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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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Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

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Neural Regeneration Research 2024年第1期19卷 16-21页

作者： Marika Alborghetti Edoardo Bianchini Lanfranco De Carolis Silvia Galli Francesco E.Pontieri Domiziana Rinaldi Neurology Unit NESMOS DepartmentFaculty of Medicine&PsychologySapienza-University of RomeSant’Andrea University HospitalRomeItaly department of clinical and Behavioral Neurology IRCCS-Fondazione Santa LuciaRomeItaly

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's *** drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the *** is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and *** studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic ***,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from *** to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now *** potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain *** purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

关键词： glial cell line-derived neurotrophic factor(GDNF) glutamate neurological disorders neuroprotection Parkinson's disease preclinical studies rasagiline safinamide selegiline type-B monoamine oxidase(MAO_(B))inhibitors

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Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis

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World Journal of Hepatology 2024年第5期16卷 822-831页

作者： Irina Efremova Roman Maslennikov Elena Poluektova Oleg Medvedev Anna Kudryavtseva George Krasnov Maria Fedorova Filipp Romanikhin Maria Zharkova Oxana Zolnikova Gyunay Bagieva Vladimir Ivashkin department of Internal medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia department of Scientific Scientific Community for the Promotion of the Clinical Study of the Human MicrobiomeMoscow 119435Russia department of pharmacology Lomonosov Moscow State UniversityMoscow 119192Russia department of Post-Genomic Research Laboratory Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscow 119991Russia

BACKGROUND The gut–liver axis and bacterial translocation are important in cirrhosis,but there is no available universal biomarker of cellular bacterial translocation,for which presepsin may be a *** To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious *** This study included 48 patients with Child–Pugh cirrhosis classes B and C and 15 healthy *** fecal microbiome was assessed using 16S rRNA gene *** levels of presepsin were measured.A total of 22 patients received a probiotic(Saccharomyces boulardii)for 3 *** Presepsin levels were higher in patients with cirrhosis than in healthy individuals[342(91-2875)vs 120(102-141)pg/mL;P=0.048].Patients with elevated presepsin levels accounted for 56.3%of all included *** had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child–Pugh *** with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation,namely Bacilli and Proteobacteria(including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas),and a low abundance of bacteria from the family Lachnospiraceae(including the minor genus Fusicatenibacter),which produce short-chain fatty acids that have a positive effect on intestinal barrier *** presepsin level directly correlated with the relative abundance of Bacilli,Proteobacteria,and inversely correlated with the abundance of Lachnospiraceae and *** 3 months of taking the probiotic,the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels[from 9(8-11)to 7(6-9);P=0.004],while there were no significant changes in the group with normal presepsin levels[from 8(7-8)to 7(6-8);P=0.123].A high level of presepsin

关键词： Dysbiosis Gut Intestinal permeability Leaky gut Gut-liver axis Liver Microbiota

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Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through b-catenin/CREB interruption

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4118-4133页

作者： Mengyi Yan Xiayun Chen Xiaotong Li Qianqian Liu Baixue Yu Yi Cen Wei Zhang Yibin Liu Xinxuan Li Ying Chen Tao Wang Shiying Li The Fifth Affiliated Hospital Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacologythe NMPA and State Key Laboratory of Respiratory Diseasethe School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China department of Anesthesiology the Second Clinical School of Guangzhou Medical UniversityGuangzhou 511436China State Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular DiseasesGuangzhou Institute of Respiratory Healththe first Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China department of Pulmonary and Critical Care medicine Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional *** this work,a transferrin receptor(TfR)targeted immunostimulant(PTI)is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting b-catenin signal *** synthesize PTI,the photosensitizer conjugated TfR targeting peptide moiety(Palmitic-K(PpIX)-HAIYPRH)is unitized to encapsulate the transcription interrupter of *** the one hand,the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumorassociated *** the other hand,PTI will interrupt the binding between b-catenin andcAMP response element-binding protein(CREB),regulating the gene transcription to downregulate programmed death ligand 1(PD-L1)while upregulating CeC motif chemokine ligand 4(CCL4).Furthermore,the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration,and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung *** work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

关键词： Transferrin receptor b-Catenin signal pathway Tumor targeting Photodynamic therapy Immunotherapy Immunogenic cell death Programmed death ligand 1

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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of Physiology and pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Differences in clinicopathological characteristics between lipohypertrophy and localized insulin-derived amyloidosis:A scoping review

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Chronic Diseases and Translational medicine 2024年第1期10卷 22-30页

