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dNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & diseases 2024年第4期11卷 368-380页

作者： dafei Chai Xu Wang praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered dNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-pd-1 *** results indicate that targeting specific mutant epitopes using dNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 pd-1 R175H

Noscapine shows antimalarial activity against plasmodium falciparum 3d7,its clinical isolate pf140/SS,and plasmodium berghei ANKA

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Asian pacific Journal of Tropical Biomedicine 2024年第8期14卷 350-358页

作者： Swaraj Kumar Babu Sameer Maharana Satyaranjan Chhatria dibya Ranjan Sahoo Ashirbad Nanda Satish Kanhar prativa KBehera Sanjib Mohanty pradeep Kumar Naik praveen Kishore Sahu Centre of Excellence in Natural products and Therapeutics Department of Biotechnology and BioinformaticsSambalpur UniversityJyoti ViharSambalpur OdishaIndia department of Molecular Biology and Infectious diseases Community Welfare Society HospitalRourkelaOdishaIndia Molecular&Immunology Laboratory Infectious Disease Biology UnitIspat General HospitalRourkelaOdishaIndia department of pharmacy Centurion University of Technology and ManagementBhubaneswarOdishaIndia

Objective:To evaluate the antimalarial activity of noscapine against plasmodium falciparum 3d7 strain(pf3d7),its clinical isolate(pf140/SS),and plasmodium berghei ANKA(pbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(dHA)in in vivo and in vitro *** addition,hemolysis and cytotoxicity tests were carried out to evaluate its ***-pCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease plasmodium falciparum falcipain-2(pfFp-2).Results:The antimalarial efficacy of noscapine against pf3d7 and pf140/SS was comparable to dHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of pbA infected *** also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high ***,pfFp-2 expression was significantly inhibited in both noscapine-treated pf3d7 and pf140/SS(ppine has antimalarial properties comparable to standard antimalarial dHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.

关键词： Malaria plasmodium falciparum plasmodium berghei Noscapine Antimalarial dihydroartemisinin Cytotoxicity Falcipain-2

Formulation development and evaluation of pioglitazone hydrochloride self-emulsifying drug delivery systems

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Journal of Chinese pharmaceutical Sciences 2015年第7期24卷 433-441页

作者： Gannu praveen Kumar d.Bikshapathi p.Madhukar department of pharmaceutics Sahasra Instituite of Pharmaceutical SciencesNear Ayyappa Swamy TempleWarangal–506007India department of pharmaceutics Vijaya college of Pharmacy Vijaya College of pharmacy

As a widely prescribed anti diabetic drug, pioglitazone belongs to class II under BCS and exhibits low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited, and its solubility and dissolution rate need to be enhanced in order to increase its oral bioavailability. In the present study, we aimed to screen various oils, surfactants and cosolvents. The highest solubility was observed in Labrafac, Tween-80 and propylene glycol. Then the feasibility of formulating pioglitazone SEddS was evaluated, and the effect of dilution on the dissolution rate and dissolution efficiency of pioglitazone was also analyzed. A comparative evaluation of pioglitazone from SEddS was made in SGF and 1% SLS. dissolution of pioglitazone from SEddS was rapid and higher compared with pure drug. The rate and extent of release of pioglitazone hydrochloride from stable SEddS （F1） were higher in 1% SLS compared with SGF. The FTIR spectra proved that there was on chemical interaction between excipients and drug. SEM studies confirmed that the size was small and spherical.

关键词： pioglitazone SEddS Solubility Size Zeta potential

predictors of cerebrospinal fluid GeneXpert MTB/RIF positivity in patients with tuberculous meningitis:A prospective cohort study

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Asian pacific Journal of Tropical Medicine 2024年第10期17卷 465-472页

作者： priyanka Gupta Neeraj Kumar Ravindra Kumar Garg Hardeep Singh Malhotra Imran Rizvi Rajesh Verma praveen Kumar Sharma Ravi Uniyal Shweta pandey Amita Jain parul Jain department of Neurology King George’s Medical UniversityLucknowIndia department of Microbiology King George’s Medical UniversityLucknowIndia

