Translational research of adult stem cell therapy

Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

Ionic liquid-based transparent membrane-coupled human lung epithelium-on-a-chip demonstrating PM0.5 pollution effect under breathing mechanostress

The plausibility of human exposure to particulate matter(PM)has witnessed an increase within the last several years.PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition.As a regulator,the lung epithelium orchestrates the innate response to local damage.Herein,we developed a lung epithelium-ona-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin,flexible,and transparent ionic liquid-based poly(hydroxyethyl)methacrylate gel membrane.The epithelium was formed through the culture of human lung epithelial cells(Calu-3)on this membrane.The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system,which applied a uniaxial tensile strength from the two sides of the chip with 10%strain and a frequency of 0.2 Hz.Subsequently,the administration of silica nanoparticles(PM0.5)with an average size of 463 nm to the on-chip platform under static,dynamic,and dynamic+mechanical stress(DMS)conditions demonstrated the effect of environmental pollutants on lung epithelium.The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α,which indicated alterations in the epithelium.

Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

Photo-induced Bacillus subtilis-spore transformation for bowel disease therapy and therapeutic outcome visualization

Efficient strategies for transforming Bacillus subtilis vegetative cells into spores(BtS transformation)are still limited,although they show promise for the treatment of inflammatory bowel disease(IBD).A novel,simple,and rapid photo-induced BtS transformation mechanism is now presented that utilizes a novel aggregation-induced emission luminogen(AIEgen)photosensitizer,triphenylamine-benzothiadiazole-pyridine-p-tolylboronic acid bromine salt(TBPBB),that generates reactive oxygen species(ROS)when exposed to light.The ROS selectively target and damage the membranes of Bacillus subtilis and trigger their transformation into spores.These spores demonstrate considerable promise for the effective treatment of IBD in a mouse disease model.Furthermore,thefluorescence signal generated by TBPBB can be used to directly visualize the recovery of damaged intestinal tis-sue.This is a valuable tool for monitoring the healing process and gaining insights into therapeutic efficacy.This study highlights the remarkable practical value of AIEgen-induced BtS transformation for identifying,localizing,and visualizing the therapeutic outcomes of IBD treatments.

Insight into small eyes: a practical description from phenotypes presentations to the management

This narrative review aimed to have an algorithmic approach to microphthalmos by a systematic search.The definition can be related to a number of special phenotypes.In the more challenging cases of complex microphthalmos,relative anterior microphthalmos,and nanophthalmos,the surgeon can approach these cases more safely if they have a deep understanding of the anatomical variations and ideal formulae for intraocular lens computation and knows how to avoid intra-and post-operative complications.In this article,we review the criteria by which we recognize and describe pre-,intra-,and post-operative considerations,as well as discuss the ideal intraocular lenses for microphthalmos,given the intricate varieties of small eye phenotypes.

Ameliorative effects of Lactobacillus fermentum isolated from individuals following vegan, omnivorous and high-meat diets on ulcerative colitis in mice

Lactobacillus spp.can be beneficial for the prevention or treatment of ulcerative colitis(UC).In this study,153 participants who followed vegan,omnivorous,or high-meat diet were recruited.Compositional analysis of the Lactobacillus community in feces revealed that Lactobacillus fermentum strains were significantly affected by diet.Administration of mixed L.fermentum strains from vegans significantly improved inflammation compared to that from omnivores and high-meat consumers,as evidenced by a significant reduction in colonic tissue damage,improvement in inflammatory cytokines,enhanced expression of ZO-1,occludin,and claudin-3,and a significant increase in short chain fatty acids concentration.The effect of a single strain of L.fermentum was similar to that of a mixed strains of L.fermentum group.Genomic analysis suggested that L.fermentum strains from the guts of vegans possessed a higher prevalence of genes involved in carbohydrate catabolism than those from the guts of omnivores and high-meat eaters.In particular,the ME2 gene is involved in the biosynthesis of acetate,a compound considered to possess anti-inflammatory properties.In conclusion,this study indicates strain-specific differences in the ability of L.fermentum strains to alleviate UC in mice,influenced by habitual diets。

Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.

Alleviative effects of Bacillus coagulans strains on irritable bowel syndrome-unraveling strain specificity through physiological and genomic analysis

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.

Strain-specific effect of Streptococcus thermophilus consumption on host physiology

Streptococcus thermophilus is one of the most prevalent species in stool samples of westernized populations due to continuous exposure to fermented dairy products.However,few studies have explored the effect on host physiology by multiple S.thermophilus strains and considered the inter-strain differences in regulating host.In the present study,we investigated how four S.thermophilus strains influenced the gut microbiota,mucin changes,and host metabolism after 28 days of intervention in conventional mice.The results indicated that the consumption of S.thermophilus affected the host with strain specificity.Among four S.thermophilus strains,DYNDL13-4 and DQHXNQ38M61,especially DQHXNQ38M61,had more effect on host physiology by modulating gut microbiota and host metabolism than LMD9 and 4M6.Ingestion of strains DYNDL13-4 and DQHXNQ38M61 resulted in more remarkable changes in amino acid metabolism and lipid metabolism than that of strains LMD9 and 4M6,which may be related to the elevation of intestinal Bifidobacterium by DYNDL13-4 and DQHXNQ38M61.The enriched Coriobacteriaceae UCG-002,Rikenellaceae RC9 gut group,and Lactobacillus only in the DQHXNQ38M61 group,had a close relationship with the prominent effect of DQHXNQ38M61 on regulating amino acid and lipid metabolism.In addition,DQHXNQ38M61 had a strong influence on degrading colonic mucin fucose by decreasedα-fucosidase activity in feces,and improving mucin sulfation by upregulated Gal3ST2 expression.Comparative genomic analysis revealed that the four S.thermophilus strains belonged to different branches in the phylogenetic tree,and DYNDL13-4 and DQHXNQ38M61 had more genes involved in carbohydrate metabolism,amino acid metabolism,membrane transport,and signal transduction,which may confer the capacity of nutrient utilization and gastrointestinal adaptation of the strains and be associated with their strong regulation in host.Our study provides valuable information for understanding the regulation of host metabolism after consuming different S.thermophilus strains and could facilitate potential personalized applications of S.thermophilus based on strain varieties.

