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cellular preconditioning and mesenchymal stem cell ferroptosis

World Journal of Stem Cells 2024年第2期16卷 64-69页

作者： Doaa Hussein Zineldeen Mazhar Mushtaq Khawaja Husnain Haider Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia department of Medical Biochemistry and molecular Biology Faculty of MedicineTanta UniversityTanta 6632110Egypt

In this editorial,we comment on the article published in the recent issue of the World Journal of Stem *** focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary *** stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured *** also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell ***,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to *** lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular *** these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related *** editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis *** presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic *** research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.

关键词： Cell survival Cell therapy Hydrogen sulfide Ferroptosis Preconditioning Stem cells Umbilical cord

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Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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Chinese Journal of Natural Medicines 2024年第05期 426-440页

作者： SI Jianchao CHEN Xue QI Kerong LI Dongli LIU Bingbing ZHENG Yuying JI Ensheng YANG Shengchang department of physiology Hebei University of Chinese Medicine department of Geriatrics First People's Hospital of Xiaogan Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine

Chronic intermittent hypoxia（CIH）, a principal pathophysiological aspect of obstructive sleep apnea（OSA）, is associated with cognitive deficits. Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions（SMSLD） can enhance cognitive function by nourishing yin and strengthening the kidneys. This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH. We exposed C57BL/6N mice to CIH for five weeks（20%-5% O2, 5 min/cycle, 8 h/day） and administered SMS-LD intragastrically(15.0 or 30 g·kg-1·day) 30 min before each CIH session. Additionally, AG490, a JJanus kinase 2（JAK2） inhibitor, was administered via intracerebroventricular injection. Cognitive function was evaluated using the Morris water maze, while synaptic and mitochondrial structures were examined by transmission electron microscopy. Oxidative stress levels were determined using DHE staining, and the activation of the erythropoietin（ER）/ER receptor（EPOR）/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting. To further investigate molecular mechanisms, HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h. Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice. Specifically, SMS-LD treatment enhanced dendritic spine density, ameliorated mitochondrial dysfunction, reduced oxidative stress, and activated the EPO/EPOR/JAK2 signaling pathway. Conversely, AG490 negated SMS-LD's neuroprotective and cognitive improvement effects under CIH conditions. These findings suggest that SMS-LD's beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany department of molecular&cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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Circulating biomarker-and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy

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Chinese Medical Journal 2024年第1期137卷 73-81页

作者： Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang department of Cardiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China department of Cardiology Institute of Vascular MedicinePeking University Third HospitalBeijing 100191China department of Cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Beijing Key Laboratory of molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100083China department of physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100083China Key Laboratory of molecular Cardiovascular Science Ministry of EducationBeijing 100191China

Background:Dilated cardiomyopathy(DCM)has a high mortality rate and is the most common indication for heart *** study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation(ACM/HTx)risk in DCM ***:The present study is a retrospective cohort *** demographic,clinical,blood test,and cardiac magnetic resonance imaging(CMRI)data of DCM patients in the tertiary center(Fuwai Hospital)were *** primary endpoint was ACM/*** least absolute shrinkage and selection operator(LASSO)Cox regression model was applied for variable *** Cox regression was used to develop a *** concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curve,and decision curve analysis(DCA)were used to evaluate the performance of the ***:A total of 218 patients were included in the present *** were randomly divided into a training cohort and a validation *** nomogram was established based on eight variables,including mid-wall late gadolinium enhancement,systolic blood pressure,diastolic blood pressure,left ventricular ejection fraction,left ventricular end-diastolic diameter,left ventricular end-diastolic volume index,free triiodothyronine,and N-terminal pro-B type natriuretic *** AUCs regarding 1-year,3-year,and 5-year ACM/HTx events were 0.859,0.831,and 0.840 in the training cohort and 0.770,0.789,and 0.819 in the validation cohort,*** calibration curve and DCA showed good accuracy and clinical utility of the ***:We established and validated a circulating biomarker-and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients,which might help risk stratification and decision-making in clinical practice.

关键词： Cardiomyopathy,dilated Heart transplantation Mortality Nomograms Least absolute shrinkage and selection operator Decision curve analysis

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State Key Laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina department of Biochemistry and molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio Charles A.Dinarello Ruben Lopez-Vales department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

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Small holes,big impact:Stomata in plant–pathogen–climate epic trifecta

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molecular Plant 2024年第1期17卷 26-49页

作者： Shuguo Hou Olivier Rodrigues Zunyong Liu Libo Shan Ping He Peking University Institute of Advanced Agricultural Sciences Shandong Laboratory of Advanced Agriculture Sciences in WeifangWeifangShandong 261325China School of Municipal&Environmental Engineering Shandong Jianzhu UniversityJinanShandong 250101China Unitéde Recherche Physiologie Pathologie et Génétique VégétalesUniversitéde Toulouse Midi-PyrénéesINP-PURPAN31076 ToulouseFrance department of molecular Cellularand Developmental BiologyUniversity of MichiganAnn ArborMI 48109USA

The regulation of stomatal aperture opening and closure represents an evolutionary battle between plants and pathogens,characterized by adaptive strategies that influence both plant resistance and pathogen *** ongoing climate change introduces further complexity,affecting pathogen invasion and host *** review delves into recent advances on our understanding of the mechanisms governing immunity-related stomatal movement and patterning with an emphasis on the regulation of stomatal opening and closure dynamics by pathogen patterns and host *** addition,the review explores how climate changes impact plant–pathogen interactions by modulating stomatal *** light of the pressing challenges associated with food security and the unpredictable nature of climate changes,future research in this field,which includes the investigation of spatiotemporal regulation and engineering of stomatal immunity,emerges as a promising avenue for enhancing crop resilience and contributing to climate control strategies.

