Serum Levels Of Biochemical Markers Research Articles

Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice

Background and aimMorinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo.MethodsIn vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells.ResultsIndividual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group.ConclusionsThe present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

Effects of NKT Cells on Metabolic Disorders Caused by High-Fat Diet Using CD1d-Knockout Mice.

The purpose of this study was to investigate whether NKT cells play an important role in preventing or exacerbating diseases caused by high-fat diet (HFD) using CD1d-knockout (KO) mice which lack NKT cells. Five-week-old male Balb/c (wild-type; WT) or CD1dKO mice were fed with control-diet (CTD) or HFD for 16 weeks. The present study revealed four main findings. First, CD1dKO mice were susceptible to obesity caused by HFD in comparison to WT mice. Second, clinical conditions of fatty liver caused by HFD were comparable between CD1dKO mice and WT mice. Third, HFD-fed WT mice showed high levels of serum biochemical markers, involved in lipid metabolisms, in comparison to WT mice fed a CTD. Notably, the serum concentrations of ALT, T-CHO, TG and HDL-C in CD1dKO mice fed a HFD were almost comparable to those of CD1dKO mice fed a CTD. Fourth, the expression of peroxisome proliferator-activated receptor (PPAR) γ, low-density lipoprotein receptor (LDLR), CD36 of epididymal adipose tissue enhanced and proprotein convertase subtilisin/kexin type (PCSK) 9 in serum decreased. NKT cells were responsible for protection against HFD-induced obesity. However, CD1dKO mice were resistant to serum biochemical marker abnormalities after HFD feeding. One possible explanation is that the epididymal adipose tissue of CD1dKO mice could take up greater amounts of excess lipids in serum in comparison to WT mice.

Integrated 16 S rRNA gene sequencing and serum metabolomics approaches to decipher the mechanism of Qingre Lidan decoction in the treatment of cholestatic liver injury

BackgroundCholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. Methodsα-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. ResultsThe intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D-lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. ConclusionsQRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.

Assessment of Four Serum Biochemical Markers in Elderly Patients with Vascular Dementia after Cerebral Infarction and Their Response to Donepezil and Idebenone.

Objective Our study aimed to explore four serum levels of biochemical markers, including brain-derived neurotrophic factor (BDNF), homocysteine (Hcy), nitric oxide (NO), and γ-interferon (IFN-γ), in elderly patients with vascular dementia (VD) after the cerebral infarction and to elucidate possible connections between them. Method The elderly patients with VD after cerebral infarction admitted in our hospital, and the elderly persons for physical examination from November 2020 to December 2021 were included in this study. The serum levels of BDNF, Hcy, NO, and IFN-γ were compared between the study group and the control group. Results In the study group, the serum levels of Hcy and IFN-γ were significantly higher than that in the control group, whereas significantly lower serum levels of BDNF and NO were found in the study group compared with the control group. After receiving the intervention of donepezil and/or idebenone, the serum levels of Hcy and IFN-γ in group B were significantly lower than that in group A, while the serum levels of BDNF and NO in group B were significantly higher than that in Group A. Conclusion The results of our study showed abnormally expressed serum levels of Hcy, IFN-γ, BDNF, and NO in elderly patients with VD after cerebral infarction which might strongly reflect the severity of VD. Moreover, after intervention of donepezil alone or combined with idebenone, the changes of serum levels of Hcy, IFN-γ, BDNF, and NO may reflect the curative effect of the disease.

Ameliorating Effects of Silymarin-Loaded PLGA on Acetaminophen-Induced Nephrotoxicity in Mice

