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1.
ACS Appl Mater Interfaces ; 16(8): 10969-10983, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38355426

ABSTRACT

The interaction of graphene with metals initiates charge-transfer interaction-induced chemical enhancements, which critically depend on the doping effect from deposited metallic configurations. In this paper, we have explored the gold nanoparticle-decorated monolayer graphene nanosheets for the large graphene-induced Raman enhancement of adsorbed analytes, indicating the surface-enhanced Raman spectroscopy (SERS) capabilities of metal-doped graphene (G-SERS). Here, the systematically sputtered Au thickness optimization procedure revealed noticeable modifications in the graphene Raman spectra and photoluminescence (PL) background quenching, which indicated favorable charge transfer through n-type doping of chemical vapor deposition-grown graphene nanosheets. The highly consistent, individually distributed morphology of the gold nanoislands over graphene nanosheets depicted a reproducibly uniform G-SERS signal with excellent relative standard deviation values (<5%), resulting in the strongest Raman intensity enhancement factors of ∼108 (MB) (methylene blue) and 107 (DPA) (2,6-pyridinedicarboxylic acid) composed of the weakest PL background. The combined charge-transfer-induced chemical enhancement and electromagnetic enhancement from individual Au nanoislands result in a lowering of detectability down to 10-16 M (MB) and 10-11 M (DPA) concentrations with efficient time-dependent signal stability. Additionally, the GAu demonstrated its effective (∼94.4%) photocatalytic degradation capabilities by decomposing MB dye molecules from a concentration of 1 µM to 2.52 fM within 60 min. Therefore, the prominent charge-transfer contribution through controlled Au decoration over graphene nanosheets provides a potential strategy for fabricating superior SERS sensors and photocatalysts exhibiting adequate signal consistency, stability, and photodegradation efficiency through overcoming the limitations of the traditional sensing platforms.

2.
Biodegradation ; 35(2): 117-135, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37684525

ABSTRACT

Industrial development and the associated generation of waste requires attention for their management, treatment, and reduction without further degrading the quality of life. Microbes and plant-based bioremediation approaches are some of the sustainable strategies for the biodegradation of harmful pollutants instead of chemical-based treatment. Bioaugmentation is one such approach where microbial strains with the ability to degrade the targeted pollutant are introduced in a polluted environment. Harnessing of microbes from various locations, especially from the site of contamination (indigenous microbes), followed by optimization of the strains, inoculum size, media, and genetic engineering of the microbes along with a combination of strategies such as bio stimulation, phytoremediation is being applied to increase the efficiency of bioaugmentation. Further, bioaugmentation is influenced by various factors such as temperature, the composition of the pollutant, and microbial inoculum which needs to be considered for maximum efficiency of the treatment process. It has numerous advantages such as low cost, sustainability, and easy handling of the contaminants however, the major limitation of bioaugmentation is to increase the survival rate of the microbes involved in remediation for a longer duration in such a highly toxic environment. The review discusses these various aspects of bioaugmentation in brief for its large-scale implementation to address the global issue of pollution and environment management.


Subject(s)
Environmental Pollutants , Soil Pollutants , Quality of Life , Biodegradation, Environmental , Soil Pollutants/metabolism
3.
Article in English | MEDLINE | ID: mdl-37697197

ABSTRACT

The organic wastes and residues generated from agricultural, industrial, and domestic activities have the potential to be converted to bioenergy. One such energy is biogas, which has already been included in rural areas as an alternative cooking energy source and agricultural activities. It is produced via anaerobic digestion of a wide range of organic nutrient sources and is an essential renewable energy source. The factors influencing biogas yield, i.e., the various substrate, their characteristics, pretreatment methods involved, different microbial types, sources, and inoculum properties, are analyzed. Furthermore, the optimization of these parameters, along with fermentation media optimization, such as optimum pH, temperature, and anaerobic digestion strategies, is discussed. Novel approaches of bioaugmentation, co-digestion, phase separation, co-supplementation, nanotechnology, and biorefinery approach have also been explored for biogas production. Finally, the current challenges and prospects of the process are discussed in the review.

