Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and ...Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line.We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate AMPK.This study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were examined.Treatment with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned medium.These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and HO-1.Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay.Thus,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect.Therapeutic response was in the order of:sitagliptin>vildagliptin>exendin-4.展开更多
An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December...An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December 2019.The disease gained global attention as it spread worldwide.Since the COVID-19 pandemic began,many studies have focused on the impact of the disease on conditions such as diabetes,cardiovascular disease,pulmonary disorders,and renal malfunction.However,few studies have focused on musculoskeletal disorders related to COVID-19 infection.In this review,we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments,which may inform clinical practice.展开更多
Diabetic peripheral neuropathy(DPN)is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia.In spite of new drug discoveries,development of effective therapy is much needed to cure ...Diabetic peripheral neuropathy(DPN)is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia.In spite of new drug discoveries,development of effective therapy is much needed to cure DPN.Here,we have developed a combinatorial approach to provide biochemical and electrical cues,considered to be important for nerve regeneration.Exosomes derived from bone marrow mesenchymal stromal cells(BMSCs)were fused with polypyrrole nanoparticles(PpyNps)containing liposomes to deliver both the cues in a single delivery vehicle.We developed DPN rat model and injected intramuscularly the fused exosomal system to understand its long-term therapeutic effect.We found that the fused system along with electrical stimulation normalized the nerve conduction velocity(57.60±0.45 m/s)and compound muscle action potential(16.96±0.73 mV)similar to healthy control(58.53±1.10 m/s;18.19±1.45 mV).Gastrocnemius muscle morphology,muscle mass,and integrity were recovered after treatment.Interestingly,we also observed paracrine effect of delivered exosomes in controlling hyperglycemia and loss in body weight and also showed attenuation of damage to the tissues such as the pancreas,kidney,and liver.This work provides a promising effective treatment and also contribute cutting edge therapeutic approach for the treatment of DPN.展开更多
Global climate change and ongoing plant invasion are the two prominent ecological issues threatening biodiversity world wide.Among invasive species,Lantana camara and Hyptis suaveolens are the two most important invad...Global climate change and ongoing plant invasion are the two prominent ecological issues threatening biodiversity world wide.Among invasive species,Lantana camara and Hyptis suaveolens are the two most important invaders in the dry deciduous forest in India.We monitored the growth of these two invasive species and seedlings of four native dry deciduous species(Acacia catechu,Bauhinia variegata,Dalbergia latifolia and Tectona grandis)under ambient(375–395μmol mol^(-1))and elevated CO_(2)(700–750μmol mol^(-1))to study the differential growth response of invasive and native seedlings.Methods Seedlings of all the species were exposed to ambient and elevated CO_(2).After 60 days of exposure,seedlings were harvested and all the growth-related parameters like plant height;biomass of root,stem and leaves;total seedling biomass;R/S ratio;allocation parameters;net assimilation rate(NAR)and relative growth rate(RGR)were determined.Important Findings Biomass,RGR and NAR of all the species increased under elevated CO_(2)but the increase was higher in invasive species and they formed larger seedlings than natives.Therefore under the CO_(2)-enriched future atmosphere,competitive hierarchies could change and may interfere with the species composition of the invaded area.展开更多
Due to abundant availability,biofuel production from bamboo residues is gaining popularity.Bamboo biomass and its residues are widely available in the north-eastern part of India,which can be sustainably exploited for...Due to abundant availability,biofuel production from bamboo residues is gaining popularity.Bamboo biomass and its residues are widely available in the north-eastern part of India,which can be sustainably exploited for green energy production.The aim of the present study was to evaluate the pretreatments of dewaxed bamboo residues with dilute alkali(NaOH),and dilute acid,and the effect of pretreatment on biomass hydrolysis was performed with a commercial enzyme(Zytex).Results showed that maximum fermentable sugars were 490 mg/g obtained from 10%biomass with 0.6%(w/v)of alkali,and acid pretreated biomass produced 320 mg/g of sugars from 2%(w/v)acid with 10%biomass.Changes in biomass structure during the pretreatment process are correlated with FTIR,SEM,and component analysis for lignin,cellulose,and hemicelluloses.Fermentation studies of the hydrolysate showed that the yield of ethanol was 77%of the theoretical maximum at 36 h.Results indicate the scope of utilization of bamboo residues as substrates for biofuels,and alkaline pretreatment is an effective pretreatment process for bioethanol production.展开更多
基金The work was supported by the Council of Scientific and Industrial Research-Junior Research Fellowship to Ms.Pooja Jaiswal(File No.09/301(0137)/2019-EMR-I)Ms.Versha Tripathi(09/301(0138)/2019-EMR-I)+1 种基金We also acknowledge the India-Belarus joint project(DST/INT/BLR/P-24/2019)funded by the Department of Science and TechnologyNew Delhi and the research grant from Devi Ahilya University,Indore(Dev/Seedmoney2.0/2020-21/655)sanctioned to Dr.Hamendra Singh Parmar.
