BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elde...Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elderly is membranous nephropathy; while its counterpart in younger population is Ig A nephropathy. The most frequent cause of nephrotic syndrome in the elderly is also membranous nephropathy. Pauci-immune crescentic glomerulonephritis(GN) rate increases both in elderly and very elderly population. Pauci-immune crescentic GNs should be regarded as urgencies in elderly patients as in their younger counterparts due to potential for causing end-stage renal disease in case of delayed diagnosis and treatment, and also causing mortality due to alveolar hemorrhage in patients with pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the elderly as in all other age groups. Renal biopsy prevents unnecessary treatments and provides prognostic data. So advanced age should not be the sole contraindication for renal biopsy. The course of primary glomerular diseases may differ in the elderly population. Acute kidney injury is more frequent in the course and renal functions may be worse at presentation. These patients are more prone to be hypertensive. The decision about adding immune suppressive therapies to conservative methods should be made considering many factors like co-morbidities, drug side effects and potential drug interactions, risk of infection, patient preference, life expectancy and renal functions at the time of diagnosis.展开更多
Introduction: Primary Glomerular Diseases are a spectrum of renal disorders of unknown aetiology with distinct characteristics, specific natural history and prognosis. A thorough evaluation is prerequisite to establis...Introduction: Primary Glomerular Diseases are a spectrum of renal disorders of unknown aetiology with distinct characteristics, specific natural history and prognosis. A thorough evaluation is prerequisite to establish the diagnosis since many systemic diseases and secondary aetiology masquerade as primary diseases. Methods: This prospective observational study was conducted at a tertiary care centre and included 30 patients, with clinical features suggestive of primary glomerular diseases, of which 23 patients (76.6%) were males and 07 patients (23.33%) were females. The mean age at presentation was 37.23 ± 12.89 years. Among the observed spectrum of Primary Glomerular Diseases, IgA Nephropathy (IgA N) was seen in 26.67% patients, Focal Segmental Glomerulosclerosis (FSGS) in 20% patients and Membranous Glomerulopathy (MGN) in 13.33% patients, whereas the incidence of other abnormalities had less percentage contribution. Proteinuria was the commonest presentation seen in 60% patients, followed by Microscopic Haematuria in 20%. Mean Serum Creatinine was 0.99 ± 0.16 mg/dl. Mean Serum Albumin was 2.51 ± 0.76 gm/dl. Overall Nephrotic range proteinuria was observed in 15 (50%) patients. Results: IgA N, FSGS & MGN were the commonest observed Primary Glomerular Diseases. Proteinuria, Haematuria, Anasarca and Pedal Oedema were the commonest observed clinical presentations. Conclusions: In this studied series IgA Nephropathy, FSGS and MGN were the most prevelant diagnoses in the patients presenting with Urinary Abnormality. Nephrotic range Protenuria was the major indication for biopsy, there is a temporal variation in glomerulopathies wherein there is increase in incidence of IgA Nephropathy and decrease in incidence of FSGS.展开更多
Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory ...Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.展开更多
Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination....Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.展开更多
Inflammatory bowel disease(IBD),the most important being Crohn's disease and ulcerative colitis,results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract.Although the pathogenes...Inflammatory bowel disease(IBD),the most important being Crohn's disease and ulcerative colitis,results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract.Although the pathogenesis of IBD remains unclear,it is widely accepted that genetic,environmental,and immunological factors are involved.Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses.To investigate the etiology of IBD,animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD.Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described.In this manuscript,we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis(e.g.dextran sodium sulfate-,2,4,6-trinitrobenzene sulfonic acid-,oxazolone-,acetic acid-,and indomethacin-induced models).We also summarize some regulatory and pathogenic factors demonstrated by these models that can,hopefully,be exploited to develop future therapeutic strategies against IBD.展开更多
AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR...AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.展开更多
AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups ...AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7^th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured. RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found (0.47+0.44, 1.09+0.86, 0.43+0.31 vs 18.73+10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.展开更多
AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for ...AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium(DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6), and the myeloperoxidase(MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase(p38MAPK) and its phosphorylated form(p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580(SB), an inhibitor of p38, was investigated in parallel experiments, andthe data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38 MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38 MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38 MAPK signaling pathway and the endogenous CB system.展开更多
Background: Osteoarthritis is a slowly progressive and debilitating disease with high prevalence in adult population. Knee is one of the joints most affected by this disorder. There are several models for animals’ os...Background: Osteoarthritis is a slowly progressive and debilitating disease with high prevalence in adult population. Knee is one of the joints most affected by this disorder. There are several models for animals’ osteoarthritis induction, however it is not identified any paper that compares these techniques. The present study was aimed to define the most appropriate model for rats osteoarthritis induction. Material and Methods: 40 Wistar rats were distributed into 4 groups of 10 animals each: normality group (NG);meniscectomy group (MG);quinolone group (QG) and iodoacetate group (IG). Radiographic images of the rat’s knees were analyzed as well as the amount of chondrocytes in the epiphyseal and articular cartilage. Results: In the radiographic analysis, there was a low correlation between the raters. Regarding the amount of chondrocytes in the epiphyseal cartilage, it was noticed that the IG and QG groups had fewer chondrocytes than NG, in contrast to MG that reported similar results to normality (p > 0.05). There was no significant difference between IG and QG groups (p > 0.05). Regarding the amount of chondrocytes in articular cartilage, it was noticed that the IG group showed fewer chondrocytes than NG (p 0.05). There was no significant difference between QG and MG groups (p > 0.05). Conclusion: Intraarticular injection of iodoacetate in rats is the model with greatest effect on reduction of chondrocytes amount.展开更多
AIM To investigate a safer way to set up the disease model of cystic echinococcosis without contamination risk and develop a novel experimental murine model of hepatic cystic echinococcosis. METHODS C57 B/6 mice were ...AIM To investigate a safer way to set up the disease model of cystic echinococcosis without contamination risk and develop a novel experimental murine model of hepatic cystic echinococcosis. METHODS C57 B/6 mice were injected with human protoscolices of three different concentrations via the portal vein. The mice were followed for 10 mo by ultrasound,gross anatomy,and pathological and immunological examinations. The protoscolex migration in the portal vein,hydatid cyst growth,host immune reaction,and hepatic histopathology were examined periodically.RESULTS The infection rates in the mice in the high,medium,and low concentration groups were 90%,100%,and 63.6%,respectively. The protoscolices migrated in the portal vein with blood flow,settled in the liver,and developed into orthotopic hepatic hydatid cysts,resembling the natural infection route and course.CONCLUSION We have established an improved experimental model of hepatic cystic echinococcosis with low biohazard risk but stable growing dynamics and immune reaction. It is especially useful for new anti-parasite medication trials against hydatid disease.展开更多
An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alp...An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.展开更多
