ObjectiveTo investigate the effect and mechanism of microRNA (miR)-146a-3p on acute lung injury (ALI) and inflammation induced by lipopolysaccharide (LPS) in mice.MethodsThirty-two BALB/c mice were randomly divided into sham group, ALI group, ALI+agomiR-negative control (NC) group, ALI+miR-146a-3p agonist (agomiR-146a-3p) group, with 8 mice in each group. The ALI model was established by instilling 5 mg/kg LPS into the lungs through the trachea, and the same amount of saline was instilled slowly in the sham group. The mice in the ALI+agomiR-146a-3p group/NC group were injected with 8 mg/kg agomiR-146a-3p or agomiR-NC respectively through the tail vein, once a day, for 3 days. The sham group and the model group were given the same amount of normal saline injection through the tail vein. After 24 hours, they were sacrificed and lung tissues were collected. The expressions of miR-146a-3p and toll-like receptor 4 (TLR4) mRNA in lung tissue were detected by RT-qPCR, the expression levels of TLR4, cleaved caspase-3, Bcl-2 related X protein (Bax), B cell lymphoma-2 (Bcl-2) protein in lung tissue were detected by Western blot. The changes of lung pathology were observed by hematoxylin-eosin staining. The apoptosis of lung tissue was detected by TdT-mediated dUTP nick-end labeling. The expression levels of IL-1β, IL-6 and TNF-α in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). The dual luciferase reporting system verified the targeting relationship between miR-146a-3p and TLR4 in MRC-5 cells. MRC-5 cells were divided into control group, LPS group, LPS+miR-146a-3p mimic group, LPS+pcDNA3.1(pc)-TLR4 group, LPS+miR-146a-3p mimic+pc-TLR4 group. 100 nmol/L miR-146a-3p mimic and pc-TLR4 plasmids were transfected into MRC-5 cells separately or jointly for 24 hours, and then treated with 1000 ng/mL LPS or normal saline for 72 hours. The apoptosis rate was detected by flow cytometry. The expression levels of TLR4, cleaved caspase-3, Bax, and Bcl-2 proteins were detected by Western blot. The levels of IL-1β, IL-6 and TNF-α were detected by ELISA.ResultsCompared with the ALI group, the expression of miR-146a-3p was up-regulated, the expressions of TLR4 mRNA and protein were down-regulated, the apoptotic rate was decreased, the expressions of cleaved caspase-3 and Bax protein was down-regulated, the expression of Bcl-2 protein was up-regulated, and the levels of TNF-α, IL-6 and IL-1β in lung tissue were decreased in the lung tissues of the ALI+agomiR-146a-3p group (P<0.05). Dual-luciferase reporter assay confirmed that miR-146a-3p regulates transcription by targeting TLR4 3’UTR sequence (P<0.05). Compared with the LPS group, the expression of TLR4 protein in MRC-5 cells of the LPS+miR-146a-3p mimic group was down-regulated, the apoptosis was reduced, the expressions of cleaved caspase-3 and Bax protein were down-regulated, and the levels of TNF-α, IL-6 and IL-1β in lung tissue were decreased (P<0.05). Overexpression of TLR4 reversed the effect of miR-146a-3p mimic overexpression on LPS-induced apoptosis and inflammation of MRC-5 cells (P<0.05).ConclusionmiR-146a-3p alleviates LPS-induced ALI in mice by down-regulating TLR4.
Objective To summarize and review the heterogeneity of bone marrow derived stem cells (BMDSCs) and its formation mechanism and significance, and to analyze the possible roles and mechanisms in intestinal epithel ial reconstruction. Methods The related l iterature about BMDSCs heterogeneity and its role in intestinal epithel ial repair was reviewed and analyzed. Results The heterogeneity of BMDSCs provided better explanations for its multi-potency. The probable mechanisms of BMDSCs to repair intestinal epithel ium included direct implantation into intestinal epithel ium, fusion between BMDSCs and intestinal stem cells, and promotion of injury microcirculation reconstruction. Conclusion BMDSCs have a bright future in gastrointestinal injury caused by inflammatory bowl disease and regeneration.
