Establishment and validation of a novel peroxisome-related gene prognostic risk model in kidney clear cell carcinoma.

BACKGROUND: Kidney clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma. Peroxisomes play a role in the regulation of tumorigenesis and cancer progression, yet the prognostic significance of peroxisome-related genes (PRGs) remains rarely studied. The study aimed to establish a novel prognostic risk model and identify potential biomarkers in KIRC. METHODS: The significant prognostic PRGs were screened through differential and Cox regression analyses, and LASSO Cox regression analysis was performed to establish a prognostic risk model in the training cohort, which was validated internally in the testing and entire cohorts, and further assessed in the GSE22541 cohort. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function and pathway differences between the high-risk and low-risk groups. The relationship between risk score and immune cell infiltration levels was evaluated in the CIBERSORT, ESTIMATE and TIMER databases. Finally, potential biomarkers were identified and validated from model genes, using immunohistochemistry. RESULTS: Fourteen significant prognostic PRGs were identified using multiple analyses, and 9 genes (ABCD1, ACAD11, ACAT1, AGXT, DAO, EPHX2, FNDC5, HAO1, and HNGCLL1) were obtained to establish a prognostic model via LASSO Cox regression analysis. Combining the risk score with clinical factors to construct a nomogram, which provided support for personalized treatment protocols for KIRC patients. GO and KEGG analyses highlighted associations with substance metabolism, transport, and the PPAR signaling pathways. Tumor immune infiltration indicated immune suppression in the high-risk group, accompanied by higher tumor purity and the expression of 9 model genes was positively correlated with the level of immune cell infiltration. ACAT1 has superior prognostic capabilities in predicting the outcomes of KIRC patients. CONCLUSIONS: The peroxisome-related prognostic risk model could better predict prognosis in KIRC patients.

Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Escitalopram is selective serotonin reuptake inhibitors (SSRIs) and one of the most commonly prescribed newer antidepressants (ADs) worldwide. We aimed to explore the efficacy, acceptability and tolerability of escitalopram in comparison with other ADs in the acute-phase treatment of major depressive disorder (MDD). METHODS: Medline/PubMed, EMBASE, the Cochrane Library, CINAHL, and Clinical Trials.gov were searched from inception to July 10, 2023. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. All randomized controlled trials comparing escitalopram against any other antidepressant for patients with MDD. Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, risk ratios (RRs) were calculated with 95% confidence intervals (CI). Continuous data were analyzed using standardized mean differences (with 95% CI) using the random effects model. RESULTS: A total of 30 studies were included in this meta­analysis, among which sixteen trials compared escitalopram with another SSRI and 14 compared escitalopram with a newer AD. Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (RR 0.67, 95% CI 0.50-0.87). Escitalopram was also more effective than citalopram in terms of remission (RR 0.53, 95% CI 0.30-0.93). CONCLUSIONS: Escitalopram was superior to other ADs for the acute phase treatment of MDD in terms of efficacy, acceptability and tolerability. However, no significant difference was found between escitalopram and other ADs in early response or follow-up response to treatment of MDD.

Changes in the Microbiota and their Roles in Patients with Type 2 Diabetes Mellitus.

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabetic subjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

Optimization of cationic polymer-mediated transfection for RNA interference.

Transfection efficiency was estimated to optimize the conditions for RNA interference (RNAi), including transfection time, validity, and nucleic acid concentration and type, using the EZ Trans Cell Reagent, a cationic polymer. An shRNA against GFP was designed and transfected into cells using the EZ transfection reagent. The shRNA significantly decreased the expression of GFP. In addition, pre-diluted transfection reagent at room temperature and small nucleic acids increased the transfection efficiency, which peaked at 24 h. Compared with circular nucleic acids, linear nucleic acids showed higher transfection efficiency and a higher genome integration rate. We optimized cationic polymer-mediated RNAi conditions, and our data will be useful for future RNAi studies.

Identification of genetic variants in a pedigree associated with epilepsy by using whole exome sequencing and whole genome sequencing.