Experimental allergic encephalomyelitis is a mouse model of human multiple sclerosis with similar pathology and pathogenesis. Thl cells play an important role in the pathogenesis of experimental allergic encephalomyel...Experimental allergic encephalomyelitis is a mouse model of human multiple sclerosis with similar pathology and pathogenesis. Thl cells play an important role in the pathogenesis of experimental allergic encephalomyelitis. This study determined the potential effect of programmed cell death 1 ligand 1 in the pathogenesis of experimental allergic encephalomyelitis induced by injecting myelin oligodendrocyte glycoprotein, complete Freund's adjuvant and Bordetella pertussis toxin into C57BL/6J mice. Experimental allergic encephalomyelitis mice developed disease and showed in- flammatory changes in the central nervous system by hematoxylin-eosin staining of spinal cord pathological sections, demyelination by Luxol fast-blue staining and clinical manifestations. The expression of programmed cell death 1 ligand 1 in mice was detected by immunohistochemistry, flow cytometry and western blot anatysis. The expression of programmed cell death 1 ligand 1 in the spinal cord and splenocytes of mice was significantly increased compared with normal mice. Our findings suggest the involvement of programmed cell death 1 ligand 1 in the pathogenesis of ex- perimental allergic encephalomyelitis and suggest this should be studied in multiple sclerosis.展开更多
AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (ma...AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (mannan group) for 30 minutes at 37℃, 0 5ml 1×10 6 B16 MBK melanoma cells were injected into the spleen of mice. Fifty five days later, melanoma metastatic nodes on the surface of the liver and in other organs as well as mouse survival time were observed. RESULTS Of the 6 mice in control (B16 cell+PBS) group, 4 died naturally within 55 days, and 2 were killed on the 55th day. All of the 6 mice had metastases in livers, the total number of the melanoma nodes on each liver surface ranged from 2 to 30, with the largest one merging into the whole liver. One mouse had a neoplasm in the remnant site of injection, and 3 had metastases in lungs. In contrast, of the 6 mice in tetrose group, only one died on the 50th day after injection, with 3 metastases in the liver, the largest being 10mm in diameter, the other 5 mice survived until being dissected on the 55th day after injection and had no liver metastasis, but 3 of them had neoplasms in their remnant sites of injection. In mannan group, all of the 6 mice survived and no metastasis was seen except for 2 liver nodes in one mouse with the largest diameter of 1mm. Neither tetrose nor mannan group had metastasis out of the liver, and the weight of liver in the two groups was significantly lower than those in the control group. CONCLUSION Both tetrose and mannan had the effects of preventing melanoma cells from experimental metastasis to and out of the liver, and prolonging the survival time of the mouse.展开更多
Tumor necrosis factor-α (TNF-α) plays a key role in the pathogenesis of experimental autoimmune neuritis (EAN) as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies invo...Tumor necrosis factor-α (TNF-α) plays a key role in the pathogenesis of experimental autoimmune neuritis (EAN) as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.展开更多
AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwe...AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR. RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle- treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice. CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.展开更多
Background: Chronic kidney disease (CKD) is an irreversible decline in the glomerular filtration due to nephrosclerosis and glomerular loss. Rat remnant kidney model enables to assess the benefits of different treatme...Background: Chronic kidney disease (CKD) is an irreversible decline in the glomerular filtration due to nephrosclerosis and glomerular loss. Rat remnant kidney model enables to assess the benefits of different treatment possibilities. Aim: The aim of our study was to investigate renal morphology and functioning after 12 weeks of treatment with Equisetum arvense and Viscum album. Methods: Male Wistar rats with 5/6 nephrectomy received herbal drug preparation Equisetum/Viscum in a dosage of 0.007 g/kg/die (herbal group) or losartan (180 mg/l, ARB group) or remained untreated. Systolic blood pressure (SBP) and proteinuria were measured. Renal cortex tissue samples examined for focal-segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF). mRNA was isolated to estimate CCL2/MCP-1 gene transcription. Results: SBP was significantly lower both in herbal group and ARB group compared with untreated animals (p between ARB group and untreated NPX (p = 0.001). Quantitative RT-PCR analysis revealed statistically significant differences of mRNA transcription for MCP-1 between herbal group and untreated group (p Conclusions: We report about beneficial impact of horsetail Equisetum arvense and mistletoe Viscum album treatment on kidney functioning and morphology.展开更多
AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with ...AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.展开更多
