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MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

Neural Regeneration Research 2022年第4期17卷 728-740页

作者： Bridget Martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered levels of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly *** the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days vs.108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and tended to improve motor neuron survival in the SOD1(G93 A)mouse *** of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improve lifespan in males and increase muscle strength in SOD1(G93 A)*** of members of mi R-17~92 cluster improved motor neuron survival in SOD1(G93 A)*** with an artificial mi RNA designed to target h SOD1 increased lifespan and improved muscle strength in SOD1(G93 A)*** studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and improved motor neuron survival in SOD1(G93 A)animals.

关键词： amyotrophic lateral sclerosis animal model brain brainstem microRNA motor neuron degeneration spinal cord therapeutic approaches

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Promising therapeutic approaches using CRISPR/Cas9 genome editing technology in the treatment of Duchenne muscular dystrophy

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Genes & Diseases 2021年第2期8卷 146-156页

作者： Hasan Mollanoori Yazdan Rahmati Bita Hassani Meysam Havasi Mehr Shahram Teimourian Department of Medical Genetics Iran University of Medical Sciences(IUMS)Tehran***Iran Department of Medical Genetics Shahid Beheshti University of Medical Sciences(SBMU)Tehran***Iran Department of Physiology Iran University of Medical Sciences(IUMS)Tehran***Iran

Duchenne muscular dystrophy is an X-linked recessive hereditary monogenic disorder caused by inability to produce dystrophin *** most patients,the expression of dystrophin lost due to disrupting mutations in open reading *** the efforts in a large number of different therapeutic approaches to date,the treatments available for DMD remain mitigative and supportive to improve the symptoms of the disease,rather than to be *** advent of CRISPR/Cas9 technology has revolutionized genome editing scope and considered as pioneer in effective genomic *** or excisions of intragenic DNA by CRISPR as well as a similar strategy with exon skipping at the DNA level induced by antisense oligonucleotides,are new and promising approaches in correcting DMD gene,which restore the expression of a truncated but functional dystrophin ***,CRISPR/Cas9 technology can be used to treat DMD by removing duplicated exons,precise correction of causative mutation by HDR-based pathway and inducing the expression of compensatory proteins such as *** this study,we briefly explained the molecular genetics of DMD and a historical overview of DMD gene *** in particular focused on CRISPR/Cas9-mediated therapeutic approaches that used to treat DMD.

关键词： CRISPR/Cas9 Duchenne muscular dystrophy Genome editing therapeutic approaches X-linked recessive

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Emerging therapeutic Strategies in The Fight Against Primary Biliary Cholangitis

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 949-957页

作者： Abigail Medford Jonathan Childs Ashleigh Little Sanjukta Chakraborty Leonardo Baiocchi Gianfranco Alpini Shannon Glaser Department of Medical Physiology Texas A&M University School of MedicineBryanTXUSA Hepatology Unit University of Tor VergataRomeItaly Division of Gastroenterology and Hepatology Department of MedicineIndiana University School of MedicineIndianapolisINUSA

The liver has a vital role in many metabolic and regulatory processes in the *** biliary cholangitis(PBC),previously known as primary biliary cirrhosis,is a chronic cholestatic autoimmune disease of the intrahepatic bile ducts associated with loss of tolerance to mitochondrial *** this time there is no definitive cure for PBC;however,ursodeoxycholic acid(UDCA)has been shown to reduce injury when administered as the first line of *** therapeutics can be given concurrently or as an alternative to UDCA to manage the symptoms and further curb disease ***,a liver transplant is the only potentially curative option when the patient has developed end-stage liver disease or intractable *** review aims to delineate the pathogenesis of primary biliary cholangitis and shed light on current therapeutic strategies in the treatment of PBC.

