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Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

World Journal of Clinical Cases 2024年第4期12卷 677-680页

作者： Venkata Buddhavarapu Rahul Kashyap Salim Surani Department of Medicine Banner Baywood Medical CenterMesaAZ 85206United States Department of Research Wellspan HealthYorkPA 17403United States Department of Medicine&pharmacology Texas A&M UniversityCollege StationTX 77843United States

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical *** evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic *** also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern *** clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic *** findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse *** such,this intervention is also recommended by the American Heart Association stroke guidelines from *** regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient ***,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation *** et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in *** caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was *** more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

关键词： Aspirin Ischemic stroke Intracranial hemorrhage CVA Antiplatelet therapy

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1,12-cyclic apelin-12 ameliorates Ang II and Apelin-13-induced cardiac hypertrophy by reducing mitochondrial oxidative damage

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Chinese Medical Journal 2024年第6期137卷 749-751页

作者： Xueqian Ouyang Wei Chen Guolong Peng Huimei Liu Sisi Fan Qin Li Liwen Wang Linxi Chen Lanfang Li The Institute of Pharmacy and pharmacology Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug ResearchUniversity of South ChinaHengyangHunan 421001China

To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart *** II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])

关键词： hypertrophy cardiac Ang

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Oleanonic acid inhibits glioma growth by inactivating STAT3 via upregulating SIRT6 in nude mice

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Food Science and Human Wellness 2024年

作者： Jiancun Wang Yuanyuan Wang Hui Gao Qin Sun Wen Li Neurosurgery Department of the First Affiliated Hospital of Soochow University Department of Neurosurgery， the Third Affiliated Hospital of Naval Medical University Department of anesthesiology， General Hospital Of Eastern Theater Command Department of pharmacology， School of Medicine， Shaoxing University

Patients with glioma have a very high mortality rate， thus improving the poor prognosis of glioma has been the goal in the therapeutic field. Searching for more effective drugs for gliomas from natural compounds is a promising strategy. In this study， both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1， but the former has a lower IC50 than the latter. Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5， and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells. Furthermore， knockdown of STAT3 expression inhibited proliferation and migration of glioma cells. Next， the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1， p-ERK1/2， p300 were increased by oleanonic acid. The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells. In addition， the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6. Furthermore， oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts， but not in nude mice bearing intracerebral SIRT6-knockdown U87 xenografts. In conclusion， oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.

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COVID-19 mortality paradox(United States vs Africa):Mass vaccination vs early treatment

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World Journal of Experimental Medicine 2024年第1期14卷 6-12页

作者： Mina Thabet Kelleni Department of pharmacology College of MedicineMinia UniversityMinya 61111Egypt

The coronavirus disease 2019(COVID-19)mortality rate in 55 African countries is almost 4.5 times lower than in the coronavirus disease 2019(COVID-19)despite Africa having over 4.2 times more *** mortality paradox is also evident when comparing Nigeria,a heavily populated,poorly vaccinated and weakly mandated country to Israel,a small,highly vaccinated and strictly mandated *** has almost 4 times lower COVID mortality than *** this Field of Vision perspective,I explain how this paradox has evolved drawing upon my academic,clinical and social *** April 2020,I’ve developed and been using the Egyptian immune-modulatory Kelleni’s protocol to manage COVID-19 patients including pediatric,geriatric,pregnant,immune-compromised and other individuals suffering from multiple ***’s unfortunate that severe acute respiratory syndrome coronavirus 2 is still evolving accompanied by more *** in Africa,we’ve been able to live without anxiety or mandates throughout the pandemic because we trust science and adopted early treatment using safe,and effective repurposed drugs that have saved the majority of COVID-19 *** article represents an African and Egyptian tale of honor.

关键词： COVID-19 Early treatment Kelleni’s Protocol Mandates Mortality Paradox SARS-CoV-2 Nucleic acid based vaccines

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Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

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Animal Models and Experimental Medicine 2024年第3期7卷 195-207页