AIM: To investigate the temporal onset and dynamic interplay of CD4^+ T helper cell subsets in experimental autoimmune encephalomyelitis (EAE).METHODS: EAE was induced in C57BL/6 mice by im-munization with myelin...AIM: To investigate the temporal onset and dynamic interplay of CD4^+ T helper cell subsets in experimental autoimmune encephalomyelitis (EAE).METHODS: EAE was induced in C57BL/6 mice by im-munization with myelin oligodendrocyte glycoprotein peptide p35-55. The clinical signs were scored and the tissue samples and immune cells isolated for analysis at different phases of EAE. The expression levels of inflammatory cytokines and related transcription fac-tors were detected by quantitative reverse transcription polymerase chain reaction (PCR) and enzyme linked immunosorbant assay (ELISA). The percentages of Th1, Th17, Th2, Treg and memory T cell subsets in EAE were analyzed by immunostaining and fow cytometry. The data were analyzed by statistical techniques.RESULTS: Quantitative real-time PCR analysis showed that EAE mice express elevated levels of Th1 [interferon gamma ( IFNγ ), interleukin ( IL ) -12p40 ], Th17 [ IL-17 , related orphan receptor gamma (RORγ ), IL-12p40] and Treg [ Foxp3, Epstein-Barr virus induced gene 3 (EBI3), IL-10] genes in the central nervous system at the peak of the disease. Whereas, the expression of Th1 ( IFNγ , T-bet, IL-12p35, IL-12p40 ), Th17 (RORγ, IL-12p40 ), Th2 ( IL-4) and Treg ( Foxp3, EBI3) response genes was reduced in the spleen during pre-disease but gradually recovered at the later phases of EAE. ELISA and fow cytometry analyses showed an increase in Th17 re-sponse in the periphery, while Th1 response remained unchanged at the peak of disease. The mRNA levels of IFNγ, IL-17 and IL-12p40 in the brain were increased by 23 (P 〈 0.001), 9 (P 〈 0.05) and 14 (P 〈 0.01) fold, respectively, on day 21 of EAE. Conversely, the mRNA expression of IL-10 was increased by 2 fold (P 〈 0.05) in the spleen on day 21. CD4^+CD25^+Foxp3+Treg response was reduced at pre-disease but recovered to na?ve levels by disease onset. The percentage of CD25 Foxp3 regulatory T cells decreased from 7.7% in the na?ve to 3.2% (P 〈 0.05) on day 7 of EAE, which then increased to 8.4% by day 28. Moreover, the CD4+CD127+CD44high memory T cell response was increased during the onset and recovery phases of EAE. The memory and effector cells showed an in-verse relationship in EAE, where the memory T cells increased from 12.3% in nave to 20% by day 21, and the effector cells decreased from 32% in na?ve to 21% (P 〈 0.01) by day 21. The wild type C57BL/6 mice with EAE showed elevated levels of effector-memory T cells (TEM) with concomitant reduction in central-memory T cells (TCM), but the EAE-resistant IL-7R defcient mice showed elevated TCM with no effect on TEM cells in EAE.CONCLUSION: Our fndings highlight the temporal on-set and dynamic interplay of effector, memory and regu-latory CD4^+ T cell subsets and its signifcance to clinical outcome in EAE and other autoimmune diseases.展开更多
Late blight caused by <i>Phytophthora</i> <i>infestans</i> (Mont.) De Bary is the most devastating disease of potato. This study was carried out to evaluate the efficacy of ten botanical extrac...Late blight caused by <i>Phytophthora</i> <i>infestans</i> (Mont.) De Bary is the most devastating disease of potato. This study was carried out to evaluate the efficacy of ten botanical extracts against the late blight disease incidence and severity in experimental potato field at University of Rajshahi, Bangladesh during 2019-2020. Crude aqueous extract of leaves of <i>Syzygium</i> <i>cumini</i>, <i>Psidium</i> <i>guajava</i>, <i>Eucalyptus</i> <i>globusus</i>, <i>Carica</i> <i>papaya</i> and <i>Lawsonia</i> <i>inermis</i>;fruits of <i>Terminalia</i> <i>bellirica</i>, <i>T.</i> <i>chebula</i> and <i>Piper</i> <i>nigrum</i>;flower buds of <i>Syzygium</i> <i>aromaticum</i> and cloves of <i>Allium</i> <i>sativum</i> were used at 5% (w/v) concentration for evaluation. Out of ten botanicals, <i>Syzygium</i> <i>cumini</i> leaves extract was found most effective in controlling the late blight disease incidence and severity up to 66 DAS (days after sowing) and increased the potato yield by 71.29% compare to untreated control. The efficacy of <i>Lawsonia</i> <i>inermis</i> extract against late blight disease was found promising and increased the potato yield by 48.51%. Other four botanical extracts (<i>Terminalia</i> <i>chebula</i>, <i>Piper</i> <i>nigrum</i>, <i>Syzygium</i> <i>aromaticum</i> and <i>Carica</i> <i>papaya</i>) showed moderate efficacy <span>against the incidence and severity of late blight disease, and increased 30% </span>more potato yield compare to control. These results suggest that botanical extract of <i>Syzygium</i> <i>cumini</i> ha<span style="font-family:;" "="">s</span><span style="font-family:;" "=""> a great potential as an alternative </span><span style="font-family:;" "="">of</span><span style="font-family:;" "=""> chemical fungicides to control the late blight disease of potato in</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">eco-friendly way.</span>展开更多