Background: Silymarin (SM) has beneficial effects against numerous different types of toxicants. However, the low bioavailability of SM has limited its therapeutic effects. Objectives: This study investigated the toxic effect of nanostructured SM (NSM) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on nephrotoxicity induced by acetaminophen (APAP) in mice. Methods: The encapsulation of SM in PLGA was performed by the solvent evaporation method. A total of 48 NMRI mice were used in this experimental study. The mice were pretreated with SM or NSM (5 mg/kg) for 7 days, and APAP (300 mg/kg) was administrated on the 6th day. The serum levels of blood urea nitrogen, creatinine, and uric acid were measured. Histological assessment and messenger ribonucleic acid expression of BAX and BCL-2 genes were also carried out. Results: The APAP destroyed the structure of the renal tissue and significantly reduced renal weight and glomerulus diameters (P < 0.01). The APAP also caused a significant increase in the serum levels of biochemical markers (P < 0.001) and expression of the BAX/BCL-2 ratio in the renal tissue (P < 0.001). The NSM could improve the renal structure and significantly increase renal weight and glomerulus in the APAP-intoxicated mice. The NSM significantly reduced the level of the biochemical tests and the BAX/BCL-2 ratio in the APAP-treated group (P < 0.01). Conclusions: The obtained data indicate that PLGA effectively enhances the nephroprotective effects of SM on nephrotoxicity induced by APAP.

Biejiajian pill inhibits progression of hepatocellular carcinoma by downregulating PDGFRβ signaling in cancer-associated fibroblasts

Ethnopharmacological relevanceBiejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. Aim of the studyThis study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. Materials and methodsC57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRβ signaling in CAFs and the underlying mechanism were demonstrated. ResultsBJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRβ, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRβ were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3β) by suppressing PDGFRβ expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRβ, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRβ activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRβ signaling. ConclusionBJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRβ signaling.

Effect of antiepileptic drugs on serum biochemical marker levels of first and second trimester screening tests.

Our aim in this study was to evaluate the effect of antiepileptic drugs on biochemical components of screening tests. This longitudinal case-control study was performed at Ankara City Hospital, Ankara, Turkey, from June 2020 to January 2021. The case group included epileptic singleton pregnant women which were using antiepileptic drugs, between 18 and 44 years of age. The control group included healthy pregnant women between 18 and 44 years old who did not use any drugs. Maternal medical, obstetric, and gynecological history were recorded. The antiepileptic agents that are used in our study were; lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, valproic acid, and clonazepam. For the aneuploidy screening program conducted in our laboratory, the biochemical markers that are analyzed include; free b-hCG and PAPP-A in the first trimester, as well as AFP, HCG, and unconjugated estriol (uE3) in the second trimester. MoM values of these markers were compared between the case and control groups. Fifty-three pregnant women with epilepsy using antiepileptic drugs were compared with 106 healthy pregnant women. The levels of serum-free b-hCG, and PAPP-A were similar between the case and control groups (p=0.653, p=0.351). For the second-trimester screening biochemical markers, the maternal serum uE3 and AFP levels expressed as MoM were significantly higher in the epileptic group than in the control patients (p=0.015 and p=0.001). Serum marker levels of second-trimester screening tests may be affected by antiepileptic drugs, which may lead to misinterpretation of the risk level. Antiepileptic drug usage should be considered when evaluating screening test results.

Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.

Glossogyne tenuifolia (GT) is a native perennial plant growing across the coastline areas in Taiwan. The current study aimed to examine the efficacy of GT extract in ameliorating physical fatigue during exercise and increasing exercise performance. Fifty male Institute of Cancer Research (ICR) mice were randomly segregated into five groups (n = 10) to GT extract orally for 4 weeks, at different concentrations (50, 100, 250, and 500 mg/kg BW/day): LGT 1X, MGT 2X, HGT 5X, and HGT 10X groups. Forelimb grip strength, endurance swimming time, serum biochemical marker levels, blood lipid profile and histological analysis of various organs were performed to assess the anti-fatigue effect and exercise performance of GT extract. The forelimb-grips strength and endurance-swimming time of GT-administered mice were increased significantly in a dose-dependent manner when compared to the control. Serum glucose, creatine kinase, and lactate levels were increased significantly in the HGT 10X group. Liver marker serum glutamic-oxaloacetic transaminase (GOT) was increased in the HGT 5X and HGT 10X groups, whereas Serum Glutamic Pyruvic Transaminase (GPT) was not altered. Renal markers, creatinine and uric acid levels, were not altered. Muscle and hepatic glycogen levels, which are essential for energy sources during exercise, were also significantly increased in a dose-dependent manner in all GT extract groups. No visible histological aberrations were observed in the vital organs after GT extract administration. The supplementation with GT extract could have beneficial effects on exercise performance and anti-fatigue function without toxicity at a higher dose.