作者： Kanae Mukai Hiromasa Tanno Junko Sugama Toshihiko Yanagita Emi Kanno department of clinical Nursing Faculty ofHealth SciencesInstitute of MedicalPharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan department of Translational Science forNursing Tohoku University Graduate School ofMedicineSendaiJapan Research Center for Implementation NursingScience Initiative School of Health SciencesFujita Health UniversityToyoakeJapan department of clinical pharmacology Schoolof NursingUniversity of MiyazakiMiyazakiJapan

Insulin is used as a therapeutic agent in patients with diabetes,and cutaneous lipohypertrophy(LH)and localized insulin-derived amyloidosis(LIDA)are well-known adverse effects associated with insulin *** clinical implications,management,assessment methods,and pathological differentiation of LH and LIDA have been recently *** review was to update our knowledge of the pathological differentiation,effects of insulin absorption,hypoglycemic events,and recent assessment methods for LH and LIDA.A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews *** studies and case reports in English were also *** and Scopus databases were searched for keywords to identify papers published up to January 2022.A total of 113 studies were identified through a database search,and 31 were eligible for inclusion in this scoping *** the 31 studies included in this review,patients with type 2 diabetes had high frequencies of LH and *** outcome parameters were assessed using pathological findings and *** is mainly determined by pathological methods,such as hematoxylin and eosin and Congo red *** in vitro and in vivo LIDA models of LIDA have been *** results suggest that pathological analysis is required to identify LH and *** is important to consider LIDA,as it likely influences insulin adsorption and glycemic *** several studies have evaluated the LIDA process,little is known about the mechanisms underlying the development of adverse effects associated with insulin injections.

关键词： diabetes mellitus insulin injection lipohypertrophy localized insulin-derived amyloidosis

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The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of clinical pharmacology University Medical Center GöttingenGöttingenGermany department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

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Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

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Cancer Innovation 2024年第3期3卷 49-64页

作者： Huiyi Liu Lu Fu Shuyu Jin Xingdong Ye Yanlin Chen Sijia Pu Yumei Xue department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina The Second School of clinical medicine Southern Medical UniversityGuangzhouGuangdongChina School of medicine South China University of TechnologyGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of clinical pharmacology Research Center of Medical SciencesGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved ***,the incidence of cardiovascular adverse events has also increased,which can affect tumor *** this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor ***:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed *** included trials examined all grade and grades 3–5 cardiac and vascular adverse *** involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target *** odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel ***:Overall,20 trials were ***-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular *** incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically ***:Our findings suggest that the

关键词： cardiovascular toxicity CTLA-4 inhibitors malignancies

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Chemical Constituents and Pharmacological Properties of Frankincense:Implications for Anticancer Therapy

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Chinese Journal of Integrative medicine 2024年第8期30卷 759-767页

作者： WU Yong-rong XIONG Wei DONG Ying-jing CHEN Xin ZHONG Yuan-yuan HE Xin-ling WANG Yu-jia LIN Qun-fang TIAN Xue-fei ZHOU Qing College of Traditional Chinese medicine Hunan University of Chinese MedicineChangsha410208China department of Andrology the First Hospital of Hunan University of Chinese MedicineChangsha41007China College of medicine Hunan University of Chinese MedicineChangsha410208China College of Traditional Chinese and Western medicine Hunan University of Chinese MedicineChangsha410208China Hunan Provincial Key Laboratory of Traditional Chinese medicine Prescription and Transformation Changsha410208China Hunan Sexual and Reproductive Health clinical Medical Research Center of Traditional Chinese medicine Changsha410021China

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug ***,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and *** different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia *** frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation *** also have comprehensive effects on regulating *** and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against *** review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.

关键词： frankincense species chemical constituents anticancer therapy Chinesemedicine

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A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

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Oncology Research 2024年第5期32卷 817-830页

作者： SHAHID KARIM ALANOUD NAHER ALGHANMI MAHA JAMAL HUDA ALKREATHY ALAM JAMAL HIND A.ALKHATABI MOHAMMED BAZUHAIR AFTAB AHMAD department of clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Biochemistry Faculty of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia department of Biochemistry College of ScienceUniversity of JeddahJeddah21959Saudi Arabia Health Information Technology department The Applied CollegeKing Abdulaziz UniversityJeddahSaudi Arabia Pharmacovigilance and Medication Safety Unit Center of Research Excellence for Drug Research and Pharmaceutical IndustriesKing Abdulaziz UniversityJeddahSaudi Arabia

Cancer frequently develops resistance to the majority of chemotherapy *** study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro *** precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 ***,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their ***,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate ***,this effect was found to be dependent on the dosages of the *** addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene *** work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of *** underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

关键词： SGLT2 Cancer Cytotoxicity ATP Cell cycle

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