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
文摘Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elderly is membranous nephropathy; while its counterpart in younger population is Ig A nephropathy. The most frequent cause of nephrotic syndrome in the elderly is also membranous nephropathy. Pauci-immune crescentic glomerulonephritis(GN) rate increases both in elderly and very elderly population. Pauci-immune crescentic GNs should be regarded as urgencies in elderly patients as in their younger counterparts due to potential for causing end-stage renal disease in case of delayed diagnosis and treatment, and also causing mortality due to alveolar hemorrhage in patients with pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the elderly as in all other age groups. Renal biopsy prevents unnecessary treatments and provides prognostic data. So advanced age should not be the sole contraindication for renal biopsy. The course of primary glomerular diseases may differ in the elderly population. Acute kidney injury is more frequent in the course and renal functions may be worse at presentation. These patients are more prone to be hypertensive. The decision about adding immune suppressive therapies to conservative methods should be made considering many factors like co-morbidities, drug side effects and potential drug interactions, risk of infection, patient preference, life expectancy and renal functions at the time of diagnosis.
文摘Introduction: Primary Glomerular Diseases are a spectrum of renal disorders of unknown aetiology with distinct characteristics, specific natural history and prognosis. A thorough evaluation is prerequisite to establish the diagnosis since many systemic diseases and secondary aetiology masquerade as primary diseases. Methods: This prospective observational study was conducted at a tertiary care centre and included 30 patients, with clinical features suggestive of primary glomerular diseases, of which 23 patients (76.6%) were males and 07 patients (23.33%) were females. The mean age at presentation was 37.23 ± 12.89 years. Among the observed spectrum of Primary Glomerular Diseases, IgA Nephropathy (IgA N) was seen in 26.67% patients, Focal Segmental Glomerulosclerosis (FSGS) in 20% patients and Membranous Glomerulopathy (MGN) in 13.33% patients, whereas the incidence of other abnormalities had less percentage contribution. Proteinuria was the commonest presentation seen in 60% patients, followed by Microscopic Haematuria in 20%. Mean Serum Creatinine was 0.99 ± 0.16 mg/dl. Mean Serum Albumin was 2.51 ± 0.76 gm/dl. Overall Nephrotic range proteinuria was observed in 15 (50%) patients. Results: IgA N, FSGS & MGN were the commonest observed Primary Glomerular Diseases. Proteinuria, Haematuria, Anasarca and Pedal Oedema were the commonest observed clinical presentations. Conclusions: In this studied series IgA Nephropathy, FSGS and MGN were the most prevelant diagnoses in the patients presenting with Urinary Abnormality. Nephrotic range Protenuria was the major indication for biopsy, there is a temporal variation in glomerulopathies wherein there is increase in incidence of IgA Nephropathy and decrease in incidence of FSGS.
基金supported by the China Postdoctoral Science Foundation (no. 2020M670599)
文摘Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.
文摘Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.
基金National Institute of Health grants,No. DK64289,DK74454,and DK43351),IBD grants from the Eli and Edythe Broad Medical Foundation
文摘Inflammatory bowel disease(IBD),the most important being Crohn's disease and ulcerative colitis,results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract.Although the pathogenesis of IBD remains unclear,it is widely accepted that genetic,environmental,and immunological factors are involved.Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses.To investigate the etiology of IBD,animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD.Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described.In this manuscript,we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis(e.g.dextran sodium sulfate-,2,4,6-trinitrobenzene sulfonic acid-,oxazolone-,acetic acid-,and indomethacin-induced models).We also summarize some regulatory and pathogenic factors demonstrated by these models that can,hopefully,be exploited to develop future therapeutic strategies against IBD.
