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Tribology of enzymatically degraded cartilage mimicking early osteoarthritis

Friction 2023年第9期11卷 1724-1740页

作者： ke REN Miguel Alejandro REINA MAHECHA Maike HÜBNER Zhiwei CUI Hans J.kAPER Hugo C.VAN DER VEEN prashant k.sharma Department of Biomedical Engineering University Medical Centre GroningenUniversity of GroningenGroningen 9713AVthe Netherlands Department of Mechanical Engineering Eindhoven University of TechnologyEindhoven 5600MBthe Netherlands Department of Orthopedic Surgery University Medical Centre GroningenUniversity of GroningenGroningen 9700RBthe Netherlands

Healthy cartilage is a water-filled super lubricious *** type II provides it structural stability,and proteoglycans absorb water to keep the cartilage in a swollen condition,providing it the ability to creep and provide weeping ***(OA)is a degenerative and debilitating disorder of diarthrodial joints,where articular cartilage damage originates from enzymatic degradation and mechanical damage(wear).The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in ***(Lat)and medial(Med)condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical *** cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans,*** loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope(AFM),respectively.A significant effect on creep due to enzymatic treatment was not *** the enzymatic treatment was found to significantly decrease the coefficient of friction(COF)at 4 N,while higher COF was shown from chondroitinase ABC degraded cartilage at 40 *** III treatment leads to the release of intact proteoglycans at the sliding interface,while chondroitinase ABC treatment leads to the loss of chondroitin sulfate(CS)from the *** ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans,collagen network,and friction behavior.

关键词： lubrication cartilage boundary lubrication osteoarthritis(OA)

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Role of lysosomal trafficking regulator in autophagic lysosome reformation in neurons:a disease perspective

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Neural Regeneration Research 2024年第5期19卷 957-958页

作者： prashant sharma Jenny Serra-Vinardell Wendy J.Introne May Christine V.Malicdan NIH Undiagnosed Diseases Program Common FundOffice of the DirectorNational Institutes of HealthBethesdaMDUSA Human Biochemical Genetics Section Medical Genetics BranchNational Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA(Serra-Vinardell JIntrone)

Lysosomes are discrete organelles that act as recycling centers for extracellular and intracellular materials,playing a pivotal role in maintaining cellular *** acidic environment,maintained by numerous hydrolytic enzymes,facilitates substrate *** in lysosomal processes can lead to abnormal substrate degradation,significantly impacting cellular *** energy-demanding cells,such as post-mitotic neurons,are especially vulnerable to these changes,often resulting in neurological ***,a conserved catabolic process,requires extensive lysosomal *** plays a key role in removing unnecessary intracellular components,ensuring cellular homeostasis,and promoting cell survival during stress conditions such as starvation,infection,or cellular damage.

关键词： homeostasis lysosomal removing

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BACE1 inhibitors:A promising therapeutic approach for the management of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 369-381页

作者： Richa Arya Smita Jain Sarvesh Paliwal kirtika Madan Swapnil sharma Achal Mishra prashant Tiwari Sunil kumar kadiri Banasthali University Banasthali-304022(Raj.)India Department of Pharmacy Guru Ghasidas VishwavidyalayaBilaspurChhattisgarh-495009India Department of Pharmacology College of Pharmaceutical SciencesDayananda Sagar UniversityBengaluru-560111India

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta(Aβ)aggregates,resulting from mutations in the amyloid precursor *** enzymeβ-secretase,also known asβ-site amyloid precursor protein cleaving enzyme 1(BACE1),plays a crucial role in generating Aβ*** no targeted therapy available for Alzheimer’s disease,inhibiting BACE1 aspartic protease has emerged as a primary treatment *** 1999,compounds demonstrating potential binding to the BACE1 receptor have advanced to human *** optimization of synthetically derived compounds,coupled with computational approaches,has offered valuable insights for developing highly selective leads with drug-like *** review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease *** summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status,indicating future directions for novel BACE1 *** promising clinical results of Elenbecestat(E-2609)catalyze the development of effective,selective BACE1 inhibitors in the future.

