Histological Changes In Liver Research Articles

Hypoglyceamic and Hepatoprotective Potentials of Dichloromethane (DCM) Fraction of Gongronema Latifolium Extract in Streptozotocin-Induced Diabetic Wistar Rats

Diabetes is a chronic health issue with devastating but preventable consequences. The increasing proportion of the aging population, intake of calorie-dense diets, weight problems and sedentary lifestyles have been directly implicated in the increased number of diabetics globally. Furthermore, diabetes confers a huge economic burden due to its management costs, especially in low income countries. This study investigated the hypoglyceamic and hepatoprotective potentials of the dichloromethane (DCM) fraction of G. latifolium stem bark extract on some biochemical parameters in streptozotocin-induced hyperglycemic rats. A total of thirty (30) Wistar rats were randomly assigned into five (5) groups with six (06) animals per group. Type 2 diabetes was induced with intraperitoneal administration of streptozotocin in Groups 2 – 4, with animals in Groups 1 and 2 acting as normal and untreated diabetic controls, respectively. Group 3 rats were treated with the standard drug, metformin, while groups 4 and 5 were orally administered 200 and 400 mg/kg body weight of DCM fraction of G. latifolium stem bark extract. Changes in the body weight, biochemical assays (ALT, AST, total protein, albumin and urea), and expression levels of selected genetic markers, as well as the changes in liver histology, were determined and compared. Data obtained from this study show that the fasting blood glucose levels in hyperglycemic rats were significantly (p < 0.05) reduced, and the body weight steadily increased in rats treated with both doses of the DCM fraction of G. latifolium stem bark extract compared to the untreated diabetic rats. Total protein, AST and ALT levels, but not albumin levels, were significantly (p < 0.05) increased in rats treated with both doses of the extract. In addition, administration of the extracts significantly (p < 0.05) reversed the streptozotocin-induced repression of NRF2 and CAT expression in diabetic rats. Furthermore, histology results show an improvement in the liver architecture in the rats treated with the extract. The results from this study show that the DCM fraction of g. Latifolium stem bark extract possesses hypoglycemic, hepatoprotective and anti-diabetic activities and could be used in the management of diabetes.

Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers.

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 μL of 0.9% NaCl or TIL dissolved in 500 μL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors.

A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

In vivo antimalarial effect of 1-hydroxy-5,6,7-trimethoxyxanthone isolated from Mammea siamensis T. Anders. flowers: pharmacokinetic and acute toxicity studies

BackgroundThe potent antiplasmodial activity of 1-hydroxy-5,6,7-trimethoxyxanthone (HTX), isolated from Mammea siamensis T. Anders. flowers, has previously been demonstrated in vitro. However, its in vivo activity has not been reported. Therefore, this study aimed to investigate the antimalarial activity and acute toxicity of HTX in a mouse model and to evaluate the pharmacokinetic profile of HTX following a single intraperitoneal administration.MethodsThe in vivo antimalarial activity of HTX was evaluated using a 4-day suppressive test. Mice were intraperitoneally injected with Plasmodium berghei ANKA strain and given HTX daily for 4 days. To detect acute toxicity, mice received a single dose of HTX and were observed for 14 days. Additionally, the biochemical parameters of the liver and kidney functions as well as the histopathology of liver and kidney tissues were examined. HTX pharmacokinetics after intraperitoneal administration was also investigated in a mouse model. Liquid chromatography triple quadrupole mass spectrometry was used to quantify plasma HTX and calculate pharmacokinetic parameters with the PKSolver software.ResultsHTX at 10 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 74.26%. Mice treated with 3 mg/kg HTX showed 46.88% suppression, whereas mice treated with 1 mg/kg displayed 34.56% suppression. Additionally, no symptoms of acute toxicity were observed in the HTX-treated groups. There were no significant alterations in the biochemical parameters of the liver and kidney functions and no histological changes in liver or kidney tissues. Following intraperitoneal HTX administration, the pharmacokinetic profile exhibited a maximum concentration (Cmax) of 94.02 ng/mL, time to attain Cmax (Tmax) of 0.5 h, mean resident time of 14.80 h, and elimination half-life of 13.88 h.ConclusionsHTX has in vivo antimalarial properties against P. berghei infection. Acute toxicity studies of HTX did not show behavioral changes or mortality. The median lethal dose was greater than 50 mg/kg body weight. Pharmacokinetic studies showed that HTX has a long elimination half-life; hence, shortening the duration of malaria treatment may be required to minimize toxicity.

