Histopathological Changes In Liver Research Articles

Microplastic-contaminated antibiotics as an emerging threat to mammalian liver: enhanced oxidative and inflammatory damages.

Poor management and disposal of plastic materials and the accumulation of microplatics in the environment and foods are an issue of increasing public concern. The current understanding of the implications of microplastics for human health has been limited to the bioeffect of individual exposure. In the bigger view of microplastic contamination, however, toxic compounds, including antibiotics, harbored on active microplastics can be collectively transported through food chains, raising questions about the effect of their combined exposure on human health. By employing a mouse model for human physiology, we discovered that a concurrent exposure to the major types of antibiotics and microplastics, namely sulfamethoxazole (SMZ) and polystyrene microplastics, respectively, would result in evident accumulation in detoxification organs; specifically, liver could amass 41.70 μg kg-1 of SMZ, while 3.83% of microplastics was accumulated in the kidney. Insights into the occurrence of liver histopathological changes (e.g., amyloidosis and necrocytosis) revealed that compared with the individual treatment of SMZ, treatment by microplastic-contaminated SMZ elicited increases in the levels of malonaldehyde and NF-κβ by 174% and 104%, respectively; while the activities of antioxidases investigated were depressed by up to 22% upon co-exposure. It is suggested that SMZ enriched on active microplastic surfaces causes enhanced hepatic damage. Profiling of the gene expression clarified the correlation of the exacerbated oxidative and inflammatory damages in the liver with the overexpression of Nrf2 to dysregulate the Keap1-Nrf2 pathway. This study acts as a reminder about the complexity of contamination and raises awareness of health issues that microplastics could cause public health through liver diseases.

IL-17 Imbalance Promotes the Pyroptosis in Immune-Mediated Liver Injury Through STAT3-IFI16 Axis.

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

Jiedu Yizhi Formula Improves Cognitive Function by Regulating the Gut Dysbiosis and TLR4/NF-κB Signaling Pathway.

The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora. A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1β protein expression in the hippocampus tissue of mice in each group was measured by Western blot. Theresultsshowedthat APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae.It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks. The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.

Gross and histopathological changes in liver and lung of cattle and sheep infected with hydatid cyst

The present study was conducted in the Al-Najaf slaughterhouse, during the period from November 2020 to March 2021, were collected 200 specimens of infected liver and lungs of sheep and cattle. The objective of the study is to investigate the number of hydatid cyst infections in cattle and sheep to investigate the macroscopic and microscopic characteristics, number and size of cysts in each lung and liver, comparison between the thickness of cysts wall in the liver of sheep and cattle infested with echinococcosis. The results of the macroscopic study showed the total number of cysts found in the liver of slaughtered sheep was 673 in different size groups while in the lung of slaughtered sheep, the total number of cysts was 216 cysts in different size groups. The examination of the lung of infected cattle during the period of our study revered no cystic lesions in the study while the total number of cysts found in the liver of slaughtered cattle was 158 in different group sizes, almost 50 % of the size of the hydatid cyst in the sheep liver is between 1-3 cm, while in cattle is between 3-5 cm. The microscopic investigation of the liver and lung specimens stained with hematoxylin and eosin stain and another stain was used in this study to evaluate the fibrous tissue proliferation via Masson's trichrome stain. showed there were features of chronic inflammation in hepatic tissue of infested sheep and cattle by cystic echinococcosis represented by marginal fibrous tissue layer surrounding the hydatid cyst, infiltration of mononuclear cells, eosinophils, neutrophils, macrophages, and fibrocytes. The main conclusions of the study revealed that there were significant differences between the thickness of germinativum, laminated and adventitial layers of hydatid cysts in different size groups, and no hydatid cysts were recognized in the lung of slaughtered cattle during the study period.

