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Mitochondria-targeted carrier-free nanoparticles based on dihydroartemisinin against hepatocellular carcinoma

Chinese Chemical Letters 2024年第10期35卷 329-333页

作者： Zhiyu Yu Xiang Luo Cheng Zhang Xin Lu Xiaohui Li Pan Liao Zhongqiu Liu Rong Zhang Shengtao Wang Zhiqiang Yu Guochao Liao Joint Laboratory for Translational Cancer res.arch of Chinese Medicine of the Ministry of Education of the People's Republic of China International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhou 510006China Guangzhou Yuemei Pharmaceutical Technology Co. Ltd.Guangzhou 510535China Afiliated Foshan Maternity&Child healthcare Hospital Southern Medical UniversityFoshan 528000China School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Laboratory Medicine Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsThe Tenth Afiliated Hospital of Southern Medical University(Dongguan People's Hospital)Dongguan 523058China

Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic ***(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and res.ltant mitochondrial ***,clinical translation is limited by several drawbacks,such as insolubility,instability and low ***,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial ***-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then *** cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stres. and in turn upregulated the downstream Bcl-2 pathway,leading to *** vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular *** findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.

关键词： Hepatocellular carcinoma Carrier-freenanoparticles Dihydroartemisinin Mitochondria targeting Apoptosis

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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 res.arch 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 pres.nce 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 addres.es 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 res.arch and development sector,and res.archers 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

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Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

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World Journal of Hepatology 2016年第32期8卷 1402-1413页

作者： Zahari Krastev Diana Petrova Iskren Kotzev Mustafa Kemal Celen Meryl Mendelson Richa Chandra Priti Pandey Kamal Hamed Clinic of Gastroenterology St.Ivan Rilsky University HospitalMedical University Department of Gastroenterology University Hospital Alexandrovska Clinic of Hepatogastroenterology University Hospital St Marina Infectious Disease Clinic Dicle University Novartis Pharmaceuticals Corporation East Hanover Novartis healthcare pvt. ltd.

AIMTo make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODSThis was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic res.onse, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA res.LTSA total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level CONCLUSIONEfficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.

关键词： Chronic hepatitis B Glomerular filtration rate Telbivudine Tenofovir Roadmap concept

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Fe₃O₄ and Fe Nanoparticles by Chemical Reduction of Fe(acac)₃ by Ascorbic Acid: Role of Water

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World Journal of Nano Science and Engineering 2016年第1期6卷 20-28页

作者： Ajinkya G. Nene Makoto Takahashi Prakash R. Somani Department of Applied Chemistry Chubu University Kasugai Japan Applied Science Innovations pvt. ltd. Pune India

Nanoparticles of Fe3O4 and Fe are chemically synthesized by reduction of Fe(acac)3 using ascorbic acid in controlled condition. It was observed that addition of water during the chemical synthesis process yields Fe3O4 nanoparticles, whereas if the reaction is carried out in absence of water yields Fe nanoparticles—which get oxidized upon exposure to air atmosphere. Fe3O4 (15 ± 5 nm) and Fe/iron oxide nanoparticles (7 ± 1 nm) were successfully synthesized in the comparative study reported herewith. Mechanism for formation/synthesis of Fe3O4 and Fe/iron oxide nanoparticles is proposed herewith in which added water acts as an oxygen supplier. Physico-chemical characterization done by SEM, TEM, EDAX, and XPS supports the proposed mechanism.

关键词： Fe3O4 Nanoparticles Fe-Nanoparticles Iron Oxide Chemical Reduction Method

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Medical decision making for older adults： an international perspective comparing the United States and India

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Journal of Geriatric Cardiology 2015年第4期12卷 329-334页

作者： Ankur Kalra Daniel E Forman Sarah J Goodlin Division of lnterventional Cardiology Beth lsrael Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA Division of Cardiology Department of Medicine Kalra Hospital SRCNC Pvt. Ltd. New Delhi India Section of Geriatric Cardiology University of Pittsburgh Medical Center Pittsburgh PA USA Geriatrics res.arch Education and Clinicai Center VA Pittsburgh Healthcare System Pittsburgh PA USA Department of Medicine-Geriatrics Oregon Health & Sciences University and Veterans Affairs Portland Health Care System Portland Oregon USA