Induction of micronuclei in blood and histopathological alterations in gill, kidney and liver of Channa punctatus (Bloch, 1793) exposed to copper sulphate

Copper is one of the most toxic metals to fish and causes cytotoxic, mutagenic and carcinogenic effects. The accumulation of copper in an aquatic environment directly impacts man and the aquatic ecosystem. The present study aimed to determine the effect of copper sulphate (CuSO4) accumulation on the induction of micronuclei in blood and histological changes in kidney and liver of the fish Channa punctatus. The test chemical LC50 was determined after 96 hours during the first experiment. Later in the second experiment, the test animal was exposed to three sub-lethal concentrations of CuSO4 [0.1 mg/l (96 h-LC50/40), 0.2 mg/l (96 h-LC50/20) and 0.4 mg/l (96 h-LC50/10)]. Physico chemical parameters of the test medium, such as pH, temperature, hardness, alkalinity, and dissolved oxygen, were observed throughout the experiment, and all values were within the ranges necessary for the fish's survival. At intervals of 7, 14, 21, and 28 days, the control (without any test chemical) and copper sulphate exposed Groups' blood, liver, kidney, and gill tissues were taken to evaluate changes in genotoxic and histological parameters. Micronuclei (MN) induction and nuclear abnormalities (NAs) were observed at regular intervals. After 28 days, the MN frequency in Groups 1, 2, 3, and 4 was 0.78±0.006, 8.40±0.052, 10.37±0.098 and 10.90±0.024 respectively. A significant (P&lt; 0.05) rise in MN frequencies and NAs indicated fish erythrocytes' DNA damage. Histological analysis of the liver, kidney, and gills revealed serious tissue injury such as necrosis, vacuolization, and degeneration after 28 days in the exposed Groups. The present study observed changes due to genotoxicity and histology, giving the most comprehensive understanding of CuSO4 stress on the fish C. punctatus and its risks to human health.

Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury.

Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1β, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1β, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.

Hazardous potential assessment of airborne and foodborne polyvinyl alcohol and polyhydroxyalkanoates nanoplastics: Comparison with polyvinyl chloride nanoplastics

Nanoplastics (NP) are emerging pollutants in the environment. Bio-based materials are attracting increasing scientific attention as their application may alleviate the environmental pollution caused by conventional plastics. However, their hazardous potentials still need to be investigated. In this study, multi-omics approaches were carried out to explore and compare the conventional polyvinyl chloride (PVC), bio-based polyhydroxyalkanoates (PHA) and water-soluble polyvinyl alcohol (PVA) NP for their lung and liver toxicity in mice. Airborne PVC NP could cause nasal and lung microbial dysbiosis, lung and serum metabolic disruption, liver transcriptomic dysregulation, and result in lung and liver toxicity. In contrast, airborne PHA and PVA NP could induce nasal and lung microbial alterations, lung and serum metabolic disruption, liver transcriptomic disturbance, and lead to mild lung toxicity. As for foodborne PHA, PVA and PVC NP, they all could induce gut microbial dysbiosis, gut and serum metabolic disruption. Foodborne PVC NP could cause similar transcriptomic alterations and greater histological changes in liver compared to PHA NP, while foodborne PVA NP could induce transcriptomic disturbance but not apparent pathology in liver. Among the various alterations, multiple lung pathways (e.g., “renal cell carcinoma”) and liver pathways (e.g., “arachidonic acid metabolism”) were commonly greatly enriched by airborne PHA and PVA NP but not PVC NP, while multiple liver pathways (e.g., “pancreatic secretion”) were commonly largely intensified by foodborne PVC and PHA NP but not PVA NP, aligning with the histological differences between groups. The relevant findings suggest PVA and PHA NP have lower lung and liver toxicity than PVC NP. The results could also benefit the clinical diagnoses of liver and lung toxicity induced by airborne and foodborne PVC, PVA and PHA NP.