文摘Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line.We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate AMPK.This study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were examined.Treatment with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned medium.These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and HO-1.Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay.Thus,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect.Therapeutic response was in the order of:sitagliptin>vildagliptin>exendin-4.
文摘An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December 2019.The disease gained global attention as it spread worldwide.Since the COVID-19 pandemic began,many studies have focused on the impact of the disease on conditions such as diabetes,cardiovascular disease,pulmonary disorders,and renal malfunction.However,few studies have focused on musculoskeletal disorders related to COVID-19 infection.In this review,we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments,which may inform clinical practice.
基金The work was funded by the Department of Biotechnology (DBT) (#BT/PR13561/MED/32/392/2016 and #DBT/IN/SWEDEN/08/AK/ 2017-1)Department of Science and Technology (DST) (#DST/NM/NT- 2018/48 and #DST/INT/SWD/P-11/2016)Ministry of Human Resource Development- IMPRINT (MHRD_6714/Healthcare), Ministry of Human Resource Development- SPARC (SPARC/2018-2019/P612/ SL), and Ministry of Human Resource Development-UAY (MHRD_IITK_006), Govt. of India. AS and PAS would like to acknowledge IIT Kanpur for fellowship for the Ph.D. program. The authors would like to acknowledge Sophisticated Analytical Instrumentation Facility (SAIF), Council for Scientific and Industrial Research- Central Drug Research Institute, Lucknow for the LC-MS/MS analysis.
文摘Diabetic peripheral neuropathy(DPN)is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia.In spite of new drug discoveries,development of effective therapy is much needed to cure DPN.Here,we have developed a combinatorial approach to provide biochemical and electrical cues,considered to be important for nerve regeneration.Exosomes derived from bone marrow mesenchymal stromal cells(BMSCs)were fused with polypyrrole nanoparticles(PpyNps)containing liposomes to deliver both the cues in a single delivery vehicle.We developed DPN rat model and injected intramuscularly the fused exosomal system to understand its long-term therapeutic effect.We found that the fused system along with electrical stimulation normalized the nerve conduction velocity(57.60±0.45 m/s)and compound muscle action potential(16.96±0.73 mV)similar to healthy control(58.53±1.10 m/s;18.19±1.45 mV).Gastrocnemius muscle morphology,muscle mass,and integrity were recovered after treatment.Interestingly,we also observed paracrine effect of delivered exosomes in controlling hyperglycemia and loss in body weight and also showed attenuation of damage to the tissues such as the pancreas,kidney,and liver.This work provides a promising effective treatment and also contribute cutting edge therapeutic approach for the treatment of DPN.
文摘Global climate change and ongoing plant invasion are the two prominent ecological issues threatening biodiversity world wide.Among invasive species,Lantana camara and Hyptis suaveolens are the two most important invaders in the dry deciduous forest in India.We monitored the growth of these two invasive species and seedlings of four native dry deciduous species(Acacia catechu,Bauhinia variegata,Dalbergia latifolia and Tectona grandis)under ambient(375–395μmol mol^(-1))and elevated CO_(2)(700–750μmol mol^(-1))to study the differential growth response of invasive and native seedlings.Methods Seedlings of all the species were exposed to ambient and elevated CO_(2).After 60 days of exposure,seedlings were harvested and all the growth-related parameters like plant height;biomass of root,stem and leaves;total seedling biomass;R/S ratio;allocation parameters;net assimilation rate(NAR)and relative growth rate(RGR)were determined.Important Findings Biomass,RGR and NAR of all the species increased under elevated CO_(2)but the increase was higher in invasive species and they formed larger seedlings than natives.Therefore under the CO_(2)-enriched future atmosphere,competitive hierarchies could change and may interfere with the species composition of the invaded area.
基金The authors would like to thank Dr.Rajeev K.Sukumaran and his group,Microbial Process and Technology Division,CSIR-National Institute for Interdisciplinary Science and Technology,for their extensive help with the characterization of biomass and the Director,IBSD,for his motivation and support(IBSD Manuscript No.IBSD/2020/01/061).
文摘Due to abundant availability,biofuel production from bamboo residues is gaining popularity.Bamboo biomass and its residues are widely available in the north-eastern part of India,which can be sustainably exploited for green energy production.The aim of the present study was to evaluate the pretreatments of dewaxed bamboo residues with dilute alkali(NaOH),and dilute acid,and the effect of pretreatment on biomass hydrolysis was performed with a commercial enzyme(Zytex).Results showed that maximum fermentable sugars were 490 mg/g obtained from 10%biomass with 0.6%(w/v)of alkali,and acid pretreated biomass produced 320 mg/g of sugars from 2%(w/v)acid with 10%biomass.Changes in biomass structure during the pretreatment process are correlated with FTIR,SEM,and component analysis for lignin,cellulose,and hemicelluloses.Fermentation studies of the hydrolysate showed that the yield of ethanol was 77%of the theoretical maximum at 36 h.Results indicate the scope of utilization of bamboo residues as substrates for biofuels,and alkaline pretreatment is an effective pretreatment process for bioethanol production.