HISTOPATHOLOGICAL CONDITION OF MALE RAT LIVER INDUCED BY CONDENSED TANNIN EXTRACT OF BELUNTAS LEAVE

This study at to determine the changes in liver histology of male rats after induction of condensed tannin extract of Beluntas leaves with control doses, 0.4 ml/kgBW, 2 ml/kgBW, and 3 ml/kgBW. This study is an experimental study for 14 days involving 24 samples of male rats. Parameters of histological structure changes were assessed by the scoring system for normal hepatocyte cell condition, parenchymatous degeneration, hydropic degeneration, and necrosis. One Way Anova test obtained a p value&lt; 0.001 which means there was a significant difference in changes in the histopathological structure of liver cells significantly. Based on the Post Hoc test, it was obtained. between the control and treatment groups showed a significant difference between the control dose of 0.4 ml/kgBW, 2 ml/KgBW dose, and 3ml/KgBW dose. Meanwhile, the changes in liver histopathology between 2 ml/KgBW, and a dose of 3ml/KgBW were significantly the same.

Quercetin-loaded chitosan nanoparticles ameliorate adjuvant-induced arthritis in rats by regulating anti-oxidant enzymes and downregulating pro- and inflammatory cytokines.

Rheumatoid arthritis (RA) is an inflammatory condition and associated with the symmetrical synovitis of the joints and cause joint pain. The use of anti-rheumatic drugs is associated with many adverse effects. Quercetin, an important polyphenolic flavonoid, possess anti-inflammatory and anti-rheumatic effects. Quercetin use is limited due to poor absorption and bioavailability. Nanomedicines are used for the targeted drug delivery, hence it reduces the adverse effects of the drug. Based upon these factors, quercetin-loaded chitosan nanoparticles (Q-NPs) were prepared by solvent evaporation method, characterized and their better anti-rheumatic effect with mechanistic insights was validated in Freund's complete adjuvant (FCA)-induced arthritic rats along with safety studies. The animals were divided into five groups, each containing 5 animals. Group I was normal control, group II was arthritic control, while groups III, IV and V were administered with quercetin (15mg/Kg) and Q-NPs (10 and 20mg/Kg), respectively. The reduction in ankle diameter, serum oxidative stress markers as well as pro- and inflammatory cytokines, e.g., tumor necrosis factor (TNFα), interleukin (IL-6) were determined. The prepared Q-NPs showed hydrodynamic size of 83.9nm, polydispersity index of 0.687, entrapment efficiency 90.5% as well as no interaction between quercetin and chitosan in Fourier transform infrared spectroscopy (FTIR). A significant reduction (p < 0.001) in ankle diameter was observed after administration of high-dose Q-NPs (4.32 ± 0.14cm to 5.13 ± 0.62cm). There was also reduction (p < 0.001) in levels of TNFα and IL-6 following high-dose Q-NPs (72.56 ± 2.30 and 308.19 ± 11.5pg). The effect on biochemical tests, hematological parameters and oxidative stress parameters was also found to be significant. Histopathological changes of kidney, liver and ankle also confirmed the anti-rheumatic effect of high-dose Q-NPs. The study concludes that administration of Q-NPs (20mg/Kg) may be used for the treatment of FCA-induced RA in rats.

The effects of ghee administration in comparison to sunflower seeds oil on liver tissue and some biochemical parameters in rats

Ghee is well known clarified butter of animal origin (namely derived from sheep milk), it has been used for decades in Iraq for preparing deserts, but nowadays, its nutritional value has been reviewed and is an area of controversy because of its high content of saturated fatty acids; however, the sunflower seeds oil available in the market may not be of that good quality. Comparing the effect of ghee to the effect of sunflower seeds oil may help better understand this controversy, the purpose of this study was to compare the effects of using animal ghee and sunflower seed oil on the liver's histopathology and related to various biochemical alterations in rats. We used 36 animals divided into three groups to accomplish this goal. The first group, which received a typical conventional diet, was regarded as a control group. The second group was given a diet that included 5% animal ghee. And the final group had a diet that included 5% sunflower oil. Blood samples were taken at intervals of 0, 2, and 4 consecutive weeks. There are an increase in the weights of animals in the sunflower oil-fed group with an increase in cholesterol and liver function enzymes ALT and AST in the blood compared with the group treated with ghee, which showed no change in animal weights and low cholesterol with decreased liver function enzymes The histopathological changes of the rat's liver revealed mild to moderate lesions in the Ghee fed group representing by vacuolar degeneration of hepatocytes and focal infiltration of inflammatory cells after four weeks of treatment. In the Sunflower seeds oil-fed group, the liver revealed more severe lesions than the rat treated in the ghee group, as severe vacuolar degeneration and necrosis of hepatocytes with fatty change, generalized congestion of blood vessels, infiltration of inflammatory cells in the portal area and hyperplasia of bile canaliculi. According to the study, animal ghee has advantages over sunflower seed oil regarding hepatic histological changes and concomitant biochemical changes in rats.