Correlation between Histological Changes of Liver and Early Surgical Outcome of Kasai Portoenterostomy in Biliary Atresia

Background: Biliary atresia (BA) is a progressive fibrosing obstructive cholangiopathy involving both resulting in the intrahepatic and extrahepatic bile ducts. Hepatic portoenterostomy was first described by Kasai and Suzuki in 1959 to re-establish bile flow in biliary atresia patients. Currently, the accepted management of infants with biliary atresia is to re-establish bile flow by Kasai portoenterostomy followed by liver transplantation when indicated. Purpose: The purpose of this study is to correlate the surgical outcome following Kasai portoenterostomy with liver histology at the time of extended Kasai Portoenterostomy for biliary atresia who are operated in this institution. Methods: This prospective study was done in the department of Pediatric Surgery, BSMMU, with study period from October 2017 to march 2020.Wedge biopsies of liver was taken at the time of Extended Kasai portoenterostomy. Liver biopsies were graded as mild (grade-1), moderate (grade-2) and severe (grade-3) degree of fibrosis by single pathologist. Serial measurement of serum bilirubin were made preoperative and postoperatively to assess the degree of bile drainage in relation to degree of liver fibrosis. Results: A total of thirty infants underwent Extended KPE during study period. The mean age at the time of surgery was 89.7 (±23.4SD) days ranging from 57days to 140 days. 16 infants were operated before 90 days and rest 14 were operated beyond 90 days of life. Out of 30 infants, 3 cases were grade -1 fibrosis, 15 cases were grade- 2 and 12 cases were grade-3 fibrosis. 12(40%) infants cleared jaundice at three months after surgery, of which only 2 patients belonged to grade-3 fibrosis. 9(30%) infants were jaundice free at 6 months, among them 8 infants belonged to lower degree of fibrosis (grade-1 and grade-2). Only 1infant belonged to higher degree of fibrosis (grade-3). Conclusion: Currently, the concept for management of infants with biliary atresia considers successful establishment ..

Role of flower extract in preventing hyperlipidemia and liver lipid peroxidation in male mice

: Hyperlipidemia leads to coronary artery disease. Although statins are used conventionally, they are often associated with side effects. It has now been attempted to study the role of flower (MOF) extract in the regulation of tyloxapol-induced hyperlipidemia and tissue lipid peroxidation (LPO) in male mice.Six groups of animals were taken. Group I acted as control and group II, receiving tyloxapol (300 mg/kg, single dose on 14 day) served as hyperlipidemic control. Group III received simvastatin (200 mg/kg), while group IV, V and VI received MOF extract at 400, 200 and 100 mg/kg every day respectively for 15 days. These four groups (III- VI) also received same amount of tyloxapol on 14 day. On day 16 changes in the serum total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and very low-density lipoprotein; hepatic LPO, super oxide dismutase, catalase, glutathione peroxidase and histological changes in liver were analyzed. Total phenolic and flavonoid contents were also estimated. The in-vitro antioxidative property was checked through DPPH and HO assays.: Results showed significant reduction in all the serum lipids except HDL, which was increased in MOF treated hyperlipidemic mice, with the parallel decrease in hepatic LPO and increase in antioxidants. Histological studies also showed reduction in hepatic damage with the pre-treatment of MOF. However, the most effective dose was found to be 400 mg/kg of MOF. : We suggest that flower extract may ameliorate hyperlipidemia with antioxidative benefits.

Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection.

We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.

Protective Effect of Centella asiatica on AlCl3 and D-Galactose Induced Hepatotoxicity in Rats through the Alleviation of Oxidative Stress as Demonstrated by Histological Changes in Liver

Background: Injury to the liver resulting from drug exposure is known as hepatotoxicity. Drug-induced liver damage is a clinical consequence that can be challenging to recognise, avoid, and manage. After administering Centella asiatica extract to rats that have hepatotoxicity induced by AlCl3 and D-galactose, we evaluated the histopathological alterations in the hepatic tissue and measured the concentration of oxidative and anti-oxidative activity. Objective: The objective of this study is to investigate the protective benefits of Centella asiatica extract on AlCl3 and D-galactose-induced hepatotoxicity. Materials and methods: Male albino Wistar rats were used in this study. Centella asiatica extract (100mg, 200mg and 300mg/kg/day) was given orally to the AlCl3 and D-gal induced hepatotoxic rats for seventy days. At the end of treatment, the liver was harvested and the activity levels of oxidative and antioxidative enzymes were determined. Histopathological changes in the liver were also documented. Results: Centella asiatica extract significantly raised the levels of SOD and catalase in liver homogenates, while lowering MDA levels and suppressing histopathological changes such as bridging necrosis, intralobular degeneration, focal necrosis, and fibrosis alterations in the liver. Conclusion: Centella asiatica extract reduced oxidative stress levels in drug-induced hepatotoxicity by attenuating histological changes and normalising the levels of oxidative stress indicators in the liver. KEYWORDS: Centella asiatica, Hepatotoxicity, AlCl3, D-galactose, Oxidative stress.

