Biology subjects

Chen, Y.-P.

Publications and source records attributed to Chen, Y.-P..

7 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

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

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↗

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↗