Objective:To identify the clinical,laboratory,and radiological markers that could predict a positive GeneXpert result in patients suspected of tuberculous ***:In this prospective,observational study,patients with tuberculous meningitis were systematically *** clinical,laboratory[including cerebrospinal fluid(CSF)microscopy,culture,and GeneXpert],and neuroimaging factors were *** participants were administered anti-tuberculous treatment and corticosteroids.A six-month follow-up was done to evaluate the ***:Of the 116 patients studied,54(46.6%)tested positive for GeneXpert,while 62(53.4%)were *** cranial nerve involvement(OR 3.71,95%CI 1.052-13.09,p=0.04)and the presence of basal exudates on neuroimaging(OR 5.22,95%CI 2.03-13.42,p=0.001)emerged as independent predictive factors for a positive GeneXpert result.A positive CSF GeneXpert result(p=0.002)and drug resistance(p=0.004)were significantly linked to adverse ***,a high score on the Medical Research Council stageⅢ(OR 5.64,95%CI 1.18-26.87,p=0.03)and elevated CSF cell counts(OR 1.002,95%CI 1.00-1.001,p=0.03)were identified as independent predictors of poor ***:Third cranial nerve involvement and the presence of basal exudates were significant indicators of a positive GeneXpert *** stageⅢdisability and elevated CSF cell counts predicted poor outcomes.

关键词： Tuberculous meningitis Mycobacterium tuberculosis Cerebrospinal fluid Ziehl-Neelsen staining GeneXpert

Magnetic fabrics in characterization of magma emplacement and tectonic evolution of the Moyar Shear Zone,South India

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Geoscience Frontiers 2013年第1期4卷 113-122页

作者： p.pratheesh V.prasannakumar K.R.praveen department of Geology University of KeralaKariavattom Campus.Thiruvananthapuram 695 581KeralaIndia

The Moyar Shear Zone （MSZ） of the South Indian granulite terrain hosts a prominent syenite pluton （-560 Ma） and associated NW-SE to NE-SW trending mafic dyke swarm （-65 Ma and 95 Ma）. preliminary magnetic fabric studies in the mafic dykes, using Anisotropy of Magnetic Susceptibly （AMS） studies at low-field, indicate successive emplacement and variable magma flow direction. Magnetic lineation and foliation in these dykes are identical to the mesoscopic fabrics in MSZ mylonites, indicating shear zone guided emplacement. Spatial distribution of magnetic lineation in the dykes suggests a common conduit from which the source magma has been migrated. The magnetic foliation trajectories have a sigmoidal shape to the north of the pluton and curve into the MSZ suggesting dextral sense of shear. Identical fabric conditions for magnetic fabrics in the syenite pluton and measured field fabrics in mylonite indicate syntectonic emplacement along the proterozoic crustal scale dextral shear zone with repeated reactivation history.

关键词： Magnetic fabrics Moyar Shear Zone Syenite pluton Mafic dykes Tectonic evolution

performance Investigation of Hybrid and Conventional pV Array Configurations for Grid-connected/Standalone pV Systems

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CSEE Journal of power and Energy Systems 2022年第3期8卷 682-695页

作者： praveen Kumar Bonthagorla Suresh Mikkili department of Electrical and Electronics Engineering National Institute of TechnologyGoaIndia

Currently,the critical challenge in solar photovoltaic(pV)systems is to make them energy *** of the key factors that can reduce the pV system power output is partial shading conditions(pSCs).The reduction in power output not only depends on a shaded region but also depends on the pattern of shading and physical position of shaded modules in the *** to pSCs,mismatch losses are induced between the shaded modules which can cause several peaks in the output power-voltage(p-V)*** series-parallel(Sp),total-cross-tied(TCT),bridge-link(BL),honey-comb(HC),and triple-tied(TT)configurations are considered as conventional configurations,which are severely affected by pSCs and generate more mismatch power losses along with a greater number of local *** reduce the effect of pSCs,hybrid pV array configurations,such as series-parallel:total-cross-tied(Sp-TCT),bridge-link:total-cross-tied(BL-TCT),honey-comb:total-cross-tied(HC-TCT)and bridge-link:honey-comb(BL-HC)are *** paper briefly discusses the modeling,simulation and performance evaluation of hybrid and conventional 7×7 pV array configurations during different pSCs in a Matlab/Simulink *** performance of hybrid and conventional pV configurations are evaluated and compared in terms of global maximum power(GMp),voltage and currents at GMp,open and short circuit voltage and currents,mismatch power loss(MpL),fill factor,efficiency,and a number of local maximum power peaks(LMpps).

