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Autophagy as a targeted therapeutic approach for skin cancer:Evaluating natural and synthetic molecular interventions

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Cancer Pathogenesis and Therapy 2024年第4期2卷 231-245页

作者： Md.Liakot Ali Amdad Hossain Roky S.M.Asadul Karim Azad Abdul Halim Shaikat Jannatul Naima Meem Emtiajul Hoque Abu Mohammed Fuad Ahasan Mohammed Murshedul Islam Md.Saifur Rahaman Arif Md.Saqline Mostaq Md.Zihad Mahmud Mohammad Nurul Amin MdAshiq Mahmud Department of pharmacy University of ChittagongChattogram 4331Bangladesh Pratyasha Health Biomedical Research Center Dhaka 1230Bangladesh Department of pharmacy International Islamic University ChittagongChattogram 4318Bangladesh Department of pharmacy Daffodil International UniversityDhaka 1216Bangladesh Department of pharmacy BGC Trust University BangladeshChattogram 4381Bangladesh School of Basic Pharmaceutical and Toxicological Sciences College of PharmacyUniversity of Louisiana at MonroeMonroeLA 71209-0497USA pioneer Dental college and Hospital Dhaka 1229Bangladesh

Skin cancer,a prevalent malignancy worldwide,poses significant health concerns owing to its increasing ***,a natural cellular process,is a pivotal event in skin cancer and has advantageous and detrimental *** duality has prompted extensive investigations into medical interventions targeting autophagy modulation for their substantial therapeutic *** systematic review aimed to investigate the relationship between skin cancer and autophagy and the contribution and mechanism of autophagy modulators in skin *** outlined the effectiveness and safety of targeting autophagy as a promising therapeutic strategy for the treatment of skin *** comprehensive review identified a diverse array of autophagy modulators with promising potential for the treatment of skin *** of these compounds demonstrates efficacy through distinct physiological mechanisms that have been elucidated in ***,findings from a literature search indicated that none of the natural,synthetic,or semisynthetic compounds exhibited notable adverse effects in either human or animal ***,this review offers novel mechanistic and therapeutic perspectives on the targeted modulation of autophagy in skin cancer.

关键词： Autophagy Skin cancer Autophagy inducers Autophagy inhibitors Nature-derived compounds Synthetic compounds

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Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

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Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin Key Laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China college of pharmacy Harbin Medical UniversityHarbin 150081China Institute of Clinical Pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China Department of Clinical Pharmacology college of pharmacy Harbin Medical UniversityHarbin 150081China State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in ***:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as *** analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of *** prescriptions were screened via the dissolution degree determination *** Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid *** toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for ***:AE-SD showed that AE existed in the carrier in an amorphous *** with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug ***,it was more suitable as a carrier material for *** addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of *** dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also *** on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than *** results showed that the drug metabolism in AE-SD was better,and the residence time was *** toxicology study showed that both AE and AE-SD had no ***:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

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A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy

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Chinese Chemical Letters 2024年第10期35卷 353-359页

作者： Han Han Bi-Te Chen Jia-Rong Ding Jin-Ming Si Tian-jiao Zhou Yi Wang Lei Xing Hu-Lin Jjiang State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China college of pharmacy .Yanbian UniversityYanji 133002China Department of Nephrology Changhai HospitalNaval Medical UniversityShanghai 200433China

Activated pancreatic stellate cells(PSCs)are the main source of collagen layer deposition and the key target in pancreatic ***,no effective treatment specific to pancreatic fibrosis clinically,owing to the drug accumulation blocked by the collagen barrier and thus it is difficult to inhibit activated PSCs ***,a PSCs-targeting nano-system based on“nanodrill”strategy(LA-PC)was designed to enhance the accumulation of all-trans retinoic acid(ATRA)in PSCs,relying on the platelet-derived growth factor receptor beta(PDGFRβ)-targeting peptide(p PB:C*SRNLIDC*)and collagenase(Col).After being injected into fibrotic mice via tail vein,the Col modified on LA-PC can remove the excess collagen layer,and the drug delivery efficiency through pPB targeting peptide was more than 5 times higher than that of free ATRA,as well as the degree of fibrosis significantly ***,this nano-system effectively inhibited platelet-derived growth factor subunit B(PDGF-BB)/PDGFRβaxis on PSCs via a down-regulated extracellular signal-regulated protein kinase(ERK)pathway,and accordingly reduced the level of ***,the smart platform provided a promising strategy for the treatment of pancreatic fibrosis to achieve the precise regulation of PSCs.

