The disorder of intestinal flora leads to the decline of anti-inflammatory reaction ability in the intestinal tract, low levels of SCFAs reduced the activation of GPR41 and GPR43, cause the ...occurrence of intestinal inflammation, insulin resistance, and as a result, lead to the occurrence of T2DM.
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•Intestinal flora disorders, such as the reduction of beneficial bacteria and the increase of harmful bacteria, are prone to occur in patients with type 2 diabetes mellitus.•The mechanisms of type 2 diabetes induced by intestinal flora imbalance include short-chain fatty acid theory, fatty acid theory, and endotoxin theory, etc.•Treatments based on the regulation of intestinal flora, such as fecal bacteria transplantation, regulating probiotics and content of intestinal SCFAs, may have a role in the prevention and treatment of type 2 diabetes.
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.
Some biochemical index changes in diabetics with kidney Yin deficiency, which are related to amino acid metabolism, energy metabolism and the changes of intestinal flora.
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•Combining ...the advantages of Chinese and modern medicine may lead to a deeper exploration and diagnosis of diabetes.•Syndromes can reveal the essence of the diabetes in a more comprehensive way, different syndromes have disparate metabolic characteristics, corresponding to disparate biomarkers.•Modern research methods are applied to analyze the main Traditional Chinese Medicine syndromes of diabetes from clinical and basic aspects.•Biomarkers of syndrome classification are intended to be searched according to its symptoms and biochemical indicators.
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.
Rice (
) responds to various abiotic stresses during growth. Plant-specific NAM, ATAF1/2, and CUC2 (NAC) transcription factors (TFs) play an important role in controlling numerous vital growth and ...developmental processes. To date, 170 NAC TFs have been reported in rice, but their roles remain largely unknown. Herein, we discovered that the TF OsNAC006 is constitutively expressed in rice, and regulated by H
O
, cold, heat, abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellin (GA), NaCl, and polyethylene glycol (PEG) 6000 treatments. Furthermore, knockout of
using the CRISPR-Cas9 system resulted in drought and heat sensitivity. RNA sequencing (RNA-seq) transcriptome analysis revealed that
regulates the expression of genes mainly involved in response to stimuli, oxidoreductase activity, cofactor binding, and membrane-related pathways. Our findings elucidate the important role of
in drought responses, and provide valuable information for genetic manipulation to enhance stress tolerance in future plant breeding programs.
In this study, LEfSe multilevel species hierarchical tree directly reflects the differences of gut microbiota between control and T1DM rats at the Phylum-to-Family level, the result showed that the ...gut microbiome of T1DM rats changed significantly. The abundance of pathogenic bacteria associated with infection and inflammation in T1DM rats was up-regulated such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes, while the abundance of beneficial bacteria and bacteria producing SCFAs were reduced such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum.
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•The incidence of type 1 diabetes is increasing year by year, some studies have pointed out that the development of type 1 diabetes is closely related to intestinal flora.•We investigate the changes of gut microbiome in type 1 diabetic mellitus rats based on high-throughput sequencing.•The result showed that the gut microbiome of type 1 diabetes rats changed significantly.•The abundance of pathogenic bacteria associated with infection and inflammation in type 1 diabetes rats was up-regulated, while beneficial bacteria were reduced.•The results indicate that dysbacteria cause to the intestinal inflammation and others, which plays an important role in the pathogenesis of type 1 diabetes.
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.
Recently, interstitial lung disease (ILD) morbidity and mortality have been increasing with insidious epidemiological characteristics. Jianghu decoction (JH) is an effective Chinese medicine for ILD.
...We aimed to reveal the material basis and mechanism of action of JH in the treatment of ILD.
In this study, an ILD mouse model was constructed with bleomycin. HE staining, transcriptome analysis, parallel reaction monitoring-mass spectrometry (PRM-MS), UPLC‒MS, and western blotting assays were conducted.