关键词： BACE1 inhibitors Amyloid precursor protein β-secretase Structure-based drug design 3D-QSAR β-amyloid precursor protein

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Systematic Assessment of Synthesized Tri-magnesium Phosphate Powders(Amorphous,Semi-crystalline and Crystalline) and Cements for Ceramic Bone Cement Applications

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Journal of Materials Science & Technology 2015年第5期31卷 437-444页

作者： Nicole Ostrowski Vidisha sharma Abhijit Roy prashant N.kumta Department of Bioengineering University of Pittsburgh Center of Complex Engineered Multifunctional Materials University of Pittsburgh Department of Chemical and Petroleum Engineering University of Pittsburgh Department of Mechanical Engineering and Materials Science University of Pittsburgh

Magnesium phosphate cements have come under investigation in recent years for use as an alternative to calcium phosphate cements for bone void repair *** indicates that magnesium phosphate cements obtain higher initial strengths after cement reaction and resorption in more clinically appropriate time frames than commercially available calcium phosphate *** this study,amorphous,partially amorphous and crystalline tri-magnesium phosphate powders were synthesized via an aqueous precipitation reaction with subsequent thermal treatment,and characterized using techniques such as X-ray diffraction and Fourier transform infrared *** materials were assessed for their functionality in cementing reaction with a 3.0 mol/L,pH 7.0 ammonium phosphate solution,including setting time and pH evolution in phosphate buffered saline *** indicated that the amorphous and semi-crystalline tri-magnesium phosphate powders were highly reactive with the setting solution but resulted in mechanically weak cements,while the crystalline tri-magnesium phosphate powder reacted efficiently with the cement solution and were mechanically strong following the cement reaction.X-ray diffraction and scanning electron microscopy analyses indicated significant changes in the phase composition and morphology of the cements following incubation in phosphate buffered *** were perceived to be detrimental to the integrity of the amorphous and semi-crystalline tri-magnesium phosphate derived cements but not to those created with fully crystalline tri-magnesium *** crystalline tri-magnesium phosphate material resulted in the most functional cement as this embodiment displayed the most clinically relevant setting time as well as the highest mechanical resilience and neutral pH during incubation in saline solution rendering them potentially viable as bone void fillers.

关键词： Amorphous magnesium phosphate Tri-magnesium phosph

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Force degradation behavior of glucocorticoid deflazacort by UPLC：isolation,identification and characterization of degradant by FTIR,NMR and mass analysis

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The Journal of Biomedical Research 2016年第2期30卷 149-161页

作者： Rajesh Deshmukh Lata sharma Muktika Tekade prashant kesharwani Piyush Trivedi Rakesh k.Tekade Macleods Pharmaceuticals Ltd. Kachigam Daman 396320 India School of Pharmaceutical Science Rajiv Gandhi Prodyogiki Vishwavidyalaya Gandhi Nagar Bhopal 462036 India TIT College of Pharmacy Technocrats Institute of Technology Anand Nagar Bhopal 462021 India Department of Pharmaceutical Sciences Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University Detroit MI 48201 USA The University of Texas Southwestern Medical Center Advanced Imaging Research Center Dallas TX 75390 USA The International Medical University School of Pharmacy Department of Pharmaceutical Technology Kuala Lumpur57000 Malaysia

In this investigation,sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation *** method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18columns（1.7 urn,2.1 mm ×150 mm） using acetonitrile and water（40：60 V/V） at a flow rate of 0.2 mL/minute in *** detection was performed at 240.1 *** was subjected to oxidative,acid,base,hydrolytic,thermal and photolytic *** drug was found to be stable in water and thermal stress,as well as under neutral stress ***,forced-degradation study performed on deflazacort showed that the drug degraded under alkaline,acid and photolytic *** degradation products were well resolved from the main peak,which proved the stability-indicating power of the *** developed method was validated as per ICH guidelines with respect to accuracy,linearity,limit of detection,limit of quantification,accuracy,precision and robustness,selectivity and *** from the aforementioned,the results of the present study also emphasize the importance of isolation characterization and identification of ***,an attempt was made to identify the degradants in *** of the degradation products of deflazacort was isolated and identified by the FTIR,NMR and LC-MS study.

