycolysis of activated HSCs through the EphA2/FAK/Src signaling pathway.

Interpretable multitemporal liver function indicator model for prediction and risk factor analysis of drug induced liver injury

The occurrence of liver injury during cancer treatment is extremely harmful. The risk factors for drug.induced liver injury (DILI) in the pancreatic cancer population have not been investigated. This study aims to develop and validate an interpretable decision tree (DT) model for the early prediction of DILI in pancreatic cancer patients using multitemporal clinical data and screening for related risk factors. A retrospective collection of data was conducted on 307 patients, the training set (n = 215) was used to develop the model, and the test set (n = 92) was used to evaluate the model. The classification and regression trees algorithm was employed to establish the DT model. The Shapley Additive explanations (SHAP) method was used to facilitate clinical interpretation. Model performance was assessed using AUC and the Hosmer‒Lemeshow test. The DT model exhibited superior diagnostic efficacy, the AUC values were 0.995 and 0.994 in the training and test sets, respectively. Four risk factors associated with DILI occurrence were identified: delta.albumin, delta.ALT, and post (AST: ALT), and post.GGT. The multiperiod liver function indicator.based interpretable DT model predicted DILI occurrence in the pancreatic cancer population and contributes to personalized clinical management of pancreatic cancer patients.

Relationship Between Xylene, Rq Xylene Concentration and Enzyme Activity as Indicators of Heart and Liver Function Among Shoe Industry Workers In Surabaya

Background Xylene, a common solvent in painting, printing, and shoemaking, enters the body through inhalation of vapors. Methods This observational analytic study aimed to examine the relationship between xylene concentration, xylene RQ, and liver function in industrial workers in Surabaya, especially in shoe industries. The chi-square method was utilized for data analysis. To ensure the validity and reliability of the study results, air and blood sampling procedures were implemented. Air sampling was conducted to measure xylene concentrations in the workplace environment, while blood samples were collected from workers to assess Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) levels. The study was conducted in five regions in Surabaya, namely Kalijudan, Ketintang, Jemursari, AUP, and Romokalisari. The population includes a total of 90 workers with 77 of them taken as samples using the accidental sampling method. Results The results show that there is a relationship between xylene concentration and Serum Glutamic Oxaloacetic Transaminase (SGOT) levels (p&gt; 0.05); (r = 0,65) and there is no relationship between xylene concentrations and Serum Glutamic Pyruvate Transaminase (SGPT) levels (p&gt; 0.05); (r = -0,12). There was no relationship between RQ and SGOT levels (p&gt; 0.05) and there was no relationship between RQ and SGPT levels (p&gt; 0.05). However, from the calculation of the prevalence ratio, workers with unsafe RQ (RQ&gt;1) have a 7.09x greater chance of experiencing damage to SGOT levels and a 1.06x greater chance of experiencing damage to SGPT levels. Conclusions Xylene exposure (concentration &amp; RQ) affects liver enzyme levels (SGOT/SGPT) in workers. Industries should consider providing nutritious food to aid xylene removal and stricter safety policies are needed. This study highlights the importance of a holistic approach to worker health and safety when dealing with hazardous chemicals.

Toxic effects of avermectin on liver function, gut microbiota, and colon barrier in the rat model

