Baicalin Is Curative Against Rotavirus Damp Heat Diarrhea by Tuning Colonic Mucosal Barrier and Lung Immune Function.

BACKGROUND: Previous studies have indicated that rotavirus (RV) is a causative factor for diarrhea and gastroenteritis in pediatric and neonatal settings. Baicalin has many functions, including antibacterial, antiinflammatory, and antihypertensive activities. However, the immunological mechanism of RV-induced diarrhea with heat-dampness syndrome (RV-DH) remains unclear. AIMS: The aim of this study is to explore the role of baicalin in RV-DH diarrhea and its underlying mechanism. METHODS: A mouse model of pediatric RV-DH diarrhea was established and treated with baicalin. The concentrations of cytokines were detected by enzyme-linked immunosorbent assay. Messenger RNA (mRNA) expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR), while protein expression levels were determined by Western blotting and immunohistochemistry. Flow cytometry was used to detect the frequency of lymphocytes. RESULTS: The concentrations of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, RVvb, and secretory immunoglobulin A (SIgA) in bronchoalveolar lavage fluid (BALF) and colonic mucosa were significantly increased in the RV-DH group. Decreased expression of occludin, claudin-1, and zonula occludens-1 (ZO-1) indicated loss of tight junction function and disturbances in intestinal mucosal permeability in the RV-DH group. Flow cytometry analysis showed a high rate of CD8+ lymphocytes and low amount of CD4+ lymphocytes in the RV-DH group. Treatment of RV-DH mice with baicalin significantly reduced the duration of diarrhea and ameliorated the symptoms and pathological and immunological changes. Furthermore, baicalin inhibited STAT1 and activated STAT3 signaling pathways. CONCLUSIONS: These findings indicate the curative and immunoregulatory properties of baicalin and have direct practical and clinical relevance for the treatment of RV-DH enteritis in humans.

Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model.

The aim of this study is to investigate the potential roles of miR-943-3p and its target gene secreted frizzled-related proteins4 (SFRP4) in allergic asthma and elucidate its underlying mechanism, which may prompt a new clue about developing novel treatments of this disease. An allergic asthma mouse model was generated by challenging with ovalbumin (OVA); lung pathological features of mice were viewed using H&E staining; thickness of subepithelial fibrosis and smooth muscle was measured using Masson's trichrome staining. Inflammatory cells from bronchoalveolar lavage fluid (BALF) were counted based on Diff-Quik staining and morphometric analysis. Expressions of miR-943-3p, SFRP4 and Wnt signal pathway-associated proteins were detected using RT-PCR or immunoblotting, respectively. SFRP4 was downregulated in the bronchial biopsies of allergic asthma patients and represented a unique intersection between differentially expressed genes (DEGs) and genes in the Wnt signal pathway. Both miR-943-3p upregulation and SFRP4 downregulation were detected in allergic asthma patients and OVA-induced mice. Besides, OVA-induced mice possessed more inflammatory cells in BALF including macrophage (mac), eosinophil (eos), lymphocyte (lym) and neutrophil (neu), higher expression of collagen, ß-catenin and c-Myc as well as thicker subepithelial fibrosis and smooth muscle in lung than control mice. In vivo delivery of miR-943-3p agomir worsened these symptoms, while both miR-943-3p antagomir and Ad-SFRP4 administration effectively alleviated this disease. Taken together, miR-943-3p accelerated the progression of airway inflammation and remodeling in allergic asthma via suppressing the activity of SFRP4 through Wnt signaling pathway in asthma patients and OVA-induced mice.

[Distribution of Syndrome Types of Chinese Medicine in Acute Infectious Diarrhea].

