Biology subjects

Xu, Q.

Publications and source records attributed to Xu, Q..

17 recordsLinked to original sources

bioRxiv2018

Dietary sulfate-driven and gut dysbiosis-triggered breast cancer-related gene upregulation

By gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.

cancer biology↗

bioRxiv2018

Single-cell RNA-seq identifies a reversible epithelial-mesenchymal transition in abnormally specified epithelia of p63 EEC syndrome

Mutations in transcription factor p63 are associated with developmental disorders that manifest defects in stratified epithelia including the epidermis. The underlying cellular and molecular mechanism is however not yet understood. We established an epidermal commitment model using human induced pluripotent stem cells (iPSCs) and characterized differentiation defects of iPSCs derived from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome patients carrying p63 mutations. Transcriptome analyses revealed distinct step-wise cell fate transitions during epidermal commitment; from multipotent simple epithelium to basal stratified epithelia, and ultimately to the mature epidermal fate. Differentiation defects of EEC iPSCs caused by mutant p63 occurred during the specification switch from the simple epithelium to the basal stratified epithelial fate. Single-cell transcriptome and pseudotime analyses identified signatures of embryonic epithelial-mesenchymal transition (EMT) associated with the deviated commitment route of EEC iPSCs. Repressing mesodermal activation reversed the EMT and enhanced epidermal commitment. Our findings demonstrate that p63 is required for specification of stratified epithelia, probably by repressing embryonic EMT during epidermal commitment. This study provides insights into disease mechanisms underlying stratified epithelial defects caused by p63 mutations and suggests potential therapeutic strategies for the disease.\n\nSignificance statementMutations in p63 cause several developmental disorders with defects of epithelial related organs and tissues including the epidermis. Our study is to dissect the unknown cellular and molecular pathomechanism. We utilized human induced pluripotent stem cells (iPSCs) derived from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome patients carrying p63 mutations and studied transcriptome changes during differentiation of these cells to epidermal cells. Our analyses showed that the specification of the proper epithelial cell fate was affected by p63 EEC mutations, with an abnormal embryonic epithelial-mesenchymal transition (EMT). Repressing mesodermal activation reversed the EMT and enhanced epidermal commitment. This study provides insights into disease mechanisms associated with p63 mutations and suggests potential therapeutic strategies.

developmental biology↗

bioRxiv2018

Spring mineral water-borne bacteria reshape gut microbiota profiles and confer health benefits

BackgroundAlthough dietary patterns are recognized to affect health by interfering with gut microbiota homeostasis, whether live or dead bacteria-bearing spring mineral water (MW) would also exert beneficial effects on health upon curing gut dysbiosis remains unknown.\n\nResultsDue to harboring live bacteria, the heated but unboiled MW from Bama, where centenarians are ubiquitously inhabited, reshapes the gut microbiota from a traveler-type to a local resident-type except for Prevotella. While chondroitin sulfate, a component occurring in livestock and poultry meats, increases the richness of sulfatase-secreting bacteria and sulfate-reducing bacteria, Bama MW dampens the overgrowth of those colon-thinning bacteria and hampers the overexpression of multiple genes responsible for anti-inflammation, anti-oxidation, anti-hypoxia, anti-mutagenesis, and anti-tumorigenesis.\n\nConclusionsBama spring MW prevents the early-phase onset of breast cancer by curating gut dysbiosis. MW also compromises chromosomal DNA damage and ameliorate mitochondrial dysfunctions, implying it may extend lifespan.

microbiology↗

bioRxiv2018

Reversal of microRNA-blocked tumor suppressors by biphenyl- dicarboxylate impedes endotoxin-induced hepatic hyperplasia

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor and the leading cause of cancer-related death worldwide. Biphenyldicarboxylate (BPDC), an intermediate of schisandrin C from Schisandra chinensis, has been used as a hepatoprotective agent that compromises hepatic injuries in China for decades. Whether BPDC is also implicated in the prevention of HCC remains understood. Here, we report that the bacterial endotoxin lipopolysaccharide (LPS) promotes hepatic inflammation and hyperplasia, during which the common tumor markers, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), were unregulated, whereas the tumor suppressors, PTEN, FOXO1 and MEN1, were downregulated through increasing the microRNAs, miR-21, miR-122 and miR-24. In contrast, BPDC dampened hepatic inflammation and hyperplasia accompanied by the upregulation of PTEN, FOXO1 and MEN1 through decreasing miR-21, miR-122 and miR-24. However, BPDC failed to downregulate the tumor marker AEG-1 via increasing miR-195. Taken together, BPDC exerts anti-tumor effects by upregulating tumor suppressors upon decreases of miRNAs rather than downregulating tumor markers by increases of miRNAs.