4.
Disaster Med Public Health Prep ; 17: e425, 2023 06 29.
Article in English | MEDLINE | ID: mdl-37381679

ABSTRACT

OBJECTIVE: The purpose of the study was to design, develop, and validate a newer tool on radiation emergency preparedness responses (RadEM-PREM IPE tool) to measure communication, knowledge, performance skills in multidisciplinary health science learners. METHODS: The study design is a prospective, single centric, pilot study. Five subject experts designed, analyzed, and selected items of the instrument for relevant content and domain. Psychometrics that the tool assessed were content validity, internal consistency, test-retest reliability, and intraclass correlation coefficient. Twenty-eight participants completed test-retest reliability for validation of 21 sorted out items calculated percentage of agreement >70% I-CVI/UA (item content validity index with universal acceptability) and S-CVI/UA (scale content validity index with universal agreement method). RESULTS: Items with percentage agreement >70% and I-CVI over 0.80 were kept, ranged from 0.70 to 0.78 were revised, and below 0.70 were rejected. Items with kappa values ranging from 0.04 to 0.59 were revised and ≥0.74 were retained. Internal consistency assessed using Cronbach's alpha was 0.449. Positive correlation between attitude and communication (r = 0.448), between performance and communication (r = 0.443) were statistically significant at 0.01 level. Overall, intraclass correlation coefficient for all the measures is 0.646, which is statistically significant at 0.05 level (P < 0.05). CONCLUSIONS: Study concludes that the RadEM-PREM IPE tool would be a new measuring tool to assess knowledge, performance, and communication skills of interprofessional radiation emergency response team learner's evaluation.


Subject(s)
Civil Defense , Humans , Pilot Projects , Prospective Studies , Reproducibility of Results , Communication
5.
Plant J ; 114(4): 855-874, 2023 05.
Article in English | MEDLINE | ID: mdl-36883862

ABSTRACT

Small RNAs (sRNAs) such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) are short 20-24-nucleotide non-coding RNAs. They are key regulators of gene expression in plants and other organisms. Several 22-nucleotide miRNAs trigger biogenesis cascades of trans-acting secondary siRNAs, which are involved in various developmental and stress responses. Here we show that Himalayan Arabidopsis thaliana accessions having natural mutations in the miR158 locus exhibit robust cascade silencing of the pentatricopeptide repeat (PPR)-like locus. Furthermore, we show that these cascade sRNAs trigger tertiary silencing of a gene involved in transpiration and stomatal opening. The natural deletions or insertions in MIR158 led to improper processing of miR158 precursors, thereby blocking synthesis of mature miR158. Reduced miR158 levels led to increased levels of its target, a pseudo-PPR gene that is targeted by tasiRNAs generated by the miR173 cascade in other accessions. Using sRNA datasets derived from Indian Himalayan accessions, as well as overexpression and knockout lines of miR158, we show that absence of miR158 led to buildup of pseudo-PPR-derived tertiary sRNAs. These tertiary sRNAs mediated robust silencing of a gene involved in stomatal closure in Himalayan accessions lacking miR158 expression. We functionally validated the tertiary phasiRNA that targets NHX2, which encodes a Na+ -K+ /H+ antiporter protein, thereby regulating transpiration and stomatal conductance. Overall, we report the role of the miRNA-TAS-siRNA-pseudogene-tertiary phasiRNA-NHX2 pathway in plant adaptation.


Subject(s)
Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , Base Sequence , RNA, Small Interfering/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Plants/metabolism , Nucleotides/metabolism , Gene Expression Regulation, Plant/genetics , RNA, Plant/genetics , RNA, Plant/metabolism
6.
Osong Public Health Res Perspect ; 13(5): 316-327, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36328236

ABSTRACT

The initial case of coronavirus disease 2019 (COVID-19) in India was reported on January 30, 2020, and subsequently, the number of COVID-19-infected patients surged during the first wave of April 2020 and the second wave in the same month of 2021. The government of India imposed a strict nationwide lockdown in April 2020 and extended it until May 2020. The second wave of COVID-19 in India overwhelmed the country's health facilities and exhausted its medical and paramedical workforce. This narrative review was conducted with the aim of summarizing the evidence drawn from policy documents of governmental and non-governmental organizations, as well as capturing India's COVID-19 vaccination efforts. The findings from this review cover the Indian government's vaccination initiatives, which ranged from steps taken to combat vaccine hesitancy to vaccination roadmaps, deployment plans, the use of digital health technology, vaccination monitoring, adverse effects, and innovative strategies such as Har Ghar Dastak and Jan Bhagidari Andolan (people's participation). These efforts collectively culminated in the successful administration of more than 1.8 billion doses of COVID-19 vaccines in India. This review also provides insights into other countries' responses to COVID-19 and guidance for future pandemics.

