Cancer is one of the most complex diseases and the second leading cause of mortality worldwide.Due to its poor prognosis and challenges in diagnosis,eradicating cancer remains highly difficult.The limitations associat...Cancer is one of the most complex diseases and the second leading cause of mortality worldwide.Due to its poor prognosis and challenges in diagnosis,eradicating cancer remains highly difficult.The limitations associated with conventional therapies have led to the emergence of copious therapeutic strategies such as chemotherapy,phototherapy,starvation therapy,radiotherapy and immunotherapy;however,limited therapeutic efficacy,poor tumor cell selectivity and substantial adverse effects remain significant concern.Attributed to the expeditious advancement of nanotechnology,the amalgamation of nanomaterials with therapeutic approaches provides an opportunity to address the shortcomings of conventional chemotherapy.Metal-organic frameworks(MOFs),which consist of bridging ligands and ions/clusters connected by coordination bonds,have been widely used in cancer therapy to address the limitations of currently therapeutic interventions,such as poor efficacy,low stability and severe side effects.This potential arises from their tuneable porosities,high specific surface area-to-volume ratio,tailorable diameters,tractable morphologies,variegated compositions,biocompatibility and facile functionalization.We summarized the role of MOF-based nanoplatforms along with mechanistic insights into emerging avenues-such as cuproptosis,ferroptosis,cell-penetrating and biomimetic MOFs,and tumor microenvironment-responsive MOFs-alongside recent advancements in mono-and multifunctional cancer therapeutics.Theragnostic and imaging functionalities,as well as regulatory considerations and future prospects of MOF-based nanoplatforms utilized in cancer treatment,are also discussed.展开更多
Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-t...Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-target side effects like hepatotoxicity and GIT-related issues.Intravenous administration causes systemic side effects.The characteristic joint-localized symptoms such as pain,stiffness,and inflammation make the localized drug delivery suitable for managing arthritis.Topical/transdermal/intraarticular routes have become viable options for drug delivery in treating arthritis.However,challenges with those localized drug delivery routes include skin barrier and cartilage impermeability.Additionally,conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue.To circumvent these limitations,researchers have developed nanocarriers that enhance drug permeability through skin and cartilage,influencing localized action.Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers.This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance.This review emphasizes deep insights into drug delivery using diverse gelbased novel nanocarriers,exploring their various applications embedded in hyaluronic acid(biopolymer)–based gels,carbopol-based gels,and others.Furthermore,this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers.The ELVIS(extravasation through leaky vasculature and inflammatory cell-mediated sequestration)effect associated with arthritis is advantageous in drug delivery.Simply put,the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures,which finally results in the accumulation of nanocarriers in the joint cavity.展开更多
Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective dat...Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective data processing for diagnosis and treatment of different diseases including stroke.This technology has vastly improved the patient classification based on their predicted stroke outcome.It helps in quicker decision-making,improves diagnosis precision,and enhances patient care.ML techniques have occasionally been applied extensively to address complex issues related to stroke such as the prediction of stroke prevalence at an early stage.The ability of deep learning(DL)algorithms,a crucial element of AI,is becoming popular in stroke imaging analysis because it automatically extracts features without requiring domain expertise.In the preclinical setup for stroke studies,ML/DL models are commendably used for the detection of vascular thrombi,stroke core,and penumbra size,to identify artery occlusion,compute perfusion maps,detect intracranial hemorrhage(ICH),prediction of infarct,assessing the severity of hemorrhagic transformation,and forecasting patient outcomes.The robust automatic data processing,excellent generalization,self-learning,and precise decision-making abilities of such models have contributed immensely to the advancement of stroke therapy.In the preclinical setup,the time-investing behavioral studies of the animals are also effectively analyzed by AI based algorithms.Understanding the algorithms and models based on AI is yet to be simplified for its appli-cation in stroke therapy in present clinical settings,thus,in the present review attempts have been made to present it in a simplified manner to facilitate translation.展开更多
