Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Approach to loss of response to advanced therapies in inflammatory bowel disease

BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

Effect of inflammatory response on joint function after hip fracture in elderly patients:A clinical study

BACKGROUND Excellent hip joint function facilitates limb recovery and improves the quality of survival.This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management.AIM To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients.METHODS The elderly patients who had hip fracture surgery at our hospital between January 1,2021,and December 31,2022 were chosen for this retrospective clinical investigation.Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared.Age,gender,fracture site,surgical technique,laboratory indices,and other variables that could have an impact on postoperative joint function were all included in a univariate study.To further identify independent risk factors affecting postoperative joint function in hip fractures,risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis.In addition to this,we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups.RESULTS A total of 119 elderly patients with hip fractures were included in this study,of whom 37 were male and 82 were female.The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin(IL)-6,IL-8,IL-10,C-reactive protein(CRP),and complement C1q(C1q)between the fair and excellent joint function groups(P<0.05).The results of multiple logistic regression analysis showed that IL-6>20 pg/mL[Odds ratio(OR)3.070,95%CI:1.243-7.579],IL-8>21.4 pg/mL(OR 3.827,95%CI:1.498-9.773),CRP>10 mg/L(OR 2.142,95%CI:1.020-4.498)and C1q>233 mg/L(OR 2.339,95%CI:1.094-5.004)were independent risk factors for poor joint function after hip fracture surgery(all P<0.05).CONCLUSION After hip fractures in older patients,inflammatory variables are risk factors for fair joint function;therefore,early intervention to address these markers is essential to enhance joint function and avoid consequences.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy

BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery

BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Effects of Qishi Shengjiang Guiyuan Granules on Inflammatory Response and T Lymphocyte Subsets in Peripheral Blood of Rats with GERD-Associated Idiopathic Pulmonary Fibrosis

[Objectives] To explore the effects of Qishi Shengjiang Guiyuan Granules on inflammatory response and T lymphocyte subsets in peripheral blood of rats with idiopathic pulmonary fibrosis (IFP) associated with gastroesophageal reflux disease (GERD).[Methods] Twenty-four SPF SD rats were randomly divided into control group, model group, Chinese medicine group and western medicine group, with 6 rats in each group. Except the control group, the other three groups were used to establish the rat model of GERD combined with IPF by injecting hydrochloric acid into the lower end of esophagus and inhaling diluted bleomycin (5 mg/kg). Rats in the Chinese medicine group (14 g/kg), rats in the western medicine group (4.17 g/kg), rats in the control group and the model group were given the same volume of saline by gavage for 14 d. Morphological and pathological changes of esophageal and lung tissues were observed under light microscope, and T lymphocyte subsets (CD + 3, CD + 4, CD + 8) and the ratio of CD + 4/CD + 8 in peripheral blood were detected by flow cytometry.[Results] Compared with the control group, the pulmonary tissue of the model group showed that the pulmonary interstitium was obviously thickened, the alveoli were mutually fused, the structure was obviously destroyed, the original alveolar structure was disappeared, the inflammatory cell infiltration was around the pulmonary capillaries and the alveolar space, and the basal cell hyperplasia and inflammatory cell infiltration were at the lower end of the esophagus. Compared with the model group, the degree of inflammatory cell infiltration and lung tissue damage in the Chinese medicine group and the western medicine group was significantly reduced, the inflammatory infiltration in the lower esophagus was significantly reduced, and the cell proliferation was reduced. Compared with the control group, the CD + 3, CD + 4, CD + 8, CD + 4/CD + 8 in the peripheral blood of the rats in the model group, the Chinese medicine group and the western medicine group decreased ( P <0.01). Compared with the model group, CD + 3, CD + 4, and CD + 4/CD + 8 increased ( P >0.05, P >0.05, P <0.01), CD + 8 decreased ( P >0.05). Compared with the Chinese medicine group, CD + 3, CD + 4, and CD + 4/CD + 8 increased ( P >0.05, P >0.05, P <0.01) and CD + 8 decreased ( P >0.05) in the western medicine group.[Conclusions] Qishi Shengjiang Guiyuan Granules can effectively improve the inflammation of the lower esophagus and lung tissues of the pulmonary fibrosis rats with GERD and IFP, and regulate the number of T lymphocyte subsets CD + 3, CD + 4, CD + 8 cells and CD + 4/CD + 8 ratio in peripheral blood.

Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries

Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.

Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.

Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation

OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.

