INTRODUCTION: Polydatin (PD) has anti-inflammatory and anti-apoptotic effects in ischemicreperfusion injury. Moreover, inflammatory responses and apoptosis play a role in the development of burn-induced lung injuries. Based on these findings, in this study we investigated the hypothesis that PD can ameliorate lung injury induced by extensive burns via reduction of inflammation and apoptosis. METHODS: Rats were subjected to 30% total body surface area burn injury followed by resuscitation. The treatment group received 45 mg/kg PD, and the burn group received the same amount of normal saline solution. No burn injury was inflicted in the sham group. Microvascular permeability, interstitial edema, neutrophil recruitment, and histopathological changes were detected by measuring Evans blue concentration, wet-to-dry lung weight ratio (W/D), myeloperoxidase (MPO) activity, and hematoxylin and eosin staining, respectively. To investigate the mechanism of action of PD, enzyme-linked immunosorbent assay, cell counting, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-triphosphate-digoxigenin nick end labeling (TUNEL) staining, fluorometric assay, and Western blot were used for assessing levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-1, and IL-6), total number of cells, and concentration of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF), the number of apoptotic cells, caspase-3 activity, and apoptosis-related proteins including Bax and Bcl-xl, respectively. RESULTS: Burn-injury rats exhibited significant lung injury characterized by the deterioration of histopathological characteristics, pulmonary microvascular hyperpermeability, and a high W/D, which were attenuated by PD (P ؍ .007 for permeability, P ؍ .004 for W/D). PD inhibited the burn-induced inflammatory response, as evidenced by the down-regulation of lung MPO activity (P ؍ .008), total number of cells, PMN concentration in BALF, and the local and systemic levels of the pro-inflammatory cytokines examined. Moreover, PD treatment dramatically prevented burn-induced pulmonary cell apoptosis in lungs, as reflected by the decrease in the number of TUNEL-positive cells (P ؍ .002) and changes in Bax, Bcl-xl, and caspase-3 activity (P ؍ .03). CONCLUSIONS: PD ameliorates burn-induced lung injury via its anti-inflammatory and anti-apoptotic effects, and PD treatment may therefore serve as a potential therapeutic target for the treatment of critical burn injuries.
Sporadic colorectal cancer (CRC) is a leading cause of worldwide cancer mortality. It arises from a complex milieu of host and environmental factors, including genetic and epigenetic changes in colon epithelial cells that undergo mutation, selection, clonal expansion, and transformation. The gut microbiota has recently gained increasing recognition as an additional important factor contributing to CRC. Several gut bacteria are known to initiate CRC in animal models and have been associated with human CRC. In this Review, we discuss the factors that contribute to CRC and the role of the gut microbiota, focusing on a recently described mechanism for cancer initiation, the so-called microbiota-induced bystander effect (MIBE). In this cancer mechanism, microbiota-driven parainflammation is believed to act as a source of endogenous mutation, epigenetic change and induced pluripotency, leading to the cancerous transformation of colon epithelial cells. This theory links the gut microbiota to key risk factors and common histologic features of sporadic CRC. MIBE is analogous to the well-characterized radiation-induced bystander effect. Both phenomena drive DNA damage, chromosomal instability, stress response signaling, altered gene expression, epigenetic modification and cellular proliferation in bystander cells. Myeloid-derived cells are important effectors in both phenomena. A better understanding of the interactions between the gut microbiota and mucosal immune effector cells that generate bystander effects can potentially identify triggers for parainflammation, and gain new insights into CRC prevention.
