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The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats with middle cerebral ischemia/reperfusion (MCAO/R), explore the brain damage mechanism of MCAO/R at protein level, and provide experimental foundation for searching specific marker proteins of MCAO/R. Rat model of MCAO/R was established by modified suture-occluded method, and the model was evaluated by the results of brain 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE) staining. Cerebral cortex of rats from sham-operated group (Sham) and MCAO/R groups was used for FASP enzymatic hydrolysis, i-TRAQ quantitative labeling, and reverse-phase liquid chromatography purification and separation. Orbitrap Q Exactive mass spectrometry was used for qualitative and quantitative analyses of total differential protein expression profiles. MCAO/R rats had obvious cerebral infarction lesions, and the relative surface area of cerebral infarction was significantly different compared with sham rats, suggesting that MCAO/R rat model was successfully prepared. There were 199 significant difference proteins (MCAO/R vs Sham, p 0.05, |fold change| 1.2), including 104 up-regulated proteins and 95 down-regulated proteins. Gene ontology (GO) enrichment analysis showed that the up-regulated proteins were mainly concentrated in the biological processes of positive regulation of NF-κB transcription and I-κB kinase-NF-κB, etc. Down-regulated proteins were mainly concentrated in long-term synaptic potentiation, cellular response to DNA damage stimulus, etc. KEGG pathway analysis showed that the pathway involved in differential proteins includes oxidative phosphorylation, metabolic pathway, and Ras signaling pathway. Network analysis of differential proteins showed that Alb, ndufb5, ndufs7, ApoB, Cdc42, Ndufa3, Igf1r, P4hb, Mbp, Gc, Nme1, Akt2, and other proteins may play an important role in regulating oxidative stress, apoptosis, and inflammatory response in MCAO/R. Quantitative proteomics based on i-TRAQ labeling reveals the effect of inflammation and apoptosis in brain damage mechanism of MCAO/R. Besides, this research provide some experimental foundation for search and determination of potential therapeutic targets of MCAO/R.

To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect. Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay. Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P

Objective To determine the effects of a high-fat diet (HFD) on the gut microbiome in rats, to explore the relationship between the intestinal flora and blood lipid profile. Methods Sprague–Dawley rats were fed an HFD for four weeks to induce hyperlipidemia, then 16S rRNA sequencing was used to compare the intestinal flora between hyperlipidemic and control diet-fed rats. Results The microbiome of rats fed an HFD for four weeks differed from that of control diet-fed rats. Bacterial species that were less abundant were most affected by HFD feeding, among which were many pathogenic species, which became significantly more abundant. Eighteen genera were present in significantly different numbers in hyperlipidemic and control rats, more than half of which have been linked to infection and inflammation, or energy intake and obesity. The results indicated a type of stress response of the flora to a high-fat environment. In addition, the age of the rats tended to influence the gut microbial composition. Conclusion These findings suggest that HFD may induce hyperlipidemia by affecting the gut microbial composition. Changes in the abundance of pro-inflammatory and pathogenic bacteria, and those that influence energy intake and obesity, may be important mediators of this.

Type 2 diabetes mellitus is the most common type of diabetes, and insulin resistance (IR) is its core pathological mechanism. Proteomics is an ingenious and promising Omics technology that can comprehensively describe the global protein expression profiling of body or specific tissue, and is widely applied to the study of molecular mechanisms of diseases. In this paper, we focused on insulin target organs: adipose tissue, liver, and skeletal muscle, and analyzed the different pathological processes of IR in these three tissues based on proteomics research. By literature studies, we proposed that the main pathological processes of IR among target organs were diverse, which showed unique characteristics and focuses. We further summarized the differential proteins in target organs which were verified to be related to IR, and discussed the proteins that may play key roles in the emphasized pathological processes, aiming at discovering potentially specific differential proteins of IR, and providing new ideas for pathological mechanism research of IR.

With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.

Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, while its pathogenesis is still inconclusive. Intestinal flora, the largest micro-ecological system in the human body, is involved in, meanwhile has a major impact on the body's material and energy metabolism. Recent studies have shown that in addition to obesity, genetics, and islet dysfunction, the disturbance of intestinal flora may partly give rise to diabetes. In this paper, we summarized the current research on the correlation between T2DM and intestinal flora, and concluded the pathological mechanisms of intestinal flora involved in T2DM. Moreover, the ideas and methods of prevention and treatment of T2DM based on intestinal flora were proposed, providing theoretical basis and literature reference for the treatment of T2DM and its complications based on the regulation of intestinal flora.

Ethnopharmacological relevance Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or “Nai-Zi-Lai” in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed. Aim of the study To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. Materials and methods A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Results Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. Conclusions HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.

The incidence of type 1 diabetes mellitus (T1DM) is increasing year by year, gut microbiota is considered to be closely related to the occurrence and development of T1DM in recent years. In this study, Sprague Dawley (SD) rats were intraperitoneally injected with 75mg/kg streptozotocin to establish T1DM model, fecal samples were collected and DNA were extracted, 16S rRNA microbial gene clone library were constructed, and lastly high-throughput sequencing and bioinformatics analysis were performed. The results showed that the abundances of pathogenic bacteria such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes associated with infection and inflammation in T1DM rats were up-regulated, while the abundances of beneficial bacteria such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum were reduced. Among them, Butyricicoccus and Allobaculum protect intestinal barrier function by producing short-chain fatty acids. This study suggests that intestinal inflammation and reduction of short chain fatty acids (SCFAs) caused by the imbalance of gut microbiota are crucial to the pathogenesis of T1DM.

With the improvement of living standards and a change in lifestyle, the incidence of type 2 diabetes mellitus (T2DM) is increasing. Its etiology is too complex to be completely understand yet. Metabonomics techniques are used to study the changes of metabolites and metabolic pathways before and after the onset of diabetes and make it more possible to further understand the pathogenesis of T2DM and improve its prediction, early diagnosis, and treatment. In this review, we summarized the metabonomics study of T2DM in recent years and provided a theoretical basis for the study of pathogenesis and the effective prevention and treatment of T2DM.