Effects of vitamin family members on insulin resistance and diabetes complications

The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Prevalence of retinal pathologies in people over 60 years:the Tehran Geriatrics Eye Study

AIM:To determine the prevalence of some retinal pathologies in people over 60y and their association with demographic and ocular factors.METHODS:A cross-sectional study was conducted in Tehran using multistage cluster sampling.After selecting subjects aged 60 and over,optometric,and ophthalmic examinations were done.For retinal examination,a 90 D lens was used and indirect ophthalmoscopy was performed after instilling tropicamide drops.Biometry was done using the IOL Master for all participants.RESULTS:Of 3791 people that were invited through cluster sampling,3310 participated in the study(response rate=82%).The prevalence of retinal pigmented epithelium(RPE)change,drusen,geographic atrophy(GA),hypertensive retinopathy(HTR),nonproliferative diabetic retinopathy(NPDR),proliferative diabetic retinopathy(PDR),choroidal neovascularization(CNV),central retinal artery occlusion(CRAO),myopic retinopathy(MR),branch retinal vein occlusion(BRVO),and central retinal vein occlusion(CRVO)was 27.42%,11.08%,4.52%,3.03%,4.05%,0.54%,0.82%,0.39%,0.20%,0.49%,and 0.19%,respectively.After removing the effect of age,the odds of NPDR were 1.68 times higher in women compared to men(P=0.014).After removing the effect of sex,the odds of drusen,RPE change,GA,CNV,BRVO,and CRVO increased with age.CONCLUSION:There is a higher prevalence of RPE change,drusen,GA,CNV and a lower prevalence of MR and CRAO in the elderly population of Tehran aged over 60y compared to global average values.Considering the correlation of most of the diseases with age and their effects on vision,attention should be paid to these diseases and the related screening programs to prevent vision impairment.

The circadian clock in enamel development

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli.Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown.Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms.Teeth enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during amelogenesis.This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis.Several physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and mineralization.Next,the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed.Circadian rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis imperfecta.Finally,future research trajectory in this field is extrapolated.It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Tumor organoids for cancer research and personalized medicine

Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer

Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Colorectal cancer(CRC)is the most common digestive malignancy across the world.Its first-line treatments applied in the routine clinical setting include surgery,chemotherapy,radiotherapy,targeted therapy,and immunotherapy.However,resistance to therapy has been identified as the major clinical challenge that fails the treatment method,leading to recurrence and distant metastasis.An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies,which can be summarized into two aspects:(1)The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism,drug transport,drug target,and the activation of signaling pathways;and(2)the suppressive features of the tumor microenvironment(TME).To combat the issue of therapeutic resistance,effective strategies are warranted with a focus on the restoration of CRC cells’sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions.To date,nanotechnology seems promising with scope for improvement of drug mobility,treatment efficacy,and reduction of systemic toxicity.The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity,as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence,metastasis,and reversion of therapy resistance.The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy,radiotherapy,immunotherapy,and targeted therapy,as well as the process of metastasis.We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone.In summary,nanomedicine is an emerging technology with potential for CRC treatment;hence,efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME.It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

Stachyose modulates gut microbiota and alleviates DSS-induced ulcerative colitis in mice

Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis(UC).The results indicated that the administration of stachyose could recover the body weight,protect against the colonic tissue damage,reduce the pro-inflammatory cytokines levels,and reverse the histological abnormalities in UC mice.Oral stachyose could restore dextran sulfate sodium(DSS)-induced disturbance in intestinal bacteria.Besides,the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice.Also,a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera.Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.

Probiotics supplementation for management of type Ⅱ diabetes risk factors in adults with polycystic ovarian syndrome: a meta-analysis of randomized clinical trial

This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome(PCOS).The meta-analysis was performed in accordance with the Cochrane Handbook guidelines and relevant the preferred reporting items for systematic reviews and meta-analyses(PRISMA)statement criteria.Of 825 identified reports,11 randomized clinical trials were included in the meta-analysis.An analysis of pooled extracted data revealed that supplementation with probiotics significantly decreased fasting blood glucose(FBG,n=7;standardized mean difference(SMD)=−0.40;95%confidence interval(CI):−2.02,−0.02;P=0.04)and insulin levels(n=6;SMD=−0.57;95%CI:−0.89,−0.25;P=0.0004)and the homeostatic model assessment of insulin resistance(n=7;SMD=−0.64;95%CI:−0.96,−0.31;P=0.0001)while increasing the quantitative insulin sensitivity check index(QUICKI,n=5;SMD=0.58;95%CI:0.08,1.09;P=0.02)in patients with PCOS.The FBG-reducing effect decreased as the baseline body mass index(BMI)and mean age of the participants increased.Indeed,a greater number of bacterial species and a higher bacterial dose were shown to reduce QUICKI effectively.The systematic review indicated that probiotic supplementation may help to control glucose homeostasis in adults with polycystic ovarian syndrome.