Combination of molecular docking and liver transcription sequencing analysis for the evaluation of salt-processed psoraleae fructus-induced hepatotoxicity in ovariectomized mice

Ethnopharmacological relevanceSalt-processed Psoraleae fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, SPF-associated hepatotoxicity is a known health hazard. Cholestasis is often associated with SPF-induced hepatotoxicity. Notably, clinical liver injury is a common side effect of SPF in the treatment of osteoporosis; however, the exact mechanism underlying this phenomenon is unclear.Aim of the study: To evaluate SPF-induced hepatotoxicity in an ovariectomized murine model of estrogen deficiency and examine the mechanisms underlying this process. Materials and methodsTo explore the molecular mechanism of SPF-induced cholestatic liver injury, different concentrations of SPF (5 and 10 g/kg) were intragastrically administered to ovariectomized and non-ovariectomized female ICR mice for 30 days. ResultsSPF-treated mice showed noticeably swollen hepatocytes, dilated bile ducts, and elevated levels of serum biochemical markers. Compared to ovariectomized mice, these changes were more prominent in non-ovariectomized mice. According to the sequence data, a total of 6689 mRNAs were identified. Compared with the control group, 1814 differentially expressed mRNAs were identified in the group treated with high SPF doses (SPHD), including 939 upregulated and 875 downregulated mRNAs. Molecular docking and Western blot experiments showed that liver injury was closely related to the estrogen levels. Compared with the negative control group, the expression levels of FXR, Mrp2, CYP7a1, BSEP, SULT1E1, HNF4a, and Nrf2 decreased in the estradiol-treated (E2), low-dose SPF-treated (SPLD), and SPHD groups. Interestingly, the expression levels of FXR, CYP7a1, SULT1E1, and HNF4α were significantly higher in the ovariectomized groups than in the non-ovariectomized groups (#P < 0.05; ###P < 0.001). ConclusionsOverall, this study demonstrates that SPF downregulates key enzymes involved in cholesterol and bile acid biosyntheses, posing a risk for cholestatic liver injury. SPF also regulates the FXR-SULT1E signaling pathway via HNF4α, which is an important causative factor of cholestasis. Moreover, the severity of liver damage was significantly lower in the ovariectomized groups than in the non-ovariectomized group. These results suggest that the estrogen level is the most critical factor determining liver injury.

Hepatoprotective activity of andrographolide possibly through antioxidative defense mechanism in Sprague-Dawley rats

The aims of this study to assess the efficiency of AGL against acetaminophen (APAP)-induced hepatic toxicity that was generated by mitochondrial oxidative stress and glutathione depletion. Free radical scavenging potentiality was analyzed by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, nitric oxide, and hydroxyl radical scavenging assays. APAP-induced liver toxicity was formed at a dose level of 640 mg/kg mg/kg BW each, p.o. for 14 days for all experimental rats except the vehicle control group. AGL (5 and 10 mg/kg) were treated orally with negative control and negative control silymarin (50 mg/kg) group. To assess the protective effect, we looked at the levels of serum biochemical markers, liver histoarchitecture, and hepatic antioxidant enzyme activity. AGL showed in vitro anti-oxidant potentialities by scavenging radicals in the respective assays. As evidenced by serum biochemical indicators and relative liver weight, AGL co-administration substantially reduced toxicant-induced hepatic damage. APAP-intoxication increased the malondialdehyde (MDA) level and declined in cellular endogenous antioxidant enzymes such as reduced catalase, superoxide dismutase, and glutathione, where, AGL treatment amended their level. In the same way, histopathological evaluation further verified that AGL protected the hepatocyte from APAP-induced damage. As AGL scavenges toxic free radicals, thereby protects mitochondria and other organelles from reactive oxygen and nitrogen species-mediated stress and its eventual consequence necrosis. Therefore, we propose the hepatoprotective activity of AGL through its antioxidant mechanism.

