Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence.

BACKGROUND: Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of its action remains to be further clarified. PURPOSE: To investigate the underlying mechanisms of WMW in the treatment of chronic ulcerative colitis (UC) through network pharmacology and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform were used to identify the ingredients and potential targets of WMW. The microarray gene data GSE75214 datasets from GEO database was used to define UC-associated targets. Cytoscape3.7.2 was employed to construct the protein-protein interaction (PPI) network and compounds-disease targets network. GO enrichment analysis and KEGG pathway analysis were performed by R software for functional annotation. UPLC-TOF-MS/MS method was used to quantitatively analyze the active ingredients of WMW. For experimental validation, three cycles of 2% dextran sulfate sodium salt (DSS) were used to construct chronic colitis model. The hub targets and signal pathway were detected by qPCR, ELISA, western blotting , immunohistochemical and immunofluorescence. RESULTS: Through network analysis, 104 active ingredients were obtained from WMW, and 47 of these ingredients had potential targets for UC. A total of 41 potential targets of WMW and 13 hub targets were identified. KEGG analysis showed that WMW involved in advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, and luteolin of WMW were the more highly predictive components related to the AGE-RAGE signaling pathway. In vivo validation, WMW improved DSS-induced colitis, reduced the expression of inflammatory cytokines and chemokines. Notably, it significantly decreased the mRNA expression of Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr and Icam1, which were associated with angiogenesis. In addition, we confirmed WMW inhibited RAGE expression and diminished DSS-induced epithelial barrier alterations CONCLUSION: Our results initially demonstrated the effective components and the strong anti-angiogenic activity of WMW in experimental chronic colitis. Sufficient evidence of the satisfactory anti-colitis action of WMW was verified in this study, suggesting its potential as a quite prospective agent for the therapy of UC.

Genomic insights revealed the environmental adaptability of Planococcus halotolerans Y50 isolated from petroleum-contaminated soil on the Qinghai-Tibet Plateau.

The Tibetan Plateau niche provides unprecedented opportunities to find microbes that are functional and commercial significance. The present study investigated the physiological and genomic characteristics of Planococcus halotolerans Y50 that was isolated from a petroleum-contaminated soil sample from the Qinghai-Tibet Plateau, and it displayed psychrotolerant, antiradiation, and oil-degraded characteristics. Whole genome sequencing indicated that strain Y50 has a 3.52 Mb genome and 44.7% G + C content, and it possesses 3377 CDSs. The presence of a wide range of UV damage repair genes uvrX and uvsE, DNA repair genes radA and recN, superoxide dismutase, peroxiredoxin and dioxygenase genes provided the genomic basis for the adaptation of the plateau environment polluted by petroleum. Related experiments also verified that the Y50 strain could degrade n-alkanes from C11-C23, and approximately 30% of the total petroleum at 25 °C within 7 days. Meanwhile, strain Y50 could withstand 5 × 103 J/m2 UVC and 10 KGy gamma ray radiation, and it had strong antioxidant and high radical scavengers for superoxide anion, hydroxyl radical and DPPH. In addition, pan-genome analysis and horizontal gene transfers revealed that strains with different niches have obtained various genes through horizontal gene transfer in the process of evolution, and the more similar their geographical locations, the more similar their members are genetically and ecologically. In conclusion, P. halotolerans Y50 possesses high potential of applications in the bioremediation of alpine hydrocarbons contaminated environment.

A critical review on the relationship of herbal medicine, Akkermansia muciniphila, and human health.

There are trillions and trillions of microorganisms in the human gut, and these microorganisms and their metabolites are closely related to human health. Recent studies have found that the abundance of Akkermansia muciniphila is decreased in many diseases. Supplementation of A. muciniphila is used to treat many diseases, suggesting it as a probiotic. Herbal medicines are considered as valuable asset of traditional Chinese medicine. Recent studies have revealed traditional Chinese medicine as a potential prebiotic agent for the treatment of many diseases. Hence, in this review, we aimed to provide a plausible mechanistic basis for the interactions between herbal medicines and A. muciniphila, and therapeutic benefits on this interaction in various illnesses.