Cellular hitchhiking is an emerging therapeutic strategy that uses an endogenous cell migration mechanism to deliver therapeutics to specific sites in the body.Owing to the low permeability and presence of the blood-b...Cellular hitchhiking is an emerging therapeutic strategy that uses an endogenous cell migration mechanism to deliver therapeutics to specific sites in the body.Owing to the low permeability and presence of the blood-brain barrier(BBB),the targeted delivery of therapeutics is limited,leading to inadequate localization in the brain.NCs fail to extravasate significantly into the tumor microenvironment(TME),demonstrating poor accumulation and tumor penetration.The novel cellular hitchhiking concept has been utilized to promote systemic half-life and therapeutic targeting.Neoplastic and neuroinflammatory diseases of the brain,including glioblastoma and neuroinflammation,face critical hurdles for efficiently delivering therapeutic entities owing to the BBB.Cellular hitchhiking can surmount these hurdles by utilizing various cell populations,such as stem cells,monocytes/macrophages,neutrophils,and platelets,as potential functional carriers to deliver the therapeutic cargo through the BBB.These carrier cells have the innate capability to traverse the BBB,transit through the brain parenchyma,and specifically reach disease sites such as inflammatory and neoplastic lesions owing to chemotactic navigation,i.e.,movement attributed to chemical stimuli.Chemotherapeutic drugs delivered by cellular hitchhiking to achieve tumor-specific targeting have been discussed.This article explores various cell types for hitchhiking NCs to the TME with indepth mechanisms and characterization techniques to decipher the backpack dissociation dynamics(nanoparticle payload detachment characteristics from hitchhiked cells)and challenges toward prospective clinical translation.展开更多
Objective:To investigate the gastroprotective activity of hydroalcoholic extract leaves of Ficus religiosa(F.religiosa) in different experimental models of gastric ulcer in rats.Methods:The hydroalcoholic extract leav...Objective:To investigate the gastroprotective activity of hydroalcoholic extract leaves of Ficus religiosa(F.religiosa) in different experimental models of gastric ulcer in rats.Methods:The hydroalcoholic extract leaves of F.religiosa were studied at two dose levels(250 and 500 mg/ kg,oral) in rats against absolute ethanol(0.2 mL oral),aspirin(200 mg/kg) and pyloric ligation induced gastric ulcer.Ranitidine(50 mg/kg,oral) was used as a standard drug.Mean ulcer indices and oxidative stress were measured.Phytochemical tests and acute toxicity tests were also carried out.Results:Administration of F.religiosa to rats significantly decreased the ulcer index value when compared with the control treated group.Ranitidine(50 mg/kg,oral) also produced a significant decrease the ulcer index value when compared with the control treated group.Phytochemical analysis revealed the presence of tannins,sterols,saponins,flavonoids, carbohydrates and proteins.Conclusions:The results suggest that the leaves of the F.religiosa possess significant anti ulcer activity.展开更多
Objective:To evaluate the antiarthritic activity of Ajuga bracteosa using albino rats.Methods: The antiarthritic activity of 70%ethanolic extract of Ajuga bracteosa(EEAB) was evaluated against turpentine oil- and form...Objective:To evaluate the antiarthritic activity of Ajuga bracteosa using albino rats.Methods: The antiarthritic activity of 70%ethanolic extract of Ajuga bracteosa(EEAB) was evaluated against turpentine oil- and formaldehyde- induced acute non immunological and complete freund's adjuvant(CFA)-induced chronic immunological arthritis in albino rats.Results:EEAB showed a significant(P<0.05) and dose dependent inhibitory effect against acute and chronic models of arthritis.EEAB exhibited better antiarthritic activity than the standard aspirin.Conclusions: EEAB exhibits a significant and promising antiarthritic activity against acute and chronic arthritis and supports the traditional use of Ajuga bracteosa for rheumatism and other inflammatory diseases.展开更多
Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been w...Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.展开更多
SARS-CoV-2(2019-nCoV)emerged in 2019 and proliferated rapidly across the globe.Scientists are attempting to investigate antivirals specific to COVID-19 treatment.The 2019-nCoV and SARS-CoV utilize the same receptor of...SARS-CoV-2(2019-nCoV)emerged in 2019 and proliferated rapidly across the globe.Scientists are attempting to investigate antivirals specific to COVID-19 treatment.The 2019-nCoV and SARS-CoV utilize the same receptor of the host which is COVID-19 of the main protease(Mpro).COVID-19 caused by SARS-CoV-2 is burdensome to overcome by presently acquired antiviral candidates.So the objective and purpose of this work was to investigate the plants with reported potential antiviral activity.With the aid of in silico techniques such as molecular docking and druggability studies,we have proposed several natural active compounds including glycyrrhizin,bicylogermecrene,tryptanthrine,β-sitosterol,indirubin,indican,indigo,hesperetin,crysophanic acid,rhein,berberine andβ-caryophyllene which can be encountered as potential herbal candidate exhibiting anti-viral activity against SARS-CoV-2.Promising docking outcomes have been executed which evidenced the worthy of these selected herbal remedies for future drug development to combat coronavirus disease.展开更多
The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress ...The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.展开更多
Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be ut...Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting.展开更多
A liquid chromatography tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous monitoring plasma levels of Sitagliptin (STG) and Pioglitazone (PIO) for applicability to pharmacokinetic stu...A liquid chromatography tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous monitoring plasma levels of Sitagliptin (STG) and Pioglitazone (PIO) for applicability to pharmacokinetic studies. The method was based on HPLC separation on the reversed phase Phenomenex Synergy C18 column (30 mm length, 4.6 mm internal diameter, and 4.0 μm particle size) at a temperature of 40?C using a binary gradient mobile phase consisting of methanol and 2 mM ammonium acetate buffer pH adjusted to 4.5 with acetic acid, at a flow rate of 1 mL?min?1. Tolbutamide was used as an internal standard. Detection of analytes was achieved with LC-MS/MS system in Multiple Reaction Monitoring (MRM) mode. The method was validated over concentration range of 10.98 - 2091.77 ng?mL?1 for SIT and 8.25 - 1571.63 ng?mL?1 for PIO and lower limit of quantification was 10.98 ng?mL?1 and 8.25 ng?mL?1 for STG and PIO respectively. Recoveries from spiked controls were within acceptance criteria for all the analytes and internal standard at all QC levels. Within batch and between batch accuracy for STG was found within 96.9% - 100.3% and for PIO was found within 100.0% - 104.3%. Within batch and between batch precision for STG was less than 3.1% CV (coefficient of variation) and for PIO was less than 5.3% CV at all concentrations levels. This method was successfully applied to monitor pharmacokinetics profile of both STG and PIO on simultaneous oral administration to rats. This method can be applicable for pharmacokinetic drug-drug interaction studies.展开更多
The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The finding...The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The findings of the solid state characterization revealed the amorphous nature of the lipospheres.These exhibited a better flowability,an aerodynamic diameter in the range of 1.76 to 3.99μm.Moreover,the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%,respectively.Moreover,lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain.Hence,the results show the potential of lipospheres for pulmonary delivery of rifampicin.展开更多
Objective:To produce comparative data on a group of Trichomonas vaginalis clonal strains with varied drug responses using identical methods and materials.Methods:Five clonal strains of Trichomonas vaginalis were isola...Objective:To produce comparative data on a group of Trichomonas vaginalis clonal strains with varied drug responses using identical methods and materials.Methods:Five clonal strains of Trichomonas vaginalis were isolated from reference strain using agar plate technique.The variability of growth kinetic and susceptibility of clonal strain to metronidazole,tinidazole, satranidazole and nitazoxanide were observed in 96 well microlilre plate.Results:Among these clonal strains there was a good correlation between rates of growth with the relative susceptibility of the strains to drugs in vitro.Regarding metronidazole,tinidazole and satranidazole susceptibility,different degrees of susceptibility were determined.However,no difference in nitazoxanide susceptibility was found between the clonal strain tested and a reference strain. Conclusions:This is the first description of biological variability in clonal stock of Trichomonas vaginalis.Different degrees of drug susceptibility were determined among clonal strains tested. Further studies will be necessary to ascertain the importance of this variability in clinical infection.展开更多