文摘AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
文摘AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7^th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured. RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found (0.47+0.44, 1.09+0.86, 0.43+0.31 vs 18.73+10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.
基金Supported by the National Natural Science Foundation of China,No.81400581(to Feng YJ) and No.81270477(to Li YY)
文摘AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium(DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6), and the myeloperoxidase(MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase(p38MAPK) and its phosphorylated form(p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580(SB), an inhibitor of p38, was investigated in parallel experiments, andthe data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38 MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38 MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38 MAPK signaling pathway and the endogenous CB system.
文摘Background: Osteoarthritis is a slowly progressive and debilitating disease with high prevalence in adult population. Knee is one of the joints most affected by this disorder. There are several models for animals’ osteoarthritis induction, however it is not identified any paper that compares these techniques. The present study was aimed to define the most appropriate model for rats osteoarthritis induction. Material and Methods: 40 Wistar rats were distributed into 4 groups of 10 animals each: normality group (NG);meniscectomy group (MG);quinolone group (QG) and iodoacetate group (IG). Radiographic images of the rat’s knees were analyzed as well as the amount of chondrocytes in the epiphyseal and articular cartilage. Results: In the radiographic analysis, there was a low correlation between the raters. Regarding the amount of chondrocytes in the epiphyseal cartilage, it was noticed that the IG and QG groups had fewer chondrocytes than NG, in contrast to MG that reported similar results to normality (p > 0.05). There was no significant difference between IG and QG groups (p > 0.05). Regarding the amount of chondrocytes in articular cartilage, it was noticed that the IG group showed fewer chondrocytes than NG (p 0.05). There was no significant difference between QG and MG groups (p > 0.05). Conclusion: Intraarticular injection of iodoacetate in rats is the model with greatest effect on reduction of chondrocytes amount.
基金Supported by Xinjiang Key Lab of Xinjiang Science and Technology Bureau Xinjiang,No.2014KL002National Natural Science Foundation of China,No.81372425National S&T Major Project,No.SQ2018ZX100301
文摘AIM To investigate a safer way to set up the disease model of cystic echinococcosis without contamination risk and develop a novel experimental murine model of hepatic cystic echinococcosis. METHODS C57 B/6 mice were injected with human protoscolices of three different concentrations via the portal vein. The mice were followed for 10 mo by ultrasound,gross anatomy,and pathological and immunological examinations. The protoscolex migration in the portal vein,hydatid cyst growth,host immune reaction,and hepatic histopathology were examined periodically.RESULTS The infection rates in the mice in the high,medium,and low concentration groups were 90%,100%,and 63.6%,respectively. The protoscolices migrated in the portal vein with blood flow,settled in the liver,and developed into orthotopic hepatic hydatid cysts,resembling the natural infection route and course.CONCLUSION We have established an improved experimental model of hepatic cystic echinococcosis with low biohazard risk but stable growing dynamics and immune reaction. It is especially useful for new anti-parasite medication trials against hydatid disease.
基金supported by National Institutes of Health grants AI070827 and CA33266American Cancer Society grant RSG-09-076-01 and the UIC Walter Payton Center GUILD
文摘An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.
基金financially sponsored by the Natural Science Foundation of Jiangsu Province in China,(General Program),No.BK2011267
文摘Experimental allergic encephalomyelitis is a mouse model of human multiple sclerosis with similar pathology and pathogenesis. Thl cells play an important role in the pathogenesis of experimental allergic encephalomyelitis. This study determined the potential effect of programmed cell death 1 ligand 1 in the pathogenesis of experimental allergic encephalomyelitis induced by injecting myelin oligodendrocyte glycoprotein, complete Freund's adjuvant and Bordetella pertussis toxin into C57BL/6J mice. Experimental allergic encephalomyelitis mice developed disease and showed in- flammatory changes in the central nervous system by hematoxylin-eosin staining of spinal cord pathological sections, demyelination by Luxol fast-blue staining and clinical manifestations. The expression of programmed cell death 1 ligand 1 in mice was detected by immunohistochemistry, flow cytometry and western blot anatysis. The expression of programmed cell death 1 ligand 1 in the spinal cord and splenocytes of mice was significantly increased compared with normal mice. Our findings suggest the involvement of programmed cell death 1 ligand 1 in the pathogenesis of ex- perimental allergic encephalomyelitis and suggest this should be studied in multiple sclerosis.