Planococcus lenghuensis sp. nov., an oil-degrading bacterium isolated from petroleum-contaminated soil.

A Gram-staining-positive and aerobic coccus with the ability to degrade petroleum bacterium, designated Y42T, was isolated from the Lenghu oil field located in the northern margin of the Qaidam Basin. Phylogenetic and signature nucleotides analyses revealed that strain Y42T belongs to the genus Planococcus. The multiple sequence alignments of 16S rRNA and housekeeping genes showed that strain Y42T formed a distinct lineage with the other Planococcus clade. The average nucleotide identity (ANI) and DNA-DNA hybridization values (DDH) between strain Y42T and the reference strains were 69.5-70.1 and 19.4-21.7%, respectively, which values were below the threshold for species delineation. The major fatty acids of strain Y42T were anteiso-C15:0. The respiratory quinone was MK-7 (71.8%) as the predominant menaquinone followed the MK-6 (28.2%) and the cell-wall hydrolysates contained LL-diaminopimelic acid. The polar lipid was composed of diphosphatidyl glycerol, phosphatidyl glycerol, phosphoglycolipid, aminophospholipid and four unidentified lipids. The peptidoglycan type was A4α (L-Lys-D-Glu). The strain Y42T possessed larger genome (approximately 4 MB) and revealed obvious differences for the abundance of the COG categories compared with the other Planococcus bacteria. Also, the strain Y42T also possessed more unique orthologous proteins. The structural characteristics of the strain Y42T genome provided a competitive advantage for better survival in petroleum-polluted environments. Combined with the 16S rRNA gene and genome sequence, phenotypic as well as chemotaxonomic characterisations, strain Y42T is considered to represent a novel species of the genus Planococcus, for which the name Planococcus lenghuensis sp. nov. be proposed. The type strain is Y42T (= CGMCC 1.15921T = JCM 32719T).

Comparison of two treatments on a covariate variable.

In clinical trials, the efficacy of treatment might be dependent on the value of a covariate variable. Therefore, it might be possible to detect the region over the covariate variable where the two treatments under investigation do not have significantly different efficacy or the region of superiority of one treatment. The non-significant region can be verified to be a confidence interval for the abscissa of the intersection point of two regression lines, and each of the complementary regions of the confidence interval corresponds to a region of superiority. In this study, we develop a method of constructing the confidence interval based on the concept of a generalized pivotal quantity, so as to perform the task of detecting the possible three regions for a clinical trial. Two real-world examples are given to illustrate the application of our proposed method, and a simulation study is conducted to evaluate its performance.

Wu Mei Wan attenuates CAC by regulating gut microbiota and the NF-kB/IL6-STAT3 signaling pathway.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality rate worldwide. Colitis-associated CRC (CAC) is used for describing the relationship between inflammation and CRC. No chemopreventive agents have been found to be both effective and safe in CRC. Therefore, the prevention and treatment of CAC are extremely urgent. Wu Mei Wan (WMW) has been used for the clinical treatment of enteritis with a remarkable efficacy. Here, we aim to investigate the underlying mechanism of WMW in the prevention of CAC. METHODS: The AOM/DSS-induced CAC mouse model was used, and the mice were divided into normal control (NC), AOM/DSS model control (MC), and AOM/DSS plus WMW (WMW). The weight of mice, the score of DAI, survival rate, number of tumors and sample collection were performed at the end of the 14th week. Histopathological examination was performed using Hematoxylin-Eosin (HE) staining. Tumor cell proliferation was indicated by the expression of PCNA, and p65 and p-STAT3 were detected by immunohistochemistry. Serum IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). The expression of p65, IL-6 and p-STAT3 in the colon was detected by Western Blot. Intestinal flora was analyzed by 16S rDNA sequencing. RESULTS: WMW improved the survival rate of mice in the MC group and also attenuated CAC symptoms such as abnormal clinical colitis and pathological changes to intestinal tissue by reducing DAI score, tumor formation, tumor volume, and grade of tumorigenesis. WMW also reduced the proliferation of tumor cells in colon tissues. WMW decreased the expression of p65, IL-6, and p-STAT3 in colon tumors of CAC mice. WMW decreased Bacteroidetes and increased Firmicutes at the phylum level, while decreasing bacteroidales_s24-7_group and increasing the number of Lachnospiraceae at the family level. CONCLUSION: WMW attenuates CAC by regulating the balance between "tumor-promoting bacteria" and "tumor-suppressing bacteria" and the NF-kB/IL-6/STAT3 pathway. WMW has the potential to be a safe and effective chemopreventive drug but further clinical evidence is necessary.