关键词： stomatal movement stomatal patterning plant resistance pathogen virulence apoplastic immunity and climate change

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Pathological and Physiological High-frequency Oscillations on Electroencephalography in Patients with Epilepsy

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Neuroscience Bulletin 2024年第5期40卷 609-620页

作者： Hongyi Ye Cong Chen Shennan A.Weiss Shuang Wang department of Neurology Epilepsy CenterSecond Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China department of Neurology State University of New York DownstateBrooklynNY11203USA department of physiology and Pharmacology State University of New York DownstateBrooklynNY11203USA department of Neurology New York City Health+Hospitals/Kings CountyBrooklynNY11203USA

High-frequency oscillations(HFOs)encompass ripples(80 Hz–200 Hz)and fast ripples(200 Hz–600 Hz),serving as a promising biomarker for localizing the epileptogenic zone in *** fast ripples are always pathological,while ripples may be physiological or *** physiological from pathological ripples is important not only for designating epileptogenic brain regions,but also for investigations that study ripples in the context of memory encoding,consolidation,and recall in patients with *** studies have sought to identify distinguishing features between pathological and physiological ripples over the past two *** and pathological ripples differ with respect to their spatial location,cellular mechanisms,morphology,and coupling with background electroencephalographic *** studies have demonstrated that differentiating between pathological and physiological ripples can improve surgical outcome *** this review,we summarize the characteristics,differences,and applications of pathological and physiological HFOs and discuss strategies for their clinical translation.

关键词： Ripples Epilepsy Memory Sleep Surgical outcome

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Duphaston as a suitable medication for women taking intracytoplasmic sperm injection to treat infertility

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Reproductive and Developmental Medicine 2024年第2期8卷 89-92页

作者： Leila Naserpour Katayon Berjis Sanaz Soleymani Moud Rahil Jannatifar department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom BranchQomIran Infertility Treatment Center Academic Center for EducationCultureand Research(ACECR)Qom BranchQomIran cellular and molecular Research Center Qom University of Medical SciencesQomIran Midwifery Ward Infertility Treatment CenterAcademic Center for EducationCultureand Research(ACECR)Qom BranchQomIran

Objective:Duphaston is used as an alternative to gonadotropin-releasing hormone(GnRH)antagonists for suppressing premature luteinizing hormone(LH)*** study aimed to compare the efficacy of Duphaston protocols with that of Cetrotide in suppressing the LH ***:In this retrospective cross-sectional study,669 infertile women(aged 25-40 years)were administered recombinant follicle-stimulating hormone(rFSH)from the third day of their menstrual *** the follicular diameter reached 13 to 14 mm,Cetrotide was prescribed orally to the control subjects,also case subjects took Duphaston *** retrieved oocytes were fertilized by an intracytoplasmic sperm injection(ICSI).Results:The levels of FSH,LH,and estradiol did not differ significantly between the groups(P>0.05).However,the findings indicated that Duphaston led to greater oocyte retrieval than Cetrotide(P=0.006).However,the number of mature oocytes and viable embryos in the case subjects did not reach a significant difference compared to that in the control subjects(P>0.05).The number of good-quality embryos(stage 1)was significantly higher in the case subjects(P=0.04).In addition,there is no significant difference in the chemical,clinical pregnancy,implantation rate,and miscarriage rate between both groups(P>0.05).Conclusion:Duphaston could be utilized as a suitable medication rather than a GnRH antagonist in women subjected to controlled ovarian hyperstimulation.

关键词： Duphaston Cetrotide Progesterone protocol Ovarian hyperstimulation GnRH antagonist

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Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

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Oncology Research 2024年第5期32卷 831-847页

作者： EFFAT ALEMZADEH LEILA ALLAHQOLI AFROOZ MAZIDIMORADI ESMAT ALEMZADEH FAHIMEH GHASEMI HAMID SALEHINIYA IBRAHIM ALKATOUT Infectious Diseases Research Center Birjand University of Medical SciencesBirjandIran department of Midwifery Ministry of Health and Medical EducationTehranIran Student Research Committee Shiraz University of Medical SciencesShirazIran department of Biotechnology Faculty of MedicineBirjand University of Medical SciencesBirjandIran cellular and molecular Research Center Birjand University of Medical SciencesBirjandIran Social Determinants of Health Research Center Birjand University of Medical SciencesBirjandIran Kiel School of Gynaecological Endoscopy Campus KielUniversity Hospitals Schleswig-HolsteinKielGermany

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to *** resistance(DR)poses the most significant challenge in treating patients with existing *** Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance ***,resistance to these new drugs has ***,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective *** this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

关键词： Chemotherapy Drug resistance mechanisms Ovarian cancer PARP inhibitors VEGF inhibitor

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