Histological Liver Changes in Experimental Obstructive Cholestasis with Partial Outflow Restoration

Objective: This work aimed to establish histological changes in the structure and activity of the liver caused by experimental obstructive cholestasis. Method: Several methodological approaches were used such as experimental, biochemical, and comparison were applied.Results: It was possible to describe the essence of such a disease as cholestasis and its impact on the liver. At the same time, it was proved that recanalization with incomplete recovery of bile outflow was possible due to the normalization of the total bilirubin (TB) level. Morphological changes in the liver were most pronounced during acute cholangitis. The study examined what processes occur in the body during the recovery of bile flow, including after the complete blockage of such organs as the liver and bile ducts. Consequently, signs that expressed the abnormality of the liver structure of animals were revealed.

Evaluation of Hemotoxic, Hepatotoxic and Nephrotoxic Potential of Profenofos-based Insecticide in Freshwater Labeo rohita Fish at Low Concentrations

Profenofos, an organophosphate, is a major pollutant that pollutes freshwater bodies, causing significant impacts on fish health. Objective: Present study was performed to assess the toxicological impacts of pesticide profenofos on hematological, biochemical and histological alterations in different organs of Labeo rohita. Methods: Fish were divided in three groups. Group one was treated as control while second and third groups were exposed to 0.6 mg/L and 1.2 mg/L profenofos respectively for 28 days. Results: Results revealed that MCV, MCHC, MCH, RDW-SD, PCT, PDW, HGB, RBC and HCT levels were significantly reduced. WBC, RDW, PLT, MPV, neutrophils, lymphocytes, monocytes and eosinophils were increased as compared to pesticide free group. Biochemical results showed significant increase in cholesterol, triglycerides, AST, albumin, A/G ratio, HDL T3, T4, blood glucose, creatinine and urea levels were documented while levels of LDL, VLDL, ALT, total proteins, globulin, TSH and blood urea nitrogen (BUN) decreased significantly in exposed fish. Furthermore, histological changes in kidney, gills and liver of fish showed degenerative effects after exposure to profenofos in both concentrations. Conclusions: The present study concluded that profenofos resulted in widespread toxic effects on aquatic organisms specially fish.

Tianhuang formula ameliorates liver fibrosis by inhibiting CCL2-CCR2 axis and MAPK/NF-κB signaling pathway

Ethnopharmacological relevanceIn the progression of chronic liver diseases, liver fibrosis is a reversible pathophysiologic event for liver diseases prognosis and risk of cirrhosis. Liver injury factors of different etiologies mediate this process. There is still a lack of effective medications for treating liver fibrosis. Additionally, the ameliorative effects of traditional herbs on liver fibrosis have been commonly reported. Tianhuang formula (THF) is a drug combination consisting of 2 traditional Chinese herbs, which has been showing significant improvement in metabolic liver diseases. However, the hepatoprotective effect and mechanism of THF in ameliorating liver fibrosis are still unclear. Aim of the studyThis study aimed to investigate the effects of THF on carbon tetrachloride (CCl4)-induced and methionine-choline-deficient (MCD) diet-induced liver fibrosis model and to reveal the potential mechanisms. It can provide experimental evidence for THF as a therapeutic candidate for liver fibrosis. Materials and methodsIn this study, CCl4-induced mice were treated with THF (80 mg/kg, 160 mg/kg) or Fuzheng Huayu (FZHY) capsules (4.8 g/kg) for 6 weeks. MCD-induced mice received the same doses of THF or FZHY for 4 weeks. FZHY is used as a comparative study in these two models. Following that, using kit reagents detected changes in relevant serum and liver biochemical indicators. Histological changes in mouse liver were measured by staining of H&E and Sirius Red. The markers expression of liver fibrosis and inflammation were detected using qRT-PCR, western blotting and immunohistochemical staining analysis. The potential regulatory mechanism of THF to ameliorate liver fibrosis was performed by RNA-sequencing analysis. Finally, the analysis results were verified by immunofluorescence co-staining, qRT-PCR and western blotting. ResultsSerum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic triglyceride (TG) levels in CCl4 and MCD-induced liver fibrosis mice were significantly improved after THF treatment. Meanwhile, the expression of fibrosis and inflammation markers were significantly suppressed. Furthermore, THF downregulated the expression of the macrophage marker CD68. According to RNA-sequencing analysis, we found the CCL2-CCR2 axis and MAPK/NF-κB as the potential signaling pathway for THF against liver fibrosis. ConclusionThis study revealed that THF ameliorated liver injury, inflammation and fibrotic process by inhibiting CCL2-CCR2 axis and its downstream MAPK/NF-κB signaling pathway.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.