The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice.

BACKGROUND: Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. METHODS: The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. RESULTS: DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. CONCLUSIONS: DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

Characterization of the genome of a Nocardia strain isolated from soils in the Qinghai-Tibetan Plateau that specifically degrades crude oil and of this biodegradation.

A strain of Nocardia isolated from crude oil-contaminated soils in the Qinghai-Tibetan Plateau degrades nearly all components of crude oil. This strain was identified as Nocardia soli Y48, and its growth conditions were determined. Complete genome sequencing showed that N. soli Y48 has a 7.3 Mb genome and many genes responsible for hydrocarbon degradation, biosurfactant synthesis, emulsification and other hydrocarbon degradation-related metabolisms. Analysis of the clusters of orthologous groups (COGs) and genomic islands (GIs) revealed that Y48 has undergone significant gene transfer events to adapt to changing environmental conditions (crude oil contamination). The structural features of the genome might provide a competitive edge for the survival of N. soli Y48 in oil-polluted environments and reflect the adaptation of coexisting bacteria to distinct nutritional niches.

Degradation of crude oil by mixed cultures of bacteria isolated from the Qinghai-Tibet plateau and comparative analysis of metabolic mechanisms.

This study investigates the biodegradation of crude oil by a mixed culture of bacteria isolated from the Qinghai-Tibet plateau using gas chromatography-mass spectrometer (GC-MS) and the gravimetric method. The results showed that a mixed culture has a stronger ability to degrade hydrocarbon than pure cultures. Once both Nocardia soli Y48 and Rhodococcus erythropolis YF28-1 (8) were present in a culture, the culture demonstrated the highest crude oil removal efficiency of almost 100% after 10 days of incubation at 20 °C. Moreover, further analysis of the degradation mechanisms used by the above strains, which revealed utilization of different n-alkane substrates, indicated the diversity of evolution and variations in different strains, as well as the importance of multiple metabolic mechanisms for alkane degradation. Therefore, it is concluded that a mixed culture of Y48 and YF28-1 (8) strains can provide a more effective method for bioremediation of hydrocarbon-contaminated soil in permafrost regions.

Nocardia mangyaensis sp. nov., a novel actinomycete isolated from crude-oil-contaminated soil.

A Gram-stain-positive, aerobic, non-motile and mycolic-acid-containing strain, designated Y48T, was isolated from soil contaminated by crude oil located in the northern margin of the Qaidam Basin. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y48T belongs to the genus Nocardia and is closely related to N. cummidelens DSM 44490T (99.0 % similarity), N. soli DSM 44488T (99.0 %), N. lasii 3C-HV12T (98.9 %), N. salmonicida NBRC 13393T (98.6 %), N. ignorata NBRC 108230T (98.6 %) and N. coubleae NBRC 108252T (98.6 %). The average nucleotide identity and DNA-DNA hybridization values between strain Y48T and the reference strains were 75.9-84.5 and 27.5-29.0 %, respectively, values that were below the thresholds for species delineation. Chemotaxonomic analysis indicated that the major fatty acids of strain Y48T were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C18 : 1ω9c and C18 : 0 10-methyl (TBSA). The respiratory quinone was MK-8(H4, ω-cycl). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, two glycolipids and three unidentified lipids. The cell-wall hydrolysates contained meso-diaminopimelic acid, with ribose, arabinose, glucose and galactose as whole-cell sugars. A combination of 16S rRNA gene sequence analysis, and phenotypic and chemotaxonomic characterizations demonstrated that strain Y48T represents a novel species of the genus Nocardia, for which the name Nocardia mangyaensis sp. nov. is proposed. The type strain is Y48T (=JCM 32795T=CGMCC 4.7494T).