7.
BMJ Open ; 12(11): e059987, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36332963

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has posed an unparalleled threat to all dimensions of human health and well-being. The Pan American Health Organization has acknowledged the crucial role of rehabilitation therapies for COVID-19 and emphasised the importance of exercise programmes for COVID-19 survivors. This scoping review outlines our strategy for systematically reviewing published and unpublished literature to investigate the volume of evidence for exercise interventions for COVID-19 survivors. METHODS AND ANALYSIS: This scoping review will be conducted based on the framework developed by Arksey and O'Malley. Six databases (PubMed/Medline, Scopus, Web of Science, Cochrane Central, ProQuest and CINAHL) will be searched in August 2022 and articles will be considered for inclusion published till July 2022. Studies will be screened by two independent reviewers at the title/abstract and full-text screening stages, as well as data extraction and critical assessment. Data will be extracted in a data extraction form and presented as figures and tables with narratives. This scoping review will give a thorough understanding of the current literature on exercise interventions for COVID-19 survivors, as well as identify knowledge gaps that will guide future research. Preliminary searches will be conducted after the publication of this scoping review protocol. ETHICS AND DISSEMINATION: No human or animal participants were involved in this review. Therefore, ethical committee approval is not required. Transparency will be followed at every review stage. Review findings will be disseminated through peer-review publications or through conference presentations.


Subject(s)
COVID-19 , Humans , Pandemics , Delivery of Health Care , Survivors , Exercise Therapy , Research Design , Review Literature as Topic
8.
J Radiol Nurs ; 41(4): 334-338, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36211628

ABSTRACT

Background: Professional quality of life is one of the growing concerns among healthcare workers especially during COVID-19 pandemic. Presence and work of radiologist and medical imaging technologist for prolonged hours with patients could be stressful and painful. Objectives: This study aimed to assess the professional quality of life among the radiologist and medical imaging technologist by analyzing professional satisfaction, compassion, and burnout during the COVID-19 pandemic. Methods: An online, cross-sectional, self-reported, and internet-based survey was carried out among 153 radiologists and medical imaging technologists. Descriptive statistics were used to summarize the sociodemographic variables and domains of professional quality of life scale. Cronbach's alpha was used to check internal consistency. Independent sample t-test (two-tailed) was used to compare the demographic variables and compassion satisfaction, burnout, and secondary traumatic stress. Results: Most participants reported moderate and higher level of compassion satisfaction, whereas moderate burnout and secondary traumatic stress was reported by most participants during COVID-19 pandemic. There was negative correlation between compassion satisfaction and burnout and secondary traumatic stress. Conclusion: The findings of this study are vital to understand the work-related quality of life among healthcare professionals not only during COVID-19 pandemic but also after the pandemic situation. There is a need to conduct qualitative evaluation to ascertain the risk factors associated with professional quality of life. The study also reflects the need to focus more on the mental health of healthcare professionals not only during and after pandemic situation.

9.
J Glob Health ; 11: 04038, 2021.
Article in English | MEDLINE | ID: mdl-34484706

ABSTRACT

BACKGROUND: By 2030, Sustainable Development Goal 3.4 aims to reduce the premature mortality caused by non-communicable diseases through prevention and treatment. Chronic obstructive pulmonary disease is the second leading cause of mortality and disability-adjusted life years in India. This review was conducted to estimate the prevalence of COPD using systematic review and meta-analysis technique. METHOD: Search was conducted using six databases for studies on COPD among population above 30 years in India between years 2000 to 2020. Cross-sectional and cohort studies reporting prevalence of COPD and associated risk factors were included in the present review. Screening and data extraction was done by two authors independently. Studies were appraised for quality using the modified New Castle Ottawa scale and reporting quality was assessed using STROBE guidelines. RESULT: Our search returned 8973 records, from which 23 records fulfilled the eligibility criteria. Overall, the prevalence of COPD among population aged 30 years and above in India was 7%. Risk factors like active and passive smoking, biomass fuel exposure, environmental tobacco smoke, occupational exposure to dust, indoor and outdoor pollution, and increasing age were reported to have a significant association with COPD among Indian population. CONCLUSION: Our findings suggest the need for a multicentric national-level research study to understand COPD burden and its contributing risk factors. The findings also suggest the need for COPD sensitive health literacy program focused on early screening and primary prevention of risk factors for COPD, which may help early initiation of self-management practices, that are crucial for better quality of life.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Quality of Life , Cross-Sectional Studies , Humans , India/epidemiology , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Factors
10.
J Antimicrob Chemother ; 76(11): 2867-2874, 2021 10 11.
Article in English | MEDLINE | ID: mdl-34383913