The liver is the major ketogenic organ of the body, and ketones are reported to possess favorable neuroprotective effects. This study aims to elucidate whether ketone bodies generated from the liver play a critical role in bridging the liver and spinal cord. Mice model with a contusive spinal cord injury (SCI) surgery is established, and SCI induces significant histological changes in mice liver. mRNA-seq of liver tissue shows the temporal changes of ketone bodies-related genes, β-hydroxybutyrate dehydrogenase (BDH1) and solute carrier family 16 (monocarboxylic acid transporters), member 6 (SLC16A6). Then, an activated ketogenesis model is created with adult C57BL/6 mice receiving the tail intravenous injection of GPAAV8-TBG-Mouse-Hmgcs2-CMV- mCherry -WPRE (HMGCS2liver ) and mice receiving equal AAV8-Null being the control group (Vectorliver ). Then, the mice undergo either a contusive SCI or sham surgery. The results show that overexpression of HMG-CoA synthase (Hmgcs2) in mice liver dramatically alleviates SCI-mediated pathological changes and promotes ketogenesis in the liver. Amazingly, liver-derived ketogenesis evidently alleviates neuron apoptosis and inflammatory microglia activation and improves the recovery of motor function of SCI mice. In conclusion, a liver-spinal cord axis can be bridged via ketone bodies, and enhancing the production of the ketone body within the liver has neuroprotective effects on traumatic SCI.

Significant histological changes are not rare in indeterminate‐phase chronic hepatitis B patients with hepatitis B e antigen‐negative and normal alanine aminotransferase levels

AbstractBackground &amp; ObjectivesThe degree of liver injury in indeterminate chronic hepatitis B (CHB) infection patients with Hepatitis B e antigen(HBeAg)‐negative and persistently normal alanine aminotransferase (PNALT) levels is yet unclear. Therefore, we aimed to assess liver histological changes in such patients by liver biopsy and explore possible predictors.MethodsOverall, 711 HBeAg‐negative CHB patients with PNALT levels who underwent liver biopsy from January 2017 to June 2022 were included in this retrospective study. The relationships between histological changes and predictors were assessed by smooth curve fitting and multivariate logistic regression analysis models. Data were also analyzed using American Association for the Study of Liver Disease (AASLD) modified alanine aminotransferase (ALT) criteria.ResultsThe proportion of significant histological changes in the indeterminate phase was higher than that in the inactive phase (53.97% vs. 41.33%). The adjusted odds ratios (aORs) of significant necroinflammation and histological changes for the indeterminate phase were 2.05 and 1.43, respectively, when compared with the inactive phase by multivariate logistic regression analyses. Significant histological changes in the‐phase were positively associated with age, ALT, Aspartate aminotransferase (AST), Hepatitis B surface antigen (HBsAg), and Hepatitis B virus (HBV) DNA levels but negatively correlated with platelet (PLT) levels. HBV DNA ≥5 log10 U/L and PLT &lt;200 × 109/L were independent predictive factors for assessing histological changes in indeterminate‐phase patients. Similar analysis findings were obtained using the two sets of modified ALT criteria.ConclusionsSignificant histological changes are not rare in indeterminate‐phase CHB patients and are higher than in the inactive phase, regardless of the ALT criteria. Histological investigation is strongly suggested for intermediate stage patients with HBV DNA &gt;5 log10 U/L or PLT &lt;200 × 109/L and antiviral therapy should be considered for such patients.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

Protective effect of Ageratum conyzoides against carbon tetrachloride –induced hepatic damage in rats

The present study was conducted toexamine the Hepatoprotective activity against the carbon tetrachloride toxicity in Wister rats. The Petroleum ether, ethyl acetate and methanol extract of was prepared and evaluated for phytochemical screening. The serum level of glutamic oxaloacetate transaminase (SGOT) Glutomicpyruvate transaminase (SGPT) and bilirubin were investigated for the assessment of hepatoprotective activity of ethyl acetate of extract . Additionally, the histological changes in liver were studied. The primary phytochemical investigation of the extract of revealed the presence of Flavonoids, tannins, and carbohydrates. Pretreatment with ethyl acetate extract of showed a significant (P&amp;#60;0.05) decrease in serum SGOT, SGPT and bilirubin when compared to control group rats treated with CCl in dose dependent manner. The outcomes of histology study revealed that there was significant reversal of histological functions of liver. In conclusion, the findings of study validated that the can improve CCl–induced hepatic toxicity.