cancer biology↗

bioRxiv2018

Short-hairpin RNA-guided single gene knockdown reverses triple-negative breast cancer

BackgroundThe origin of breast cancer remains poorly understood. Here, we testify a putative mechanism of \"breast cancer origin from inducible nitric oxide synthase (iNOS) activation and oestrogen receptor alpha (ER) inactivation\", which are classified as the essential outcomes of chronic inflammatory responses.\n\nMethodsTo reverse breast cancer status, iNOS was downregulated by short-hairpin RNA (shRNA)-guided NOS2 knockdown from human triple-negative breast cancer (TNBC) cells. To re-enact breast cancer origin, ER was downregulated by shRNA-directed ESR1 knockdown in human mammary epithelial cells.\n\nResultsUpon NOS2 knockdown from HCC1937 cells, the specific TNBC transcription factor genes, RUNX1 and BCL11A, were downregulated, hypoxia was compromised, Warburg effects were attenuated, and tumourigenic proliferation was halted, accompanied by an increase in the tumour marker cyclin D1 (CD1) and a decrease in the tumour suppressor cyclin-dependent kinase inhibitor (CKI). In contrast, ESR1 knockdown from MCF-10A cells led to upregulated BCL11A and RUNX1 expression, augmented hypoxic responses, pronounced Warburg effects, and enhanced PI3K/Akt/mTOR signalling, together with low levels of CD1 and high levels of CKI induction.\n\nConclusionsBreast cancer should originate from inflammatory signalling, during which iNOS activation and ER inactivation elicit hypoxia, oxidation, mitochondrial dysfunction, and breast cancer-like hyperplasia, demonstrating that iNOS inhibitors and ER activators represent promising candidate prodrugs enabling breast cancer prevention in the early stage.

cancer biology↗

bioRxiv2018

An improved high-quality genome assembly and annotation of Qingke, Tibetan hulless barley

BackgroundThe Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called \"Qingke\" in Chinese and \"Ne\" in Tibetan, is the staple food for Tibetans and an important livestock feed in the Tibetan Plateau. The Tibetan hulless barley in China has about 3500 years of cultivation history, mainly produced in Tibet, Qinghai, Sichuan, Yunnan and other areas. In addition, Tibetan hulless barley has rich nutritional value and outstanding health effects, including the beta glucan, dietary fiber, amylopectin, the contents of trace elements, which are higher than any other cereal crops.\n\nFindingsHere, we reported an improved high-quality assembly of Tibetan hulless barley genome with 4.0 Gb in size. We employed the falcon assembly package, scaffolding and error correction tools to finish improvement using PacBio long reads sequencing technology, with contig and scaffold N50 lengths of 1.563Mb and 4.006Mb, respectively, representing more continuous than the original Tibetan hulless barley genome nearly two orders of magnitude. We also re-annotated the new assembly, and reported 61,303 stringent confident putative protein-coding genes, of which 40,457 is HC genes. We have developed a new Tibetan hulless barley genome database (THBGD) to download and use friendly, as well as to better manage the information of the Tibetan hulless barley genetic resources.\n\nConclusionsThe availability of new Tibetan hulless barley genome and annotations will take the genetics of Tibetan hulless barley to a new level and will greatly simplify the breeders effort. It will also enrich the granary of the Tibetan people.

genomics↗

bioRxiv2018

Application of clinical genomic sequencing among Chinese advanced cancer patients to guide precision medicine decisions