Epilepsy is a common heterogeneous group of neurological disorders including electroencephalographic and brain imaging. We used whole exome sequencing and whole genome sequencing to identify variants in a pedigree associated with epilepsy. Cranium CT scan showed that the lateral right parietal lobe was hyperdense, and there were no clear boundaries with brain tissue in affected cases. Using WES, one exclusive nonsynonymous mutant in gene TSC2 (Chr16:2138307; c.5240 T > G; p.Ile1747Ser) was involved in this disease. Further analysis showed that de novo variant in TSC2 was high conserved across different species. Moreover, the two affected sisters and their father had the same compound heterozygous variants in TSC2, while the father had no epilepsy but depigmentation. These variants demonstrated that variant in TSC2 may result in epilepsy with incomplete penetrance in humans, and the CNV and SV variants we identified probably be involved in this disease.

Immunoglobulin D-λ/λ biclonal multiple myeloma: A case report.

BACKGROUND: Immunoglobulin D (IgD) multiple myeloma (MM) is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System (ISS) when admitted. As a special type of IgD myeloma, IgD-λ/λ biclonal MM is rarer. Its serum protein electrophoresis and serum immuno-fixation electrophoresis (IFE) might find no anomalies even if the bone marrow (BM) examination is performed. Thus, it is easy to miss the diagnosis. CASE SUMMARY: A 62-year-old man diagnosed as IgD-λ/λ myeloma (ISS stage III) was admitted with fatigue and weight loss. The physical examination suggested an anemic face, a few moist rales at the left lung base, and mild concave edema in both lower extremities. Laboratory examinations showed the elevated creatinine levels, ß2-microglobulin, lactic dehydrogenase, and erythrocyte sedimentation rate, while the decreased neutrophils, granulocytes, and hemoglobin. In the serum protein electrophoresis, there appeared two inconspicuous M-spikes. Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands in λ region, but only one corresponding heavy chain band in the antisera to IgD region. The BM histology and BM cytology both supported the diagnosis of IgD-λ/λ myeloma. CONCLUSION: This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λ myeloma to help minimize the chance of misdiagnosis.

Colorectal cancer occurrence and treatment based on changes in intestinal flora.

Colorectal cancer (CRC) is the most common cancer in the world, and its incidence has been increasing in recent years. The occurrence of CRC is believed to be related to a variety of factors. Epidemiological data indicate that CRC is mainly affected by environmental factors, eating habits, physical activity and genetic factors. As a newly recognized functional component, the intestinal microbiota plays important roles in preventing CRC formation and maintaining intestinal immunity. In this review, we summarize the mechanisms by which the gut microbiota causes CRC through alterations to immune function, focusing on the mechanisms by which intestinal microbial dysfunction promotes CRC. Furthermore, we describe the changes in the intestinal flora observed in CRC and their potential for CRC treatment with the goal of facilitating future research on the roles of the intestinal flora.

Primary pulmonary plasmacytoma accompanied by overlap syndrome: A case report and review of the literature.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare kind of soft tissue plasma cell neoplasm without bone marrow involvement; this type of plasma cell neoplasm involves a lack of other systemic characteristics of multiple myeloma. Primary pulmonary plasmacytoma (PPP), with no specific clinical manifestations, is an exceedingly rare type of EMP. Because of its complexity, PPP is often difficult to diagnose, and there is no report in the literature on cases accompanied by overlap syndrome (OS). CASE SUMMARY: A 61-year-old woman without a familial lung cancer history was admitted to our hospital in 2018, for intermittent cough, expectoration, and a stuffy feeling in the chest for 50 years; these symptoms appeared intermittently, especially occurred after being cold, and had been aggravated for the last 10 d. She was diagnosed with pulmonary fibrosis and emphysema, bronchiectasis, OS, and autoimmune hepatic cirrhosis in 2017. A pulmonary examination revealed rough breath sounds in both lungs; other physical examinations found no obvious abnormalities. A routine laboratory work-up showed decreased haemoglobin, increased ESR, and abnormal GGT, ALT, IgG, γ-globulin, κ-light chain, λ-light chain, rheumatoid factor, and autoimmune antibodies. Emission computed tomography demonstrated abnormally concentrated 99mTc-MDP. Chest computed tomography revealed a soft tissue mass in the middle and lower lobes of the right lung. After right middle and inferior lobe resection with complete mediastinal lymph node dissection, immunohistochemical analysis revealed an isolated pulmonary plasmacytoma. The patient received chemotherapy for more than 1.5 years and remains in good general condition. CONCLUSION: PPP is a type of EMP, and we report an exceedingly rare presentation of PPP accompanied by OS.