Diversity of crude oil-degrading bacteria and alkane hydroxylase (alkB) genes from the Qinghai-Tibet Plateau.

The aim of this study was to survey the response of the microbial community to crude oil and the diversity of alkane hydroxylase (alkB) genes in soil samples from the Qinghai-Tibet Plateau (QTP). The enrichment cultures and clone libraries were used. Finally, 53 isolates and 94 alkB sequences were obtained from 10 pristine soil samples after enrichment at 10 °C with crude oil as sole carbon source. The isolates fell into the phyla Proteobacteria, Actinobacteria, and Bacteroidetes, with the dominance of Pseudomonas and Acinetobacter. The composition of degraders was different from polar habitats where Acinetobacter sp. is not a predominant responder of alkane degradative microbial communities. Phylogenetic analysis showed that the alkB genes from isolates and enrichment communities formed eight clusters and mainly related with alkB genes of Pseudomonas, Rhodococcus, and Acinetobacter. The alkB gene diversity in the QTP was lower than marine environments and polar soil samples. In particular, a total of 10 isolates exhibiting vigorous growth with crude oil could detect no crude oil degradation-related gene sequences, such as alkB, P450, almA, ndoB, and xylE genes. The Shannon-Wiener index of the alkB clone libraries from the QTP ranged from 1.00 to 2.24 which is similar with polar pristine soil samples but lower than that of contaminated soils. These results indicated that the Pseudomonas, Acinetobacter, and Rhodococcus genera are the candidate for in situ bioremediation, and the environment of QTP may be still relatively uncontaminated by crude oil.

The effect of Chinese herbal medicine on hemorrhagic shock: A systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been widely used in the treatment of hemorrhagic shock (HS) in China. Many controlled trials have been undertaken to investigate its efficacy. OBJECTIVE: To evaluate the effectiveness and safety of CHM for Hemorrhagic Shock patients. METHODS: We screening the Web of ScienceDirect database, PubMed, the Cochrane Library, EMBASE, China Biomedical Database web (CBM), China National Knowledge Infrastructure (CNKI) and WanFang database (WF), from inception to January 2015. All the randomized controlled trials (RCTs) that compared CHM plus conventional therapy with conventional therapy alone for HS patients were included. Meta-analysis on included studies was performed using fixed-effects model with RevMan 5.2. Risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) was used as effect measure. STATA 12.0 was used for publication bias. RESULTS: Fifteen RCTs involving 1076 participants were included in the meta-analysis. CHM combined with conventional therapy was tested to be more effective in reduce mortality (RR=0.24, 95%CI:0.13-0.46, P<0.0001), reduce the incidence of MODS (RR=0.47, 95%CI: 0.34-0.66,P<0.00001), symptomatic improvement: increase blood pressure (BP) (MD=8.83, 95%CI:6.82-10.84,P<0.00001), regulate heart rate (MD=-7.6,95%CI:-9.17 to -6.02,P<0.00001), increase urine volume (MD=7.26, 95%CI:5.00-9.53, P<0.00001), compared with conventional therapy alone. No serious adverse events were reported. CONCLUSIONS: CHM combined with conventional therapy seems to be more effective on HS patients. However, the analysis results should be interpreted with caution due to the low methodological quality of the included trials. Future, the rigorously designed, high methodological quality, multicenter and large-scale trials are needed to confirm these conclusions.

Efficacy of Chinese Herbal Medicine as an Adjunctive Therapy on in-Hospital Mortality in Patients with Acute Kidney Injury: A Systematic Review and Meta-Analysis.