PurposeA number of studies have suggested that high-throughput genomic analyses might improve the outcomes of cancer patients. However, whether integrative information about genomic sequencing and related clinical interpretation may benefit Chinese cancer patients with stage IV disease to date has not investigated.\n\nMethodsTargeted gene panel and whole exome of tumor/blood samples in > 1,000 Chinese cancer patients were sequenced. Then we provided patients and their oncologists with the sequencing results and a clinical recommendation roadmap based on evidence-based medicine, defined as CWES. Only patients with stage IV disease who failed the previous treatment upon receiving the CWES reports were included for analyzing the impact of CWES on clinical outcomes in 1-year follow-ups.\n\nResultsWe identified the mutational signatures of 953 Chinese cancer patients, with some being unique. Approximately 88.6% of patients had clinically actionable somatic genomic alterations. We successfully followed up 22 stage IV patients. Of these, 11 patients treatment followed the CWES reports defined as group A. Eleven patients received the next treatment, but did not follow the CWES suggestions, and are defined as group B. The types of therapies before CWES were similar in the two groups. The median PFS of group A was 12 months and 45% patients failed this round of therapy. The median PFS of group B was 4 months and 91% of patients failed the treatment.\n\nConclusionThe current study suggested that CWES has the potential to help explore the clinical benefits in multiple line therapies among advanced stage tumor patients.

cancer biology↗

bioRxiv2018

Comprehensive analysis of potential immunotherapy genomic biomarkers in 1,000 Chinese patients with cancer

BackgroundTumor mutation burden (TMB), DNA mismatch repair deficiency (dMMR), microsatellite instability (MSI), and PD-L1 amplification (PD-L1 AMP) may predict the efficacy of PD-1/PD-L1 blockade. In this study, we aimed to characterize the distributions of these biomarkers in over 1,000 Chinese patients with cancer.\n\nMethodsTMB, MSI, dMMR, and PD-L1 AMP were determined based on whole-exome sequencing of tumor/blood samples from > 1,000 Chinese patients with cancer.\n\nResultsIncidence rates among 953 Chinese patients with cancer showing high TMB (TMB-H), high MSI (MSI-H), dMMR and PD-L1 AMP were 35%, 4%, 0.53% and 3.79%, respectively. We found higher rates of TMB-H among hepatocellular carcinoma, breast cancer, and esophageal cancer patients than was reported for The Cancer Genome Atlas data. Lung cancer patients with EGFR mutations had significantly lower TMB values than those with wild-type EGFR, and increased TMB was significantly associated with dMMR in colorectal cancer (CRC). The frequency of tumors with MSI-H was highest in CRC (14%) and gastric cancer (4%). PD-L1 AMP occurred most frequently in lung squamous cell carcinoma (14.3%) and HER2-positive breast cancer (8.8%). Most MSI-H and dMMR cases exhibited TMB-H, but the overlap among the other biomarkers was low.\n\nConclusionWhile MSI and dMMR are associated with higher mutational loads, correlations between TMB-H and other biomarkers, between MSI-H and dMMR, and between PD-L1 AMP and other biomarkers were low, indicating different underlying causes of the four biomarkers. Thus, it is recommended that all four biomarkers be assessed for certain cancers before administration of PD-1/PD-L1 blockade treatment.

cancer biology↗

bioRxiv2018

Eradication of ENO1-deleted Glioblastoma through Collateral Lethality

Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We recently demonstrated that SF2312, a natural product phosphonate antibiotic, is a potent inhibitor of the glycolytic enzyme Enolase with potential utility for the collateral lethality-based treatment of Enolase-deficient glioblastoma (GBM). However, phosphonates are anionic at physiological pH, limiting cell and tissue permeability. Here, we show that addition of pivaloyloxymethyl (POM) groups to SF2312 (POMSF) dramatically increases potency, leading to inhibition of glycolysis and killing of ENO1-deleted glioma cells in the low nM range. But the utility of POMSF in vivo is dose-limited by severe hemolytic anemia. A derivative, POMHEX, shows equipotency to POMSF without inducing hemolytic anemia. POMHEX can eradicate intracranial orthotopic ENO1-deleted tumors, despite sub-optimal pharmacokinetic properties. Taken together, our data provide in vivo proof-of-principal for collateral lethality in precision oncology and showcase POMHEX as a useful molecule for the study of glycolysis in cancer metabolism.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC=\"FIGDIR/small/331538_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (20K):\norg.highwire.dtl.DTLVardef@1b78ebcorg.highwire.dtl.DTLVardef@1fc0ccforg.highwire.dtl.DTLVardef@ad268corg.highwire.dtl.DTLVardef@1bdee32_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2018

The MarR Family Regulator BmrR is involved in Bile Tolerance of Bifidobacterium longum BBMN68 via Controlling the Expression of an ABC-Transporter