关键词： Deflazacort forced degradation degradant characterization

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Design of high-strength refractory complex solid-solution alloys

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npj Computational Materials 2018年第1期3卷 519-526页

作者： prashant Singh Aayush sharma A.V.Smirnov Mouhamad S.Diallo Pratik k.Ray Ganesh Balasubramanian Duane D.Johnson Ames Laboratory U.S.Department of EnergyIowa State UniversityAmesIA 50011USA Mechanical Engineering Iowa State UniversityAmesIA 50011USA Materials Science&Engineering Iowa State UniversityAmesIA 50011USA Mechanical Engineering&Mechanics Lehigh UniversityBethlehemPA 18015USA

Nickel-based superalloys and near-equiatomic high-entropy alloys containing molybdenum are known for higher temperature strength and corrosion ***,complex solid-solution alloys offer a huge design space to tune for optimal properties at slightly reduced *** refractory Mo-W-Ta-Ti-Zr,we showcase kkR electronic structure methods via the coherent-potential approximation to identify alloys over five-dimensional design space with improved mechanical properties and necessary global(formation enthalpy)and local(short-range order)*** is modeled with classical molecular dynamic simulations,validated from our first-principle *** predict complex solid-solution alloys of improved stability with greatly enhanced modulus of elasticity(3×at 300 k)over near-equiatomic cases,as validated experimentally,and with higher moduli above 500 k over commercial alloys(2.3×at 2000 k).We also show that optimal complex solid-solution alloys are not described well by classical potentials due to critical electronic effects.

关键词： alloys strength corrosion

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Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats

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Asian Pacific Journal of Tropical Biomedicine 2012年第9期2卷 691-695页

作者： prashant sharma Subhash L Bodhankar Prasad A Thakurdesai Department of Pharmacology Poona College of PharmacyBharati Deemed Vidyapeeth University

Objective:To evalueate hepatoprotective effects Feronia elephantum(***)correa against thioacctamide(TA)induced liver necrosis in diabetic ***:Male wistar rats were made diabetic with alloxan(160 mg/kg)on day 0 of the *** were intoxicated with hepatotoxicant(thioacetamide,300 mg/kg,ip)on day 9 of study to produce liver *** of 7 day daily once administration(day 2 to day 9)of EF(400 and 800 mg/kg,po)were evaluated on necorosis of liver in terms of mortality,liver volume,liver weight,serum aspartate aminotransferase(AST)and serum alanine transaminase(ALT),and histopathology of liver sections(for signs of necorosis and inflammation)on day-9 of the *** groups of rats with treated only with alloxan(DA control),thioacetamide(TA control)and both(TA+DA control)were ***:FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight,volume and serum glucose ***:FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM.

关键词： Feronia elephantum correa Hepatic necrosis Diabetes mellitus Thioacetamide

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Role of Moringa oleifera in regulation of diabetes-induced oxidative stress

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Asian Pacific Journal of Tropical Medicine 2013年第6期6卷 426-432页

作者： Dolly Jaiswal prashant kumar Rai Shikha Mehta Sanjukta Chatterji Surekha Shukla Devendra kumar Rai Gaurav sharma Bechan sharma Shahidul khair Geeta Watal Alternative Therapeutics Unit Drug Development DivisionMedicinal Research Lab.Department of ChemistryUniversity of Allahabad Christopher Bond Life Sciences Center Department of Molecular Microbiology & ImmunologyUniversity of Missouri School of Medicine Department of NMR All India Institude of Medical Sciences Department of Biochemistry.University of Allahabad National Medicinal Plants Boord Alternative Therapeutics Unit Drug Development DivisionMedicinal Research Lab.Department of ChemistryUniversity of Allahahad

Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta ***) young leaves by in vivo as well as in vitro ***:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic *** effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were ***:Significant increase in activities of ***, GST while,a decrease in LPO content was ***,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAk,40.5 mg/g of QEk and 12.12 mg/g of QE,*** the other *** assay results of *** leaves was(85.00±5.00)μM of Fe^+/g of extract ***:The significant antioxidant activities of *** leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.