OBJECTIVE: To observe syndrome types of Chinese medicine (CM) and distribution features of acute infectious diarrhea patients. METHODS: A retrospective study was performed in 465 acute infectious diarrhea patients. The distribution of CM syndrome and syndrome types in different seasons and genders were analyzed. RESULTS: Lack of appetite [381 (81.94%)], fatigue [350 (75.27%)], abdominal pain [338 (72.69%)], tenesmus [325 (69.89%)], anal scorching hot [276 (59.35%)], nausea [25 (55.48%)], diarrhea [249 (53.55%)], short yellow-urine [240 (51.61%)], thirsty [210 (45.16%)], and abdominal distention [206 (44.30%)] were most often seen. The syndrome distribution were sequenced as intestinal damp heat syndrome [268 (57.63%)], dyspeptic retention in intestine and stomach syndrome [106 (22.80%)], cold-damp invading exterior syndrome [47 (10.11%)], Pi-Wei qi deficiency syndrome [23 (4.95%)], cold-damp disturbing Pi syndrome [21 (4.52%)]. The incidence ratio of intestinal damp heat syndrome was the highest in autumn (P < 0.01), while that of cold-damp invading exterior syndrome was the highest in winter (P < 0.01). Cold-damp disturbing Pi syndrome was more often seen in females than in males (P < 0.01), and its incidence ratio was the highest in autumn (P < 0.05). The incidence ratio of dyspeptic retention in intestine and stomach syndrome was the highest in winter (P < 0.01). CONCLUSIONS: Intestinal damp heat syndrome was the most often seen in acute infectious diarrhea. Incidence ratios of in- testinal damp heat syndrome and cold-damp disturbing Pi syndrome were higher in autumn, while those of cold-damp invading exterior syndrome and dyspeptic retention in intestine and stomach syndrome were higher in winter. Cold-damp disturbing Pi syndrome was more often seen in females.

Neuroprotection of Oral Edaravone on Middle Cerebral Artery Occlusion in Rats.

Edaravone has been widely used in the treatment of acute ischemic stroke. However, there has been no oral preparation of edaravone in the clinic. In this study, we assessed the effect and possible mechanisms of oral edaravone on the middle cerebral artery occlusion (MCAO) model in rats. Highly bioavailable form of novel edaravone formulation developed using self-nanomicellizing solid dispersion strategy which showed up to 16.1-fold improved oral bioavailability was considered oral edaravone. The male rats (n = 84) were randomly divided into sham; model; oral edaravone in low dose (10 mg/kg), medium dose (20 mg/kg), and high dose (30 mg/kg); and edaravone by intraperitoneal administration group (IP group, 10 mg/kg). Rats were treated with different drugs 5 h after the operation, twice a day for 7 days. The behavioral data were dose-dependently improved by oral edaravone and sensorimotor functions of the high dose group were similar to those of the edaravone by IP route group. Furthermore, oral edaravone significantly reduced cerebral infarction area and downregulated the levels of caspase-3, GFAP, Iba1, 3-NT, and 4-HNE, whereas upregulated those of Vamp-2 and Map-2 in a dose-dependent manner. Especially effect of the high dose on these molecules was equal to that of edaravone by IP administration. Taken together, our data suggest that the improvement of sensorimotor deficits by oral edaravone in high doses after ischemia is similar to that in edaravone by IP administration. Neuroprotection of oral edaravone is at least partial by minimizing oxidative stress, the overactivation of glial cells, and the levels of the apoptosis-associated proteins, and alleviating synaptic damage in a dose-dependent manner.

[Pathogenic role of leukotriene B4 in pulmonary microvascular endothelial cell hyper- permeability induced by one lung ventilation in rabbits].

OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in increased pulmonary microvascular endothelial cell permeability induced by one lung ventilation (OLV) in rabbits. METHODS: Forty-eight healthy Japanese white rabbits were randomly divided into control group (group C), saline pretreatment group (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV group (group SO) and bestatin plus saline pretreatment with OLV group (group BO). ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and phospholipase Cεl (PLCEl) expressions were examined by Western blotting and quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in the lung tissues were determined to evaluate the permeability of the pulmonary microvascular endothelial cells (PMVECs). The severities of lung injury were evaluated by lung histomorphological scores. RESULTS: No significant differences were found among groups C, S and B except that LTA4H expressions was significantly lower in group B than in groups C and S (P<0.05). OLV significantly increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05). CONCLUSION: Bestatin plays a protective role in OLV-induced rabbit lung injury by downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV-induced lung injury.