关键词： Cholestatic liver disease therapeutic approaches Biliary epithelia ursodeoxycholic acid

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Regulating the microenvironment with nanomaterials:Potential strategies to ameliorate COVID-19

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药学学报:英文版 2023年第9期13卷 3638-3658页

作者： Zhicheng Liu Zhuolei Han Xin Jin Jusung An Jaewon Kim Wenting Chen Jong Seung Kim Ji Zheng Jun Deng Department of Urology Xinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China Department of Urology Urological Surgery Research InstituteSouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Institute of Burn Research Southwest HospitalState Key Lab of TraumaBurn and Combined InjuryChongqing Key Laboratory for Disease ProteomicsThird Military Medical University(Army Medical University)Chongqing 400038China Tianjin Key Laboratory of Composite and Functional Materials School of Materials Science and EngineeringTianjin UniversityTianjin 300350China Department of Chemistry Korea UniversitySeoul 02841South Korea Department of Rheumatology and Clinical Immunology Army Medical CenterThird Military Medical University(Army Medical University)Chongqing 400042China

COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health *** treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being ***,accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in *** addition,recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection,providing new insight into COVID-19 *** literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 *** fill this gap,this review systematically discusses alterations of homeostasis in COVID-19 patients and potential ***,advances in nanotechnology-based strategies for promoting homeostasis restoration are ***,we discuss the challenges and prospects of using nanomaterials for COVID-19 *** review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.

关键词： Coronavirus disease 19 Severe acute respiratory syndrome coronavirus 2 therapeutic approaches Nanotechnology Nanomaterial technologies Microenvironment Microenvironmental disorder Altered homeostasis

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Adipose-derived stem cells:Pathophysiologic implications vs therapeutic potential in systemic sclerosis

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World Journal of Stem Cells 2021年第1期13卷 30-48页

作者： Irene Rosa Eloisa Romano Bianca Saveria Fioretto Marco Matucci-Cerinic Mirko Manetti Department of Experimental and Clinical Medicine Section of Anatomy and HistologyUniversity of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine Division of RheumatologyUniversity of FlorenceFlorence 50134Italy

Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular *** preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc ***,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition ***,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy *** light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.

关键词： Systemic sclerosis Adipose-derived stromal vascular fraction Adiposederived stem cells therapeutic approaches Pathogenesis Adipocyte-to-myofibroblast transition

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Crimean-Congo hemorrhagic fever from the immunopathogenesis, clinical, diagnostic, and therapeutic perspective: A scoping review

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Asian Pacific Journal of Tropical Medicine 2021年第6期14卷 254-265页

作者： Mohammad Ali Hamidinejad Hadi Esmaeili Gouvarchin Ghaleh Mahdieh Farzanehpour Masoumeh Bolandian Ruhollah Dorostkar Applied Virology Research Center Baqiyatallah University of Medical ScienceTehranIran

Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.

关键词： Crimean-Congo hemorrhagic fever virus(CCHFV) CCHF disease Immunopathogenesis Animal models Diagnosis Vaccines therapeutic approaches

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Pharmacogenomics in oncology

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中国药理学与毒理学杂志 2019年第10期33卷 753-754页

作者： Ingolf CASCORBI Institute of Experimental and Clinical Pharmacology University Hospital Schleswig-Holstein

Precision therapy in the field of oncology is rapidly developing. Numerous somatic genetic markers in eg tyrosine kinase receptors or transcription factors have been identified to be indicative for the treatment with anti-cancer drugs. In contrast, only some recommendations have been developed considering hereditary variants in drug metabolizing enzymes such as TPMT, DYPD or UGT1A1. Although a huge knowledge has been gained on the association of drug transporters variants such as ABCB1 or ABCG2 and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. However, there is increasing evidence that individual phenotypic differences may result not only from genetics, but also from epigenetic alterations such as histone-acetylation or DNA-methylation. Moreover,interactions with non-coding RNAs contribute to protein expression and may modulate drug action. Currently intriguing developments of novel therapeutic approaches through epigenetic drugs are emerging. The overall complexity of epigenetics in drug action is so far only little understood. Of significant importance are the consequences of mi RNA interaction for drug resistance in cancer by regulating target genes and efflux transporters. Further intriguing findings address DNAmethylation as modifier of transporter function and its consequences in cancer development and treatment. The progress of science may lead to the discovery of rare, but functionally relevant SNPs and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

关键词： therapeutic approaches epigenetic drugs oncology

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