In order to colonize the human gastrointestinal tract and exert their beneficial effects, bifidobacteria must effectively cope with the toxic bile salts in the intestine, but the molecular mechanism underlying bile tolerance is poorly understood. In this study, heterologous expression of a MarR family transcriptional regulator BmrR significantly reduced ox-bile resistance of Lactococcus lactis NZ9000, suggesting that it might play a role in bile stress response. In silico analysis combined with RT-PCR assay demonstrated that bmrR was co-transcribed with bmrA and bmrB, which encoded multidrug resistance (MDR) ABC transporters. Promoter prediction and EMSA assay revealed that BmrR could autoregulate the bmrRAB operon by binding to bmr box (ATTGTTG-6nt-CAACAAT) in the promoter region. Moreover, heterologous expression of bmrA and bmrB in L. lactis showed 20.77-fold higher tolerance to 0.10% ox-bile compared to wild type strain. In addition, ox-bile could disrupt the DNA binding activity of BmrR as a ligand. Taken together, our findings indicate that bmrRAB operon is autoregulated by transcriptional regulator BmrR and ox-bile serves as an inducer to activate the bile efflux transporter BmrAB in response to bile stress in B. longum BBMN68.\n\nImportanceBifidobacteria are natural inhabitants of the human intestinal tract. Some bifidobacterial strains are used as probiotics in fermented dairy production because of their health-promoting effects. Following consumption, bifidobacteria finally colonize the lower intestinal tract where the concentration of bile salts remains nearly 0.05% to 2.0%. Bile salts as detergent-like antimicrobial compounds can cause disruption of the cellular membrane, protein misfolding and DNA damage. Therefore, tolerance to physiological bile stress is indeed essential for bifidobacteria to survive and exert the probiotic effects in gastrointestinal tract. In B. longum BBMN68, the MarR-type regulator BmrR was involved in bile stress response by auto-regulating bmrRAB operon and ox-bile as an inducer could increase the expression of BmrAB transporter to enhance the bile tolerance of BBMN68.This is the first report about functional analysis of bmrRAB operon in bile stress response, which will provide new insight into bile tolerance mechanisms in Bifidobacterium and other bacteria.

microbiology↗

bioRxiv2018

Profiling copy number alterations in cell-free tumour DNA using a single-reference

BackgroundThe accurate detection of copy number alterations from the analysis of circulating cell free tumour DNA (ctDNA) in blood is essential to realising the potential of liquid biopsies. However, currently available approaches require a large number of plasma samples from healthy individuals, sequenced using the same platform and protocols to act as a reference panel. Obtaining this reference panel can be challenging, prohibitively expensive and limits the ability to migrate to improved sequencing platforms and improved protocols.\n\nMethodsWe developed qCNV and sCNA-seq, two distinct tools that together provide a new approach for profiling somatic copy number alterations (sCNA) through the analysis of cell free DNA (cfDNA) without a reference panel. Our approach was designed to identify sCNA from cfDNA through the analysis of a single plasma sample and a matched normal DNA sample -both of which can be obtained from the same blood draw. qCNV is an efficient method for extracting read-depth from BAM files and sCNA-seq is a method that uses a probabilistic model of read depth to infer the copy number segmentation of the tumour. We compared the results from our pipeline to the established copy number profile of a cell-line, as well as the results from the plasma-Seq analysis of cfDNA-like mixtures and real, clinical data-sets.\n\nResultsWith a single, unmatched, germline reference sample, our pipeline recapitulated the known copy number profile of a cell-line and demonstrated similar results to those obtained from plasma-Seq. With less than 1X genome coverage, our approach identified clinically relevant sCNA in samples with as little as 20 % tumour DNA. When applied to plasma samples from cancer patients, our pipeline identified clinically significant mutations.\n\nConclusionsThese results show it is possible to identify therapeutically-relevant copy number mutations from plasma samples without the need to generate a reference panel from a large number of healthy individuals. Together with the range of sequencing platforms supported by our qCNV+sCNA-Seq pipeline, as well as the Galaxy implementation of this solution, this pipeline makes cfDNA profiling more accessible and makes it easier to identify sCNA from the plasma of cancer patients.

bioinformatics↗

bioRxiv2018

Study on tumor cell RNA cross-anticancer mechanism in non-tumor mice experimental model

