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Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance

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Genes & Diseases 2024年第1期11卷 148-175页

作者： Divya Ajmeera Rajanna Ajumeera Cell Biology Department ICMR-National Institute of Nutrition(NIN)HyderabadTelangana 500007India

Chemotherapy is an effortless and frequently used approach in cancer ***,in most cases,it can only prolong life expectancy and does not guarantee a complete ***,chemotherapy is associated with severe adverse effects,one of the major complications of effective cancer *** addition,newly published research outputs show that cancer stem cells are involved in cancer disease progression,drug resistance,metastasis,and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to *** strategies are therefore required for better management of cancer *** prime approach would be to synthesize and develop novel drugs that need extensive resources,time,and endurance to be brought into therapeutic *** subsequent approach would be to screen the anti-cancer activity of avail-able non-cancerous *** concept of repurposing non-cancer drugs as an alternative to current cancer therapy has become popular in recent years because using existing anticancer drugs has several adverse *** have also been investigated for cancer ther-apy due to their significant anti-cancer effects with negligible or no side effects and availabil-ity in food *** this paper,we discuss an ideal hypothesis for screening available non-cancerous drugs with anticancer activity,with a focus on cancer stem cells and their clinical application for cancer ***,drug repurposing and the combination of micronu-trients that can target both cancers and cancer stem cells may result in a better therapeutic approach leading to maximum tumor growth control.

关键词： Cancerstem cells Chemotherapy Combination therapy micronutrients Non-cancer drugs Novel strategies

Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 73-81,I0006-I0009页

作者： Tiasha Dasgupta Venkatraman Manickam Department of Biomedical Sciences School of Biosciences and TechnologyVellore Institute of TechnologyVellore 632014Tamil NaduIndia

Objective:To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 ***:RAW 264.7 macrophages were treated with ethanol(100 mM)and benzydamine hydrochloride(7.5μM).The imflammatory status was confirmed by measuring pro-(TNF-αand IL-6)and anti-inflammatory(IL-10)cytokines through ELISA and RT-PCR *** oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative *** detection was also investigated using flow cytometry and acridine orange/ethidium bromide ***:Benzydamine hydrochloride significantly decreased the secretion of TNF-αand IL-6,as well as the generation of reactive oxygen species inside the cells,thereby stabilizing the mitochondrial membrane potential and reducing DNA *** ethanol-induced cellular necrosis was also reversed by the administration of benzydamine ***:Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

关键词： Alcohol Benzydamine hydrochloride Inflammation Oxidative stress Apoptosis

Liposomal dual delivery systems in visceral leishmaniasis enhance the synergistic effects of combination therapy:A promise for the future

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Asian Pacific Journal of Tropical Medicine 2024年第2期17卷 47-60页

作者： Raghunath Hazra Amrita Kar Santanu Kar Mahapatra Department of Paramedical and Allied Health Sciences Biodiversity and Environmental Studies Research CentreMidnapore City CollegeKuturiyaBhadutalaPaschim Medinipur-721129West BengalIndia

Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its *** also highlights alternative approaches used by research groups in India and around the world to develop cutting-edge and potent anti-leishmanial *** though numerous medications could be utilized to treat VL,the limitations of current treatments including their toxicity,cost,route of administration,and duration of doses,have contributed to the emergence of *** therapy might be a better option due to its shorter duration,easier route of administration,and ability to extend the lifespan of individual ***,there is a risk of not delivering both the drugs to the target site together,which can be overcome by the liposomal entrapment of those drugs and at a time knock an opportunity to reduce the dosage of amphotericin B if the combination drug provides a synergistic effect with ***,this review presents a novel strategy to fight against VL by introducing dual drug-loaded liposomes.

