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LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China(Life Sciences) 2024年第8期67卷 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun Department of pharmacology Harbin Medical University(State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical UniversityHarbin 150081China

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier *** study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following *** effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full ***,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of *** increased SERCA2a protein stability by upregulating FTO *** direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown *** of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in *** study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in ***,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

关键词： CCRR calcium homeostasis FTO myocardial infarction SERCA2a

Nitrosamines crisis in pharmaceuticals Insights on toxicological implications, root causes and risk assessment: A systematic review

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Journal of Pharmaceutical Analysis 2024年第5期14卷 639-652页

作者： Hemanth P.R.Vikram Tegginamath Pramod Kumar Gunjan Kumar Narasimha M.Beeraka Rajashree Deka Sheik Mohammed Suhail Sandeep Jat Namitha Bannimath Gayatiri Padmanabhan Ravandur S.Chandan Pramod Kumar Bannimath Gurupadayya Department of Pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare Pvt.Ltd. New Delhi110076India Department of Pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Human Anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation Department of pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal Physiology and Biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India Department of pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India Department of pharmacology University of GalwayGalwayH91 TK33Ireland

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic *** systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for *** review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological ***,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk *** comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

关键词： Carcinogenicity Genotoxicity Mutagenicity Molecular toxicity Nitrosamine impurities Nitrosamine drug substance-related impurities

Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 207-214页

作者： Duaa M.Bakhshwin Foziya W.Alhalabi Mohamad Omar Barasheed Ahmed M.Bakhshwin Maha H.Jamal Mohammed A.Bazuhair Fatemah O.Kamel Rania M.Magadmi Zoheir A Damanhouri Samar M.Alsaggaf Department of Clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Hera General Hospital MakkahSaudi Arabia Department of Pathology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Department of Clinical Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in ***:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and ***_(3)and D-GAL were used to induce *** tests,brain beta-amyloid protein,and oxidative stress biomarkers were ***:The Morris water maze test indicated an enhanced memory in the combination ***,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain *** inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were ***:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

关键词： Alzheimer’s disease Cognitive function Glucagonlike peptide-1 Liraglutide Memantine

Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu Jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao Wen Xie Mengxi Jiang Department of pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 794-805页

作者： Muhammad Zulfiqah Sadikan Nurul Alimah Abdul Nasir Mohammad Johari Ibahim Igor Iezhitsa Renu Agarwal Department of pharmacology Faculty of MedicineManipal University College Malaysia(MUCM)Bukit BaruMelaka 75150Malaysia Centre for Neuroscience Research(NeuRon) Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia Department of Medical Education Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia Department of Biochemistry and Molecular Medicine Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia School of Medicine International Medical UniversityBukit JalilKuala Lumpur 57000Malaysia Department of pharmacology and Bioinformatics Volgograd State Medical UniversityVolgograd 400131Russia

AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat ***:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic *** stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)***:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic *** 18s gene was expressed consistently in both normal control and diabetic rats’retinal *** this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic ***,there was no ideal gene stably expressed for use in all experimental ***:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.

关键词： housekeeping genes stability real-time reverse transcription polymerase chain reaction retinal tissue streptozotocin-induced diabetic rats

Foeniculum vulgare *** lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 28-39页

作者： Sushruta Koppula Ramesh Alluri Spandana Rajendra Kopalli College of Biomedical and Health Sciences Konkuk UniversityChungju-SiChungcheongbuk Do27478Republic of Korea Cognitive Science Research Initiative Lab Department of PharmacologyVishnu Institute of Pharmaceutical Education and ResearchNarsapurTelangana502313India Department of Bioscience and Biotechnology Sejong UniversityGwangjin-guSeoul 05006Republic of Korea

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in ***:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA *** antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western *** in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic *** and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced ***:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(P<0.05).Moreover,LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract(P<0.05).The extract also regulated the NF-κB/MAPK signaling in BV-2 *** an in vivo study,Foeniculum vulgare extract(50,100,and 200 mg/kg)markedly mitigated the LPS-induced cognitive and locomotor impairments in *** fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable ***:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

关键词： Foeniculum vulgare Microglia Lipopolysaccharide Antioxidant Neuroinflammation MAPK signaling Cognition

Alzheimer's disease and low-dose radiation therapy:A new hope

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Radiation Medicine and Protection 2024年第1期5卷 1-6页

作者： Neal E.Dunlap Robert P.Friedland Lu Cai Department of Radiation Oncology University of Louisville School of MedicineLouisvilleKY40202USA Department of Neurology The University of Louisville School of MedicineLouisvilleKY40202USA Pediatric Research Institute Departments of PediatricsPharmacology and ToxicologyUniversity of Louisville School of MedicineLouisvilleKY40202USA

The concept of low-dose radiation(LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in *** the end of the 1990s,discussions regarding the potential applications of LDRinduced hormesis and adaptive responses for preventing or treating chronic diseases,such as Alzheimer’s disease(AD)had taken *** 2016,reports on radiotherapy for the subjects with AD and for genetic AD model mice were ***,several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted.A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical *** mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose *** of this Systematic Review cover promising outcomes,challenges,and new questions,followed by discussion of potential mechanisms.

关键词： Alzheimer’s disease Low-dose radiation Radiation adaptive response Radiation hormesis

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

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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

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