关键词： Pancreatic fibrosis Pancreatic stellate cells Liposome PDGFRβ pPB peptide

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The Mechanism by Which Pereskia aculeata *** Ferroptosis and Interferes with Colon Cancer Based on Network Pharmacology

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Medicinal Plant 2024年第2期15卷 26-29页

作者： Kaifei LIU Yingyuan QIN Linhao LIU Ye CHU Huanjin HUANG Jingwei LUO Xiaolong CHEN Yang YANG Yifei CHEN college of pharmacy Guilin Medical UniversityGuilin 541199China Guangxi Key Laboratory of Drug Discovery and Optimization Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability EvaluationCollege of PharmacyGuilin Medical UniversityGuilin 541199China Department of Nephrology Guilin Municipal Hospital of Traditional Chinese MedicineGuilin 541002China

[Objectives]The paper was to investigate the mechanism by which Pereskia aculeata *** ferroptosis and interferes with colon cancer using network pharmacology.[Methods]The effect of *** on HCT116 cells was observed by examining cell *** intersection of ***,colon cancer,and ferroptosis targets was determined using the Venny 2.1.0 online *** database was used to perform GO and KEGG enrichment ***_v3.10.0 was used for network mapping and PPI analysis.[Results]The observation of cell morphology indicated that *** suppressed the growth of HCT116 *** and KEGG analysis identified 67 genes involved in potential pathways,including the MAPK signaling pathway and Apoptosis,18 of which were located on the MAPK *** conducting PPI visualization analysis and ranking based on degree values,we identified TP53,TNF,EGFR,MAPK14,and AKT1 as the top five targets with the highest degree values.[Conclusions]*** may activate the p53 gene through the MAPK signaling pathway,inducing ferroptosis and ultimately resulting in tumor cell death.

关键词： Pereskia aculeata Mill. Ferroptosis MAPK signal pathway Colon cancer

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Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

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Acupuncture and Herbal Medicine 2024年第1期4卷 92-101页

作者： Li Liu Yanqing Liu Shujie Zhang Junzhe Zhang Yuqing Meng Dandan Liu Liwei Gu Ying Zhang Liting Xu Ziyue Zhang Minghong Zhao Yinkwan Wong Qixin Wang Yongping Zhu Jigang Wang college of pharmacy Gannan Medical UniversityGanzhouChina State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijingChina Department of Pharmacological Sciences Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium *** study aims to provide a scientific basis for the rational development and use of celastrol in breast ***:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer ***:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its ***,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis *** the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of ***,apoptosis was reversed by the overexpression of ***,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling *** also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)***:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.

关键词： Activity-based protein profiling Apoptosis Celastrol HSDL2

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The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen college of pharmacy and Department of Hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development Immunity Multifaceted functions Therapeutic target Tumorigenesis

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Distribution of licensed acupuncturists and educational institutions in the United States at the start of 2023,during the late stage of the COVID-19 pandemic

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Journal of Integrative Medicine 2024年第4期22卷 379-384页

作者： Arthur Yin Fan De-guang He Anu Sangraula Sarah Faggert Alemi Amy Matecki American Traditional Chinese Medicine Association ViennaVA 22182USA McLean Center for Complementary and Alternative Medicine ViennaVA 22182USA New England School of Acupuncture Massachusetts College of Pharmacy and Health SciencesBostonMA 02115USA Lombardi Comprehensive Cancer Center Cancer Prevention and Control ProgramGeorgetown UniversityWashington DC 20057USA Eastern Roots Wellness PLCMcLeanVA 22101USA Sutter Health Alta Bates Summit Medical CenterOaklandCA 94609USA