文摘AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (mannan group) for 30 minutes at 37℃, 0 5ml 1×10 6 B16 MBK melanoma cells were injected into the spleen of mice. Fifty five days later, melanoma metastatic nodes on the surface of the liver and in other organs as well as mouse survival time were observed. RESULTS Of the 6 mice in control (B16 cell+PBS) group, 4 died naturally within 55 days, and 2 were killed on the 55th day. All of the 6 mice had metastases in livers, the total number of the melanoma nodes on each liver surface ranged from 2 to 30, with the largest one merging into the whole liver. One mouse had a neoplasm in the remnant site of injection, and 3 had metastases in lungs. In contrast, of the 6 mice in tetrose group, only one died on the 50th day after injection, with 3 metastases in the liver, the largest being 10mm in diameter, the other 5 mice survived until being dissected on the 55th day after injection and had no liver metastasis, but 3 of them had neoplasms in their remnant sites of injection. In mannan group, all of the 6 mice survived and no metastasis was seen except for 2 liver nodes in one mouse with the largest diameter of 1mm. Neither tetrose nor mannan group had metastasis out of the liver, and the weight of liver in the two groups was significantly lower than those in the control group. CONCLUSION Both tetrose and mannan had the effects of preventing melanoma cells from experimental metastasis to and out of the liver, and prolonging the survival time of the mouse.
文摘Tumor necrosis factor-α (TNF-α) plays a key role in the pathogenesis of experimental autoimmune neuritis (EAN) as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.
文摘AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR. RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle- treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice. CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.
文摘Background: Chronic kidney disease (CKD) is an irreversible decline in the glomerular filtration due to nephrosclerosis and glomerular loss. Rat remnant kidney model enables to assess the benefits of different treatment possibilities. Aim: The aim of our study was to investigate renal morphology and functioning after 12 weeks of treatment with Equisetum arvense and Viscum album. Methods: Male Wistar rats with 5/6 nephrectomy received herbal drug preparation Equisetum/Viscum in a dosage of 0.007 g/kg/die (herbal group) or losartan (180 mg/l, ARB group) or remained untreated. Systolic blood pressure (SBP) and proteinuria were measured. Renal cortex tissue samples examined for focal-segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF). mRNA was isolated to estimate CCL2/MCP-1 gene transcription. Results: SBP was significantly lower both in herbal group and ARB group compared with untreated animals (p between ARB group and untreated NPX (p = 0.001). Quantitative RT-PCR analysis revealed statistically significant differences of mRNA transcription for MCP-1 between herbal group and untreated group (p Conclusions: We report about beneficial impact of horsetail Equisetum arvense and mistletoe Viscum album treatment on kidney functioning and morphology.
文摘AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.