The present work reportes the pertinence of samarium(Sm) doped spinel nanoferrites as magnetically recoverable photocatalyst for the removal of organic pollutants from wastewater.Thus,a series of Sm substituted spinel...The present work reportes the pertinence of samarium(Sm) doped spinel nanoferrites as magnetically recoverable photocatalyst for the removal of organic pollutants from wastewater.Thus,a series of Sm substituted spinel nano ferrites,MSm_(x)Fe_(2-x)O_(4)(M=Ni,Co;x=0,0.02,0.06,0.1) we re synthesized via sol-gel methodology.The effect of Sm doping on the structural,morphological,optical and magnetic properties of pristine nanoferrites was investigated systematically.Further,the fabricated samples were explored as photocatalysts for the oxidative degradation of antibiotics(ofloxacin and norfloxacin) and dyes(methyl orange and safranin O).The Sm doped nanoferrites exhibit astonishing catalytic efficacy that can be attributed to higher surface area,octahedral site preference of Sm ions and reduced band gap.The synthesized nanoferrites display excellent recyclability which enables them to be utilized as potential photocatalysts for wastewater treatment.展开更多
Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,...Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially screened.During the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.展开更多
Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GE...Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GES-1),and to explore the mechanism of EtAc-LME induced apoptosis.Methods:The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases,PARP cleavage,expression of cytochrome-c (Cyt-c) was determined by western blotting,mRNA expression of Bcl-2,Bax by RT-PCR,loss of mitochondrial potential using DiOC6 dye,annexin binding assay and its influence on cell cycle arrest by flow cytometry.Results:The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells(NUCC and MKN-74) compared to normal gastric cells(GES-1),suggesting more specific cytotoxicity to the malignant cells.Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.Conclusions:The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.展开更多
基金funding support by the Department of Pharmaceuticals(DoP),Ministry of Chemicals and Fertilizers,Govt.of India to“Pharmaceutical Innovation and Translational Research Lab”(PITRL),National Institute of Pharmaceutical Education and Research(NIPER),Hyderabad,INDIA.
文摘Cancer is one of the most complex diseases and the second leading cause of mortality worldwide.Due to its poor prognosis and challenges in diagnosis,eradicating cancer remains highly difficult.The limitations associated with conventional therapies have led to the emergence of copious therapeutic strategies such as chemotherapy,phototherapy,starvation therapy,radiotherapy and immunotherapy;however,limited therapeutic efficacy,poor tumor cell selectivity and substantial adverse effects remain significant concern.Attributed to the expeditious advancement of nanotechnology,the amalgamation of nanomaterials with therapeutic approaches provides an opportunity to address the shortcomings of conventional chemotherapy.Metal-organic frameworks(MOFs),which consist of bridging ligands and ions/clusters connected by coordination bonds,have been widely used in cancer therapy to address the limitations of currently therapeutic interventions,such as poor efficacy,low stability and severe side effects.This potential arises from their tuneable porosities,high specific surface area-to-volume ratio,tailorable diameters,tractable morphologies,variegated compositions,biocompatibility and facile functionalization.We summarized the role of MOF-based nanoplatforms along with mechanistic insights into emerging avenues-such as cuproptosis,ferroptosis,cell-penetrating and biomimetic MOFs,and tumor microenvironment-responsive MOFs-alongside recent advancements in mono-and multifunctional cancer therapeutics.Theragnostic and imaging functionalities,as well as regulatory considerations and future prospects of MOF-based nanoplatforms utilized in cancer treatment,are also discussed.