ABSTRACT

OBJECTIVES: FtsZ is an essential bacterial protein and an unexplored target for the development of antibacterial drugs. The development of a novel inhibitor targeting FtsZ offers a potential opportunity to combat drug resistance. DS01750413, a new derivative of PC190723, is a novel FtsZ inhibitor with improved in vitro and in vivo activity. The objective of this study was to investigate the efficacy of DS01750413 against Staphylococcus spp., including MRSA, in in vitro and in vivo models. METHODS: In vitro activities of DS01750413 and standard-of-care antibiotics were evaluated against clinical isolates of Gram-positive pathogens. The in vivo efficacy was evaluated in a murine systemic infection model caused by MRSA. RESULTS: DS01750413 showed potent in vitro activity against MRSA clinical isolates with MIC ranges of 0.5-1 mg/L and also demonstrated concentration-dependent bactericidal killing. In the murine bacteraemia infection model of MRSA, treatment with DS01750413 resulted in prolonged survival of animals compared with placebo-treated animals and exhibited a significant reduction in the bacterial load in liver, spleen, lungs and kidneys. CONCLUSIONS: DS01750413 showed encouraging in vitro and in vivo activity against MRSA. As a novel chemical class, DS01750413 has the potential to become clinically viable antibiotics to address the drug resistance problem by its unique novel targeting mechanism of action.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cytoskeletal Proteins , Mice , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcus aureus
11.
Future Microbiol ; 16: 871-877, 2021 08.
Article in English | MEDLINE | ID: mdl-34318681

ABSTRACT

Aim: To investigate the antileishmanial activity of novel azole compounds against Leishmania donovani, which causes deadly visceral leishmaniasis disease. Materials & methods: A focused azole-based library was screened against both promastigotes and amastigotes forms of L. donovani strains in flat-bottomed 96-well tissue culture plates and J774A.1 macrophage cell-line infected with L. donovani. The comprehensive screening of azole-based library against L. donovani strains provided novel hits, which can serve as a good starting point to initiate hit to lead optimization campaign. Results: Hits identified from azole-based library exhibited potent in vitro activity against promastigotes and amastigotes of L. donovani. Conclusion: These potent novel azole hits could be a good starting point to carry out for further medicinal chemistry exploration for antileishmania program.


Subject(s)
Azoles , Leishmania donovani , Animals , Azoles/pharmacology , Cell Line , Leishmania donovani/drug effects , Macrophages/parasitology , Mice
12.
Extremophiles ; 25(3): 203-219, 2021 May.
Article in English | MEDLINE | ID: mdl-33768388

ABSTRACT

Technological advances in the field of life sciences have led to discovery of organisms that live in harsh environmental conditions referred to as extremophiles. These organisms have adapted themselves to thrive in extreme habitat giving these organisms an advantage over conventional mesophilic organisms in various industrial applications. Extremozymes produced by these extremophiles have high tolerance to inhospitable environmental conditions making them an ideal enzyme system for various industrial processes. A notable application of these extremophiles and extremozymes is their use in the degradation of recalcitrant lignocellulosic biomass and application in biorefineries. For maximum utilization of the trapped carbon source from this obstinate biomass, pretreatment is a necessary step that requires various physiochemical and enzymatic treatments. From search for novel extremophiles and extremozymes to development of various genetic and protein engineering techniques, investigation on extremozymes with enhanced stability and efficiency is been done. Since extremozymes are easily calibrated to work under such conditions, they have become an emerging topic in the research field of biofuel production. The review discusses the various extremozymes that play an important role in lignocellulose degradation along with recent studies on their molecular and genetic evolution for industrial application and production of biofuels and various value-added products.