Mechanism and Active Components of Qingre Lidan Tablets Alleviate Intrahepatic Cholestasis by Activating the Farnesoid X Receptor.

Qingre Lidan tablets (QLTs) are a compound preparation of Chinese medicine that have long been used clinically to treat poor bile circulation caused by the inflammation and obstruction of the gallbladder and bile duct and to relieve jaundice and other symptoms. However, its material basis and mechanism are still unclear. The purpose of this study was to investigate the mechanism and active components of QLTs for treating intrahepatic cholestasis (IHC) in rat models. In vivo experiments verified the effect of QLTs on alpha-naphthyl isothiocyanate (ANIT)-induced IHC models in rats. The mRNA and protein expression levels of farnesoid X receptor (FXR), bile salt export pump (BSEP), and multidrug-associated protein 2 (MRP2) in the rat liver were detected. UPLC/Q-TOF-MS was used to separate and identify the monomers in QLTs, and a dual-luciferase reporter assay was used to select effective the monomers that stimulate FXR. Among the selected monomers, baicalein was used as a representative to verify the effect on rat IHC models. QLTs and baicalein significantly reduced the serum biochemical indicators reflecting the changes in liver function among IHC rats and remitted the ANIT-induced liver histopathological changes. The expression levels of FXR, BSEP, and MRP2 in the liver were significantly increased after QLT treatment in a dose-dependent manner. Moreover, six types of active components that activate FXR were selected in QLTs, namely baicalein, wogonin, baicalein II, emodin, dibutyl phthalate, and diisooctyl phthalate. QLTs and the active component, baicalein, can alleviate IHC in model rats.

Ethyl Acetate Extract from Artemisia argyi Prevents Liver Damage in ConA-Induced Immunological Liver Injury Mice via Bax/Bcl-2 and TLR4/MyD88/NF-κB Signaling Pathways.

Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI.

Avocado Seeds-Mediated Alleviation of Cyclosporine A-Induced Hepatotoxicity Involves the Inhibition of Oxidative Stress and Proapoptotic Endoplasmic Reticulum Stress.

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4+ and CD8+ T Cells through NF-κB p65 Signaling Pathway in Mice.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.

Accumulation of Heavy Metals in Long-Evans Rat Through Feeding Fishes of Buriganga River and Their Histopathological Evaluation.

The study was conducted to evaluate the impacts of industrial discharges, including from tanneries, in terms of heavy metal loads in fin-fish of the Buriganga river, Dhaka, Bangladesh, and to find out the ultimate effects of feeding those heavy metal-contaminated fishes to Long-Evans rats to examine rats' heavy metal accumulation along with viable architectural alterations on various organs through histopathological screenings. Being the most edible by the populace, Labeo rohita was chosen for this purpose. Labeo rohita was collected from five different spots in the river close to the industrial outlets, covering three seasons: monsoon, winter, and summer throughout the year. Experiments unearthed that the deposition of heavy metals inside fishes always surpassed the standard margin, implying a pernicious aquatic milieu. The empirical data suggests that the mean concentrations of Cu, Pb, Cr, and Cd were higher than the permissible limits of WHO and FAO after feeding heavy metal-contaminated fishes for a period of 120days. Seasonal variations were also taken into account, and it was noticed that rats fed with fish collected in winter had the highest heavy metal concentrations (P < 0.05). Significant architectural changes were observed during histopathological screening of rats' livers and kidneys characterized by necrosis, inflammation, and congestion. After gauging the obtained data, it might be concluded that consumption of heavy metal-contaminated fish entails accumulation of heavy metals, which causes histopathological changes in rats' livers and kidneys, including necrosis and severe structural deformational changes compared to those of control groups.