文摘Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-target side effects like hepatotoxicity and GIT-related issues.Intravenous administration causes systemic side effects.The characteristic joint-localized symptoms such as pain,stiffness,and inflammation make the localized drug delivery suitable for managing arthritis.Topical/transdermal/intraarticular routes have become viable options for drug delivery in treating arthritis.However,challenges with those localized drug delivery routes include skin barrier and cartilage impermeability.Additionally,conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue.To circumvent these limitations,researchers have developed nanocarriers that enhance drug permeability through skin and cartilage,influencing localized action.Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers.This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance.This review emphasizes deep insights into drug delivery using diverse gelbased novel nanocarriers,exploring their various applications embedded in hyaluronic acid(biopolymer)–based gels,carbopol-based gels,and others.Furthermore,this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers.The ELVIS(extravasation through leaky vasculature and inflammatory cell-mediated sequestration)effect associated with arthritis is advantageous in drug delivery.Simply put,the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures,which finally results in the accumulation of nanocarriers in the joint cavity.
基金Department of Pharmaceuticals Ministry of Chemicals and Fertilizer,Government of India and National Institute of Pharmaceutical Education and Research(NIPER)Ahmedabad,Gandhinagar,India。
文摘Artificial intelligence(AI)technology is expanding at a rapid pace,offering means of improving the precision of judgments made by medical professionals.AI-driven machine learning(ML)facilitates rapid and effective data processing for diagnosis and treatment of different diseases including stroke.This technology has vastly improved the patient classification based on their predicted stroke outcome.It helps in quicker decision-making,improves diagnosis precision,and enhances patient care.ML techniques have occasionally been applied extensively to address complex issues related to stroke such as the prediction of stroke prevalence at an early stage.The ability of deep learning(DL)algorithms,a crucial element of AI,is becoming popular in stroke imaging analysis because it automatically extracts features without requiring domain expertise.In the preclinical setup for stroke studies,ML/DL models are commendably used for the detection of vascular thrombi,stroke core,and penumbra size,to identify artery occlusion,compute perfusion maps,detect intracranial hemorrhage(ICH),prediction of infarct,assessing the severity of hemorrhagic transformation,and forecasting patient outcomes.The robust automatic data processing,excellent generalization,self-learning,and precise decision-making abilities of such models have contributed immensely to the advancement of stroke therapy.In the preclinical setup,the time-investing behavioral studies of the animals are also effectively analyzed by AI based algorithms.Understanding the algorithms and models based on AI is yet to be simplified for its appli-cation in stroke therapy in present clinical settings,thus,in the present review attempts have been made to present it in a simplified manner to facilitate translation.
基金the research funding support by the Department of Pharmaceuticals(DoP),Ministry of Chemicals and Fertilizers,Govt.of India to“Pharmaceutical Innovation and Translational Research Lab”(PITRL),Department of Pharmaceutics,National Institute of Pharmaceutical Education and Research(NIPER)Hyderabad,INDIA.
文摘Cellular hitchhiking is an emerging therapeutic strategy that uses an endogenous cell migration mechanism to deliver therapeutics to specific sites in the body.Owing to the low permeability and presence of the blood-brain barrier(BBB),the targeted delivery of therapeutics is limited,leading to inadequate localization in the brain.NCs fail to extravasate significantly into the tumor microenvironment(TME),demonstrating poor accumulation and tumor penetration.The novel cellular hitchhiking concept has been utilized to promote systemic half-life and therapeutic targeting.Neoplastic and neuroinflammatory diseases of the brain,including glioblastoma and neuroinflammation,face critical hurdles for efficiently delivering therapeutic entities owing to the BBB.Cellular hitchhiking can surmount these hurdles by utilizing various cell populations,such as stem cells,monocytes/macrophages,neutrophils,and platelets,as potential functional carriers to deliver the therapeutic cargo through the BBB.These carrier cells have the innate capability to traverse the BBB,transit through the brain parenchyma,and specifically reach disease sites such as inflammatory and neoplastic lesions owing to chemotactic navigation,i.e.,movement attributed to chemical stimuli.Chemotherapeutic drugs delivered by cellular hitchhiking to achieve tumor-specific targeting have been discussed.This article explores various cell types for hitchhiking NCs to the TME with indepth mechanisms and characterization techniques to decipher the backpack dissociation dynamics(nanoparticle payload detachment characteristics from hitchhiked cells)and challenges toward prospective clinical translation.
