Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy.

Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 µM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP+-treated PC12 cells, CB6 inhibited cell apoptosis and increased cell viability by inducing autophagy. In MPTP-induced mouse model of PD, oral administration of CB6 (10, 20 mg· kg-1· d-1, for 21 days) significantly improved motor dysfunction and prevented the loss of dopaminergic neurons in the striatum and substantia nigra pars compacta. Collectively, compound CB6 is a brain-permeable autophagy enhancer via PIK3C3 complex activation, which may help the prevention or treatment of PD.

Authentication of Shenqi Fuzheng Injection via UPLC-Coupled Ion Mobility-Mass Spectrometry and Chemometrics with Kendrick Mass Defect Filter Data Mining.

Nearly 5% of the Shenqi Fuzheng Injection's dry weight comes from the secondary metabolites of Radix codonopsis and Radix astragali. However, the chemical composition of these metabolites is still vague, which hinders the authentication of Shenqi Fuzheng Injection (SFI). Ultra-high performance liquid chromatography with a charged aerosol detector was used to achieve the profiling of these secondary metabolites in SFI in a single chromatogram. The chemical information in the chromatographic profile was characterized by ion mobility and high-resolution mass spectrometry. Polygonal mass defect filtering (PMDF) combined with Kendrick mass defect filtering (KMDF) was performed to screen potential secondary metabolites. A total of 223 secondary metabolites were characterized from the SFI fingerprints, including 58 flavonoids, 71 saponins, 50 alkaloids, 30 polyene and polycynes, and 14 other compounds. Among them, 106 components, mainly flavonoids and saponins, are contributed by Radix astragali, while 54 components, mainly alkaloids and polyene and polycynes, are contributed by Radix codonopsis, with 33 components coming from both herbs. There were 64 components characterized using the KMDF method, which increased the number of characterized components in SFI by 28.70%. This study provides a solid foundation for the authentification of SFIs and the analysis of its chemical composition.

[Research advance in metabolism of effective ingredients from traditional Chinese medicines by probiotics].

The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine.This review summarizes and analyses the research progress on metabolism effects of gut microbiota on Chinese medicines components, the regulating effect of effective ingredients from Chinese medicine on intestinal probiotics, the application status of probiotics in traditional Chinese medicines, and the main problems and prospects in the research and development of Chinese medicines products with probiotic, aiming to provide theoretical guidance and practical value for the fermentation engineering of Chinese herbal medicine.

LC-MS-based urinary metabolite signatures in idiopathic Parkinson's disease.

Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of Parkinson's disease (PD). These body fluids include urine; however, the relationship between, specifically, urinary metabolic phenotypes and PD is not fully understood. In this study, urinary metabolites from a total of 401 clinical urine samples collected from 106 idiopathic PD patients and 104 normal control subjects were profiled by using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Our study revealed significant correlation between clinical phenotype and urinary metabolite profile. Metabolic profiles of idiopathic PD patients differed significantly and consistently from normal controls, with related metabolic pathway variations observed in steroidogenesis, fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism, tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism. In the fruit fly Drosophila melanogaster, the alteration of the kynurenine pathway in tryptophan metabolism corresponded with pathogenic changes in the alpha-synuclein overexpressed Drosophila model of PD. The results suggest that LC-MS-based urinary metabolomic profiling can reveal the metabolite signatures and related variations in metabolic pathways that characterize PD. Consistent PD-related changes across species may provide the basis for understanding metabolic regulation of PD at the molecular level.

