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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological *** intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune *** disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health *** is an urgent need for novel interventions to reduce CRC incidence and improve clinical *** the intestinal microbiota has emerged as a promising approach for CRC prevention and *** research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical *** paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of *** underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune *** paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and *** all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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Sexual dimorphism of G protein-coupled receptor signaling in the brain

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Neural Regeneration Research 2024年第8期19卷 1635-1636页

作者： Sara Aljoudi Hamdan Hamdan Khaled S.Abd-Elrahman Department of Physiology and Immunology College of Medicine and Health SciencesKhalifa UniversityAbu DhabiUnited Arab Emirates healthcare Engineering Innovation Center(HEIC) Khalifa UniversityAbu DhabiUnited Arab Emirates Department of Anesthesiology Pharmacology and Therapeuticsand Djavad Mowafaghian Center for Brain HealthUniversity of British ColumbiaVancouverBCCanada Department of Pharmacology and therapeutics College of Medicine and Health ScienceKhalifa UniversityAbu DhabiUnited Arab Emirates Department of Pharmacology and Toxicology Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by *** and Drug Administration-approved *** of the preclinical research to understand the pharmacology of... 详细信息

关键词： drugs clinical targeted

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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： Courtney J.Rouse Victoria N.Jensen Coy D.Heldermon Lacerta therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

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An Extensive Review of Vitiligo-Associated Conditions

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International Journal of Dermatology and Venereology 2024年第1期7卷 44-51页

作者： Madhavi Premkumar Iyshwarya Bhaskar Kalarani Vajagathali Mohammed Ramakrishnan Veerabathiran human Cytogenetics and Genomics Laboratory Faculty of Allied Health SciencesChettinad Hospital and Research InstituteChettinad Academy of Research and EducationKelambakkamTamil Nadu 603103India

Vitiligo is an autoimmune disorder caused by the destruction of melanocytes in various body *** diseases may accompany *** prevalence of vitiligo varies among geographical regions and shows no relation to sex or ***,vitiligo most commonly affects people aged 10 to 30 *** clinical symptoms of vitiligo include irregular patches on the skin and various diseases associated with this *** present review focuses on the clinical effects and risk factors of vitiligo-associated conditions and the current therapeutics for treating *** systematic review was performed based on the PRISMA guidelines and articles published from 2000 to 2023 in Web of Science,PubMed,PsycINFO,and *** most clinically significant diseases associated with vitiligo are alopecia areata,autoimmune thyroid disease,Addison disease,and type 1 diabetes *** targeted population is specifically prone to vitiligo;it does not affect any particular race or ***,awareness of the diseases associated with vitiligo is necessary to control them through various medical and surgical treatments with the proper facilities.

关键词： vitiligo autoimmune disorder melanocyte Addison disease atopic dermatitis

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Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

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World Journal of Gastroenterology 2024年第22期30卷 2923-2926页

作者： Marwan SM Al-Nimer Department of therapeutics and Clinical Pharmacology College of MedicineUniversity of DiyalaBaqubah 32001Iraq

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of *** has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those *** is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD *** addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental ***,irisin produces changes in the diversity of the ***,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

关键词： Irisin Inflammatory bowel disease Physical activity Myokines Prognostic marker

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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in human health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in human health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery Research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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NLRP3 inflammasome plays a vital role in the pathogenesis of age-related diseases in the eye and brain

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Neural Regeneration Research 2024年第7期19卷 1425-1426页

作者： Jack Jonathan Maran Odunayo Omolola Mugisho Buchanan Ocular therapeutics Unit Department of OphthalmologyNew Zealand National Eye CentreUniversity of AucklandAucklandNew Zealand

Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular *** of the NLRP3 inflammasome appears to be a common denominator in the pathogenesis of age-related diseases of the eye and *** inhibition of the NLRP3 inflammasome may be a potent therapy for preventing the development and progression of age-related eye and brain diseases.

关键词： NLRP3 pathogenesis inflam

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Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA Department of Molecular Pharmacology and therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver Diseases Columbia UniversityNew YorkNY 10032USA Center for human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity

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