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A systematic scoping review of study methodology for randomized controlled trials investigating probiotics in athletic and physically active populations

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Journal of Sport and health Science 2024年第1期13卷 61-71页

作者： Alex E.Mohr David B.Pyne Geovana Silva Fogaça Leite Deborah Akins Jamie Pugh College of health Solutions Arizona State UniversityPhoenixAZ 85004USA Research Institute for Sport and Exercise University of CanberraCanberraACT 2617Australia Laboratory of Functional Fermented Food Faculty of Pharmaceutical SciencesUniversity of São PauloSão Paulo 05508-030Brazil Research Institute for Sport and Exercise Sciences Liverpool John Moores UniversityLiverpool L33AFUK

Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of

关键词： Exercise Experimental methodology Gastrointestinal symptoms Gut microbiota Probiotic supplementation

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Strategies that regulate LSD1 for novel therapeutics

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acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu School of pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

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Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 75-82页

作者： Yu-Xi Huang Jing-Jing Fan Lu-Lu Xu Rong Yu Yi Kuang Yue Chai Rui Zheng Xiao-Yu Zhang Hong-Cai Shang Xue Qiao Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina Key Laboratory of Chinese Internal Medicine of ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Yunnan Baiyao International Medical Research Center Peking UniversityBeijingChina Key Laboratory of Molecular Cardiovascular Sciences of ministry of Education Peking UniversityBeijingChina

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

关键词： Contribution index heart failure network pharmacology traditional Chinese medicine yiqi fumai lyophilized injection

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Harnessing bacteria for tumor therapy:Current advances and challenges

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Chinese Chemical Letters 2024年第2期35卷 97-106页

作者： Lina Guo Jinsong Ding Wenhu Zhou Xiangya School of pharmaceutical Sciences Central South UniversityChangsha 410013China Changsha Medical University Academician WorkstationChangsha 410219China Key Laboratory of Biological Nanotechnology of National health Commission Changsha 410008China

After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treatments.Obligate and facultative anaerobes with active tropism can selectively colonize at tumor sites and suppress tumor growth via different mechanisms,serving as attractive tools for tumor treatment either as a monotherapy or combining with other therapies for synergistic anti-tumor effects.In this critical review,we introduce the recent advances of bacteria-based tumor therapy from the following aspects.First,the general properties of bacteria are reviewed emphasizing on their structural components related to tumor immunotherapy,and the main bacteria that have been used in tumor therapy are listed.Then,the benefits of bacteria for tumor therapy are illustrated,such as tumor targetability,deep penetration,and facile genetic engineering for attenuation,enhanced efficacy,as well as bioimaging.Next,anti-tumor mechanisms of bacteria are summarized,which refer to intrinsic tumoricidal activities,immune activation,bacteria metabolism,and their capability to regulate gut microbiota homeostasis.Moreover,bacteria could act as carriers to deliver various types of therapeutics to achieve combination therapy with improved efficacy.In addition,several challenges for anti-tumor applications of bacteria are discussed regarding the delivery,efficacy and safety issues,and potential solutions are also provided.Finally,the possible improvements and perspectives are discussed in the end,which provide a guideline for the design of advanced bacteria-based tumor therapeutics in the future.

关键词： Bacteria Tumor targeting Immunotherapy Combination therapy Genetic engineering Surface decoration

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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatri

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment

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Oncology Research 2024年第1期32卷 19-47页

作者： ABHISHEK WAHI MAMTA BISHNOI NEHA RAINA MEGHNA AMRITA SINGH PIYUSH VERMA PIYUSH KUMAR GUPTA GINPREET KAUR HARDEEP SINGH TULI MADHU GUPTA Department of Pharmaceutics School of Pharmaceutical SciencesDelhi Pharmaceutical Sciences and Research University(DPSRU)Pushp ViharNew Delhi110017India Department of pharmaceutical Sciences Gurugram UniversityHaryana122003India Department of Life Sciences Sharda School of Basic Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh201310India Department of Biotechnology Graphic Era(Deemed to be University)DehradunUttarakhand248002India Department of Pharmacology Shobhaben Pratapbhai Patel School of Pharmacy&Technology ManagementSVKM’s NMIMSVile Parle(West)Mumbai400056India Department of Bio-Sciences and Technology Maharishi Markandeshwar Engineering CollegeMaharishi Markandeshwar(Deemed to be University)MullanaAmbala133207India

Cancer is a leading cause of death globally,with limited treatment options and several limitations.Chemotherapeutic agents often result in toxicity which long-term conventional treatment.Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance.These phytoconstituents act in several ways and deliver optimum effectiveness against cancer.Nevertheless,the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility,bioavailability,and stability.Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems,which possess a range of advantageous characteristics such as biocompatibility,targeted and sustained release capabilities,and enhanced protective effects.This holds significant potential for future advancements in cancer management.Herein,this review aims to provide intensive literature on diverse nanocarriers,highlighting their applications as cargos for phytocompounds in cancer.Moreover,it offers an overview of the current advancements in the respective field,emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings.Lastly,clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

关键词： Phyto-formulations Cancer Nanocarriers Nanotechnology Clinical development

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Comprehensive integration of single-cell transcriptomic data illuminates the regulatory network architecture of plant cell fate specification

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Plant Diversity 2024年第3期46卷 372-385页

作者： Shanni Cao Xue Zhao Zhuojin Li Ranran Yu Yuqi Li Xinkai Zhou Wenhao Yan Dijun Chen Chao He State Key Laboratory of pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China National Key Laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.