Subject(s)
Extremophiles , Biofuels , Biomass , Lignin
13.
Can J Respir Ther ; 57: 14-17, 2021.
Article in English | MEDLINE | ID: mdl-33542948

ABSTRACT

BACKGROUND: The Sustainable Development Goals and the National Health Policy of India aim to reduce premature mortality from noncommunicable diseases (NCD) by one-third in the next decade and by 25% by 2025, respectively. Among NCDs globally, chronic obstructive pulmonary disease (COPD) is a major contributor to death and disability. This underscores the need to understand the burden of COPD at the national level by synthesizing evidence and collating the state-wise COPD data to estimate the prevalence of COPD and to highlight the associated risk factors to inform policymakers. METHOD: The systematic literature search will be carried out in PubMed, Cochrane, Scopus, Web of Science, CINAHL, and ProQuest databases with restrictions for studies published between 2000 and 2020 and available in English. Cross-sectional or cohort studies conducted in and among the Indian population aged 30 years and above will be included. Case reports, randomized trials, meta-analysis, commentaries, and qualitative studies will be excluded from the review. Quality assessment of the included studies will be performed using New Castle Ottawa scale and adherence to reporting standards will be checked using STROBE checklist for Observational Cohort and Cross-Sectional Studies. DISCUSSION: Prevalence of COPD in the population aged 30 years and above, diagnosed through spirometry and nonspirometry, will be compared and reported and a meta-analysis will be performed to obtain pooled prevalence rates of COPD and the risk factors associated with COPD.

14.
Clin Epidemiol Glob Health ; 9: 110-115, 2021.
Article in English | MEDLINE | ID: mdl-32838065

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread throughout the world and become a global pandemic. This has hampered and led to drastic changes in the functioning of healthcare services, forcing the professionals to adapt and work efficiently. The present study aimed to explore the impact of COVID-19 on the professional practices of audiologists and speech-language pathologists in India using a cross-sectional knowledge, attitude and practices survey. MATERIAL AND METHODS: The study was conducted in two phases; phase one involved development and validation of the questionnaire, while phase II involved data collection. A cross-sectional self-reported internet-based study using convenience sampling was carried out. RESULTS: Two hundred and eleven audiologists and speech-language pathologists responded to the survey. Overall, the professionals exhibited good knowledge levels regarding the COVID-19 outbreak. However, there were differences in their attitudes towards service delivery in the midst of the pandemic. Further, poor practices towards infection control measures especially in terms of hand washing was noted. CONCLUSION: The findings of the present study are useful in highlighting the need to create better awareness among these professionals about appropriate and standard infection control measures. There is a need to have in place standard operating protocols for hand wash and infection control as well as inclusion in curriculum.

15.
Biotechnol Rep (Amst) ; 28: e00525, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32963975

ABSTRACT

For sustainable growth, concept of biorefineries as recourse to the "fossil derived" energy source is important. Here, the Carbohydrate Active enZymes (CAZymes) play decisive role in generation of biofuels and related sugar-based products utilizing lignocellulose as a carbon source. Given their industrial significance, extensive studies on the evolution of CAZymes have been carried out. Various bacterial and fungal organisms have been scrutinized for the development of CAZymes, where advance techniques for strain enhancement such as CRISPR and analysis of specific expression systems have been deployed. Specific Omic-based techniques along with protein engineering have been adopted to unearth novel CAZymes and improve applicability of existing enzymes. In-Silico computational research and functional annotation of new CAZymes to synergy experiments are being carried out to devise cocktails of enzymes for use in biorefineries. Thus, with the establishment of these technologies, increased diversity of CAZymes with broad span of functions and applications is seen.