关键词： Visceral leishmaniasis Liposomal anti-leishmanial drug Dual drug liposome

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 *** 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 *** 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 *** review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and ***,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

Perspectives and challenges of tropical medicinal herbs and modern drug discovery in the current scenario

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Asian Pacific Journal of Tropical Medicine 2019年第1期12卷 1-7页

作者： Rajesh Kumar Kesharwani Krishna Misra Dev Bukhsh Singh Department of Advanced Science & Technology NIET Nims University Rajasthan Department of Applied Science Indian Institute of Information Technology Allahabad Department of Biotechnology Institute of Biosciences and Biotechnology Chhatrapati Shahu Ji Maharaj University

Tropical diseases such as malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for a large number of deaths annually. Herbs are an excellent source of tropical medicines. Many advancements and discoveries have taken place in the field of drug discovery but still, a major population of tropical diseases relies on herbal traditional medicine. There are some challenges related to policy implementation, efficacy, resistance and toxicity of tropical medicines. There are many tropical diseases such as such as schistosomiasis, leishmaniasis, African sleeping sickness, filariasis and chagas disease which are neglected because very few pharmaceutical companies have shown their interest in developing therapeutics against these diseases of poor people. There are many benefits associated with herbal medicine such as the cost of production, patient tolerance, large scale availability, efficacy, safety, potency, recyclability, and environment friendly. A large number of natural extracts such as curcumin, artemisinin, morphine, reserpine, and hypericin, are in use for treatment of different tropical diseases for a long time. The current review is to discuss the overview of tropical medicinal herbs, its scope and limitations in the modern drug discovery process.

关键词： Herbs Natural sources Lead compounds Drug discovery Computational approaches

Prediction modelling in the early detection of neonatal sepsis

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World Journal of Pediatrics 2022年第3期18卷 160-175页

作者： Puspita Sahu Elstin Anbu Raj Stanly Leslie Edward Simon Lewis Krishnananda Prabhu Mahadev Rao Vijayanarayana Kunhikatta Department of Pharmacy Practice Manipal College of Pharmaceutical SciencesManipal Academy of Higher Education(MAHE)Manipal 576104KarnatakaIndia Department of Paediatrics Kasturba Medical CollegeManipal Academy of Higher Education(MAHE)ManipalKarnatakaIndia 576104 Department of Biochemistry Kasturba Medical CollegeManipal Academy of Higher Education(MAHE)ManipalKarnatakaIndia 576104

Background Prediction modelling can greatly assist the health-care professionals in the management of diseases,thus sparking interest in neonatal sepsis *** main objective of the study was to provide a complete picture of performance of prediction models for early detection of neonatal *** PubMed,Scopus,CINAHL databases were searched and articles which used various prediction modelling measures for the early detection of neonatal sepsis were *** extraction was carried out based on Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies *** data consisted of objective,study design,patient characteristics,type of statistical model,predictors,outcome,sample size and *** model Risk of Bias Assessment Tool was applied to gauge the risk of bias of the *** An aggregate of ten studies were included in the review among which eight studies had applied logistic regression to build a prediction model,while the remaining two had applied artificial *** predictors like neonatal fever,birth weight,foetal morbidity and gender,cervicovaginitis and maternal age were identified for the early detection of neonatal ***,birth weight,endotracheal intubation,thyroid hypofunction and umbilical venous catheter were promising factors for predicting late-onset sepsis;while gestational age,intrapartum temperature and antibiotics treatment were utilised as budding prognosticators for early-onset sepsis *** Prediction modelling approaches were able to recognise promising maternal,neonatal and laboratory predictors in the rapid detection of early and late neonatal sepsis and thus,can be considered as a novel way for clinician decisionmaking towards the disease diagnosis if not used alone,in the years to come.