HE staining results showed that JH effectively reduced inflammation and fibrosis foci in the lungs of the ILD model. Furthermore, transcriptome analysis revealed that JH regulates a set of biological signaling pathways related to immune inflammation and fibrosis. PRM-MS combined with western blotting was applied to detect inflammation and fibrosis involving proteins in lung tissue. JH effectively reversed the aberrant expression of HMGB1, RAGE, SEPTIN4, ACTA2, and ITGAV proteins in the model group. AMPK was identified as the core upstream regulatory protein for JH-mediated ILD regulation. In addition, UHPLC‒MS technology was applied to determine the active ingredients of JH. A total of 80 components were identified from JH, and polydatin (PD) was identified as the active ingredient that effectively alleviated lung fibrosis and inflammatory injury in ILD mice. To illustrate the molecular regulatory network of JH and PD in alleviating lung fibrosis and inflammatory injury, we also examined inflammation and fibrosis-related molecules downstream of the AMPK pathway with RT‒qPCR and western blotting.
The results showed that both JH and its active component PD exert synergistic inhibition on pulmonary fibrosis and inflammation. Specifically, the AMPK/PGC1α/PPARγ signaling pathway was activated, and the AMPK/HMGB1/RAGE signaling pathway was inhibited in ILD lungs responding to JH or PD administration.
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•Polydatin is the active ingredient of Jianghu Decoction on ILD.•Jianghu Decoction and polydatin target AMPK/PGC1α/PPARγ pathway to reduce fibrosis.•Jianghu Decoction and polydatin target AMPK/HMGB1/RAGE pathway to anti-inflammation.•Regulating AMPK signaling network is a promising strategy for ILD treatment.
Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to ...be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.
In this study, the compositions of QWZK were determined
the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.
A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.
The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was
inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.
Depressive disorders induced by acute myocardial infarction (AMI) play a pivotal role in the deterioration of cardiac function, and Shuangxinfang (Psycho-cardiology Formula, PCF) was reported to ...alleviate heart function damage and improve depression-like behavior, but the complex mechanism in such process has not been clarified.
AMI models were established and PCF was administered in rats. Subjects were then assessed in open field test (OFT) and forced swimming test (FST) recapitulating symptoms of depressive disorder. Afterward, pharmacoproteomic profiling of the hippocampus and peri-infarct border zone (BZ) was performed using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique, to identify contributing proteins and pathways responsible for myocardial ischemia and behavioral allostasis. Bioinformatics analysis was processed for further investigation, while western blotting was employed for testing dominating proteins to validate proteomic results.
Rats in the AMI group showed depression-like behavior in OFT and FST, which was improved by PCF. There were 131 differentially expressed proteins (DEPs) in BZ and 64 proteins in the hippocampus being detected and quantified shared by the sham group, the AMI group, and the PCF group. Subsequently, pertinent pathways and molecular functions were further identified. Altered molecules were discovered to be enriched in the apoptotic process, innate immune response, and NF-κB transcription factor activity in BZ, as well as chemical synaptic transmission, axon, collagen binding, cell adhesion, response to carbohydrate, laminin binding, and cellular response to nitric oxide in the hippocampus. Groups of signal transducers were also able to select multiple pathways, including innate immunity and arginine biosynthesis in the heart, also integrin signaling in the brain. DEPs were intersected from the myocardium and hippocampus to screen out the protein S100A9, which was up-regulated in the AMI group compared with the sham, and showed a down-regulation trend after treatment with PCF.
Taken together, we present a comprehensive proteomics analysis of rat models with depression post-AMI. Reviewing the literatures concerned, it’s hypothesized that macrophage/microglia inflammation mediated by S100A9 might be the pivotal pathogenic process of psycho-cardiology disease, as well as potential mechanisms for the treatment of PCF.
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•PCF could improve heart function and depression developed from AMI.•S100A9 is a pivotal target of depression-like behavior in rats after AMI.•Macrophage/microglia inflammation mediated by S100A9 might be a significant pathogenic process in PCF treating psycho-cardiology disease.
Abstract Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma ...longa . The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1 , regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases.
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.
Cerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment ...target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.
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