Autoimmune uveitis (AU) and mood disorders, such as anxiety and depression, share a close bidirectional association. Visual impairment caused by AU and the side effects of glucocorticoid therapy significantly increase the incidence of anxiety and depression. Conversely, mood disorders disrupt immune homeostasis through neuro-endocrine-immune mechanisms, exacerbating inflammatory responses and elevating the risk of AU recurrence. The primary reasons for AU-induced mood disorders include visual impairment, unpredictable fluctuations in vision, long-term treatment, and glucocorticoid-related psychiatric reactions. Meanwhile, mood disorders not only trigger the onset and recurrence of AU but also interfere with treatment efficacy by reducing patient adherence. The underlying mechanisms involve psychological stress leading to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, inflammatory factor-mediated “brain-eye axis” regulation, synergistic effects of the gut microbiota-brain-immune axis, and stage-specific immune regulatory characteristics of acute and chronic stress. Therefore, clinical management should emphasize the synergistic integration of psychological interventions and anti-inflammatory therapy to enable early detection and treatment of extramedullary lesions, optimize diagnostic and therapeutic protocols, and improve the prognosis of AU patients. Future research should further elucidate the molecular mechanisms underlying the interaction between mood and inflammation, establish multidisciplinary collaborative diagnosis and treatment systems, validate the efficacy of psychological interventions through large-scale clinical studies, and explore the development of neuroprotective anti-inflammatory drugs.
ObjectiveTo explore the effects of simvastatin on the expression of matrix metalloproteinase (MMP) and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease (COPD). Methods40 male Wistar rats were randomly divided into four groups, including a normal group (group A), a simvastatin group (group B), a COPD model group (group C) and a simvastatin intervention group (group D). The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time, the rats of group B and D were given by gavage 5 mg/(kg·d) with simvastatin, and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay (ELISA) method was used to measure the content of MMP-2, MMP-9, IL-6, IL-8, TNF-α in lung tissue homogenate. ResultsThe airway resistance of group C and group D was significantly higher than the group A and group B (P<0.01), and the airway resistance of group D was significantly lower than group C (P<0.01). The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2, MMP-9, IL-6, IL-8, TNF-α in group C were all significantly higher than those in group D. ConclusionSimvastatin has inhibitory effect on pulmonary inflammation of COPD, and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.
ObjectiveTo improve the diagnosis and treatment of the disease, the clinical symptoms, pathological features, diagnosis and differential diagnosis, treatment and prognosis of massive lung inflammatory myofibroblastic tumor (IMT) were analyzed.MethodsA case, admitted to the Department of Respiratory and Critical Care Medicine of Xiangya Hospital, Central South University, diagnosed as massive lung IMT, was retrospectively analyzed. His clinical and chest radiological data were collected and literature which searched through CNKI, WanFang Med online and PubMed on this subject were reviewed.ResultsThe patient, middle-age male, was presented with cough, dyspnea and weight loss, whose chest radiology was characterized by a large thoracic cavity occupation. He was confirmed with massive lung IMT by several lung biopsy. From above databases, 8 cases were retrieved, including 6 articles in English and 2 articles in Chinese. In 9 cases of massive lung IMT, there were 4 males and 5 females. The age was from 1.5 to 75 years old and the average age was 28 years old. The clinical symptoms were non-specific, and chest imaging was characterized by a large thoracic occupation. One case had distant metastases with bone, adrenal gland and lymph node, and one case had distant metastasis with brain after complete surgery.ConclusionsLung massive IMT has no characteristic clinical and radiological features. And a definite diagnosis depends on pathological biopsy and immunohistochemical analysis. It needs to be differentiated from other thoracic giant tumors. The preferred treatment is complete surgical resection. The prognosis after complete resection is usually good, and probably affected by size.
ObjectiveTo investigate the prognostic factors for inflammatory breast cancer based on the data from West China Hospital with a relatively large sample. MethodsClinical data of 41 patients with histopathologically confirmed inflammatory breast cancer (IBC) who received treatment at West China Hospital Oncology Center of Sichuan University between January 2009 and December 2014 were collected and analyzed. Log-rank test and Cox regression model were used for statistical analysis. ResultsIn the study, negative estrogen receptor, negative progestrone receptor and positive human epidermal growth factor receptor-2 were identified in 58.5%, 61.0% and 34.2% of the inflammatory breast cancer tissues, respectively. Progress free survival (PFS) were between 2 and 60 months, with a median of 35 months. Univariate analysis showed that Tumor Node Metastasis (TNM) stage (P=0.016) and therapeutic effect (P=0.002) influenced the survival. Multivariate analysis showed that TNM stage (P=0.006), therapeutic effect (P=0.002), and anthracycline-taxane based chemotherapy (P=0.041) were the significant prognostic factors. ConclusionTNM stage is the major prognostic factor for IBC. Preoperative chemotherapy with paclitaxel-epirubicin combination can improve the PFS of IBC. Comprehensive treatment mode with operation is recommended for the treatment of IBC.
ObjectiveTo summarize the recent advancements in the researches on the pathogenesis of postoperative ileus and explain the clinical significances of postoperative ileus mechanisms for the diagnosis, treatment, and prevention. MethodsRelevant literatures about the postoperative ileus mechanism published recently were collected and reviewed. ResultsThe occurrence of postoperative ileus were related to postoperative nerve reflex inhibition, inflammatory response, effects of drugs, and other factors, it was a variety of mechanisms modulating each other. ConclusionThe gastrointestinal motility of postoperative ileus is mainly regulated by neural reflexes, inflammatory reactions, and drug interactions, three of which act differently but as a whole in different time segments while the inflammatory response play a key role of postoperative ileus persistence.