Avermectin (AVM), a compound derived from the fermentation of Avermectin Streptomyces, has insecticidal, acaricidal, and nematicidal properties. Widely employed in agriculture, it serves as an effective and broad-spectrum insecticide for pest control. Although the toxicity of AVM at low doses may not be readily apparent, prolonged and extensive exposure can result in poisoning. To investigate the toxic effects of AVM on the body, this study established rat models of AVM poisoning with both low and high concentrations of the compound. Fifteen male rats were randomly assigned to one of three groups (n=5 per group): a control group, a low-concentration group, and a high-concentration group. The low-concentration group was administered an oral dose of 2 mg/kg AVM once daily for a duration of seven days, while the high-concentration group received an oral dose of 10 mg/kg AVM once daily for the same period. This study examined the impact of AVM on liver function and gut microbiota in rats using weight monitoring, liver function indicator detection, liver metabolomics sequencing, colon barrier function testing, and gut microbiota sequencing. The findings of this study demonstrated that exposure to 2 or 10 mg/kg AVM for seven days can lead to a notable decrease in rat weight, as well as induce liver dysfunction and metabolic disturbances. Additionally, AVM exposure can disrupt the composition of the intestinal microbiota and impair the integrity of the colon mucosal barrier, causing downregulation of Occludin expression and upregulation of inflammation-related protein expression levels such as IL-1β, Myd88, and TLR4. Furthermore, bioinformatics analysis revealed a significant association between liver dysfunction and dysbiosis of the gut microbiota. These findings have implications for the agricultural use of AVM and its potential contribution to environmental pollution. Consequently, individuals involved in AVM usage should prioritize safety precautions and monitor liver function.

IL6 Derived from Macrophages under Intermittent Hypoxia Exacerbates NAFLD by Promoting Ferroptosis via MARCH3-Led Ubiquitylation of GPX4.

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by intermittent hypoxia (IH) and is associated with the occurrence and development of nonalcoholic fatty liver disease (NAFLD). However, the specific mechanism by which OSA induces NAFLD remains unclear. Therefore, effective interventions are lacking. This study aims to investigate the role and mechanism of ferroptosis in OSA-related NAFLD using clinical data analyses, cell-based molecular experiments, and animal experiments. Indicators of liver function, lipid accumulation, and ferroptosis are also examined. RNA-seq, qPCR, western blotting, gene intervention, and E3 ligase prediction using UbiBrowser and co-IP are used to explore the potential underlying mechanisms. The results show that ferroptosis increases in the liver tissues of patients with OSA. Chronic IH promotes NAFLD progression in mice and is alleviated by a ferroptosis inhibitor Fer-1. The increased secretion of IL6 by macrophages can promote the expression of MARCH3 in hepatocytes under intermittent conditions, and subsequently promote the ubiquitination and degradation of GPX4 to regulate ferroptosis and lipid accumulation in hepatocytes. Hence, targeted inhibition of MARCH3 may alleviate IH-induced ferroptosis and lipid accumulation in liver tissues and inhibit the progression of NAFLD.

Comparing the prognostic impact of 131I and/or artificial liver support system on liver function failure combined with hyperthyroidism.

Hyperthyroidism, a prevalent endocrine disorder, can lead to complications such as liver failure due to the liver's essential role in thyroid hormone metabolism. The study aimed to elucidate the respective contributions of 131I and/or ALSS in managing hyperthyroidism alongside liver failure. A retrospective analysis was carried out on 74 patients diagnosed with severe liver failure in the context of Graves' disease. Patients were categorized into three groups: group A (n = 34) received 131I treatment, group B (n = 17) underwent 131I and ALSS treatment, and group C (n = 24) received artificial liver support system (ALSS) treatment alone. Throughout the treatment period, the liver function indexes in all groups exhibited a declining trend. The thyroid function of group A and group B treated with 131I was significantly improved compared to that before treatment. There was no significant change in thyroid function in group C. After the correction of hyperthyroidism, significant improvements were observed in the liver function of individuals in groups A and B, particularly with more noticeable amelioration compared to group C. After two months of treatment, the efficacy rates for the three groups were 79.41%, 82.35%, and 60.87% respectively. Mortality rates of the three groups were 5.88%, 17.65%, and 36% (P < 0.01). Group B, receiving both 131I and ALSS treatments, exhibited a lower mortality rate than group C. In cases of severe liver failure accompanied by hyperthyroidism, prompt administration of 131I is recommended to alleviate the adverse effects of hyperthyroidism on liver function and facilitate a conducive environment for the recovery of liver functionality.

Cystic plate approach combined with ICG fluorescence in laparoscopic anatomical hepatectomy.

The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intrahepatic and extrahepatic vascular system more conveniently and accurately has been gradually emphasized. Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy. Based on the theory of cystic plate and hepatic portal plate, the authors have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy. A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates. This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.