Effects of O-1602 and CBD on TNBS-induced colonic disturbances.

BACKGROUND: This study attempted to provide the effects and mechanisms of two cannabinoids, O-1602 and cannabidiol (CBD), on colonic motility of 2,4,6-trinitro-benzene sulfonic acid (TNBS) colitis. METHODS: TNBS was used to induce the model of motility disorder. G protein-coupled receptor 55 (GPR55) expression was detected using real-time PCR and immunohistochemistry in colon. Pro-inflammatory cytokines and myeloperoxidase were also measured. The colonic motility was measured by upper GI transit in vivo and recorded using electrical stimulation organ bath technique in vitro. Freshly isolated smooth muscle from the rat colon were applied to determine the membrane potential and Ca2+ -ATPase activity, respectively. KEY RESULTS: CBD or O-1602 separately improved inflammatory conditions significantly in TNBS-induced colitis rats. However, sole CBD pretreatment reduced GPR55 expression, which was up-regulated in TNBS colitis. O-1602 and CBD each lowered MPO and IL-6 levels remarkably in TNBS colitis, while TNF-α levels experienced no change. CBD rescued the downward colonic motility in TNBS colitis in vivo; however, it decreased the upward contraction of the smooth muscle strip under electrical stimulation in vitro. Pretreatment with CBD prevented against TNBS-induced changes of Ca2+ -ATPase activity of smooth muscle cells. However, membrane potential of the smooth muscle cells decreased by TNBS experienced no change after O-1602 or CBD import. CONCLUSIONS & INFERENCES: The present study suggested that CBD participated in the regulation of colonic motility in rats, and the mechanisms may be involved in the regulation of inlammatory factors and Ca2+ -ATPase activity through GPR55.

Toxic effects of the Emamectin Benzoate exposure on cultured human bronchial epithelial (16HBE) cells.

Pesticides pollution has caused serious environmental problems in recent years, and mounting evidence has shown that more and more insecticides have serious risk in human health. Emamectin Benzoate formally regarded as a highly safety insecticide based on its exclusive targets, but the cytotoxicity to human lung was ignored for a long time. In the present study, bioassay experiments were used to assess the toxicity of the Emamectin Benzoatein on human non-target cells including cell viability assay, DNA damage assay, flow cytometer assay and western blotting assay. The results indicated that Emamectin Benzoatecan cause the inhibition of the proliferation, cytochrome c release, activation of caspase-3/9 and increase Bax/Bcl-2 ratio, which means it induced the cytotoxicity on 16HBE cells associated with the mitochondrial apoptosis. Besides, the DNA damge caused by the Emamectin Benzoate suggest it has a potential genotoxic effect on human lung cells.

Short-term efficacy of transvaginal specimen extraction for right colon cancer based on propensity score matching: A retrospective cohort study.