Exploring the impact of OSA on short-term survival in patients with AECOPD admitted to the ICU.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms, which significantly contributes to hospitalizations related to COPD symptoms. Previous research has mainly focused on the correlation between obstructive sleep apnea (OSA) and COPD. However, there were few studies that investigated the short-term mortality rate of AECOPD patients with or without OSA. METHODS: Data for our research was taken from the Medical Information Mart for Intensive Care Database IV. A total of 1332 patients were included in the study based on well-defined criteria for selection and exclusion. By analyzing the characteristics of AECOPD patients, we compared those with and without OSA. RESULTS: There were 1122 AECOPD patients without OSA, 210 patients with OSA. In comparison to those without OSA, patients with OSA exhibited lower 30-day and 90-day ICU mortality with unadjusted HR, as well as lower hospital mortality with unadjusted OR. However, after adjustments were made, there were no significant associations observed between OSA and short-term mortality, including 30-day ICU mortality, 90-day ICU mortality, ICU mortality, and hospital mortality in AECOPD patients. Subgroup analysis revealed that OSA may act as a risk factor for AECOPD patients with a BMI lower than 30 kg/m2. CONCLUSIONS: There is no impact on short-term survival in AECOPD patients with OSA under intensive care unit (ICU) management and nursing.

Causal relationships between gut microbiome and obstructive sleep apnea: a bi-directional Mendelian randomization.

Background: Previous studies have identified a clinical association between gut microbiota and Obstructive sleep apnea (OSA), but the potential causal relationship between the two has not been determined. Therefore, we aim to utilize Mendelian randomization (MR) to investigate the potential causal effects of gut microbiota on OSA and the impact of OSA on altering the composition of gut microbiota. Methods: Bi-directional MR and replicated validation were utilized. Summary-level genetic data of gut microbiota were derived from the MiBioGen consortium and the Dutch Microbiome Project (DMP). Summary statistics of OSA were drawn from FinnGen Consortium and Million Veteran Program (MVP). Inverse-variance-weighted (IVW), weighted median, MR-Egger, Simple Mode, and Weighted Mode methods were used to evaluate the potential causal link between gut microbiota and OSA. Results: We identified potential causal associations between 23 gut microbiota and OSA. Among them, genus Eubacterium xylanophilum group (OR = 0.86; p = 0.00013), Bifidobacterium longum (OR = 0.90; p = 0.0090), Parabacteroides merdae (OR = 0.85; p = 0.00016) retained a strong negative association with OSA after the Bonferroni correction. Reverse MR analyses indicated that OSA was associated with 20 gut microbiota, among them, a strong inverse association between OSA and genus Anaerostipes (beta = -0.35; p = 0.00032) was identified after Bonferroni correction. Conclusion: Our study implicates the potential bi-directional causal effects of the gut microbiota on OSA, potentially providing new insights into the prevention and treatment of OSA through specific gut microbiota.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

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Hippocampal metabolomics using ultrahigh-resolution mass spectrometry reveals neuroinflammation from Alzheimer's disease in CRND8 mice.

In the wake of genomics, metabolomics characterizes the small molecular metabolites revealing the phenotypes induced by gene mutants. To address the metabolic signatures in the hippocampus of the amyloid-beta (Aß) peptides produced in transgenic (Tg) CRND8 mice, high-field ion cyclotron resonance-Fourier transform mass spectrometry supported by LC-LTQ-Orbitrap was introduced to profile the extracted metabolites. More than 10,000 ions were detected in the mass profile for each sample. Subsequently, peak alignment and the 80% rule followed by feature selection based on T score computation were performed. The putative identification was also conducted using the highly accurate masses with isotopic distribution by interfacing the MassTRIX database as well as MS/MS fragmentation generated in the LTQ-Orbitrap after chromatographic separation. Consequently, 58 differentiating masses were tentatively identified while up to 44 differentiating elemental compositions could not be biologically annotated in the databases. Nonetheless, of the putatively annotated masses, eicosanoids in arachidonic acid metabolism, fatty acid beta-oxidation disorders as well as disturbed glucose metabolism were highlighted as metabolic traits of Aß toxicity in Tg CRND8 mice. Furthermore, a web-based bioinformatic tool was used for simulation of the metabolic pathways. As a result of the obtained metabolic signatures, the arachidonic acid metabolism dominates the metabolic perturbation in hippocampal tissues of Tg CRND8 mice compared to non-Tg littermates, indicating that Aß toxicity functions neuroinflammation in hippocampal tissue and new theranostic opportunities might be offered by characterization of altered arachidonic acid metabolism for Alzheimer's disease.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Systematic review on the efficacy and safety of herbal medicines for vascular dementia.