Wheat Germ Oil and Propolis Decrease Parasite Burden and Restore Marked Histopathological Changes in Liver and Lung in Mice with Chronic Toxoplasmosis.

Toxoplasmosis is a parasitic zoonotic disease with a worldwide distribution. Its effects can be critical in immunocompromised patients. However, there is a limited availability of effective, low-toxicity drugs against this disease, particularly in its chronic form. The present study evaluated the effect of propolis and wheat germ oil (WGO) as safe, natural products to reduce Toxoplasma cysts in experimentally infected mice. For the experiment, five groups (10 mice per group) were examined: Group 1: negative control (noninfected, nontreated); Group 2: positive control (infected, nontreated); Group 3: infected and treated with WGO at a dose of 0.2 mg/1.5 mL per kg body weight/day; Group 4: infected and treated with 0.1 mL propolis extract/day; and Group 5: infected and treated with a combination of WGO and propolis at the same doses as Group 3 and 4. After the mice were sacrificed, liver and lung specimens underwent histopathological examination, and the parasite burden was investigated by parasitological methods and quantified using real-time polymerase chain reaction. Notably, the results showed a substantial decrease in parasitic burden in Group 5 compared to the control group. These results were further confirmed by molecular analysis and quantification of the DNA concentration of the Toxoplasma P29 gene after treatment in all tested samples. Furthermore, the combination of propolis and WGO restored all histopathological changes in the liver and lungs. Taken together, these findings provide remarkably promising evidence of the effects of the combination of WGO and propolis against chronic toxoplasmosis in mice.

Histopathological Changes in Liver of Patients With Chronic Pancreatitis Requiring Surgical Intervention and Their Clinical Significance.

The histopathological changes in the liver and their clinical implication in chronic pancreatitis (CP) have not been studied well. We analyzed the incidence, risk factors, and long-term outcomes of these changes in CP. Chronic pancreatitis patients who underwent surgery with intraoperative liver biopsy from 2012 to 2018 formed the study group. Based on liver histopathology, 3 groups were formed: normal liver, group NL; fatty liver, group FL; and inflammation/fibrosis, group FS. The risk factors and long-term outcomes, including mortality, were evaluated. Among 73 patients, 39 (53.4%) had idiopathic, and 34 (46.6%) had alcoholic CP. The median age was 32 years, 52 (71.2%) were males and comprised NL, n = 40 (55%); FL, n = 22 (30%); and FS, n = 11 (15%). The preoperative risk factors were comparable among NL and FL groups. Overall 14 of 73 patients (19.2%) (NL, 5 of 40; FL, 5 of 22; FS, 4 of 11 [P = 0.82]) had died at median follow-up of 36 months (range, 25-85 months). The main causes of mortality were tuberculosis and severe malnutrition secondary to pancreatic insufficiency. The mortality is higher in patients with inflammation/fibrosis or steatosis in liver biopsy, and such patients need monitoring for progression of liver disease and pancreatic insufficiency.

