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Immunotherapy for hepatocellular carcinoma:Current status and future perspectives

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World Journal of Gastroenterology 2023年第6期29卷 1054-1075页

作者： Deepa S Mandlik Satish K Mandlik Heena B Choudhary Department of Pharmacology BVDUPoona College of PharmacyPune 411038MaharashtraIndia Department of Pharmaceutics BVDUPoona College of PharmacyPune 411038MaharashtraIndia

Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor *** develops in the context of chronic liver *** resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of *** treatments for advanced HCC are ineffective and aggravate the underlying liver *** promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical *** current years,cancer immunotherapy has made significant progress,opening up new treatment options for ***,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of *** the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced *** this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitors Alpha-fetoprotein Cancer vaccine Combination therapies

Investigation of the nutraceutical potential of monofloral Indian mustard bee pollen

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Journal of Integrative Medicine 2014年第4期12卷 379-389页

作者： Sameer S.Ketkar Atul S.Rathore Sathiyanarayanan Lohidasan Lakshmi Rao Anant R.Paradkar Kakasaheb R.Mahadik centre for Advanced Research in Pharmaceutical Sciences Poona College of Pharmacy Bharati Vidyapeeth University Central Bee Research and Training Institute centre for Pharmaceutical Engineering Sciences University of Bradford

OBJECTIVE： This study was designed to investigate the nutraceutical potential of monofloral Indian mustard bee pollen （MIMBP）. METHODS： The nutritional value of MIMBP was examined in terms of proteins, fats, carbohydrates, and energy value. Its chemical composition in terms of total polyphenol and flavonoid content was determined. MIMBP was screened for free flavonoid aglycones by developing and validating a high-performance liquid chromatography-photo diode array （HPLC-PDA） method. MIMBP was analyzed for in vitro antioxidant effect in terms of 2,2-diphenyl-l-picrylhydrazyl （DPPH） radical-scavenging activity. RESULTS： MIMBP was found to be comprised of proteins （（182.2±5.9） g/kg）, fats （（137.7±6.8） g/kg） and carbohydrates （（560.6±17.4） g/kg）, which result in its high energy value （（17 616.7±78.6） kJ/kg）. MIMBP was found to contain polyphenols （（18 286.1±374.0） mg gallic acid equivalent/kg） and flavonoids （（1 223.5±53.1） mg quercetin equivalent/kg）. The HPLC-PDA analysis revealed the presence of kaempferol （（65.4±0.5） mg/kg） and quercefin （（51.4±0.4） mg/kg） in MIMBP, which can be used as markers for determining the quality of bee pollen. The MIMBP extract showed DPPH free radical-scavenging activity with a half maximal inhibitory concentration of 54.79 μg/mL. CONCLUSION： The MIMBP was found to be a rich source of nutrients providing high caloric value, which makes it a candidate for a potential nutraceutical agent. The study also illustrated the high antioxidant content of MIMBP, especially in the principle polyphenols and flavonoids, which suggests its potential role in the prevention of free radical-implicated diseases. The DPPH-scavenging effect of MIMBP further confirmed its antioxidant potential. Additionally, we developed a simple, specific and accurate HPLC-PDA method for the identification and quantification of free flavonoid aglycones. This can be applied in future screenings of the quality of pollen collected by honeybees.

关键词： dietary supplements bee pollen flavonoids mustard plants

Anti-epileptic effect of morin against experimental pentylenetetrazol-induced seizures via modulating brain monoamines and oxidative stress

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Asian Pacific Journal of Tropical Biomedicine 2018年第7期8卷 352-359页

作者： Amit D.Kandhare Anwesha A.Mukherjee Subhash L.Bodhankar Department of Pharmacology Poona College of Pharmacy Bharati Vidyapeeth Deemed University

Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.

关键词： Brain GABA Epilepsy Morin Nitric oxide Pentylenetetrazol Oxidative stress Xanthine oxidase

Determination of the mitigating effect of colon-specific bioreversible codrugs of mycophenolic acid and aminosugars in an experimental colitis model in Wistar rats

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World Journal of Gastroenterology 2018年第10期24卷 1093-1106页

作者： Shakuntala Santosh Chopade Suneela Sunil Dhaneshwar Department of Pharmaceutical Chemistry Poona College of Pharmacy Bharati Vidyapeeth University

AIM To design colon-targeted codrugs of mycophenolic acid(MPA) and aminosugars as a safer option to mycophenolate mofetil(MMF) in the management of inflammatory bowel disease. METHODS Codrugs were synthesized by coupling MPA with aminosugars(D-glucosamine and D-galactosamine) using EDCI coupling. The structures were confirmed by infrared radiation, nuclear magnetic resonance, mass spectroscopy and elemental analysis. The release profile of codrugs was extensively studied in aqueous buffers, upper gastrointestinal homogenates, faecal matter and caecal homogenates(in vitro) and rat blood(in vitro). Anti-colitic activity was assessed in 2,4,6-trinitrobezenesulfonic acid-induced colitis in Wistar rats by the estimation of various demarcating parameters. Statistical evaluation was performed by applying one-way and two-way ANOVA when compared with the disease *** The prodrugs resisted activation in HCl buffer(pH 1.2) and stomach homogenates of rats with negligible hydrolysis in phosphate buffer(p H 7.4) and intestinal homogenates. Incubation with colon homogenates(in vitro) produced 76% to 89% release of MPA emphasizing colon-specific activation of codrugs and the release of MPA and aminosugars at the site of action. In the in vitro studies, the prodrug of MPA with D-glucosamine(MGLS) was selected which resulted in 68% release of MPA in blood. in vitro studies on MGLS revealed its colon-specific activation after a lag time of 8 h which could be ascribed to the hydrolytic action of N-acyl amidases found in the colon. The synthesized codrugs markedly diminished disease activity score and revived the disrupted architecture of the colon that was comparable to MMF but superior to MPA. CONCLUSION The significant attenuating effect of prodrugs and individual aminosugars on colonic inflammation proved that the rationale of the codrug approach is valid.