16.
Nanotechnology ; 30(38): 385502, 2019 Sep 20.
Article in English | MEDLINE | ID: mdl-31181546

ABSTRACT

Metal nanostructures with highly branched morphologies are attractive due to their fascinating plasmonic properties which are related to their unique morphological features. In this work a simple fabrication methodology is used for fabrication of surface-enhanced Raman spectroscopy (SERS) substrates composed of branched silver nanostructures with dendritic morphology. The high Raman intensity enhancement factor of the order ∼1010 was achieved which allows the detection of ∼zeptomole thiram molecules by SERS substrates. The appearance of new bands at 344 cm-1 and 1521 cm-1 provides an evidence of contribution of chemical enhancement in SERS. The observed spectral changes in SERS spectrum originate from the adsorption of the analyte on the metal surface and provide an insight into molecule-metal interaction in SERS. The extreme sensitivity of SERS substrates is discussed in terms of the distinction between electromagnetic and chemical enhancement mechanisms. Moreover, the highly sensitive SERS substrates were used for simultaneous detection of Rhodamine B and thiram molecules from their mixture with different individual concentrations demonstrating detection capabilities for the identification of pesticides with dye molecules.

17.
Sci Rep ; 9(1): 441, 2019 01 24.
Article in English | MEDLINE | ID: mdl-30679759

ABSTRACT

Plant populations growing along an altitudinal gradient are exposed to different environmental conditions. They are excellent resources to study regulatory mechanisms adopted by plants to respond to different environmental stresses. Regulation by miRNA is one of such strategies. Here, we report how different miRNAs are preferentially expressed in the three natural populations of A. thaliana originating from a wide altitudinal range. The expression level of miRNAs was mostly governed by temperature and radiation. Majority of the identified miRNAs expressed commonly in the three populations. However, 30 miRNAs expressed significantly at different level between the low and the high altitude populations. Most of these miRNAs regulate the genes associated with different developmental processes, abiotic stresses including UV, cold, secondary metabolites, etc. Further, the expression of miR397 and miR858 involved in lignin biosynthesis and regulation of secondary metabolites respectively, may be regulated by light intensity. A few miRNAs expressed at increasing level with the increase in the altitude of the site indicating environment driven tight regulation of these miRNAs. Further, several novel miRNAs and isomiR diversity specific to the Himalayas are reported which might have an adaptive advantage. To the best of our knowledge, this is the first report on miRNA expression from natural plant populations.


Subject(s)
Altitude , Arabidopsis/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Plant/genetics , MicroRNAs/genetics , Stress, Physiological/genetics , Adaptation, Physiological/genetics , Adaptation, Physiological/radiation effects , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant/radiation effects , Lignin/biosynthesis , Models, Genetic , Stress, Physiological/radiation effects , Temperature , Ultraviolet Rays
18.
Bioorg Med Chem Lett ; 27(15): 3454-3459, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28587823

ABSTRACT

A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.H37Rv strain) around the identified hit 1. A scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against MTb.H37Rv.


Subject(s)
ATP Synthetase Complexes/antagonists & inhibitors , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/enzymology , Quinolines/chemistry , Quinolines/pharmacology , ATP Synthetase Complexes/metabolism , Antitubercular Agents/chemical synthesis , Drug Design , Humans , Mycobacterium tuberculosis/drug effects , Pyrazines/chemical synthesis , Pyrazines/chemistry , Pyrazines/pharmacology , Quinolines/chemical synthesis , Structure-Activity Relationship , Tuberculosis/drug therapy , Tuberculosis/microbiology
19.
Biomed Pharmacother ; 83: 942-957, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27522257