Congenital nephrogenic diabetes insipidus (CNDI) is a rare renal disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). The clinical signs of CNDI include polyuria, compensatory polydipsia, dehydration, electrolyte disorder, and developmental retardation without prompt treatment. In this study we report a rare case of CNDI caused by a single base transition in AQP2 gene. A 4.5 years old male patient suffered from oral dryness, polydipsia, and polyuria for more than 3 years. Laboratory examinations showed hypernatremia, hyperchloremia, and decreased urine osmolality and specific gravity. Ultrasound and MRI found bilateral upper ureteral dilatation and hydronephrosis. Furthermore, sequencing analysis found a C>T transition leading to a T108M missense mutation of AQP2. The patient was given low sodium diet and treated with hydrochlorothiazide followed by amiloride with indomethacin. The patient's clinical course improved remarkably after 1 year of treatment. This study reports the first case of CNDI featuring T108M missense mutation alone. These findings demonstrate a causative role of T108M mutation for CNDI and contribute to the mechanistic understanding of CNDI disease process.
Problem Chronic endometritis (CE) can cause infertility. Enterococcus faecalis is an opportunistic pathogen that is often found in the endometrium of CE patients. However, the mechanisms by which E. faecalis affects endometrial health are still unclear. In this study, we investigated the mechanism how extracellular superoxide produced by E. faecalis affected the endometrial receptivity. Method of Study Superoxide production was blocked by deleting menB gene in E. faecalis OG1RF. Endometrial epithelial cells were infected by superoxide‐producing E. faecalis OG1RF and superoxide‐deficient strain WY84. Inflammatory cytokines, apoptosis, and biomarkers for the endometrial receptivity were analyzed. Results Infection of endometrial epithelial cells with superoxide‐producing E. faecalis OG1RF induced expression of inflammatory cytokines, promoted apoptosis, and down‐regulated expression of receptivity biomarkers compared to uninfected control. In contrast, superoxide‐deficient E. faecalis WY84 had little effect on inflammatory cytokine production, apoptosis, and endometrial receptivity biomarkers. Conclusions Extracellular superoxide produced by E. faecalis is an important virulence factor for E. faecalis‐induced endometritis leading to reduced receptivity of endometrial epithelial cells.
Background: Cervical cancer (CC) is the most common malignancy inwomen on the earth. Cervical cancer usually develops from cervical intraepithelial neoplasia (CIN) grade 1 or above. Early detection of CIN1 or above precancerous lesion can effective control of cervical cancer incidence. The goal of this study was to evaluate the accuracy of p16/Ki67 dual staining in triaging hr-HPV positive population aged ≤ 30 years. Methods: A total of 336 women with an average age of 27.8 years old were included in this study. Liquid based cytology (LBC) samples were detected by p16/Ki67 immunocytochemical dual staining, liquid-based cytology, high-risk human papillomavirus (hr-HPV) and HPV 16/18 test. Diagnosis of each method was verified by histopathological test. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and AUC (area under the receiver operating characteristic curve, ROC curve) was obtained. Results: All assays had a high sensitivity for the detection of CIN2+. p16/Ki67 dual staining had similar sensitivity with hr-HPV test for CIN2+ detection (89.9% vs 93.9%, P = 0.781), and had similar sensitivity with LBC test (89.9% vs 82.7%, P=0.588). However, p16/Ki67 dual staining had higher specificity than that of both hr-HPV test (70.1% vs 25.5%, P<0.001) and LBC test (70.1% vs 38.9%, P=0.002) for CIN2+ detection. p16/Ki67 dual staining had bigger AUC (0.80) than that of hr-HPV test (0.60) and LBC test (0.61), the P value was 0.002, 0.003, respectively. The specificity of dual staining for CIN2+ detection in hr-HPV positive women was 70.1%, which was higher than that of LBC test (41.9%, P=0.020). Colposcopy referral rate of p16/Ki67 was lower than that of both hr-HPV and LBC (P=0.002, <0.001, respectively). HPV infection was significantly associated with p16/Ki67 expression in all patients. p16/Ki67 expression in HPV16/18 and other 15 types of hr-HPV infection was significantly higher than negative hr-HPV infection, odds ratio (OR) was 12.16 (95% confidence interval, 95% CI = 5.82-25.41) and 2.65 (95% CI = 1.27-5.51), respectively. Conclusions: p16/Ki67 dual staining has a good specificity of high-grade cervical lesions detection and is a promising tool in triage of CIN2+ and hr-HPV positive population and avoid over diagnosis and treatment.
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