BACKGROUND: Recently, the incidence of colorectal cancer has increased each year. Natural orifice specimen extraction surgery (NOSES) removes the specimen from a natural cavity of the human body (anal or vaginal) and completes reconstruction of the digestive tract. There are only a few trocar scars in the abdomen after surgery. Transvaginal specimen extraction for right-sided colon cancer is one of the classic NOSES surgeries. As NOSES is accepted by increasing numbers of colorectal surgeons, NOSES technology is becoming increasingly widely used in China and abroad. Studies have confirmed the feasibility and safety of NOSES. Therefore, it is necessary to conduct further clinical studies to evaluate the short-term efficacy of the NOSES procedure. OBJECTIVE: To investigate the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer (NOSES). METHODS: We conducted a retrospective analysis of 90 cases of laparoscopic right colon cancer radical surgery performed continuously in the anorectal surgery of our Hospital from June 2015 to December 2018. Thirty-two patients underwent complete laparoscopic anastomosis and transvaginal specimen removal (NOSES group), and 58 patients underwent conventional abdominal wall removal specimen surgery (LAP group). The general data of the patients were matched by the propensity score matching (PSM) method 1:1. Thirty-one pairs of cases were successfully matched, and the intraoperative and postoperative data were analysed. RESULTS: After PSM, the baseline data were balanced between the two groups. A total of 62 patients in the two groups were successfully operated without conversion. There were no significant differences in intraoperative blood loss, lymph node dissection, sputum tumour cell positive rate, bacterial culture positive rate, postoperative follow-up and postoperative pelvic floor function evaluation (P > 0.05). Neither tumour cells nor bacteria were detected in the rinse solution at the start of the operation. Compared with the LAP group, the incidence of postoperative complications was lower in the NOSES group (6.4% vs. 29.0%, P = 0.006), and the gastrointestinal function recovery time was shorter (2.58 ±â€¯0.92 vs. 3.42 ±â€¯0.92, P = 0.001), postoperative hospital stay was shorter (6.68 ±â€¯1.47 vs. 9.58 ±â€¯2.22, P < 0.001), postoperative pain score was lower (postoperative day 1: 2.35 ±â€¯1.52 vs. 4.87 ±â€¯1.50; postoperative day 3: 1.81 ±â€¯1.11 vs. 4.00 ±â€¯1.18; postoperative day 5: 1.45 ±â€¯1.00 vs. 2.97 ±â€¯1.17; P < 0.001), additional analgesic drug use rate was lower (12.9% vs. 61.3%, P < 0.001), and patients were more satisfied with the appearance of the abdominal wall after surgery (100% vs. 23.6%, P < 0.001). CONCLUSION: This study used PSM to remove confounding factors and retrospectively analysed the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer radical resection. The results showed that the laparoscopic right colon cancer radical resection was satisfactory, ensuring sterility. At the same time, there is a clear advantage in reducing postoperative pain, shortening postoperative hospital stays, reducing the incidence of postoperative complications, and improving the appearance of the abdominal wall.

Short-term efficacy of natural orifice specimen extraction surgery for low rectal cancer.

BACKGROUND: This case-control study compared the short-term clinical efficacy of natural orifice specimen extraction surgery (NOSES) using a prolapsing technique and the conventional laparoscopic-assisted approach for low rectal cancer. AIM: To further explore the application value of the transanal placement of the anvil and to evaluate the short-term efficacy of NOSES for resecting specimens of low rectal cancer, as well as to provide a theoretical basis for its extensive clinical application. METHODS: From June 2015 to June 2018, 108 consecutive laparoscopic-assisted low rectal cancer resections were performed at our center. Among them, 26 specimens were resected transanally using a prolapsing technique (NOSES), and 82 specimens were resected through a conventional abdominal wall small incision (LAP). A propensity score matching method was used to select 26 pairs of matched patients, and their perioperative data were analyzed. RESULTS: The baseline data were comparable between the two matched groups. All 52 patients underwent the surgery successfully. The operative time, blood loss, number of harvested lymph nodes, postoperative complication rate, circumferential margin involvement, postoperative follow-up data, and postoperative anal function were not statistically significant. The NOSES group had shorter time to gastrointestinal function recovery (2.6 ± 1.0 d vs 3.4 ± 0.9 d, P = 0.006), shorter postoperative hospital stay (7.1 ± 1.7 d vs 8.3 ± 1.1 d, P = 0.003), lower pain score (day 1: 2.7 ± 1.8 vs 4.6 ± 1.9, day 3: 2.0 ± 1.1 vs 4.1 ± 1.2, day 5: 1.7 ± 0.9 vs 3.3 ± 1.0, P < 0.001), a lower rate of additional analgesic use (11.5% vs 61.5%, P = 0.001), and a higher satisfaction rate in terms of the aesthetic appearance of the abdominal wall after surgery (100% vs 23.1%, P < 0.001). CONCLUSION: NOSES for low rectal cancer can achieve satisfactory short-term efficacy and has advantages in reducing postoperative pain, shortening the length of postoperative hospital stay, and improving patients' satisfaction in terms of a more aesthetic appearance of the abdominal wall.