Establishment of primary liver cancer model in mice

Objective: Three modeling methods were used to establish a mouse primary liver cancer model, and compared them to find a more optimal modeling method. Methods: Forty 15-day-old C3H/HeN male mice were randomly divided into groups I-IV, 10 mice in each group. Group Ⅰ were not treated; Group Ⅱ were intraperitoneally injected with 25 mg/kg diethylnitrosamine (DEN) once; Group Ⅲ were intraperitoneally injected with 100 mg/kg DEN once; Group Ⅳ were intraperitoneally injected with 25 mg/kg DEN once and followed by another intraperitoneal injection of 100 mg/kg DEN at 42 days of age. The mortality of mice in each group was analyzed. At the 18th week of modeling, blood was collected from eyeballs after anesthesia, and liver was taken from abdominal cavity after neck was broken. The appearance of liver, the number of cancer nodules and the incidence of liver tumor were observed. The histopathological changes of liver were observed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Results: At the 18th week of modeling, compared with the group I, serum levels of ALT and AST in groups II-IV were increased significantly (P＜0.05); The number of cancer nodules and the incidence of tumors in the surviving mice of groups III and IV were also increased significantly (P＜0.05). At the 18th week of modeling, no mice died in both groups I and II, and the incidence of liver cancer was 0%; The incidence of liver cancer in surviving mice in both groups III and IV was 100%, but the mortality rate of mice in group III was as high as 50%, and that in group IV was only 20%. Conclusion: C3H/HeN male mice can successfully establish a mouse liver cancer model by intraperitoneal injection of 25 mg/kg of DEN once at the age of 15 days and another intraperitoneal injection of 100 mg/kg of DEN once at the age of 42 days with short cycle and low mortality, which is an ideal method to establish a primary liver cancer model.

Validation of MAPK signalling pathway as a key role of paeoniflorin in the treatment of intrahepatic cholestasis of pregnancy based on network pharmacology and metabolomics

Numerous studies have clarified the effectiveness of paeoniflorin in the treatment of cholestasis. However, the therapeutic efficacy and mechanisms of action of paeoniflorin in intrahepatic cholestasis of pregnancy (ICP) were still unknown. This study aimed to investigate the molecular biological mechanisms of paeoniflorin against ICP by combining network pharmacology and metabolomics. The effects of paeoniflorin were investigated in the ICP rat model induced by 17α-ethinylestradiol, showing improvements in the liver indices, liver histopathological changes, bile flow rate, and serum levels of TBA and ALP. The underlying mechanisms and metabolic pathways of paeoniflorin were revealed by network pharmacology and untargeted metabolomics, showing that paeoniflorin exerted its curative effect against ICP-induced ferroptosis through PI3K/AKT and MAPK signalling pathways. In conclusion, paeoniflorin protected against ICP-induced liver injury through MAPK signaling pathways.

Auricularia polytricha and Flammulina velutipes reduce liver injury in DSS-induced Inflammatory Bowel Disease by improving inflammation, oxidative stress, and apoptosis through the regulation of TLR4/NF-κB signaling pathways

Auricularia polytricha and Flammulina velutipes are two dietary mushrooms mostly consumed in China and known for their traditional use on gastric ulceration and to boost bowel movement. Considering the gut-liver axis, which has been recognized for its role in the autoimmune modulation, and the implications of the intestinal barrier in the pathogenesis of liver diseases that remain unclear, the therapeutic effects of A. polytricha (APE) and F. velutipes (FVE) on inflammatory bowel disease (IBD)-induced liver injury in mice was investigated as well as their potential mechanism via the signaling pathways they could involve. 3% DSS was administered to the mice in drinking water, to induce ulcerative colitis, followed by oral administration of APE and FVE. The biochemical, oxidative stress and inflammatory parameters, mRNA and protein expressions were assessed. The results revealed that DSS-induced liver histopathological changes were ameliorated by APE and FVE treatment. APE and FVE administration also improved the ALT and AST activity as well as the pro-inflammatory cytokines and oxidative factors. Data also showed that, in addition to their regulation of tight junctions’ disruption, APE and FVE attenuated genes and proteins expression involved in apoptosis, lipid metabolism, and bile acid homeostasis via inhibiting TLR4/NF-κB and caspase signaling pathways and stimulating Keap1/Nrf2 signaling pathways. In conclusion, APE and FVE regulated liver injury on DSS-induced ulcerative colitis by alleviating inflammation, oxidative stress, and apoptosis, suggesting that they could be used as therapeutic alternatives against liver diseases in addition to their functions as dietary supplements.