关键词： Fill factor global maximum power(GMp) hybrid pV array configuration maximum power point(Mpp) mismatch power loss(MpL) partial shading triple-tied(TT)

The effect of pH on stability and thermal performance of graphene oxide and copper oxide hybrid nanofluids for heat transfer applications:Application of novel machine learning technique

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Journal of Energy Chemistry 2023年第7期82卷 359-374,I0009页

作者： praveen Kumar Kanti prabhakar Sharma K.V.Sharma M.p.Maiya department of Mechanical Engineering Indian Institute of Technology MadrasChennai 600036India department of Mechanical Engineering Delhi Skill and Entrepreneurship UniversityDelhi 110089India Center for Energy Studies Department of Mechanical EngineeringJNTUH College of EngineeringKukatpallyHyderabad 500085Telangan1India

This paper investigates the effects of pH on stability and thermal properties of copper oxide(CuO),graphene oxide(GO),and their hybrid nanofluid(HNF)at different mixing ***,sol-gel and Hummer’s method was employed for the synthesis of CuO and GO nanoparticles(Nps),and they are characterized with various *** effects of two different surfactants were analyzed on nanofluid’s(NF’s)stability at different pH *** properties like thermal conductivity(TC)and viscosity(VST)of NFs were measured at different volume concentration(0.1 vol%to 1.0 vol%)and temperature range of 30-60℃,*** TC and VST of GO/CuO(50:50)HNF are higher than that of GO/CuO(20:80).The figure of merit(FOM)is determined for the studied *** correlations were presented to calculate the TC as well as VST of *** modern novel machine learning-based ensemble approaches were employed for predictive model development for TC and VST of considered *** comparison of prognostic models with Taylor’s diagram revealed that Bayesian optimized support vector machine(BoASVM)was superior to Bayesian optimized boosted regression trees(BoA-BRT)for both TC and VST models.

关键词： CuO Figure of merit Graphene oxide Machine learning pH Stability

Optimal pV Array Configuration for Extracting Maximum power Under partial Shading Conditions by Mitigating Mismatching power Losses

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CSEE Journal of power and Energy Systems 2022年第2期8卷 499-510页

作者： praveen Kumar Bonthagorla Suresh Mikkili the Electrical and Electronics Engineering department National Institute of Technology Goa403401India

The grid-connected or standalone pV central inverter architecture is comprised of several pV modules which are connected in different ways to form the pV *** power generation capability of the pV array is primarily affected by partial shading conditions(pSC).due to pSCs,the power output of the pV array is dramatically reduced,and mismatching losses are induced in the pV *** on the extent of these problems,multiple peaks also appear in the power-voltage(p-V)curve,which makes it very difficult to track the global maximum power point(GMpp).The main objective of this research paper is to model and simulate the series(S),series-parallel(Sp),bridge-link(BL),honey-comb(HC),total-cross-tied(TCT)and proposed triple-tied(TT)solar pV array configurations under various partial shading *** performance of all pV configurations is evaluated under a uniform approach,considering eight different shading *** performance of the considered pV configurations is analyzed in terms of their mismatching power losses,fill factors,efficiency,global maximum power points(GMpps),local maximum power points(LMpps),voltages and currents at GMpps,open circuit voltage and short circuit *** above-mentioned pV configurations are modeled and simulated in a Matlab/Simulink environment by considering the KC-200GT module parameters.

关键词： photo voltaic(pV) pV array configurations triple-tied(TT) maximum power point(Mpp) partial shading mismatching power losses fill factor efficiency

Visible light photocatalysis in the synthesis of pharmaceutically relevant heterocyclic scaffolds

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Organic Chemistry Frontiers 2022年第5期9卷 1485-1507页

作者： Vishal Srivastava pravin K.Singh Shraddha Tivari praveen p.Singh department of Chemistry CMP Degree CollegeUniversity of AllahabadPrayagraj 211002India department of Chemistry United College of Engineering&ResearchNainiPrayagraj 211010India

Visible light and photoredox catalysis have emerged as a powerful and long-lasting tool for organic syn-thesis,demonstrating the importance of a variety of chemical bond formation *** products,physiologically active substances,medicines,and agrochemicals all contain heterocyclic *** impact of visible light-promoted chemistry on the functionalization of heterocycles as well as the syn-thesis and modification of heterocyclic compounds of medicinal importance is summarized in this review.

关键词： heterocyclic Visible synthesis