Authenticity of pulmonary Lophomonas blattarum infection: A case report.

Pulmonary protozoal infections are rare. A 28-year-old woman was admitted to hospital with chief complains of cough, sputum, and dyspnea. The clinical laboratory tests for blood revealed an increased eosinophil percentage of 31.3% and significantly elevated total IgE. The chest computed tomography scan revealed that bilateral bronchial walls were thickening, accompanied with patchy spots scattered throughout bilateral lungs. A suspected multiflagellated protozoan was observed under a light microscope. But some different features were observed by electron microscopy, such as the orientation of flagella and nucleus. Besides, both bronchoalveolar lavage fluid and bronchoscopic brush smears underwent Gram staining and Pap staining, which revealed that numerous respiratory ciliated cells were scattered or accumulated in the sample. Finally, she was diagnosed with eosinophil pneumonia. Metronidazole, bronchodilators, and mucolytics were taken for 5 d and symptoms and pulmonary ventilation function improved. We herein report a case of chronic eosinophilic pneumonia, which was misdiagnosed as multiflagellated protozoan infection, and it is suggested that reliable diagnosis approaches are necessary, rather than clinical symptoms and morphological features.

The Immunologic Role of Gut Microbiota in Patients with Chronic HBV Infection.

Hepatitis B can cause acute or chronic liver damage due to hepatitis B virus (HBV) infection. Cirrhosis or hepatocellular carcinoma (HCC) caused by chronic HBV infection often leads to increased mortality. However, the gut and liver have the same embryonic origin; therefore, a close relationship must exist in terms of anatomy and function, and the gut microbiota plays an important role in host metabolic and immune modulation. It is believed that structural changes in the gut microbiota, bacterial translocation, and the resulting immune injury may affect the occurrence and development of liver inflammation caused by chronic HBV infection based on the in-depth cognition of the concept of the "gut-liver axis" and the progress in intestinal microecology. This review aims to summarize and discuss the immunologic role of the gut microbiota in chronic HBV infection.

Functional characterization of CXCR4 in mediating the expression of protein C system in experimental ulcerative colitis.

The present study aimed to explore the role of CXCR4 and protein C system (PCS) in the experimental ulcerative colitis (UC). The expression of CXCR3, CCR10, and CXCR4 in dextran sulfate sodium (DSS)-induced colitis mouse model was measured by immunohistochemistry and western blot analysis. In vitro studies with microvascular endothelial cells (MVECs) were performed. The expression of endothelial protein C receptor (EPCR) and thrombomodulin (TM) were detected by RT-PCR and western blot analysis. Activities of protein C (PC), protein S (PS), activated PC (APC) were evaluated in cells pre-treated with JNK inhibitor SP600125 and c-Jun silencing. DSS mice showed up-regulated expression of CXCR4, higher macroscopic score and histological score (P<0.05), as well as elevated levels of SDF-1α (P<0.05) compared with wild type, CXCR4-/-, or CXCR4-/- +DSS mice. In DSS mice, EPCR expression was down-regulated (P<0.05), accompanied by decreased activity of PC and PS (P<0.05 or P<0.01) with an up-regulated expression of pJNK MAPK and pc-Jun (P<0.05). Moreover, the macroscopic score and histological score index, SDF-1α levels, EPCR expression, PC activity, pJNK, and pc-Jun were reversed in CXCR4-/- +DSS mice (P<0.05). In vitro, SDF-1α-induced inhibition of the PCS was blunted by SP600125 (P<0.05). Meanwhile, down-regulation of c-Jun rescued the inhibition of PCS (P<0.05). MVECs with retrovirus-mediated transfection of c-Jun demonstrated a strong trans-inactivation effect on the EPCR promoter (P<0.05). These findings suggest that CXCR4 is involved in UC pathogenesis and could be a promising therapeutic target for UC treatment.