关键词： Mycophenolic acid Mutual prodrug Inflammatory bowel disease Mycophenolate mofetil

Flood basalt hosted palaeosols:Potential palaeoclimatic indicators of global climate change

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Geoscience Frontiers 2014年第6期5卷 791-799页

作者： M.R.G.Sayyed Department of Geology Poona College (University of Pune)CampPune 411 001MaharashtraIndia

Since continental sediments （in addition to the marine geological record） offer important means of deciphering environmental changes, the sediments hosted by the successive flows of the continental flood basalt provinces of the world should be treasure houses in gathering the palaeoclimatic data. Palaeosols developed on top of basalt flows are potentially ideal for palaeoenvironmental reconstructions because it is easy to determine their protolith geochemistry and also they define a definite time interval. The present paper summarizes the nature of the basalt-hosted palaeosols formed on the flood basalts provinces from different parts of the ~lobe havin~ different ages.

关键词： Continental flood basalts Palaeosols Weathering Palaeoclimates Global change

Marker-based standardization and investigation of nutraceutical potential of Indian propolis

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Journal of Integrative Medicine 2017年第6期15卷 483-494页

作者： nanaware sadhana sathiyanarayanan lohidasan kakasaheb ramoo mahadik department of pharmaceutical chemistry bharati vidyapeeth universitypoona college of pharmacyPune 411038MaharashtraIndia

OBJECTIVE： Propolis, a resinous material collected by honey bees from various plants, has been explored globally for its medicinal and nutritional properties. However, research over Indian propolis is at infancy. This study was designed to investigate nutraceutical potential of Indian propolis. METHODS： In the present study, propolis extract was standardized with respect to markers caffeic acid phenethyl ester, caffeic acid, galangin, luteolin, curcumin, apigenin, pinocembrin and quercetin by new high-performance thin-layer chromatographic （HPTLC） methods. The physico-chemical analysis, residues analysis and in vitro antioxidant activity analysis were performed. Nutraceutical value was examined in terms of fats, fibers, minerals, proteins, polysaccharides, total carbohydrates, and energy value. RESULTS： The developed HPTLC methods were found to be simple, reliable accurate, and the validation parameters were within the limits of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. Macerated ethanolic extract of propolis （MEEP） was found to have polyphenolic content of （20.99 ＋ 0.24） mg/g and flavonoids content of （8.39 ＋ 0.04） mg/g. MEEP was found to comprise of （283.33 ＋ 51.31） g/kg fats, （30.07 ＋ 7.30） g/kg fibers, （102.56 ＋ 2.84） g/kg proteins and （389.36 ＋ 57.50） g/kg carbohydrate with a calorie value of （38 409.33 ＋ 6 169.80） kJ/kg. It was found that Indian propolis exhibited high nutraceutical value and showed absence of pesticides and heavy metals. The MEEP showed in vitro antioxidant activity with inhibitory concentration of （12.24 ＋ 4.64） pg/mL. CONCLUSION： The present work explores Indian propolis as a potential nutritious candidate. The proposed analytical methods can be applied in future screening of the quality of Indian propolis.

关键词： propolis high-performance thin-layer chromatography nutraceutical value antioxidant activity

Understanding peroral absorption:regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

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Acta Pharmaceutica Sinica B 2017年第3期7卷 260-280页

作者： Prachi B.Shekhawat Varsha B.Pokharkar Department of Pharmaceutics Poona College of PharmacyBharati Vidyapeeth Deemed UniversityErandwaneKothrudPune 411038India

Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system(BCS) was introduced in early90's and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.

关键词： BCS Solubility Permeability Formulation strategies Factors affecting absorption

LC-UV and LC-MS evaluation of stress degradation behavior of desvenlafaxine

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Journal of Pharmaceutical Analysis 2012年第4期2卷 264-271页

作者： Shubhangi M.Pawar Laxman D.Khatal Satish Y.Gabhe Sunil R.Dhaneshwar Research and Development centre in Pharmaceutical Sciences and Applied Chemistry Poona College of PharmacyBharati Vidyapeeth University Bioanalytical Research Department BioAnalytical Technologies Pvt.Ltd.

The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutical dosage form in the presence of degradation products. Forced degradation studies were performed on bulk sample of desvenlafaxine as per ICH prescribed stress conditions using acid, base, oxidative and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed under acidic stress condition and the degradation product formed was identified by LC-MS and a degradation pathway for drug has been proposed. Successful separation of drug from degradation products formed under stress conditions was achieved on a SymmetryShield column C 18 (5 mm, 250 mm 4.6 mm, i.d.) using the mobile phase consisting of a mixture of 0.2% (v/v) triethylamine in ammonium acetate (0.05 M; pH 6.5) and methanol using isocratic gradient.

关键词： Reversed-phase liquid chromatography Liquid chromatography mass spectrometer (LC/MS) Desvenlafaxine Stress studies Validation Degradation

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acidinduced colitis in Wistar rats: Design, kinetics and biological evaluation

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World Journal of Gastroenterology 2017年第7期23卷 1147-1162页

作者： Ajinkya Sarkate Suneela S Dhaneshwar Department of Pharmaceutical Chemistry Poona College of PharmacyBharati Vidyapeeth UniversityMaharashtra 411038India

To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in *** of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way *** were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs *** outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.

关键词： Inflammatory bowel disease Boswellic acid Complementary and alternative medicine Colon-targeting Mutual prodrugs Amino acids TNBS-induced colitis