In vivo impact assessment of orally administered polystyrene nanoplastics: biodistribution, toxicity, and inflammatory response in mice

To assess the in vivo impact of nanoplastics (NP) and coagulation-based purified NP (PurNP), this study analyzed for alterations in the biodistribution, toxicity and inflammatory response in ICR mice exposed to three different doses of NP (5, 25, and 50 mg/kg) and PurNP for 2 weeks. Except water consumption, which was dose-dependently and significantly increased in all NP-treated groups, most factors assessed for feeding behaviors and excretions remained constant, without any significant change. Orally administered NP was detected in the intestine, kidneys, and liver at all concentrations, although the accumulation was higher in the intestine than in the kidneys and liver. No significant alterations were detected in the levels of serum biochemical markers and histopathological structures. However, compared to the vehicle group, expressions of the inflammatory response proteins (iNOS and COX-2) and mRNA levels of the inflammatory cytokines were remarkably increased in the liver, kidneys, and intestine of NP-treated mice. A similar increase was detected in the oxidative stress responses, including ROS concentration, SOD activity, and Nrf2 expression. Furthermore, similar inflammatory responses were observed in the PurNP-treated group, as compared to the vehicle-treated group. The results presented in this study provide the first strong evidence that oral administration of NP for 2 weeks results in high accumulation in the liver, kidneys, and intestine of ICR mice, and induces severe inflammatory and oxidative stress responses. These results additionally confirm the efficacy of water purification using the tannic acid-mediated coagulation removal technique.

In vivo protective effect of cinnamon aqueous extract in carbon tetrachloride-treated male albino rats

The liver as an organ is important for the metabolism of drugs and toxins. However, it is not immune from environmental insults. Exposure of liver cells to carbon tetrachloride (CCl4) results in the generation of tricholoromethyl radicals, which induce liver toxicity. This study aims at investigating the ameliorative effect of the cinnamon aqueous extract (CAE) against CCl4-induced hepatotoxicity in male albino rats. Hepatotoxicity was induced in rats through the intraperitoneal administration of 0.5 mL kg-1 body weight of CCl4. The analyses of the results obtained showed significant reduction in the levels of serum biochemical markers for 400 and 600 mg kg-1 bw of CAE protected rats as compared with CCl4 group. In addition, CAE administration reversed liver tissue damaged via increased antioxidants markers. Histopathological examination of CAE treatment on rats showed improved changes to the liver damage caused by CCl4 with no evidence of steatosis and inflammation. This result hence suggests that CAE has marked hepatoprotective and healing activities against CCl4-induced liver damage and could serve as a suitable candidate in drug discovery for the treatment of liver toxicity.

Protective effect of propolis from Tigzirt on epirubicin-induced cardiotoxicity and nephrotoxicity

Context: Epirubicin (EPI), belonging to the anthracycline family, is one of the most effective chemo-therapeutic agents used in the treatment of a variety of solid and hematologic malignant tumors but Its anti-tumor efficacy is dose-dependent, but its clinical use is limited by the development of cardiac, hepatic and nephrotic toxicities. Aims: To evaluate the protective effect of ethyl acetate extract of propolis (EAP) native to Tigzirt on selected antioxidant status parameters and biomarkers of epirubicin-induced cardiotoxicity and nephrotoxicity in rats. Methods: Thirty male Wistar albino rats were divided into five groups. It orally dosed with (EAP) or quercetin during 15 days before being subjected to toxicity by injection (i.v) of a cumulative dose of 9 mg/kg of epirubicin to repair cardiac and renal damage. Results: Injection of epirubicin to rats induced cardiac and renal dysfunction as evidenced by a significant increase (P&lt;0.05) in serum levels of biochemical markers (CKmb, BNP, LDH, troponin, urea, creatinine and uric acid). This toxicity thus caused lesions, necrosis, and inflammatory infiltrate in the heart and kidneys. The administration of 250 mg/kg of EAP allowed restoring these functions by lowering the level of these parameters. Thus, a balance of oxidative stress was demonstrated with a decrease of +50% in the level of malondialdehyde and nitric oxide and an increase in superoxide dismutase, catalase and glutathione peroxidase. Therefore, significant restoration was observed on organ architecture. Conclusions: These results show that propolis is rich in phenolic substances, which gave the protective and curative effects against epirubicin-induced cardiotoxicity and nephrotoxicity in Wistar rats.