关键词： Moringa oleifera leaves Diabetes Free radical Oxidative damage Scavenging Antioxidant

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A review on re-emerging bacteriophage therapy in the era of XDR

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生物细胞(英文) 2023年第9期47卷 1915-1930页

作者： POOJA BHADORIYA RICHA sharma REkHA MEHROTRA SIMRAN kAUR ISHA SRIVASTAVA MUkUL JAIN prashant kAUSHIk Department of Microbiology Shaheed Rajguru College of Applied Sciences for WomenUniversity of DelhiVasundhara EnclaveNew Delhi110096India Lab-209 Cell&Developmental biology labCenter of Research for DevelopmentParul UniversityVadodara391760GujaratIndia Instituto de Conservacióny Mejora de la Agrodiversidad Valenciana Universitat Politècnica de ValènciaValencia46022Spain

In the present medicine world antibiotic resistance is one of the key threats to universal health *** continue to work hard to combat this global health *** therapy,an age-old practice during the early twentieth century,was outshined by the discovery of *** the advent of widespread antibiotic resistance,phage therapy has again redeemed itself as a potential alternative owing to its adeptness to target bacteria *** side effects,the ability to migrate to different body organs,a distinct mode of action,and proliferation at the infection site,make phages a profitable candidate to replace conventional *** progressive outcome of numerous in vitro studies and case reports has validated the clinical efficacy of phage *** bright perspective of using phages to treat bacterial infections has fueled enormous medical research to exploit their potential as *** gaps in the information about phages and the lack of consent for clinical trials is major hurdle for consideration of phage *** phage therapy as a reality in medicine requires a coordinated effort from different *** this review,we aim to emphasize the importance of phage therapy in modern *** review explains their historical journey,basic phage biology,cross-talk with the host immunity,obstacles with phage therapy,and their possible *** data on the various significant clinical trials of phage therapy has been *** evaluated the efficacy of antibiotics and phage therapy in part and in combination,along with recent progress and future perspectives of phage therapy.

关键词： Bacteriophages Antibiotic resistance Phage biology Phage therapy Phage therapy clinical trials Phage therapy in India

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Role of fibrinogen,albumin and fibrinogen to albumin ratio in determining angiographic severity and outcomes in acute coronary syndrome

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World Journal of Cardiology 2023年第1期15卷 13-22页

作者： kunaal Makkar Yash Paul sharma Akash Batta Juniali Hatwal prashant kumar Panda Department of Cardiology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Cardiology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia Department of Internal Medicine Post Graduate Institute of Medical Education and ResearchChandigarh 160012India

BACkGROUND Coronavirus disease 2019(COVID-19)pandemic unmasked the huge deficit in healthcare resources *** highlighted the need for efficient risk stratification in management of cardiovascular *** To study the applicability of the old,available and affordable nonconventional biomarkers:albumin and fibrinogen in their ability to predict angiographic severity and clinical outcomes in patients with acute coronary syndrome(ACS).METHODS In this prospective,observational study,166 consecutive patients with ACS were ***,albumin and their ratio were determined from *** with underlying chronic liver disease,active malignancy,autoimmune disease,active COVID-19 infection and undergoing thrombolysis were *** Mean age of the population was 60.5±1.5 years,74.1%being *** elevation myocardial infarction(STEMI)was most common presentation of ACS seen in 57%*** albumin ratio(FAR)≥19.2,had a sensitivity of 76.9%and specificity of 78.9%[area under the receiver operating characteristic curves(AUROC)=0.8,P=0.001]to predict≤thrombolysis in myocardial infarction(TIMI)1 flow in culprit artery in STEMI *** in non-STEMI patients,FAR≥18.85 predicted the same with 80%sensitivity and 63%specificity(AUROC=0.715,P=0.006).CONCLUSION Novel biomarkers,with their high cost,lack of availability and long turn over time are impractical for real-world ***≤TIMI 1 flow in the culprit artery has significant impact of management and *** study has shown that readily available biomarkers like fibrinogen and albumin can help identify these high-risk patients with good *** allows risk-stratification and individualization of treatment in ACS.

关键词： Acute coronary syndrome Albumin Fibrinogen Fibrinogen to albumin ratio Total occlusion of culprit artery

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