We present a systematic review of existing research that aims to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (OM), mainly comprised of cholinesterase inhibitors, for vascular dementia (VaD). We included 47 studies conducted in mainland China, each testing different HM. Of 43 HM monotherapy studies, 37 reported HM to be significantly better than OM or placebo; six reported similar efficacy between HM and OM. All four HM adjuvant studies reported significant efficacy. No major adverse events for HM were reported. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies suggested that HM can be a safe and effective treatment for VaD, either alone or in conjunction with OM. However, methodological flaws in the design of the studies limited the extent to which the results could be interpreted. Thirty most commonly used herbal constituents, including Rhizoma Chuanxiong (Chuanxiong in Chinese), Radix Polygoni Multiflori (Heshouwu in Chinese) and Radix Astragali (Huangqi in Chinese). were ranked. Further multi-center trials with large sample sizes, high methodological quality and standardized HM ingredients are necessary for clinical recommendations to be made.

Carbon stock stability in drained peatland after simulated plant carbon addition: Strong dependence on deeper soil.

Peatlands are vital soil carbon sinks, yet this function is jeopardized by plant carbon which could change the decomposition rate of soil organic carbon, knowing as "priming effect". How the priming effect depends on depth is a critical question in drained peatland given the heterogeneity of soil layers defined by the water table, which include the surface acrotelm, inter-mesotelm and deep catotelm. Here, through incubation, we quantified the response of these three soil layers to addition of 13C-labeled oxalate, glucose, cellulose, or cinnamic acid under anoxic or oxic conditions on the Zoige Plateau in Tibet. Soil carbon in the inter-mesotelm showed the greatest decomposition, with the highest humification index and lowest microbial biomass carbon, while the soil carbon at the surface acrotelm was least decomposed. Under anoxic conditions, exogenous carbon addition reduced CO2 emission by 12.2% at the surface acrotelm but increased by 59.8% in the inter-mesotelm and 23.5% in the deep catotelm. In the inter-mesotelm, oxalate addition significantly increased CO2 emission by 63.9%, while cinnamic acid significantly increased it by 92.9%. In the deep catotelm, cinnamic acid significantly increased CO2 emission by 55.3%. These results suggested that deeper soil organic carbon was more sensitive to plant carbon, particularly complex or recalcitrant carbon, than surface acrotelm soil. Under oxic conditions, carbon addition increased surface soil CO2 emission by 18.9%, and triggered even greater increase at inter-mesotelm and deep catotelm soil, with proportions of 48.3% and 32.0%, respectively. Under both conditions, peat profile CO2 release increased by 17.2-31.4% after exogenous carbon addition, and more than 77.8% of the increase came from the deeper two layers. These findings highlighted the need to take full account of priming effect of deeper soil in order to assess and predict the stability of carbon stocks in drained peatland.

Baicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aß peptide fibrillation and oligomerisation.

Abnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-ß peptide (Aß) aggregation and toxicity. We found that baicalein can also inhibit Aß fibrillation and oligomerisation, disaggregate pre-formed Aß amyloid fibrils and prevent Aß fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders.

Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson's Disease.

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson's disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

Structure and distribution of nitrite-dependent anaerobic methane oxidation bacteria vary with water tables in Zoige peatlands.