基金Supported by Methodist Research Institute,Indiana University Health
文摘AIM: To investigate the temporal onset and dynamic interplay of CD4^+ T helper cell subsets in experimental autoimmune encephalomyelitis (EAE).METHODS: EAE was induced in C57BL/6 mice by im-munization with myelin oligodendrocyte glycoprotein peptide p35-55. The clinical signs were scored and the tissue samples and immune cells isolated for analysis at different phases of EAE. The expression levels of inflammatory cytokines and related transcription fac-tors were detected by quantitative reverse transcription polymerase chain reaction (PCR) and enzyme linked immunosorbant assay (ELISA). The percentages of Th1, Th17, Th2, Treg and memory T cell subsets in EAE were analyzed by immunostaining and fow cytometry. The data were analyzed by statistical techniques.RESULTS: Quantitative real-time PCR analysis showed that EAE mice express elevated levels of Th1 [interferon gamma ( IFNγ ), interleukin ( IL ) -12p40 ], Th17 [ IL-17 , related orphan receptor gamma (RORγ ), IL-12p40] and Treg [ Foxp3, Epstein-Barr virus induced gene 3 (EBI3), IL-10] genes in the central nervous system at the peak of the disease. Whereas, the expression of Th1 ( IFNγ , T-bet, IL-12p35, IL-12p40 ), Th17 (RORγ, IL-12p40 ), Th2 ( IL-4) and Treg ( Foxp3, EBI3) response genes was reduced in the spleen during pre-disease but gradually recovered at the later phases of EAE. ELISA and fow cytometry analyses showed an increase in Th17 re-sponse in the periphery, while Th1 response remained unchanged at the peak of disease. The mRNA levels of IFNγ, IL-17 and IL-12p40 in the brain were increased by 23 (P 〈 0.001), 9 (P 〈 0.05) and 14 (P 〈 0.01) fold, respectively, on day 21 of EAE. Conversely, the mRNA expression of IL-10 was increased by 2 fold (P 〈 0.05) in the spleen on day 21. CD4^+CD25^+Foxp3+Treg response was reduced at pre-disease but recovered to na?ve levels by disease onset. The percentage of CD25 Foxp3 regulatory T cells decreased from 7.7% in the na?ve to 3.2% (P 〈 0.05) on day 7 of EAE, which then increased to 8.4% by day 28. Moreover, the CD4+CD127+CD44high memory T cell response was increased during the onset and recovery phases of EAE. The memory and effector cells showed an in-verse relationship in EAE, where the memory T cells increased from 12.3% in nave to 20% by day 21, and the effector cells decreased from 32% in na?ve to 21% (P 〈 0.01) by day 21. The wild type C57BL/6 mice with EAE showed elevated levels of effector-memory T cells (TEM) with concomitant reduction in central-memory T cells (TCM), but the EAE-resistant IL-7R defcient mice showed elevated TCM with no effect on TEM cells in EAE.CONCLUSION: Our fndings highlight the temporal on-set and dynamic interplay of effector, memory and regu-latory CD4^+ T cell subsets and its signifcance to clinical outcome in EAE and other autoimmune diseases.
文摘Late blight caused by <i>Phytophthora</i> <i>infestans</i> (Mont.) De Bary is the most devastating disease of potato. This study was carried out to evaluate the efficacy of ten botanical extracts against the late blight disease incidence and severity in experimental potato field at University of Rajshahi, Bangladesh during 2019-2020. Crude aqueous extract of leaves of <i>Syzygium</i> <i>cumini</i>, <i>Psidium</i> <i>guajava</i>, <i>Eucalyptus</i> <i>globusus</i>, <i>Carica</i> <i>papaya</i> and <i>Lawsonia</i> <i>inermis</i>;fruits of <i>Terminalia</i> <i>bellirica</i>, <i>T.</i> <i>chebula</i> and <i>Piper</i> <i>nigrum</i>;flower buds of <i>Syzygium</i> <i>aromaticum</i> and cloves of <i>Allium</i> <i>sativum</i> were used at 5% (w/v) concentration for evaluation. Out of ten botanicals, <i>Syzygium</i> <i>cumini</i> leaves extract was found most effective in controlling the late blight disease incidence and severity up to 66 DAS (days after sowing) and increased the potato yield by 71.29% compare to untreated control. The efficacy of <i>Lawsonia</i> <i>inermis</i> extract against late blight disease was found promising and increased the potato yield by 48.51%. Other four botanical extracts (<i>Terminalia</i> <i>chebula</i>, <i>Piper</i> <i>nigrum</i>, <i>Syzygium</i> <i>aromaticum</i> and <i>Carica</i> <i>papaya</i>) showed moderate efficacy <span>against the incidence and severity of late blight disease, and increased 30% </span>more potato yield compare to control. These results suggest that botanical extract of <i>Syzygium</i> <i>cumini</i> ha<span style="font-family:;" "="">s</span><span style="font-family:;" "=""> a great potential as an alternative </span><span style="font-family:;" "="">of</span><span style="font-family:;" "=""> chemical fungicides to control the late blight disease of potato in</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">eco-friendly way.</span>