文摘Objective:To investigate the gastroprotective activity of hydroalcoholic extract leaves of Ficus religiosa(F.religiosa) in different experimental models of gastric ulcer in rats.Methods:The hydroalcoholic extract leaves of F.religiosa were studied at two dose levels(250 and 500 mg/ kg,oral) in rats against absolute ethanol(0.2 mL oral),aspirin(200 mg/kg) and pyloric ligation induced gastric ulcer.Ranitidine(50 mg/kg,oral) was used as a standard drug.Mean ulcer indices and oxidative stress were measured.Phytochemical tests and acute toxicity tests were also carried out.Results:Administration of F.religiosa to rats significantly decreased the ulcer index value when compared with the control treated group.Ranitidine(50 mg/kg,oral) also produced a significant decrease the ulcer index value when compared with the control treated group.Phytochemical analysis revealed the presence of tannins,sterols,saponins,flavonoids, carbohydrates and proteins.Conclusions:The results suggest that the leaves of the F.religiosa possess significant anti ulcer activity.
基金financially supported by National Institute ofPharmaceutical Education and Research
文摘Objective:To evaluate the antiarthritic activity of Ajuga bracteosa using albino rats.Methods: The antiarthritic activity of 70%ethanolic extract of Ajuga bracteosa(EEAB) was evaluated against turpentine oil- and formaldehyde- induced acute non immunological and complete freund's adjuvant(CFA)-induced chronic immunological arthritis in albino rats.Results:EEAB showed a significant(P<0.05) and dose dependent inhibitory effect against acute and chronic models of arthritis.EEAB exhibited better antiarthritic activity than the standard aspirin.Conclusions: EEAB exhibits a significant and promising antiarthritic activity against acute and chronic arthritis and supports the traditional use of Ajuga bracteosa for rheumatism and other inflammatory diseases.
基金Department of Biotechnology Govt of India,for their financial support to Dr.Ashutosh Kumar via grant BT/527/NE/TBP/2013the financial support from Department of Pharmaceuticals,Ministry of Chemical and Fertilizers and NIPER Hyderabad for their support
文摘Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.
文摘SARS-CoV-2(2019-nCoV)emerged in 2019 and proliferated rapidly across the globe.Scientists are attempting to investigate antivirals specific to COVID-19 treatment.The 2019-nCoV and SARS-CoV utilize the same receptor of the host which is COVID-19 of the main protease(Mpro).COVID-19 caused by SARS-CoV-2 is burdensome to overcome by presently acquired antiviral candidates.So the objective and purpose of this work was to investigate the plants with reported potential antiviral activity.With the aid of in silico techniques such as molecular docking and druggability studies,we have proposed several natural active compounds including glycyrrhizin,bicylogermecrene,tryptanthrine,β-sitosterol,indirubin,indican,indigo,hesperetin,crysophanic acid,rhein,berberine andβ-caryophyllene which can be encountered as potential herbal candidate exhibiting anti-viral activity against SARS-CoV-2.Promising docking outcomes have been executed which evidenced the worthy of these selected herbal remedies for future drug development to combat coronavirus disease.
文摘The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.
基金the Department of Science and Technology and SERB (INSPIRE Grant no: IFA-LSBM-13 and EMR/2016/007966/HS) for project funds。
文摘Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting.