Live Combined B. subtilis and E. faecium Alleviate Liver Inflammation, Improve Intestinal Barrier Function, and Modulate Gut Microbiota in Mice with Non-Alcoholic Fatty Liver Disease.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic, progressive liver disease with an increasing incidence rate. This study investigated the protective effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on NAFLD, and its possible mechanisms.Material/MethodsFive-week-old C57BL/6 mice were randomly divided into 3 groups: chow, HFD, and HFD+LCBE groups. The levels of serum biochemical markers, glucose tolerance, insulin, the inflammatory cytokines IL-1β, IL-6, and TNF-α, LPS, and histological staining were measured using commercial kits. qPCR was used to examine the mRNA expression levels of inflammatory cytokines in the liver. Western blotting was used to determine the protein levels of TLR4, NF-κB p65, PPAR-α, and CPT-1 in the liver, and occludin and Claudin1 in the intestine. The intestinal flora of the mice was analyzed by high-throughput sequencing of the V3–V4 region of 16S rDNA.ResultsLCBE significantly lowered the body weight, liver/body weight ratio, and serum glucose level, and increased the serum insulin level in NAFLD mice. In addition, LCBE treatment improved the liver function and lipid profile, decreased the levels of LPS and inflammatory cytokines, and downregulated the expression of TLR4 and NF-κB p65. Moreover, LCBE enhanced the intestinal barrier function by increasing the expression of occludin and Claudin1. Furthermore, LCBE modulated the composition of the gut microbiota by reducing the Firmicutes to Bacteroidetes ratio, and the proportion of inflammation-related and LPS-producing bacteria, thus re-arranging the structure of the gut microbiota.ConclusionsLCBE protects against NAFLD by alleviating inflammation, restoring the intestinal barrier, and modulating gut microbiota composition.

Inhibition of HMGB1 involved in the protective of salidroside on liver injury in diabetes mice

High mobility group box 1 (HMGB1) is a nuclear protein that is released on injury triggers inflammation. This study aims to elucidate the effects of salidroside on diabetes-induced liver inflammation. The levels of glucose, inflammatory cytokines and hepatic functional parameters in serum and liver of type 2 diabetic db/db mice were examined. Immunohistochemistry, immunofluorescence and western blot tests were performed to determine the mechanisms underlying the action. Palmitic acid (PA) or HMGB1–stimulated was adopted as an in vitro cell model. Salidroside treatment improved glucose tolerance, lipid profiles while decreased the production of inflammatory cytokines. It also reduced the levels of serum biochemical markers. In addition, salidroside inhibited HMGB1 signaling pathway in db/db mice. In the salidroside treatment significantly inhibited PA or HMGB1 induced inflammatory signaling pathway, too. HMGB1 inhibitors and HMGB1 knockdown both hindered PA-induced HMGB1 signaling pathway, showing the same effect as salidroside. Salidroside treatment significantly alleviates insulin resistance, hyperglycemia and hepatic inflammation in db/db mice, and also showed beneficial to PA-stimulated. Salidroside proves to control hyperglycemia and hepatic inflammation via inhibiting HMGB1/RAGE/NF-κB and HMGB1/TLR4/NLRP3 signaling pathways.

Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney.

Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of this study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rats were randomly divided into five groups. Control group; APAP (1 g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups: APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that the extract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC.

Case-control study for assessment of factors associated with periodontitis among adults attending a university hospital in Karachi, Pakistan.

To compare the physiological and biochemical markers in healthy and periodontitis subjects, and to relate these markers with the periodontal health condition. The case-control study was conducted at the Dow University of Health Sciences, Karachi, from April 2017 to March 2018, and comprised systematically healthy controls and periodontitis cases. Periodontal probing depth, clinical attachment loss, oral hygiene indices, educational status and body mass index were recorded for all the subjects. Serum levels of biochemical markers, including calcium, phosphate and interleukin-6, were also measured. Data was analysed using SPSS 16. Of the 150 subjects, 75(50%) each were in the case and control groups. The overall mean age was 31.23±3.7 years (range: 22-42 years). The cases had relatively poor oral hygiene indices and educational status compared to the controls (p<0.05). Serum calcium level was lower, whereas mean body mass index was higher in the cases compared to the controls (p<0.05). No significant difference was found in interleukin-6 and phosphate levels (p>0.05). Clinical attachment loss showed significant correlation (p<0.05). Low serum calcium and educational levels, higher body mass index and poor oral hygiene were found to be the risk factors for the progression of periodontitis.