作者： Maryam Golmohammadi Seyed Arash Aghaei Meibodi Sulieman Ibraheem Shelash Al-Hawary Jitendra Gupta Ibrohim B.Sapaev Mazin A.A.Najm Marim Alwave Mozhgan Nazifi Mohammadreza Rahmani Mohammad Yasin Zamanian Gervason Moriasi School of Medicine Shahid Beheshti University of Medical SciencesTehranIran Department of Business Administration Business SchoolAl al-Bayt UniversityMafraqJordan Institute of Pharmaceutical Research GLA UniversityMathuraIndia Tashkent Institute of Irrigation and Agricultural Mechanization Engineers TashkentUzbekistan New Uzbekistan University TashkentUzbekistan Pharmaceutical Chemistry Department College of PharmacyAl-Ayen UniversityThi-QarIraq Medical Technical College Al-Farahidi UniversityBaghdadIraq Department of Neurology Hamadan University of Medical SciencesHamadanIran Physiology-pharmacology Research Center Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran Department of Physiology and pharmacology School of MedicineRafsanjan University of Medical SciencesRafsanjanIran Neurophysiology Research Center Hamadan University of Medical SciencesHamadanIran Department of pharmacology and Toxicology School of PharmacyHamadan University of Medical SciencesHamadanIran Department of Medical Biochemistry School of MedicineCollege of Health SciencesMount Kenya UniversityThikaKenya

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and *** damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative *** the disease progresses,the loss of RGCs leads to vision ***,protecting RGCs from damage and promoting their survival are important goals in managing *** this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of *** present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the ***,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed *** was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling *** could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt ***,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

关键词： glaucoma ischemic-reperfusion injury oxidative stress resveratrol retinal ganglion cells

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Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2804-2818页

作者： Fenglian He Zhongen Wu Chenglong Liu Yuanyuan Zhu Yan Zhou Enming Tian Rina Rosin-Arbesfeld Dehua Yang Ming-Wei Wang Di Zhu Department of pharmacology Minhang Hospitaland Key Laboratory of Smart Drug DeliveryShanghai Engineering Research Center of Immune TherapySchool of PharmacyFudan UniversityShanghai 201203China The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai 201203China Department of Microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources SanyaChina Department of Chemistry School of ScienceThe University of TokyoTokyoJapan Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education School of PharmacyHainan Medical UniversityHaikouChina Shandong Academy of Pharmaceutical Science JinanChina

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor *** B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against ***,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely ***,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into *** inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell ***,targeting BCL9/BCL9L promoted antigen presentation in *** is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 ***,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 ***,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor *** BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

关键词： immunity Targeting markedly

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Phomaketals A and B,pentacyclic meroterpenoids from a eupC overexpressed mutant strain of Phoma sp.

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Chinese Chemical Letters 2024年第7期35卷 350-354页

作者： Chuan Li Yangyang Han Yanan Zhai Ke Li Xingzhong Liu Zhuan Zhang Cai Jia Yongsheng Che NHC Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Toxicology&Medical Countermeasures Beijing Institute of Pharmacology&ToxicologyBeijing 100850China Department of Microbiology College of Life SciencesNankai UniversityTianjin 300071China

Phomaketals A(1)and B(2),two tropolonic meroterpenoids with the unprecedented pentacyclic skeletons,were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of the fungus Phoma sp.,together with a biogenetically related secondary metabolite pughiinin B(3),and the known one noreupenifeldin B(4).The structures of 1–3 were elucidated primarily by nuclear magnetic resonance(NMR)*** absolute configurations of 1 and 2 were assigned by electronic circular dichroism calculations and the calculated NMR with DP4+analysis,while that of 3 was established by single-crystal X-ray diffraction analysis using Cu Kα***,phomaketals A(1)and B(2)could be derived from the hypothetical tropolonic sesquiterpene intermediates neosetophomone B(6)and 9-R-neosetophomone B(6),respectively,via different reactions *** 1 showed antiproliferative effect only against the SUPB15 cells,with an 50%inhibitory concentration(IC50)value of 4.85μmol/L,while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines,SUPB15,EL4,and H9,showing IC50values of 0.36–27.08μmol/L.

关键词： Phoma sp. Tropolonic sesquiterpenes Biosynthetic pathways Hetero-Diels–Alder Cytotoxicity

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Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

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Acta Pharmaceutica Sinica B 2024年第1期14卷 273-291页

作者： Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park Department of pharmacology Hanoi University of PharmacyHanoi 100000Viet Nam College of Pharmacy Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Medical Biotechnology Yeungnam UniversityGyeongsan 38541Republic of Korea Research Institute of Cell Culture Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Precision Medicine School of MedicineSungkyunkwan UniversitySuwon 16419Republic of Korea

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese *** this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of ***-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese *** effects were also observed in lean *** addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced ***,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a *** findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关键词： Adiponectin Adipose-derived stromal cells Colitis Glycolytic induction HIF1a Immunomodulation Mesenchymal stromal cells Obesity

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Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials Research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of Traditional Chinese Medicine pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota Inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

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Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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