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Skin neuropathy and immunomodulation in diseases

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Fundamental Research 2024年第2期4卷 218-225页

作者： Manze Zhang Tingting Liu Jing Yang department of Biology Stanford UniversityStanfordCA 94305USA department of biochemistry Weill Cornell Medical CollegeNew YorkNY 10065USA IDG/McGovern Institute for Brain Research Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China Peking University Third Hospital Cancer Center Beijing 100191China

Skin is a vital barrier tissue of the *** responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic *** evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin ***,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological *** in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic ***,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.

关键词： Skin Neuropathy Neuroimmune Psoriasis Atopic dermatitis Pathogenic infection

The gasdermin family:emerging therapeutic targets in diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1905-1937页

作者： Chenglong Zhu Sheng Xu Ruoyu Jiang Yizhi Yu Jinjun Bian Zui Zou Faculty of Anesthesiology Changhai HospitalNaval Medical UniversityShanghai 200433China School of Anesthesiology Naval Medical UniversityShanghai 200433China National Key Laboratory of Immunity&Inflammation Naval Medical UniversityShanghai 200433China d 4 department of biochemistry and Molecular Biology College of Basic Medical SciencesNaval Medical UniversityShanghai 200433China

The gasdermin(GSDM)family has garnered significant attention for its pivotal role in immunity and disease as a key player in *** recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization,pyroptosis,and the follow-up inflammatory response,which are crucial self-defense mechanisms against irritants and *** have been implicated in a range of diseases including,but not limited to,sepsis,viral infections,and cancer,either through involvement in pyroptosis or independently of this *** regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various *** strategies for inhibiting GSDMD primarily involve binding to GSDMD,blocking GSDMD cleavage or inhibiting GSDMD-N-terminal(NT)oligomerization,albeit with some off-target *** this review,we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis,elucidate the activation mechanisms of GSDMs,explore their associations with a range of diseases,and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

关键词： diseases therapeutic immunity

Internal m^(6)A and m^(7)G RNA modifications in hematopoietic system and acute myeloid leukemia

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Chinese Medical Journal 2024年第9期137卷 1033-1043页

作者： Xiaoxu Zhang Yanni Ma Jia Yu Rui Su Xiaoshuang Wang State Key Laboratory of Common Mechanism Research for Major Diseases State Key Laboratory for ComplexSevereand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100005China department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA The Institute of Blood Transfusion Chinese Academy of Medical Sciences/Peking Union Medical CollegeChengduSichuan 610052China Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China department of biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China

Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene *** past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications,as prompted by the emergence of potent analytical *** hematopoietic system provides a lifelong supply of blood cells,and gene expression is tightly controlled during the differentiation of hematopoietic stem cells(HSCs).The dysregulation of gene expression during hematopoiesis may lead to severe disorders,including acute myeloid leukemia(AML).Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis,which has led to the development of small-molecule inhibitors that target N6-methyladenosine(m^(6)A)modification machinery as ***,we summarize the latest findings and our most up-to-date information on the roles of m^(6)A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic ***,we will discuss the therapeutic potential and limitations of cancer treatments targeting m^(6)A.

关键词： N6-methyladenosine N7-methylguanine Hematopoiesis Acute myeloid leukemia Therapeutic target RNA modifications

Genetic Variability and Phenotypic Correlations Study among Grain Quality Traits and Mineral Elements Concentrations in Colored and Non-Colored Rice (Oryza sativa L.)

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1733-1748页

作者： Adel A.Rezk Mohamed M.El-Malky Heba I.Mohamed Hossam S.El-Beltagi Agricultural Biotechnology department College of Agricultural and Food ScienceKing Faisal UniversityAl-Ahsa31982Saudi Arabia Plant Pathology Research Institute Agriculture Research CenterGiza12619Egypt Rice Research and Training Center Field Crop Research InstituteAgriculture Research Center33717Egypt Biological and Geological Sciences department Faculty of EducationAin Shams UniversityCairo11511Egypt biochemistry department Faculty of AgricultureCairo UniversityGiza12613Egypt

Twenty-four rice genotypes were examined to assess genetic variability,heritability,and correlations for seven-grain quality traits,eight nutritional elements,and *** revealed signiﬁcant differences for the quality traits *** every trait under study,the phenotypic coefﬁcient of variation was higher than the correspon-dence genotypic coefﬁcient of *** in a broad sense varied from 29.75%for grain length to 98.31%for the elongation *** percentage recovery had a highly signiﬁcant positive correlation with milling and head rice ***,milling percentage had a highly positive correlation with head rice *** amylose percentage,all the genotypes belonged to low amylose except the Hassawi-1 variety,which had intermediate amylose *** nutrition contents of magnesium(Mg),sodium(Na),potas-sium(K),calcium(Ca),copper(Cu),manganese(Mn),zinc(Zn),iron(Fe),or protein percentage gave different variations for 24 rice genotypes under all the nutritional *** the 24 genotypes,ten rice genotypes–HighNutrient-1,HighNutrient-2,HighNutrient-9,HighNutrient-8,HighNutrient-3,Hassawi-2,HighNutrient-7,HighNutrient-6,Hassawi-1,and HighNutrient-4–had the highest heist value for all nutritional and protein con-tents,and could be used as a donor to improving new *** was a positive and signiﬁcant correlation between magnesium Mg,K,Zn and ***,K had a positive correlation with zinc Zn,Fe,and protein *** analysis was divided into two groups:theﬁrst group included all genotypes rich in nutri-ents,while the remaining genotypes with low nutritional content were included in the second group.