Inflammatory bowel disease (IBD) is a group of chronic, recurrent, and non-specific intestinal inflammatory diseases. It usually occurs between 20 and 40 years old, overlapping with the patient’s childbearing age. Active IBD may lead to decreased fertility and adverse pregnancy outcomes, and pregnancy may also lead to recurrence of IBD. Through studying domestic and foreign related literature on pregnancy and IBD, this article elaborates on the guidance and management of IBD before pregnancy, the disease management of IBD during pregnancy, the disease management of IBD during lactation, and the current status and prospects of traditional Chinese medicine treatment. It aims to provide references for patients and clinicians to have a more scientific understanding of pregnancy with IBD.
ObjectiveTo isolate and identify the cartilage progenitor cells (CPCs) from normal cartilage, and to explore the influence of interleukin 1β (IL-1β) in different concentrations on its chondrogenesis. MethodsCPCs were isolated from normal cartilage of adult New Zealand white rabbit with the fibronectin adhesion assay;the cell phenotype was identified;and the cloning and differentiation of CPCs were observed. CPCs were incubated with H-DMEM in group A, with chondrogenic induced medium in group B, with chondrogenic induced medium+0.1 ng/mL IL-1β in group C and chondrogenic induced medium+1.0 ng/mL IL-1β in group D for 3 weeks. The histology, biochemistry, and real-time fluorescence quantitative PCR were performed to observe the effect of IL-1β on the chondrgenic differentiation. ResultsThe CPCs from normal cartilage expressed positively stem cell phenotype, which have similar ability of cloning and differentiation to stem cells. The cell pellets in groups C and D were significantly smaller than those in group B, and cell showed hypertrophic morphology change. There were more expressions of collagen type Ⅱ and collagen type X in group B than in group A, in group B than in groups C and D, and in group C than group D with Safranin O staining. The biochemistry results showed that collagen type Ⅱ content, glycosaminoglycan (GAG) content, and the ratio of GAG/DNA were significantly lower in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05);but the DNA content was significantly higher in groups C and D than in group B (P<0.05), and no significant difference between groups C and D (P>0.05). The real-time fluorescence quantitative PCR results showed that the relative mRNA expressions of collagen type Ⅱ, collagen type X, and Sox-9 were significantly lower in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05), but the relative mRNA expressions of Runx-2 and matrix metalloproteinase 13 were significantly higher in groups C and D than in group B (P<0.05), and in group D than in group C (P<0.05). ConclusionThere are CPCs having the character of stem cells in normal cartilage, and they have the capability of cloning and potential differentiation. IL-1β can inhibit the chondrogenesis of CPCs, and possibly promote the osteogenic differentiation.
ObjectiveTo systematically review the tumor necrosis factor-α (TNF-α) -308G/A polymorphism and the risk of inflammatory bowel disease (IBD). MethodsAll eligible case-control studies published up to Jan 25th 2015 were identified by searching PubMed, EMbase, CNKI, WanFang Data, CBM and VIP databases. Two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted data and assessed methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 and Stata 12.0 softwares. ResultsA total of 20 studies involving 2 860 IBD cases and 5 033 controls were included. The results of meta-analysis showed:Compared with the wild genotype GG, genotype GA, AA and genotype GA+AA were associated with susceptibility of ulcerative colitis (UC) (GA vs. GG:OR=1.45, 95%CI 1.02 to 2.07, P=0.04; AA vs. GG:OR=2.01, 95%CI 1.32 to 3.05, P=0.001; GA+AA vs. GG:OR=1.51, 95%CI 1.07 to 2.13, P=0.02); Compared with genotype GA+AA, genotype AA increased the risk of UC (AA vs. GA+GG:OR=1.92, 95%CI 1.26 to 2.91, P=0.002); allele A did not increase the risk of UC; Compared with genotype GG, genotype AA increased the risk of Crohn disease (CD) (AA vs. GG:OR=1.49, 95%CI 1.07 to 2.08, P=0.02); Compared with genotype GA+GG, while genotype AA increased the risk of CD (AA vs. GA+GG:OR=1.50, 95%CI 1.08 to 2.09, P=0.02); genotype GA, GA+AA and allele A did not increase the risk of CD. In stratification analyses by ethnicity, we found that the TNF-α-308G/A was significat associated with IBD in Europeans. ConclusionCurrent evidence indicates that TNF-α-308G/A polymorphism is associated with the susceptibility of IBD, genotype GA, AA and GA+AA increase the risk of suffering from UC while genotype AA increase the risk of suffering from CD. Due to the limited quantity of the included studies, more researches are needed to verify the above conclusion.