The recently discovered nitrite-dependent anaerobic methane oxidation (n-damo) is an important methane sink in natural ecosystems performed by NC10 phylum bacteria. However, the effect of water table (WT) gradient due to global change on n-damo bacterial communities is not well studied in peatlands. Here, we analysed the vertical distribution (0-100 cm) of n-damo bacterial communities at three sites with different WTs of the Zoige peatlands in the Qinghai-Tibetan Plateau. Using an n-damo bacterial specific 16S rRNA gene clone library, we obtained 25 operational taxonomic units (OTUs) that could be divided into Groups A, B, C, D and E (dominated by A and B). The dominant group was Group B at the high (OTU14 and OTU20) and intermediate (OTU7 and OTU8) WT sites and Group A was dominant at the low WT site (OTU6 and OTU5). Using high-throughput sequencing, we observed that n-damo bacteria mainly distributed in subsurface soils (50-60 and 20-30 cm), and their relative abundances were higher at the low WT site than at the other two sites. In addition, we found that pH and nitrate were positively correlated with Group A, while total organic carbon, total nitrogen and ammonia were positively associated with Group B. Our study provides new insights into our understanding of the response of n-damo bacteria to WT gradient in peatlands, with important implications for global change.

[Study on the antitussive and antiasthmatic effects of Radix Fici Hirtae].

OBJECTIVE: To observe the antitussive and antiasthmatic effects of Radix Fici Hirtae (RFH). METHODS: Antitussive effects were observed by ammonia water steaming test in mice and by citric acid test in guinea pigs. Antiasthmatic actions in guinea pigs were observed by histamine and acetylcholine ultrasonic atomization test, involved isolated guinea pig tracheal smoth muscle experiment and anaphylactic shock of guinea pigs. RESULTS: RFH decreased the frequency of cough induced by ammonia in mice and by citric acid in guinea pig, prolonged the latent period of cough and inhibited the experimental asthma by histamine and acetylcholine solution in conscious guinea pigs, antagonisted the contraction of tracheal smooth muscle by histamine phosphate in guinea pigs and could compete anaphylactic shock in guinea pigs. CONCLUSION: RFH has obvious antitussive and antiasthmatic effects.

Study of BDE-47 induced Parkinson's disease-like metabolic changes in C57BL/6 mice by integrated metabolomic, lipidomic and proteomic analysis.

As the predominant congener of polybrominated diphenyl ethers (PBDEs) detected in human serum, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) has been reported to induce neurotoxicity. However, the possible linkage between BDE-47 and typical neurodegenerative diseases such as Parkinson's disease (PD) is still unclear. Here we carried out omics studies using liquid chromatography-orbitrap mass spectrometry (LC-orbitrap MS) to depict the BDE-47 induced metabolic changes in C57BJ/L mice to explore the possible contribution of BDE-47 exposure to PD pathology. BDE-47 dissolved in corn oil was orally administered to mice for 30 consecutive days. Results of metabolomics and lipidomics studies of PD-related brain regions revealed significant metabolite changes in pathways involved in oxidative stress and neurotransmitter production. Moreover, isobaric tags for relative and absolute quantitation (iTRAQ) proteomics study of the striatum, which is the part of brain that is most intensively studied in PD pathogenesis, revealed that BDE-47 could induce neurotransmitter system disturbance, abnormal phosphorylation, mitochondrial dysfunction and oxidative stress. Overall, this study depicts the possible contribution of BDE-47 exposure to PD pathology and highlights the powerfulness of omics platforms to deepen the mechanistic understanding of environmental pollutant-caused toxicity.

Comparison of methane emissions among invasive and native mangrove species in Dongzhaigang, Hainan Island.