There has been a significant decline in cardiovascular morbidity and mortality amidst pervasive advances in care, including percutane- ous revascularization, mechanical circulatory support, and transcatheter valvular therapies. While advancing therapies may add significant longevity, they also bring about new end-of-life decision-making challenges for patients and their families who also must weigh the advan- tages of reduced mortality to the possibility of longer lives consisting of high morbidity, frailty, pain, and poor quality of living. Advance care entails options of withholding or withdrawing therapies, and has become a familiar part of cardiovascular care for older patients in Western countries. However, as advanced cardiovascular practices extend to developing countries, the interrelated concept of advance care is rarely straight forward as it is affected by local cultural traditions and mores. and can lead to very different inferences and use. This paper discusses the concepts of advance care planning, surrogate decision-making, orders for res.scitation and futility in patients with cardiac dis- ease with comparisons of West to East, focusing particularly on the United States versus India.

关键词： Advance care planning Advance directive End-of-life India Surrogate decision-making

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Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations

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Acta Pharmaceutica Sinica B 2014年第5期4卷 333-349页

作者： Sivacharan Kollipara Rajesh Kumar Gandhi Formulations Department Pharmaceutical&Analytical DevelopmentTechnical R&DNovartis Healthcare Pvt.Ltd.Hyderabad 500078Andhra PradeshIndia

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal *** formulations offer multiple advantages such as reduction in food effect and inter-individual variability,ease of preparation,and the possibility of manufacturing using common excipients available in the *** these advantages,very few products are available in the pres.nt market,perhaps due to limited knowledge in the in vitro tests(for prediction of in vivo fate)and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral *** current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations,their pharmacokinetic aspects and in vitro in vivo correlation(IVIVC)*** pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion,bioavailability enhancement mechanisms,impact of excipients on efflux transporters,and lymphatic transport are discussed with *** addition,various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation,in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.

关键词： Pharmacokinetics Lipolysis IVIVC Efflux transporters Lymphatic delivery Food effect

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Design, Synthesis and Biological Evaluation of Novel Antitubercular Agents by Combining Pyrazoline and Benzoxazole Pharmacophores

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International Journal of Organic Chemistry 2016年第3期6卷 157-176页

作者： Hemal M. Soni Popatbhai K. Patel Mahesh T. Chhabria Ashish K. Patel Dharmraj N. Rana Pathik S. Brahmkshatriya M/S Piramal Enterprises ltd. Piramal Discovery Solutions Plot No. 18 Pharmaceutical Special Economic Zone Village Matoda Ta. Sanand Ahmedabad India M.G. Science Institute Opp. Gujarat University Navrangpura Ahmedabad India Department of Pharmaceutical Chemistry L. M. College of Pharmacy Navrangpura Ahmedabad India oxygen healthcare res. pvt. ltd. Plot No. 35 Panchratna Industrial Estate Near IBP Laxminarayan Petrol Pump Changodar Ahmedabad India

Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB i.e. multiple-drug res.stance tuberculosis, XDR-TB i.e. extensively-drug res.stance tuberculosis & TDR-TB i.e. total-drug res.stance tuberculosis has forwarded an urgent need to discover novel antitubercular agents. The current work is aimed at combining two previously well-known pharmacophores.(pyrazoline and benzoxazole nucleus) in order to design and synthesize a series of novel benzoxazole-based pyrazoline derivatives. The synthesized target compounds were structurally confirmed by LCMS, 1H-NMR and 13C-NMR analysis. The target compounds were In vitro evaluated against M. tuberculosis H37Rv strain, multidrug-res.stant TB (MDR-TB) and extensively drug-res.stant TB (XDR-TB) strains. The In vitro screening res.lts depicted that majority of the target compounds displayed potent activity with MIC in a range of ~0.8 to 6.25 μg/mL. Many compounds were found to be more potent than isoniazid against MDR-TB with MIC value 3.12 μg/mL and XDR-TB with MIC value 12.5 μg/mL. Cytotoxicity assay of these active compounds on VERO cell lines also displayed good selectivity index.