关键词： Neonatal sepsis Predictors Prediction modelling Systematic review Validation

Intestinal permeability and its association with the patient and disease characteristics in Crohn's disease

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World Journal of Gastroenterology 2008年第9期14卷 1399-1405页

作者： Jaya Benjamin Govind K Makharia Vineet Ahuja Mani Kalaivan Yogendra K Joshi Department of Gastroenterology & Human Nutrition All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India Department of Biostatistics All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India Department of Gastroenterology & Human Nutrition All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India

AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorptio

关键词： Lactulose mannitol ratio Crohn's disease Inflammatory bowel disease Intestinal barrier Crohn's disease activity index Intestinal permeability

Aloe barbadensis Miller peptide/polypeptide fraction alleviates inflammation through inhibition of proinflammatory cytokines and mediators in vitro and in rats with Freund’s adjuvant-induced hind paw edema

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Asian Pacific Journal of Tropical Biomedicine 2019年第12期9卷 524-530页

作者： Spoorthy N.Babu Ayesha Noor Centre for Bio Separation Technology Vellore Institute of TechnologyVelloreIndia

Objective:To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo ***:The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid *** anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation,membrane stabilization *** effect of the fraction on RAW 264.7 cell viability was examined by MTT *** nitric oxide level was determined through Griess ***-αand IL-6 levels were estimated using ELISA *** vivo studies were carried out in male Wistar rats through injection of Freund’s adjuvant in the hind *** edema was measured through the Vernier scale and levels of alanine aminotransferase,aspartate transaminase,TNF-α,IL-6,and secretory phospholipase A2 were estimated through their respective kits after fourteen days of *** Pad Prism6 was used for analyzing the ***:The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of(218.9±15.6)μg/m L and stabilized the membrane of red blood cells with an IC50 value of(275.9±19.1)μg/m *** extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20μg/mL in MTT *** peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo ***:The results indicate that the peptide/polypeptide fraction of Aloe vera has antiinflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways.

关键词： Aloe vera Peptide/Polypeptide Inflammation Proinflammatory cytokines

Spectrum, Manifestations and Outcomes of Dengue Infection in Individuals with and without Liver Disease

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 106-111页

作者： Anand VKulkarni Ashok K.Choudhury Madhumita Premkumar Priyanka Jain Ekta Gupta Shiv Kumar Sarin Department of Hepatology and Transplant Institute of Liver and Biliary SciencesNew DelhiIndia Department of Virology Institute of Liver and Biliary SciencesNew DelhiIndia Department of Statistics Institute of Liver and Biliary SciencesNew DelhiIndia

Background and Aims:Dengue infection is a major health burden,which can result in mild self-limited febrile illness to highly fatal hemorrhagic *** is paucity of literature describing the manifestations of dengue in patients with underlying liver *** studied and compared the manifestations of this tropical infection in patients with and without liver ***:Patients with serologically-confirmed dengue infection were included in this retrospective study,obtained for over a period of 1 *** and laboratory variables were compared for the individuals with no underlying liver disease(Group A,n=71),chronic hepatitis(Group B,n=12),and cirrhosis(Group C,n=12).Results:Males predominated the study population(61%),with a higher mean age in the cirrhotic *** most common clinical manifestation was classical dengue fever,seen in 89 *** presented as dengue hemorrhagic fever(1 each in Group A and Group B),1 presented as acute liver failure,and 3 as acute-on-chronic liver *** was less evident in Group C as compared to Group A and Group B(p in Group C had significantly prolonged International Normalized Ratio(INR)and enhanced thrombocytopenia compared to patients in Group A and Group *** in Group C also required prolonged hospital stay(Group A:4.83±2.88,Group B:7.33±2.3,Group C:13±5 days;p patients expired in Group C compared to the 1 in Group A and none in Group B(p=0.01).On univariate analysis,hemoglobin,albumin,INR,and bilirubin predicted development of liver *** multivariate analysis,INR and bilirubin predicted development of liver ***:Dengue infection can have varied manifestations,ranging from simple fever to acute-on-chronic liver failure and acute liver *** patients lack classical features of dengue and have relatively poor *** should be suspected as a cause of liver failure in endemic areas,where no etiological ca

关键词： Dengue Cirrhosis Acute-on-chronic liver failure Acute liver failure