The Association Between Serum Levels of Leptin and Lipid Profiles in Cardiovascular Patients With Valve Calcification

Adipose tissue-derived hormones known as adipokines, like leptin, have multiple bioactions. Notwithstanding the key roles of leptin in regulating energy homeostasis and metabolism, its cardiovascular functions are complex and not fully understood. This study aimed to investigate the association between serum concentrations of leptin and lipid profiles in patients with valve calcification. Seventy-two patients with valve calcification and 72 healthy individuals participated in this case-control study. The serum levels of biochemical markers and leptin were measured by the standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA) technique, respectively. Significantly increased serum concentrations of FBS (P=0.001), urea (P&lt;0.0001), creatinine (P=0.018), P (P&lt;0.0001), LDL-C (P=0.011) and lower Ca (P=0.006), and HDL-C (P&lt;0.0001) levels were observed in patients compared to controls. There was no significant difference in the serum level of TG and TC of patients than controls. Systolic and diastolic blood pressures were significantly increased in patients relative to controls (P&lt;0.0001). However, a significantly diminished serum level of leptin was observed in patients than controls (P&lt;0.0001). The correlation analysis demonstrated that the serum leptin concentration is negatively correlated with creatinine, but it is positively correlated with systolic blood pressure (P=0.0302, P=0.0362, respectively). There was no statistically significant association between serum levels of leptin and lipid profiles. Our findings indicated dyslipidemia and reduced serum leptin concentrations in patients with valve calcification, suggesting the role of lipid abnormalities and reduced leptin levels in the development and pathogenesis of valve calcification diseases.

Ultrasound-targeted microbubble destruction optimized HGF-overexpressing bone marrow stem cells to repair fibrotic liver in rats

Background/aimsBone marrow mesenchymal stem cells (BMSCs) have shown their therapeutic potential in cytotherapy for liver fibrosis. However, the insufficient homing of BMSCs and undefined proliferation of BMSCs represent a significant challenge and largely limit the effective implementation. The aims of the present study were to determine whether stable expression of hepatic growth factor (HGF) in BMSCs coupled with ultrasound-targeted microbubble destruction (UTMD) technique could effectively and definitely alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in rats.Materials and methodsA rat model of liver fibrosis was acquired by injection of carbon tetrachloride (CCl4). The experimental rats were randomly assigned to the four groups: normal, CCl4, BMSCs-HGF/US, and BMSCs-HGF/UTMD groups. The BMSCs, transfected by recombinant adeno-associated virus vector encoding human genome sequence of HGF (BMSCs-HGF), were transplanted in rat via the tail vein. The homing efficiency of BMSCs was observed by immunofluorescence staining. The liver function and its morphological changes were analyzed by biochemical tests and liver histology. The expression of liver fibrosis markers including α-smooth muscle actin (α-SMA), collagen I, and vimentin were examined by immunohistochemistry and quantitative real-time polymerase chain reaction.ResultsThe homing efficiency of BMSCs in the fibrotic liver was significantly greater with the application of UTMD. The biochemical markers of liver function and histopathological results showed significantly better improvement in BMSCs-HGF/UTMD group than the other groups, and the serum levels of biochemical markers returned to normal ranges in 12 weeks in this group. Furthermore, the expression levels of liver fibrosis markers (α-SMA, collagen I, and Vimentin) were all significantly lower in BMSCs-HGF/UTMD group in comparison with other groups.ConclusionsOur findings have demonstrated that stable expression of HGF in BMSCs and application of the UTMD technique facilitate the homing of BMSCs, and more importantly, which could further improve their alleviation of liver fibrosis. Therefore, these findings have an important clinical implication that AAV-BMSCs-HGF and UTMD hold promise as a novel therapeutic approach for liver fibrosis.