Objective. We aimed to systematically assess the efficacy of Chinese herbal medicine (CHM) as an adjunctive therapy on in-hospital mortality in patients with acute kidney injury (AKI). Methods. We did a systematic review of articles published in any language up until Jun 23, 2015, by searching PubMed, Embase, the Cochrane Library, CBM, and CNKI. We included all RCTs that compared outcomes of patients with AKI taking CHM plus Western treatment (WT) with those taking WT alone. We applied Cochrane risk-of-bias tool to assess the methodological quality of the included trials. Results. Of 832 citations, 15 studies involving 966 patients met inclusion criteria. The methodological quality was assessed with unclear risk of bias. In the primary outcome of meta-analysis, pooled outcome of in-hospital mortality showed that patients randomly assigned to CHM treatment group were associated with low risk of in-hospital mortality compared with those randomly assigned to WT alone (RR = 0.41; 95% CI = 0.24 to 0.71; P = 0.001). Conclusions. CHM as an adjunctive therapy is associated with a decreased risk of in-hospital mortality compared with WT in patients with AKI. Further studies with high quality and large sample size are needed to verify our conclusions.

Complete genome sequence of Acinetobacter sp. TTH0-4, a cold-active crude oil degrading strain isolated from Qinghai-Tibet Plateau.

Acinetobacter sp. strain TTH0-4 was isolated from a permafrost region in Qinghai-Tibet Plateau. With its capability to degrade crude oil at low temperature, 10°C, the strain could be an excellent candidate for the bioremediation of crude oil pollution in cold areas or at cold seasons. We sequenced and annotated the whole genome to serve as a basis for further elucidation of the genetic background of this promising strain, and provide opportunities for investigating the metabolic and regulatory mechanisms and optimizing the biodegradative activity in cold environment.

Effect of Combination of Chinese Herbal Medicine versus Western Medicine on Mortality in Patients after Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction. Although Chinese herbal medicine (CHM) treatment combined with conventional western therapy has been widely used and reported in many clinical trials in China, there is uncertainty about the efficacy of this combination in the treatment of patients after cardiopulmonary resuscitation (CPR). This systematic review aimed to assess whether the risk of mortality has decreased comparing the combination of CHM treatment with conventional western therapy. Methods. To identify relevant studies, the literature search was conducted in Medline, Embase, the Cochrane Library, CBM, CNKI, VIP, and Wanfang database. We included all randomized controlled trials (RCTs) that compared outcomes of patients after CPR taking combination of CHM treatment with those taking just conventional western therapy. Results. This meta-analysis showed that patients randomly assigned to combined CHM treatment group had a statistically significant 23% reduction in mortality compared with those randomly assigned to conventional western therapy group (RR: 0.77; 95% CI: 0.70-0.84). Conclusions. This meta-analysis provides evidence suggesting that a combined CHM therapy is associated with a decreased risk of mortality compared with conventional western therapy in patients after CPR. Further studies are needed to provide more evidence to prove or refute our conclusion and identify reasons for the reduction of mortality.

Calcinosis cutis complicated by compartment syndrome following extravasation of calcium gluconate in a neonate: a case report.

Hypocalcemia most frequently occurs in premature neonates. It is usually treated by intravenous (iv) calcium supplementation. However, complications caused by extravasation of iv calcium gluconate include localized soft tissue calcification, necrosis, cellulitis, osteomyelitis, and even compartment syndrome. We present a rare case of iatrogenic calcinosis cutis complicated by compartment syndrome secondary to extravasation of iv calcium gluconate in a neonate. Emergent fasciotomy was performed twice for decompression of compartment syndrome. Histologic findings revealed necrosis and calcification. Appropriate antibiotics were administered to control secondary infection. To the best of our knowledge, there were no previous case reports of calcinosis cutis with compartment syndrome in infants. Although iatrogenic calcinosis cutis is generally a benign entity, the early recognition of the presentation of extravasation of calcium gluconate is important to avoid severe complications and possible medical malpractice disputes. This report aims to raise doctors' awareness of the presentation, course, and management of this relatively rare iatrogenic complication.