To report the experiments of fractal structure and self-similar function in biological coupled oscillation brings life system waving growth in life organism. At the same time by self-organization the system openness come into being to maintain stability features of growth survival. From this, the orderly oscillation of tumor cell RNA was recognized that this process could lead to system sequentiality openness. According to waving growth of basic research the procedure could be sure to turn into a model as out of control of growing in tumor. Then in complete contrast that derived from the same component which have cross resistance effect. It shows that its biological behavior is converted as only a single physical power to play action by inactivated processing. Subsequent further confirms the essential roles whether essential roles link up with recovery of physiological function. The result in that it could exhibit feature of anticancer owing to be endowed tissue embryonization response. So that it also exerts preventing on senile chronic diseases. In theory, the concept of this tissue response in life organism closely link up with the single physical power of RNA component so as to bring up specific procedure of growing and subsisting that deal with keeping life vigor generalized explanatory.

cancer biology↗

bioRxiv2017

Human macrophages survive and adopt activated genotypes in living zebrafish

The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer and neurodegenerative disorders. Here, we sought a model to interrogate human immune behavior in vivo. We determined that primary human monocytes and macrophages survive in zebrafish for up to two weeks. Flow cytometry revealed that human monocytes cultured at the physiological temperature of the zebrafish survive and differentiate comparable to cohorts cultured at human physiological temperature. Moreover, key genes that encode for proteins that play a role in tissue remodeling were also expressed. Human cells migrated within multiple tissues at speeds comparable to zebrafish macrophages. Analysis of gene expression of in vivo educated human macrophages confirmed expression of activated macrophage phenotypes. Here, human cells adopted phenotypes relevant to cancer progression, suggesting that we can define the real time immune modulation of human tumor cells during the establishment of a metastatic lesion in zebrafish.

developmental biology↗

bioRxiv2017

Insulin Does Not Augment In Vitro Tumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner

BackgroundWhether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).\n\nMethodology/Principle FindingsWe cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated by NOS2 knockdown.\n\nConclusions/SignificanceCellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.

cancer biology↗

bioRxiv2017

Artemisinin mimics nitric oxide to reduce adipose weight by targeting mitochondrial complexes

It remains obscure how to medically manage visceral obesity that predisposes metabolic disorders. Here, we show for the first time that a trace amount of artemisinin (0.25 mg/kg) reduces adipose weight in an inflammatory obese mouse model induced by a high-fat diet with lipopolysaccharide (HFD+LPS). HFD+LPS trigger pro-inflammatory responses, upregulate NOS2 expression, elicit potent nitric oxide (NO) burst, and reinforce adipose mitochondrial dysfunctions that facilitate adipogenesis for visceral weight gain. By targeting mitochondrial complexes, artemisinin resembles the NO donor nitroglycerin to exert anti-inflammatory effects, downregulate NOS2 expression, maintain stable NO release, and augment adipose mitochondrial functions that necessitate adipolysis for visceral weight loss. Taken together, artemisinin plays adipose weight-reducing roles by rectifying inflammation-driven mitochondrial dysfunctions.

pharmacology and toxicology↗

bioRxiv2017

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

BackgroundAn interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.\n\nResultsA metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor (TNF-) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.\n\nConclusionsCS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

pathology↗

bioRxiv2017

Chondroitin sulfate elicits systemic pathogenesis in mice by interfering with gut microbiota homeostasis

Whether chondroitin sulfate (CS), a common ingredient naturally occurring in livestock and poultry products, improves osteoarthritis remains debating. Here, we show for the first time that CS induces steatogenesis, atherogenesis, and dementia-like pathogenesis in mice. Gut microbiome analysis revealed the sulfatase-secreting bacteria Rikenella and the sulfate-reducing bacteria Desulfovibrio are enriched. Surprisingly, berberine use boosts CS-induced multi-loci inflammatory manifestations by further increasing the abundance of Rikenella and Desulfovibrio, whereas cephalosporin reinforces the colon mucus barrier via flourishing Akkermansia muciniphila and upregulating mucin expression. Mechanistically, berberine aggravates mucus lining injury by prompting mucin degradation, endotoxin leakage, neutralizing antibody induction, pro-inflammatory cytokine burst, lactic acid accumulation and energy currency depletion in multiple organs and tissues. Taken together, CS evokes the early-phase pathogenesis toward steatohepatitis, atherosclerosis, and dementia upon augmenting gut opportunistic infection, and a sustained antibiotic monotherapy does not deprive the risk of CS-driven systemic inflammatory disorders.

pharmacology and toxicology↗