This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active LAcs as of January 1,2023 was 34,524,potentially33,364 after removing license duplication in multiple states,among which the largest three states were California(with 7317 LAcs[21.19%of the total]),New York(5024[14.55%])and Florida(2644[7.66%]).The total number of LAcs decreased by 8.87%from 2018,and fell short of our projected number of LAcs in 2023 by 9037,or 20.75%.The overall LAc density in the *** as the number of LAcs per 100,000 populationDwas 10.36,less than in *** were 56 active,accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing[entry-level],12 for an advanced practicing degree[advanced-level],and 14 for certifications).Broken down further,offerings included 50 master's degrees in acupuncture,40 master's degrees in Oriental medicine,31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine),and 12advanced-level doctorate degrees in *** certification programs included one in East-Asian Medical Bodywork and 13 in *** these schools in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national ***,Florida and Illinois represented 39.29%.There were 48 jurisdictions with acupuncture practice laws in *** data suggests that the acupuncture profession in the *** been significantly impacted during the coronavirus disease 2019 pandemic.

关键词： Acupuncturist Acupuncture educational institution Distribution Density Oriental medicine United States

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Identifying and validating MMP family members(MMP2,MMP9,MMP12,and MMP16)as therapeutic targets and biomarkers in kidney renal clear cell carcinoma(KIRC)

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Oncology Research 2024年第4期32卷 737-752页

作者： KUNLUN LI DANDAN LI BARBOD HAFEZ MOUNIR M.SALEM BEKHIT YOUSEF A.BIN JARDAN FARS KAED ALANAZI EHAB I.TAHA SAYED H.AUDA FAIQAH RAMZAN MUHAMMAD JAMIL The Second Affiliated Hospital of Harbin Medical University Harbin Medical UniversityHarbinChina Department of Pharmaceutical Engineering Jiangsu Ocean UniversityLianyungangChina Department of Biological Engineering University of SalfordSalfordUK Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia Department of Animal and Poultry Production Faculty of Veterinary and Animal SciencesGomal UniversityDera Ismail KhanPakistan Department of Arid Zone Research PARC instituteDera Ismail KhanPakistan

Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and *** MMP family assumes a crucial role in tumor invasion and *** study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular ***,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for *** performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree *** analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to *** notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC ***,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic *** MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.

关键词： KIRC MMP gene family Chemotherapy Overall survival

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Novel anticancer agents from plant sources

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中国天然药物 2013年第1期11卷 16-23页

作者： Shah Unnati Shah Ripal Acharya Sanjeev Acharya Niyati pioneer pharmacy degree college Vadodara-390019 India Sun Pharma Advanced Research Centre Vadodara-390020 India ~nstitute of pharmacy Nirma University Sarkhej-Gandhinagar Highway Ahmedabad-382481 India

植物仍然是新药，新药领先和新化学实体的重要来源。植物基于的药发现主要导致了 anticancer 和反传染的代理人的发展，并且继续在临床的试用贡献新领先。自然产品药在药品的照顾起一个主导的作用。几导出植物的混合物成功地当前在癌症... 详细信息

植物仍然是新药，新药领先和新化学实体的重要来源。植物基于的药发现主要导致了 anticancer 和反传染的代理人的发展，并且继续在临床的试用贡献新领先。自然产品药在药品的照顾起一个主导的作用。几导出植物的混合物成功地当前在癌症治疗被采用。有为药的进一步的改进和开发学习的导出植物的细胞毒素的自然产品的许多类。从关于植物 antitumor 代理人的研究导出的新 anticancer 药将连续地被发现。这评论的基本目的是从药用的植物探索最新发现的 anticancer 混合物的潜力，作为为 anticancer 药开发的领先。在地球附近为研究人员和科学家从他们探索植物并且为新药发现的药用的价值将是有用的。

关键词： Cancer Anticancer agents Medicinal plants

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Quantitative assessment of the relevance of organic-aniontransporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

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Journal of Pharmaceutical Analysis 2023年第6期13卷 660-672页

作者： Ji-Hun Jang Seung-Hyun Jeong Yong-Bok Lee Department of pharmacy College of PharmacyChonnam National UniversityGwangju61186Republic of Korea Department of pharmacy College of PharmacySunchon National UniversitySuncheon-si57922Republic of Korea

Fexofenadine is useful in various allergic disease ***,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very *** study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic *** of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic ***,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and ***1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic ***/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 *** the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,*** of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism *** on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic *** on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as *** population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.

关键词： OATP1B1 OATP2B1 Fexofenadine Population pharmacometrics Genetic polymorphism

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