Effect of Omega-3 Drug and Virgin Coconut Oil in Histopathological and Molecular Changes in Liver of Experimentally Obese Pregnant Albino Rats

The study aimed to evaluate the role of omega-3 and coconut oil in the histological changes caused by obesity in the liver of pregnant obese female rats and to evaluate the molecular change by estimating the gene expression of the insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein (IGFBP-1) genes. The study used 50 albino female rats aging (90-110) and weighting (185-200gr). The experiment included two stages. First stage was to induce obesity by adding (45% fat) to the standard diet, except for the control group. In the second stage, female rats were left to mate and were divided into 5 groups (10 for each group) as follows: G1 was the Control group that remained on a standard diet, G2 was fed a high-fat diet only, G3 was orally dosed with Omega-3 (260 g/kg), G4 was orally dosed with coconut oil (200 mg/kg), G5 was orally dosed with both Omega 3 and coconut oil with the same doses. Animals were sacrificed on the 18th day of pregnancy. Histological examination of the G2 liver showed severe steatosis in hepatocytes, cellular swelling, and congestion in the central portal vein; lipid profile results showed a reduction in total Cholesterol, triglycerides, and LDL-C in the blood serum of groups treated with both omega3 and Coconut oil. Liver in the group treated with Omega 3 alone or with coconut oil showed the normal histological features of the liver tissue. The liver of the G4 group, treated with coconut oil, showed slight cloudy degeneration of some hepatocytes with individual necrosis of some of the others and congestion in the portal vein. Groups treated with omega-3 and coconut oil separately or together showed an increase in the gene expression of IGF-1 and IGFBP-1.

Mesenchymal stem cells alleviate aging in vitro and in vivo.

Aging is a natural and multi-factorial phenomenon associated with multiple human pathologies. Mesenchymal stem cells (MSCs) hold great promise in clinical fields of medicine including tissue repair, cardiovascular disease, and brain ischemic injury. The purpose of this study was to explore the roles of MSCs in improving the condition of aging cells, repairing aging tissues and organs, and extending the life span of elderly mice. This study was carried out both in vitro and in vivo. We used MSCs to intervene with IMR-90 senescent cells induced by D-galactose and aged C57BL/6 mice. After 48 hours of co-culturing the aged cells with MSCs, the up-regulated expression of inflammatory factor, interleukin 6 (IL6), and the down-regulated expression of several growth factors, such as transforming growth factor (TGFβ1) and growth differentiation factor (GDF11), in D-galactose induced senescent cells were reversed. Moreover, compared with aged cells, the number of mitochondria and the telomere length were increased with MSC treatment. Similarly, in aged mice, the symptoms related to aging were improved after MSC treatment: the mouse hair became shiny and dense, and the symptoms of bladder overactivity were relieved. Hematoxylin and eosin (H&E) and Masson's trichrome staining showed that the histopathological changes in skin, bladder, liver, and lung were apparently improved. Treatment with MSCs effectively improves aging-related phenotypes and plays a beneficial role in improving aging and aging-related diseases.

Corynoline protects against zearalenone-induced liver injury by activating the SIRT1/Nrf2 signaling pathway.

Corynoline has been reported to have anti-inflammatory and antioxidative effects. In the present study, the potential protective effects of corynoline against zearalenone (ZEA)-induced liver injury were investigated. ZEA was administered daily for 5 days. Then, liver tissues were used for subsequent experiments. Corynoline attenuated liver histopathological changes induced by ZEA. The production of tumor necrosis factor-α and interleukin-1β in liver tissues, as well as aspartate aminotransferase and alanine aminotransferase in serum, was also inhibited by corynoline. Meanwhile, ZEA-induced MPO activity and MDA content were both attenuated by corynoline. ZEA-induced NF-κB p65 and IκBα phosphorylation were inhibited by corynoline. Furthermore, SIRT1, Nrf2, and HO-1 expression were increased by corynoline. In addition, the protective effects of corynoline against liver injury were reversed by the SIRT1 inhibitor EX-527. Taken together, corynoline protected against ZEA-induced liver injury by activating the SIRT1/Nrf2 signaling pathway.