ABSTRACT

OBJECTIVE: This study aims to evaluate the skeletal effects of dalbergin (DBN), isolated from Dalbergia sissoo heartwood, in ovariectomized (OVx) BALB/c mice, a postmenopausal osteoporosis model of bone loss. METHODS: Adult BALB/c mice were used and randomly assigned in to six groups with 6 animals (n=6) in each group: sham (surgery operated without ovariectomy) with vehicle, ovariectomy with vehicle, ovariectomy (OVx) with estradiol (E2 5.0µgkg-1day-1), or ovariectomy with dalbergin at three different doses of DBN (1.0, 5.0 and10mgkg-1day-1). Daily oral administration of the vehicle, estradiol, or DBN was started 8 weeks post-surgery and continued for 8 weeks. At the end of experiment, mice were sacrificed and assessed for trabecular bone structure of tibia, lumbar vertebra (L5) and alterations in biochemical and uterine parameters, pharmacokinetic profile and gene expression were monitored for each group. RESULTS: Treatment with DBN prevented trabecular bone loss in cancellous bone in the tibial metaphysis and lumbar vertebra region of the ovariectomized mice. Micro-CT data showed that mice treated with DBN at 1.0mgkg-1day-1 exhibited improved bone micro-architecture that was sustained with decreased expression of bone resorption markers like TRAP and RANK and caused an increase in osteogenic markers like RUNX2, BMP2 and OPG/RANKL ratio compared with OVx+vehicle treated mice. Moreover, DBN treatment induced no uterine estrogenicity and significantly lowered the osteocalcin amount in serum when compared with OVx+V group. DBN reached its maximum concentration (Cmax) 238.49±21.37ngml-1 in serum as early as 1h of administration. Overall, DBN (1.0mgkg-1day-1) treatment exhibited similar bone conserving effect against bone-loss as estradiol treatment. CONCLUSION: Daily oral administration of DBN for 8 weeks showed significant anabolic effects on bone micro-architectural parameters along with down regulation of bone resorptive markers without compromising safety at uterine level. Therefore, our study provides basis for DBN as a therapeutic candidate against postmenopausal osteoporosis.


Subject(s)
Coumarins/therapeutic use , Dalbergia/chemistry , Femur/pathology , Flavonoids/therapeutic use , Osteoporosis/drug therapy , Ovariectomy , Protective Agents/therapeutic use , Administration, Oral , Alkaline Phosphatase/metabolism , Animals , Biomarkers/blood , Biomarkers/metabolism , Biomechanical Phenomena/drug effects , Body Weight/drug effects , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone Remodeling/drug effects , Calcification, Physiologic/drug effects , Cancellous Bone/drug effects , Cancellous Bone/pathology , Coumarins/administration & dosage , Coumarins/chemistry , Coumarins/pharmacokinetics , Disease Models, Animal , Female , Femur/drug effects , Femur/physiopathology , Flavonoids/administration & dosage , Flavonoids/chemistry , Flavonoids/pharmacokinetics , Gene Expression Regulation/drug effects , Liver/drug effects , Liver/pathology , Mice, Inbred BALB C , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/pathology , Osteocalcin/blood , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/pathology , Osteoporosis/diagnostic imaging , Osteoporosis/genetics , Osteoporosis/pathology , Protective Agents/administration & dosage , Protective Agents/chemistry , Protective Agents/pharmacokinetics , Uterus/drug effects , Uterus/pathology , X-Ray Microtomography
20.
Int Immunopharmacol ; 10(4): 467-73, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20093202

ABSTRACT

The p38 mitogen activated protein kinase (MAPK) is a key signaling molecule that plays a crucial role in the progression of various inflammatory diseases such as rheumatoid arthritis (RA), asthma and chronic obstructive pulmonary disease. The objective of the present study was to evaluate the anti-inflammatory activity of a p38 MAPK inhibitor, AW-814141. AW-814141 inhibited enzymatic activity of recombinant p38-alpha and beta isoforms with IC(50) value of 100nM and 158nM, respectively. AW-814141 also inhibited the release of tumor necrosis factor (TNF)-alpha by lipopolysaccharide (LPS) treated human peripheral blood mononuclear cells with an IC(50) value of 212nM and demonstrated selectivity against a panel of few kinases. Oral administration of AW-814141 (10mpk) in LPS-injected mice resulted in a significant reduction in TNF-alpha production in the circulation. In a carrageenan-induced rat paw edema model and collagen-induced arthritis model (CIA), AW-814141 dose dependently inhibited paw swelling. In different in vivo efficacy models, efficacy of AW-814141 was found to be better as compared to the reference compounds (Vx-745 and BIRB-796). This study demonstrated that AW-814141 is a novel p38 MAPK inhibitor and it displays promising in vitro and in vivo anti-inflammatory activities and can be used for the treatment of rheumatoid arthritis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridones/pharmacology , Pyrimidines/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Carrageenan , Cell Death/drug effects , Collagen , Cytokines/metabolism , Edema/chemically induced , Edema/prevention & control , Enzyme Activation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Kinetics , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/toxicity , Male , Mice , NF-kappa B/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacokinetics , Pyridones/pharmacokinetics , Pyrimidines/pharmacokinetics , Rats , Rats, Wistar , Substrate Specificity , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/pharmacokinetics
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