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Background The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression. Methods In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored. Conclusion The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

Background Gastric cancer (GC) may arise in any region of the stomach. Poorly diagnosed GC results in almost one million mortalities annually worldwide. Kirenol is a bioactive compound present in the Sieges beckia sps. Objective In this current, we investigate the anticancer capacity of kirenol against the MNG-stimulated GC in rats via modulating the antioxidants status and inhibition of NF-κB cascade. Methodology GC was provoked in the rats via supplementing 100 mg/kg of MNU through the intragastric route for 16 weeks concomitantly with 30 mg/kg of kirenol treatment. The body weight, tumor volume, and incidence of all animals were tabulated every week. The status of gastrin, ALP, LDH, and γ-GT was studied through the ELISA tests. The lipid peroxidation, enzymatic, and nonenzymatic antioxidants were determined via standard procedures. Expression of thioredoxin, glutaredoxin, NF-κB, TNF-α, IL-6, PGE2 was studied through RT-PCR. The gastric mucosa was analyzed microscopically. Results Kirenol treatment appreciably improved the body weight and diminished the tumor volume and incidences in the MNG-challenged rats. The lipid peroxidation was diminished and the enzymatic and non-enzymatic antioxidants were improved by the kirenol treatment. Kirenol suppressed the status of serum markers of GC and gastrin, ALP, LDH, and γ-GT. The mRNA expression of thioredoxin, glutaredoxin, NF-κB, TNF-α, IL-6, PGE2 was downregulated via the kirenol in the MNG-challenged rats. Histopathological analysis result also confirmed the therapeutic role of kirenol. Conclusion These findings proved that the kirenol appreciably prevented the MNG-triggered GC in rats and it may become a potential drug for the GC treatment in the future.

Ulcerative colitis (UC) is an intractable ailment, in which may chronic inflammations/ulcerations may develop in the mucosal lining of the colon with multiple recurrences. Various drugs such as steroids, immunosuppressants, and antibiotics are extensively used to treat UC. The patients suffer from adverse effects of these advanced drugs. So, they need a harmless therapeutic agent from natural sources. The therapeutic D-carvone has an anti-inflammatory action against the investigational colon cancer models. Therefore, we analyzed the effect of D-carvone on dextran sulfate sodium (DSS) provoked colitis model in mice as follows: Group I: noncolitis healthy control mice; Group II: ulcerative colitis mice models; Group III: D-carvone (40 mg/kg) + ulcerative colitis models; Group IV: sulfasalazine (50 mg/kg) + ulcerative colitis models. On the 8th day, the experimental study was terminated and serum samples and colon tissues were processed for further analysis. The effect of D-carvone at different concentration was studied on the LPS challenged RAW 264.7 cell lines. The D-carvone (40 mg/kg) treatment maintained the colon length and decreased disease activity index (DAI) score in UC animals. The increased antioxidant enzymes status and decreased oxidative stress and pro-inflammatory markers were noted in the D-carvone (40 mg/ kg) + UC mice. Histopathological study of colon tissue of D-carvone (40 mg/kg) treated UC mice displayed less mucosal damage and improved crypt integrity and goblet cells compared with DSS only provoked mice. The im-munohistochemical expression of iNOS and COX-2 was drastically diminished in the D-carvone treated UC mice. D-carvone (40 mg/kg) treatment appreciably diminished the LPS provoked NO production and pro-inflammatory modulators in the RAW 264.7 macrophage cell lines. These findings proved that D-carvone has a potential therapeutic effect to prevent LPS induced inflammation in in vitro cells and chemically induced ulcerative colitis in vivo models.

Objective The purpose of this study is to compare the difference of clinical efficacy between conventional intraperitoneal chemotherapy and HIPEC, so as to explore the clinical application value and advantages of HIPEC. Design A retrospective analysis was conducted on 80 patients with malignant ascites admitted to our hospital from June 2017 to June 2019. The general clinical data and qualitative data of the treatment results of 80 patients with malignant ascites were processed by SPSS19.0 using χ2 test, and quantitative data were processed by t test. P < 0.05, statistical data can be considered statistically significant. Results There was no significant change in vital signs and temperature in the observation group during the treatment, and the difference was not statistically significant. The short-term total effective rate of patients in the observation group was 91.11%, and the short-term total effective rate of the patients in the control group was 40%. There was no significant difference in the incidence of adverse reactions between the two groups of patients. Conclusion Intraperitoneal hyperthermic chemotherapy combined with intravenous chemotherapy can significantly control malignant ascites and has small adverse reactions, which is worthy of clinical promotion and application.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that results in a chronic and inflammatory disorder. Dynamic balance of helper T cells (Th) 1 and 17 and regulatory T cells (Treg) is broken in RA. Since there is no cure for RA at present, it is necessary to find a truly effective and convenient treatment. Several studies have intended to induce ergotopic regulation to treat autoimmune diseases. This study was undertaken to find potential ergotope peptides and investigate their effects in treating the animal model of RA and their underlying regulatory mechanisms. First, we selected functional ergotope peptides from 25 overlapping peptides derived from the interleukin 2 receptor (IL-2R) α chain, and then used these peptides to treat collagen-induced arthritis (CIA). We showed ergotope peptides as immunomodulatory factors with great benefits at the clinical and pathologic levels. This effect was associated with inhibition of type II collagen (CII)-specific proliferation and autoantibody production as well as induction of antiergotypic immune response, downregulation of both Th1 and Th17 cells and their related components, and emergence of Treg cells that had suppressive action on autoreactive T cells. We also proved that cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and IL-10 are two important mediators that are critical to Treg suppressive function. Inhibition of Th1 and Th17 in established CIA could be attributed to ergotope-induced Treg cells. Our findings reveal that ergotope peptides induce regulatory immune responses and restore immune tolerance, suggesting that treatment with ergotope peptides may be a novel approach to therapy for RA patients and has good application prospects, with cheap, effective, convenient, wide-spectrum features.

Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases characterized by axonal loss, demyelination and neurodegeneration of the central nervous system (CNS). Overactivation of CD4(+)T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. In this study, we investigated the immunomodulatory effects of IFN-β treatment in EAE. IFN-β significantly inhibits disease severity, and decreases levels of CCR2, CCR4, CCR5, CCR6 and CXCR3 in the CNS. This was associated with fewer Th1/Th17 cells expressing these chemokine receptors. Furthermore, levels of their corresponding ligands CCL2, CCL3, CCL4, CCL5, CCL20, CCL22 and CXCL10 were also reduced, coinciding with reduced CNS inflammation and demyelination. Chemokine expression significantly correlated with disease severity. Furthermore, we demonstrate that IFN-β reduces CCL2/CCL5 induced-T cell migration by inhibiting p38-MAPK and ERK1/2 activation. Our results reveal that IFN-β reduces the expression of chemokines and chemokine receptors expressed by encephalitogenic Th1/Th17 cells, thereby decreasing their migration into the CNS.

Multiple sclerosis (MS) and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases. Increased activation of CD4+T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. IFN-β is widely used in the treatment of MS and is found to decrease IL-17 and OPN production in MS patients and EAE mice. However, a definitive molecular mechanism has not yet been fully elucidated. In this study, we investigated the immunomodulatory effect of IFN-β on the EAE model. We observed disease progression and determined the percentage of Th1/Th17 cells in the peripheral immune organs, brain, and spinal cord of mice. Furthermore, the levels of related cytokines and transcription factors were measured in splenocytes, and the effects of IFN-β on Th17 differentiation were assessed in vitro. Compared to the control group, IFN-β treatment significantly reduced the incidence of EAE and the associated pathological damage. Th1 and Th17 cells in IFN-β-treated mice were significantly reduced, and the levels of cytokines, such as IFN-γ, IL-17, and OPN, were significantly decreased in splenocyte supernatants as well as the levels of corresponding transcription factors. IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes. Moreover, IFN-β inhibited Th17 differentiation and neutralizing OPN antibodies offset the inhibitory effect of IFN-β on Th17 cells. Meanwhile, IFN-β influenced the acetylation of the Il17a and Opn gene promoters. The findings described herein provide novel evidence for the role of IFN-β in Th17 differentiation partly through the inhibition of OPN.

Th1 and Th17 cells, and their associated cytokines, have been associated with the pathogenesis of Crohn's disease. Berberine (BBR), a compound long used in traditional Chinese medicines, has been reported to have therapeutic effects in treating experimental colitis. In this study, we show that BBR had a protective effect on mice with TNBS-induced colitis. BBR inhibited levels of IFN-γ, IL-17, IL-6, IL-1β and TNF-α both in the local colon and sera, and transiently increased levels of IL-22. BBR also markedly increased sIgA expression in the colon. BBR had pronounced effects on macrophage populations. Treatment with BBR adjusted the M2/M1 ratio. In addition, BBR exerted effects on adaptive immunity by suppressing numbers of Th1 and Th17 cells, as well as expression levels of their associated cytokines and transcriptional factors. BBR downregulated STAT3 and STAT1 phosphorylation, and inhibited phosphorylation of NF-kB. In vitro experiments showed that BBR inhibited the differentiation of Th17 and, to a lesser degree, Th1 cells, without affecting regulatory T cells. Therefore, we conclude that BBR plays a regulatory role in modulating the balance of immune responses in TNBS-induced colitis. Our study will help us understand the regulatory mechanisms exerted by BBR in the treatment of IBD.

The aim of this study is to determine whether the regulatory role of T cell vaccination (TCV) is through inhibition of Th1/Th17/Tfh and production of autoantibodies on collagen-induced arthritis (CIA). First, CIA mice were treated with TCV. After disease onset, the incidence and severity of change in joint histopathology were evaluated. Mice in the TCV-treated group showed less disease severity and less infiltration of inflammatory cells in the joint sections. TCV decreased the frequencies of Th1/Th17/Tfh cells and related cytokines. Reduction of IL-21 may be associated with both Tfh and Th17, which further influence B cell and T cell responses. In addition, inhibition of Th1/Th17/Tfh frequencies led to the reduced expression of T-bet, RORα, RORγt, and Bcl6. Lastly, the proliferation of type-II-collagen-(CII-) specific T cells and the production of anti-CII antibodies were inhibited in the TCV-treated group. The results provide novel evidence that the therapeutic effects of TCV on CIA are associated with the inhibition of Th1/Th17/Tfh frequencies and autoantibodies production.