[Role of IgG plasma cells in the change of protein C system in ulcerative colitis].

The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54+CD38+ and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA. After co-incubation of microvascular endothelial cells with TNF-α or IL-6, the expressions of endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity of activated protein C (APC) were examined. As the results showed, the IgG type plasma cells infiltration and the quantity of IgG type immune complex were increased in DSS group in comparison with control group. After incubation with IgG type immune complex, the levels of TNF-α and IL-6 in the supernatant of macrophages were increased (P < 0.01) in a concentration-dependent manner. Meanwhile, after incubation with TNF-α or IL-6, the expressions of EPCR and TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01), while the activity of APC was reduced (P < 0.05 or P < 0.01). These results suggested that the quantity of IgG type plasma cells increases in UC and forms immune complexes, which affect the secretion of cytokines from macrophage, thereby affecting the function of endothelial cells and finally inhibiting PCS in UC. Therefore, plasma cell may be a novel target for the treatment of UC.

[Emodin ameliorates the peritoneal dialysis-related peritoneal fibrosis via inhibiting the activation of Notch pathway].

Long term peritoneal dialysis (PD) is often associated with peritoneal fibrosis. The aim of this study was to explore the effect of emodin on PD-related peritoneal fibrosis and its related cellular and molecular mechanism. PD-related peritoneal fibrosis rats and cultured rat peritoneal mesothelial cells were recruited in the experiment. PD-related peritoneal fibrosis was induced by intraperitoneal injection of lactate-buffered solution containing 4.25% glucose. The peritoneal equilibrium test (PET) was performed at the end of 2 weeks, 4 weeks, and 6 weeks, respectively. HE staining and Masson staining were used for histopathological evaluation. Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma N-terminal procollagen III propeptide (PIIINP) level. Real-time PCR technique was used to detect the mRNA levels of Notch1, Jagged-1, and Hes-1 in peritoneal tissue. Western blot was applied to identify the protein levels of Notch1, Jagged-1, Hes-1, and Notch intracellular domain (NICD). In vitro, Notch1 overexpressing or knockdown rat peritoneal mesothelial cells were established and Western blot was used to examine the effect of emodin on the expressions of Hes-1 and Hey. Compared with the control group, HE staining revealed that PD rats suffered from decreasing in mesothelial cells, or detaching from surface of parietal peritoneum, accompanied by infiltration of inflammatory cells; Masson staining result showed thickened peritonea (P < 0.01), and the collagen deposition in the parietal peritoneum was increased; also, PIIINP level in plasma was elevated (P < 0.01). Treatment of the PD rats with emodin increased mesothelial cells in peritoneal tissue, and decreased the peritoneal thickness (P < 0.01), collagen depositions, as well as the plasma PIIINP level (P < 0.05). The expressions of Notch1, Jagged-1, Hes-1 and NICD in peritoneal tissue were also attenuated (P < 0.05 or P < 0.01). In cultured rat peritoneal mesothelial cells, compared with emodin group, emodin further inhibited the expressions of Hes-1 and Hey induced by Notch1-overexpression (P < 0.05), but not the expressions of Hes-1 and Hey induced by Notch1-knockdown (P > 0.05). Therefore, the activation of Notch pathway may be involved in the pathological process of PD-induced peritoneal fibrosis. Emodin may ameliorate the PD-related peritoneal fibrosis through inhibiting the activation of Notch pathway.

Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK.

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, and the 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 p38MAPK 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 p38MAPK. 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 p38MAPK signaling pathway and the endogenous CB system.