关键词： Antitubercular Benzoxazole Pyrazoline Pharmacophore Microplate Alamar Blue Assay

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Comparative efficacy of secukinumab against adalimumab and infliximab in patients with moderate-to-severe plaque psoriasis

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Chinese Medical Journal 2022年第1期135卷 11-19页

作者： Ran Pan Xiaolun Wang Min Shu Jaydeep Das Manik Kalra Zhidong Wang Beijing Novartis Pharma Co.ltd. ShanghaiChina Novartis healthcare pvt.ltd. HyderabadIndia

Background: Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque ***: A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interes. were SEC, ADA, INF, and placebo (PLA), while outcomes of interes. were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI res.onses in different categories of PASI thres.olds within a single ***: A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better res.onse compared with PLA and ADA for PASI 75 and 90, while res.onse res.lts were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SECvs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), res.ectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and ***: Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA.

关键词： Moderate-to-severe plaque psoriasis Secukinumab against adalimumab and infliximab Indirect comparison PASI res.onse

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Design and implementation of various datapath architectures.for the ANU lightweight cipher on an FPGA

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Frontiers of Information Technology & Electronic Engineering 2020年第4期21卷 615-628页

作者： Vijay DAHIPHALE Gaurav BANSOD Ankur ZAMBARE Narayan PISHAROTY Pune Institute of Computer Technology Pune 411043India Iziel healthcare pvt.ltd. Pune 411028India

Since the dawn of the Internet of Things(IoT),data and system security has been the major concern for *** most IoT devices operate on 8-bit controllers with limited storage and computation power,encryption and decryption need to be implemented at the transmitting and receiving ends,res.ectively,using lightweight *** pres.nt novel architectures.for hardware implementation for the ANU cipher and pres.nt res.lts associated with each *** ANU cipher is implemented at 4-,8-,16-,and 32-bit datapath sizes on four different field-programmable gate array(FPGA)platforms under the same implementation condition,and the res.lts are compared on every performance *** previous ANU architectures.the new architectures.have parallel substitution boxes(S-boxes)for high throughput and hardware *** these different datapath designs,ANU cipher proves to be the obvious choice for implementing security in extremely res.urceconstrained systems.

关键词： Lightweight cryptography Internet of Things(IoT) Embedded security Encryption FPGA Datapath design

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New Method for Synthesis of Coatings of Molybdenum, Tungsten, Their Carbides and Composites

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Open Journal of Synthesis Theory and Applications 2013年第2期2卷 78-85页

作者： Rhushikesh V. Godbole Mahendra A. More Anil S. Gupte Vijay P. Godbole Center for Nano-Materials and Quantum Systems (CNQS) Department of Physics University of Pune Pune India Technical Director Poona Shims Pvt. Ltd. Pune India

In this paper we report, for the first time, a new approach for synthesis of high quality faceted microcrystalline coatings of molybdenum (Mo), tungsten (W), their carbides and composites. These studies are carried out using Hot Filament Chemical Vapor Deposition (HF-CVD) method wherein parent materials (Mo and/or W) are taken in the form of wires.(~0.5 mmdia) and are heated to a high temperature (TF ~ 1500 - 2000 C), in ambient of “oxygen (O2) diluted hydrogen (H2) gas”. Due to high filament temperature (TF), a series of pyrolytic reactions take place. Firstly, the gasification of wire material (Mo and/or W) occurs in the form of its oxide. The oxide molecules reach the substrate which is kept underneath the filament assembly. Secondly, molecular hydrogen gets dissociated into atomic hydrogen and subsequently reaches the substrate to react with oxide molecules, finally leading to the precipitation of a pure metal. This method can also be used, in situ, to convert metallic coatings into their carbides and/or composites. The method offers many other attractive features. which can not be rendered by the conventionalCVD/PVDmethods. The res.lts are discussed in terms of temperature induced “Red-ox” reactions.

关键词： CVD Coatings Pyrolysis Ceramics Refractories

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