Prognostic value of preoperative prognostic nutritional index and its associations with systemic inflammatory response markers in patients with stage Ⅲ colon cancer

Background: The prognostic nutritional index(PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stage III colon cancer.Methods: Medical records of 274 consecutive patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic(ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio(LMR), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP)level, and clinicopathologic characteristics were assessed using the Chi square or Fisher's exact test. Correlation analysis was performed using Spearman's correlation coefficient. Disease-free survival(DFS) and overall survival(OS)stratified by PNI were analyzed using Kaplan-Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses.Results: The preoperative PNI was positively correlated with LMR(r= 0.483, P < 0.001) and negatively correlated with NLR(r =-0.441, P < 0.001), PLR(r =-0.607, P < 0.001), and CRP level(r =-0.333, P < 0.001). A low PNI(≤49.22)was significantly associated with short OS and DFS in patients with stage ⅢC colon cancer but not in patients with stage ⅢA/ⅢB colon cancer.In addition, patients with a low PNI achieved a longer OS and DFS after being treated with6-8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was independently associated with DFS(hazard ratios 2.001; 95% confidence interval 1.157-3.462; P = 0.013).Conclusion: The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage Ⅲ colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.

Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn&#x02019;s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

Systemic inflammatory response following acute myocardial infarction

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Iuflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction （AMI）, Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes （such as death, recurrent myocardial in- farction, and heart failure） in patients with AMI.

MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases

In spite of the introduction in therapy of highly effective biological agents,glucocorticoids(GCs)are still employed to induce remission in moderate to severe inflammatory bowel diseases(IBD),but considerable inter-individual differences in their efficacy and side effects have been reported.The effectiveness of these drugs is indeed very variable and side effects,particularly severe in pediatric patients,are common and often unpredictable:the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability.In this context,microRNAs(miRNAs)represent a new and promising field of research.miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level,and are fine-tuning regulators of diverse biological processes,including the development and function of the immune system,apoptosis,metabolism and inflammation.Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases,such as IBD.There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response;however,the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study.The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis,represents an important innovative approach that could be translated into clinical practice.In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs,and their potential role as molecular markers useful for predicting in advance GC response.

Effect of glutarnate on inflammatory responses of intestine and brain after focal cerebral ischemia

AIM: To study the modulation of glutamate on post-ischemic intestinal and cerebral inflammatory responses in a ischemic and excitotoxic rat model.METHODS: Adult male rats were subjected to bilateral carotid artery occlusion for 15 min and injection of monosodium glutamate intraperitoneally, to decapitate them at selected time points. Tumor necrosis factor alpha (TNF-α) level and nuclear factor kappa B (NF-κB) activity were determined by enzyme-linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA), respectively.Hemodynamic parameters were monitored continuously during the whole process of cerebral ischemia and reperfusion.RESULTS: Monosodium glutamate (MSG) treated rats displayed statistically significant high levels of TNF-α in cerebral and intestinal tissuess within the first 6 h of ischemia. The rats with cerebral ischemia showed a minor decrease of TNF-α production in cerebral and intestinal tissuess. The rats with cerebral ischemia and treated with MSG displayed statistically significant low levels of TNF-α in cerebral and intestinal tissues. These results correlated significantly with NF-κB production calculated at the same intervals. During experiment, the mean blood pressure and heart rates in all groups were stable.CONCLUSION: Glutamate is involved in the mechanism of intestinal and cerebral inflammation responses. The effects of glutamate on cerebral and intestinal inflammatory responses after ischemia are up-regulated at the transcriptional level,through the NF-κB signal transduction pathway.

Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines:A meta-analysis

AIM:To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease(IBD)by conducting a meta-analysis.METHODS:Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD.The search terms were:"herb"or"plant"or"herbal"and"inflammatory bowel disease".Data were collected from 1966 to 2013(up to Feb).The"clinical response","clinical remission","endoscopic response","endoscopic remission","histological response","histological remission","relapse","any adverse events",and"seriousadverse events"were the key outcomes of interest.We used the Mantel-Haenszel,Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects.For subgroup analyses,we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.RESULTS:Seven placebo controlled clinical trials met our criteria and were included(474 patients).Comparison of herbal medicine with placebo yielded a significant RR of 2.07(95%CI:1.41-3.03,P=0.0002)for clinical remission;a significant RR of 2.59(95%CI:1.24-5.42,P=0.01)for clinical response;a non-significant RR of 1.33(95%CI:0.93-1.9,P=0.12)for endoscopic remission;a non-significant RR of 1.69(95%CI:0.69-5.04)for endoscopic response;a non-significant RR of 0.64(95%CI:0.25-1.81)for histological remission;a non-significant RR of 0.86(95%CI:0.55-1.55)for histological response;a non-significant RR of 0.95(95%CI:0.52-1.73)for relapse;a non-significant RR of 0.89(95%CI:0.75-1.06,P=0.2)for any adverse events;and a non-significant RR of 0.97(95%CI:0.37-2.56,P=0.96)for serious adverse events.CONCLUSION:The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes,but the number of studies is limited to make a strong conclusion.

Inflammatory response and neuronal necrosis in rats with cerebral ischemia

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap- peared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia,