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Critical Review on Balanites aegyptiaca Delile: Phytoconstituents, Pharmacological Properties and Nanointerventions

Chinese Journal of Integrative Medicine 2024年第7期30卷 653-663页

作者： Surendra Kumar Gautam Rakesh Kumar Paul Devesh M.Sawant Amita Sarwal Kaisar Raza Department of pharmacy School of Chemical Sciences and Pharmacy Central University of Rajasthan University Institute of Pharmaceutical sciences Panjab University

Balanites aegyptiaca Delile(BA) is an enduring xerophytic woody and spinous flowering tree and is commonly known as desert date or Ingudi(Hingot). It belongs to the family Zygophyllaceae, which is specific to be drought areas of Nigeria, Africa, South Asia and India(Rajasthan). In Ayurveda, this traditional medicinal plant is reported for the management of jaundice, syphilis, yellow fever, metabolic disorders, liver, and spleen problems. The main aim of the review is to compile its medicinal uses and further advancements to showcase the promises inherited in various parts of the plant for the benefit of mankind. As per the literature survey, various researchers have focused on the detailed investigation of BA including the phytopharmacological evidence, chemical constituents, nano-formulations, commercialized products, and clinical trials. Several remarkable scaffolds and isolated compounds like diosgenin, yamogenin, balanitin1/2, balanitin 3, bal4/5, bal6/7, rutin-3-glycosides, 3,7-diglycosides,(3, 12, 14, 16)–(12-hydroxycholest-5-ene-3,16-diyl-bis)-D-glucopyranoside and balanitoside have been identified. Additionally, this traditional plant has been scientifically proven by in vitro and in vivo. Based on the complete review of this plant, most of the compounds have been isolated from the fruit and kernel part. Additionally, based on the literature, a histogram was developed for pharmacological activity in which antidiabetic study was found to be more compared to other pharmacological activity. As a spinous desert dates, this plant needs to be explored more to bring out newer phytochemicals in the management of various diseases.

关键词： Delile desert date phytochemicals nano-phytopharmaceutical pharmacological activities traditional medicine

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of biomedical sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body.They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases.Some of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric disorders.In addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS diseases.This review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies.In addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases.Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

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Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A_(2)receptors

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Science China(Life sciences) 2024年第5期67卷 986-995页

作者： Yuan Weng Xinyu Yang Qiansen Zhang Ying Chen Yueming Xu Chenyu Zhu Qiong Xie Yonghui Wang Huaiyu Yang Mingyao Liu Weiqiang Lu Gaojie Song Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.

关键词： adenosine receptor A2AR A2BR inhibitor dual-antagonism drug discovery

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of Pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor

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Chinese Chemical Letters 2024年第4期35卷 382-388页

作者： Shiyu Hou Maolin Sun Liming Cao Chaoming Liang Jiaxin Yang Xinggui Zhou Jinxing Ye Ruihua Cheng school of Chemical Engineering East China University of Science and TechnologyShanghai 200237China school of biomedical and Pharmaceutical sciences Guangdong University of TechnologyGuangzhou 510006China school of pharmacy East China University of Science and TechnologyShanghai 200237China

Microchannels enable the fast and efficient mixing of multiphase fluids.In this study, a millimeter-scale three-dimensional(3D) circular cyclone-type microreactor was designed for the mixing.The flow characteristics and mixing intensity were simulated by computational fluid dynamics simulations at a flow rate range of 12–96 m L/min using a water/ethyl acetate system.In the 3D variable-diameter structure,the microreactor induced paired opposite vortices and abruptly changed the local pressure to achieve a stable turbulent effect within the theoretical range of laminar flow.Tracer injection simulations indicated that sufficient mixing units successfully promote fluid dispersion.Diazo-coupling experiments showed a segregation index of X_S= 0.00,039 within a residence time of 9 s.Extraction experiments on the nbutanol/succinic acid/water system showed that the 3D circular cyclone-type microreactor achieved 100%extraction efficiency(E) in 4.25 s, and the overall volume mass transfer coefficient(K_La) reached 0.05–1.5s^(-1) in 12–96 m L/min.The isolated yield of the phase transfer alkylation and oxidation reactions in the 3D circular cyclone-type microreactor achieved 99% within 36 s, which was superior to the coil microreactor and batch reactor.

关键词： Microfluidics Passive microreactor CFD simulation Extraction Liquid-liquid biphase reaction

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

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Targeting autophagy by polyphenols to prevent glycative stress-toxicity in the brain

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Neural Regeneration Research 2024年第5期19卷 941-942页

作者： Alejandro Ponce-Mora Eloy Bejarano Department of biomedical sciences School of Health Sciences and Veterinary SchoolUniversidad Cardenal Herrera-CEUCEU UniversitiesValenciaSpain

Glycative stress-a pathological hub in brain dysfunction:The nervous system is an intricate network that requires precise and complex maintenance.In recent years,growing evidence highlights the detrimental impact of glycative stress on brain homeostasis,which disables a network of vital processes,necessary for optimal function(Gómez et al.,2021).

关键词： homeostasis stress

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Neurogenic potential of NG2 in neurotrauma:a systematic review

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Neural Regeneration Research 2024年第12期19卷 2673-2683页

作者： Yuri R.Rigo Radharani Benvenutti Luis V.Portela Nathan R.Strogulski Departamento de Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do Sul(UFRGS)Porto AlegreBrazil school of pharmacy and Biomolecular sciences RCSI University of Medicine and Health SciencesDublinIreland school of Biochemistry and Immunology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain injuries.Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research.Recent studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed brain.As these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them.In the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to 2022.Here,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro.We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment.These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

关键词： neural-glial antigen 2 neural-glial factor 2 neuron differentiation NG2 cell regeneration spinal cord injury(SCI) traumatic brain injury(TBI)

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Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

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Animal Models and Experimental Medicine 2024年第3期7卷 297-309页

作者： Yasodha Krishna Janapati Sunil Junapudi school of pharmacy&Health sciences United States International University-AFRICA(USIU-A)NairobiKenya Department of Pharmaceutical Chemistry Geethanjali College of PharmacyKeesaraIndia

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.

关键词： animal models diabetes mellitus typeⅠ diabetes mellitus typeⅡ in vitro and in vivo models

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of biomedical Engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Shanghai World Foreign Language Academy Beijing Advanced Innovation Center for biomedical Engineering School of Engineering MedicineBeihang University Beijing Key Lab of Cryo-biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc.Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed.Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

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