The strength of methane (CH4) source of mangroves is not well understood, especially when including all CH4 pathways in consideration. This study measured CH4 fluxes by five pathways (sediments, pneumatophores, water surface, leaves, and stems) from four typical mangrove forests, including Kandelia candel without pneumatophores and three species with pneumatophores: Sonneratia apetala, Laguncularia racemosa and Bruguiera gymnorhiza-Bruguiera sexangula. The CH4 fluxes from sediments were 4.82±1.46mgCH4m-2h-1 for K. candel and 1.36±0.17mgCH4m-2h-1 for the other three with pneumatophores. Among the three communities with pneumatophores, S. apetala community had significantly greater emission rate than the other two (P<0.05). Pneumatophores in S. apetala were found to significantly decrease CH4 emission from sediments (P<0.01), while those in B. gymnorhiza-B. sexangula were significantly increase it (P<0.05). CH4 fluxes from waters were 3.48±1.11mgCH4m-2h-1, with the highest emission rate in the K. candel community for the duck farming. Leaves of mangroves except for those of K. candel were a weak CH4 daytime sink, but stems were a weak source. The total 72ha of mangroves in the Changning river basin emitted about 8.10Gg CH4 per year, with a weighted emission rate of about 1.29mgCH4m-2h-1. Our results suggested that mangroves are only a small methane source to atmosphere with great contribution from sediments and waters, only slight contribution from leaves and stems. Pneumatophores of different mangrove species played different roles in CH4 fluxes from sediments.

Network pharmacology study reveals energy metabolism and apoptosis pathways-mediated cardioprotective effects of Shenqi Fuzheng.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng (SQ) is a renowned traditional Chinese medicine extracted from Radix Codonopsis and Radix Astragali. Although SQ is widely used to treat myocardial ischemia-reperfusion (I/R) injury, the molecular mechanisms supporting its clinical application remain elusive. AIM OF THE STUDY: The purpose of current study was to understand its cardioprotective effects at the molecular level using network pharmacology approach. MATERIALS AND METHOD: In an I/R injury animal model, the beneficial pharmacological activities of SQ were confirmed by decreased infarct range observed on drug treated rats versus control group. Additionally, several serum biochemical indicators were in concord with this observation. Subsequently, a microarray experiment was performed to reveal the influence on injured heart at the gene expression level by this TCM injection. We then proposed a network analysis algorithm NTRA to discover the key nodes based on both disease network structure and transcriptomics. Using NRIODN, a method developed by our group previously, the holistic changes on the gene network induced by for I/R injury and SQ treatment were evaluated. RESULTS: Pathway enrichment analysis of highly ranked genes by NTRA showed that PPAR and apoptosis pathways were highly related to I/R injury. Finally, western blot results showed increased level of the PPARα and BAX protein in the heart after injection treatment which confirmed the hypothesis. CONCLUSION: In conclusion, our results suggest that SQ injection exerts protective effect against myocardial ischemia-reperfusion injury through multiple pathways, including myocardial energy metabolism improvement, cell adhesion inhibition, inflammatory reaction perturbation, myocardial apoptosis reduction and ventricular remodeling avoidance.

Water table drawdown shapes the depth-dependent variations in prokaryotic diversity and structure in Zoige peatlands.

Microbial communities are important to ecosystem function and sensitive to hydrological dynamics. However, we lack predictable knowledge about how soil microorganisms respond to water table drawdown in different depths. This research used a high-throughput sequencing method to determine the responses of prokaryotic communities to the changes of water table and depth on Zoige peatlands. Our results showed that water table drawdown reduced alpha diversity indices (observed species, Shannon diversity and Chao1 richness) of prokaryotic communities. Intriguingly, the reduction of diversity varied in different depths, and was statistically significant in intermediate layers (20-30 cm and 50-60 cm), but not in the surface (0-10 cm) or deep layer (90-100 cm). In deeper layers there was greater relative abundance of most anaerobic microorganisms (e.g. Chloroflexi, Planctomyctes and NC10), but lesser amounts of most aerobes (e.g. Proteobacteria and Acidobacteria). However, the vertical distribution of prokaryotic microbiota along the depth gradient was altered by water table drawdown, mainly by enriching oligotrophs (e.g. Acidobcteria) over copiotrophs (e.g. Bacteriodetes). In addition, we found that the most important soil parameters influencing community structure were soil pH, total organic carbon and total nitrogen. Our study illuminates that the variations of prokaryotic communities caused by water table drawdown are depth-dependent, and that water table drawdown leads to predictive changes of microbiota in peatlands.