文摘A liquid chromatography tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous monitoring plasma levels of Sitagliptin (STG) and Pioglitazone (PIO) for applicability to pharmacokinetic studies. The method was based on HPLC separation on the reversed phase Phenomenex Synergy C18 column (30 mm length, 4.6 mm internal diameter, and 4.0 μm particle size) at a temperature of 40?C using a binary gradient mobile phase consisting of methanol and 2 mM ammonium acetate buffer pH adjusted to 4.5 with acetic acid, at a flow rate of 1 mL?min?1. Tolbutamide was used as an internal standard. Detection of analytes was achieved with LC-MS/MS system in Multiple Reaction Monitoring (MRM) mode. The method was validated over concentration range of 10.98 - 2091.77 ng?mL?1 for SIT and 8.25 - 1571.63 ng?mL?1 for PIO and lower limit of quantification was 10.98 ng?mL?1 and 8.25 ng?mL?1 for STG and PIO respectively. Recoveries from spiked controls were within acceptance criteria for all the analytes and internal standard at all QC levels. Within batch and between batch accuracy for STG was found within 96.9% - 100.3% and for PIO was found within 100.0% - 104.3%. Within batch and between batch precision for STG was less than 3.1% CV (coefficient of variation) and for PIO was less than 5.3% CV at all concentrations levels. This method was successfully applied to monitor pharmacokinetics profile of both STG and PIO on simultaneous oral administration to rats. This method can be applicable for pharmacokinetic drug-drug interaction studies.
文摘The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The findings of the solid state characterization revealed the amorphous nature of the lipospheres.These exhibited a better flowability,an aerodynamic diameter in the range of 1.76 to 3.99μm.Moreover,the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%,respectively.Moreover,lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain.Hence,the results show the potential of lipospheres for pulmonary delivery of rifampicin.
基金One of us (HC) is grateful to NIPER for providing financial assistance
文摘Objective:To produce comparative data on a group of Trichomonas vaginalis clonal strains with varied drug responses using identical methods and materials.Methods:Five clonal strains of Trichomonas vaginalis were isolated from reference strain using agar plate technique.The variability of growth kinetic and susceptibility of clonal strain to metronidazole,tinidazole, satranidazole and nitazoxanide were observed in 96 well microlilre plate.Results:Among these clonal strains there was a good correlation between rates of growth with the relative susceptibility of the strains to drugs in vitro.Regarding metronidazole,tinidazole and satranidazole susceptibility,different degrees of susceptibility were determined.However,no difference in nitazoxanide susceptibility was found between the clonal strain tested and a reference strain. Conclusions:This is the first description of biological variability in clonal stock of Trichomonas vaginalis.Different degrees of drug susceptibility were determined among clonal strains tested. Further studies will be necessary to ascertain the importance of this variability in clinical infection.
基金Project supported by Council of Scientific and Industrial Research of India(CSIR)(09/135(0760)/2017-EMR-I)Department of Science and Technology of India(DST/TMD(EWO)/OWUIS-2018/RS-15(G))。
文摘The present work reportes the pertinence of samarium(Sm) doped spinel nanoferrites as magnetically recoverable photocatalyst for the removal of organic pollutants from wastewater.Thus,a series of Sm substituted spinel nano ferrites,MSm_(x)Fe_(2-x)O_(4)(M=Ni,Co;x=0,0.02,0.06,0.1) we re synthesized via sol-gel methodology.The effect of Sm doping on the structural,morphological,optical and magnetic properties of pristine nanoferrites was investigated systematically.Further,the fabricated samples were explored as photocatalysts for the oxidative degradation of antibiotics(ofloxacin and norfloxacin) and dyes(methyl orange and safranin O).The Sm doped nanoferrites exhibit astonishing catalytic efficacy that can be attributed to higher surface area,octahedral site preference of Sm ions and reduced band gap.The synthesized nanoferrites display excellent recyclability which enables them to be utilized as potential photocatalysts for wastewater treatment.
文摘Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially screened.During the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.
文摘Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GES-1),and to explore the mechanism of EtAc-LME induced apoptosis.Methods:The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases,PARP cleavage,expression of cytochrome-c (Cyt-c) was determined by western blotting,mRNA expression of Bcl-2,Bax by RT-PCR,loss of mitochondrial potential using DiOC6 dye,annexin binding assay and its influence on cell cycle arrest by flow cytometry.Results:The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells(NUCC and MKN-74) compared to normal gastric cells(GES-1),suggesting more specific cytotoxicity to the malignant cells.Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.Conclusions:The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.