关键词： Amylose cluster analysis genotypes grain quality mineral nutrition rice

Managing type 2 diabetes:targeting a microbial enzyme as a novel treatment option

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Signal Transduction and Targeted Therapy 2024年第1期9卷 3-5页

作者： Anikó Keller-Pintér Tamás Korcsmáros Tibor Vellai department of biochemistry Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged6720Hungary department of Metabolism Digestion and ReproductionImperial College LondonLondonW120NNUK Quadram Institute Bioscience Norwich Research ParkNorwichNR47UQUK department of Genetics Eötvös Loránd University(ELTE)Budapest1117Hungary Hungarian Research Network HUN-REN-ELTE Genetics Research Group Budapest1117Hungary

In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.

关键词： homeostasis stimulating clinical

Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua S.Fleishman Sunil Kumar department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

Elucidating the anti-obesity phytochemicals in Chenpi and their molecular mechanisms

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Food Science and Human Wellness 2024年

作者： Jinhai Luo Weiqi Yan Zhi Chen Baojun Xu Guangdong Provincial Key Laboratory IRADS and department of Life Sciences BNU-HKBU United International college Centre for Cancer and Inflammation Research School of Chinese Medicine Hong Kong Baptist University Faculty of biochemistry and Molecular Medicine University of Oulu

Obesity has become a significant global public health issue. Previous studies have found that the Chenpi has the anti-obesity activity. However， the anti-obesity phytochemicals and their mechanisms are still unclear. This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking. Seventeen bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified. The KEGG pathway analysis showed that the PI3K/Akt signaling pathway， MAPK signaling pathway， AMPK signaling pathway， and NF-kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi. According to molecular docking analysis， the phytochemicals of Chenpi can bind to central anti-obesity targets. Based on the ADMET analysis and network pharmacology results， tangeretin exhibited the lowest predicted toxicity and the highest potential for anti-obesity effects. In the in vitro lipid accumulation model， tangeretin effectively suppressed the FFA-induced lipid in HepG2 cells by upregulating the PI3K/Akt/GSK3β signaling pathway based on the result of q-PCR and Western Blotting. The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi， also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.

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Nitrosamines crisis in pharmaceuticals Insights on toxicological implications, root causes and risk assessment: A systematic review

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Journal of Pharmaceutical Analysis 2024年第5期14卷 639-652页

作者： Hemanth P.R.Vikram Tegginamath Pramod Kumar Gunjan Kumar Narasimha M.Beeraka Rajashree Deka Sheik Mohammed Suhail Sandeep Jat Namitha Bannimath Gayatiri Padmanabhan Ravandur S.Chandan Pramod Kumar Bannimath Gurupadayya department of Pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare Pvt.Ltd. New Delhi110076India department of Pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India department of Human Anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation department of Pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal Physiology and biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India department of Pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India department of Pharmacology University of GalwayGalwayH91 TK33Ireland

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic *** systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for *** review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological ***,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk *** comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

关键词： Carcinogenicity Genotoxicity Mutagenicity Molecular toxicity Nitrosamine impurities Nitrosamine drug substance-related impurities

Facile synthesis of graphene anchored rare earth doped mixed metal ferrite nanorods:A potential candidate for azo dye mineralization

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Journal of Rare Earths 2024年第5期42卷 907-916,I0004页

作者： Tehmina Kousar Muhammad Aadil Sonia Zulfiqar Sobhy MIbrahim Sidra Mubeen Warda Hassan Kashuf Shafiq Farzana Mahmood Institute of Chemical Sciences Bahauddin Zakariya UniversityMultan60800Pakistan department of Chemistry Rahim Yar Khan CampusThe Islarnia University of BahawalpurRahim Yar Khan64200Pakistan department of Chemistry Faculty of ScienceUniversity of Ostrava30.Dubna 22Ostrava70103Czech Republic department of Chemical and Biological Engineering Iowa State UniversitySweeney Hall618 Bissell RoadAmeslowa50011United States department of biochemistry College of ScienceKing Saud UniversityPO.Box 2455Riyadh11451Saudi Arabi department of Chemistry The Women University Multan66000Pakistan

Bandgap tuning using rare earth metals as dopants in ferrite-based photocatalytic materials has received a lot of interest because the Fermi 4f energy of these metals generates a sub-energy state in the bandgap generated by the overlapping of Fe-3d and O-2p ***,dysprosium-doped cobalt-nickel mixed ferrite(D-CNFO)and its graphene-reinforced composite(D-CNFO@G)were prepared and an ideal photocatalyst material for azo dye mineralization was proposed.A cost-effective combination of wetchemical and ultrasonication methods was used to prepare the doped and composite *** characterization methodologies were used to scrutinize the optical,compositional,structural,morphological,and photocatalytic characteristics of as-prepared *** X-ray diffraction analysis identified the spinel phase's(cubic)structure,while the electronic spectroscopy examination confirmed the prepared samples'rod-like *** UV/visible absorbance spectrum shows the higher light harvesting behavior of the D-CNFO@G in the visible *** mineralization performance of the DCNFO and D-CNFO@G composites was analyzed using Congo-red(an anionic dye),a well-known azo *** D-CNFO@G sample removes Congo-red dye at a rate almost 2.4%faster than the D-CNFO *** experiment involving trapping free radicals indicates that hydroxyl radical play s a crucial role in dye *** the D-CNFO@G catalyst is magnetic and can be isolated easily from the photocatalytic system,it shows an awkward cycle activity of more than 96%after five mineralization *** asprepared D-CNFO@G composite is proved as an excellent option for azo dye mineralization because of the combined impacts of rare earth doping,graphene reinforcement and nanotechnology.

关键词： azo-dye Composite Graphene Dy-doped Nanotechnology Rare earths