关键词： Arabidopsis Single cell transcriptome Gene regulatory network Data integration Plant cell atlas

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Synthesis and anti-HIV activities of phorbol derivatives

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Chinese Journal of Natural Medicines 2024年第2期22卷 146-160页

作者： HUANG Xiaolei TANG Chengrun HUANG Xusheng YANG Yun LI Qirun MA Mengdi ZHAO Lei YANG Liumeng CUI Yadong ZHANG Zhenqing ZHENG Yongtang ZHANG Jian College of pharmaceutical Science Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out,demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation.These derivatives exhibited a higher safety index compared with the positive control drug.Among them,12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol,designated as compound 3c,exhibited the most potent anti-HIV-1 activity(EC_(50)2.9 nmol·L^(−1),CC50/EC_(50)11117.24)and significantly inhibited the formation of syncytium(EC_(50)7.0 nmol·L^(−1),CC50/EC_(50)4891.43).Moreover,compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor.Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C(PKC).Therefore,compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

关键词： Phorbol esters Anti-HIV-1 activity Syncytia formation 12-(Trans-4-fluorocinnamoyl)-13-decanoyl phorbol Safety index HIV-1 entry inhibitor HIV-1 reverse transcriptase inhibitor PKC activator

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Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis

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Genes & Diseases 2024年第3期11卷 102-105页

作者： Jie Ding Shanshan Mei Kaili Wang Wen Cheng Shuai Sun Zhexin Ni Xiaoqiu Wang Chaoqin Yu Department of Gynecology of Traditional Chinese Medicine Changhai Hospital Affiliated to Naval Medical UniversityShanghai 200433China Obstetrics and Gynecology Department The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouZhejiang 310006China Department of pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Obstetrics and Gynecology Hospital of Fudan University Shanghai 200433China

Endometriosis(EM)is a common disease that affects approximately 10%-15%of women of childbearing age.The pathogenesis of EM is unclear,but studies have shown a strong association between EM and inflammation,as well as oxidative stress.^(1) Pyroptosis is also called inflammatory cell death.When pyroptosis occurs,it activates a strong inflammatory response.Pyroptosis is associated with oxidative stress,and Ros act as intermediate triggers to activate pyroptosi.

关键词： inflammatory death oxidative

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Insights into the anorexic mechanism of Khat:an integrated in vivo,ex vivo,and in silico investigations

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Traditional Medicine Research 2024年第10期9卷 36-51页

作者： Ahmed Ali Jerah Manal Mohamed Elhassan Taha Abdullah Farasani Sivakumar Sivagurunathan Moni Emad Sayed Shaheen Andleeb Khan Ibrahim Abdo Khardali Magbool Oraiby Heyam Mohamed Ali Sidahmed Siddig Ibrahim Abdelwahab Department of Medical Laboratory Technology College of Applied Medical SciencesJazan UniversityJazan 45142Saudi Arabia health Research Centre Jazan UniversityJazan 45142Saudi Arabia Department of Pharmaceutics College of PharmacyJazan UniversityJazan 45142Saudi Arabia Department of Biosciences Faculty of ScienceIntegral UniversityLucknow 226026India Poison Control and Medical Forensic Chemistry Center General Directorate of Health AffairsJazan 45142Saudi Arabia Department of pharmaceutical Chemistry Faculty of PharmacyAl-Neelain UniversityKhartoum 16458Sudan

Background:Chewing Khat(Catha edulis)releases cathine and cathinone,which may reduce appetite via an unknown mechanism.This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract(CEWE)on appetite biomarkers,gene expression,and body weight,using in vivo,ex vivo,and in silico models.Methods:Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments.Liquid chromatography-mass spectroscopy(LC-MS)-MS was used to detect cathinone and cathine in the murine blood.The effect of Khat on serotonin receptors was studied in isolated rat fundus samples.Docking of the two Khat ligands was performed on G(The 5-hydroxytryptamine-type 2C receptor(5-HT2C)in an agonist-bound active conformation)and H(5-HT2C in an antagonist-bound inactive conformation)proteins to determine which ligands are most likely to act as agonists or antagonists.Results:Significant differences(P0.05).The expression of the ghrelin and leptin genes was also unaffected,but the expression of the 5-hydroxytryptamine(5-HT)gene decreased(Pact may suppress appetite by antagonizing the 5-HT receptors.Further research is required to understand its mechanism and potential applications.

关键词： Catha edulis appetite leptin ghrelin 5-hydroxytryptamine molecular docking

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