Publications by authors named "Amit Kumar"

1,793 Publications

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Orphan legumes: harnessing their potential for food, nutritional and health security through genetic approaches.

Authors:
Sunil Kumar Chongtham Elangbam Lamalakshmi Devi Kajal Jeshima Khan SamantaraYasin Shabir Hussain Wani Soumya Mukherjee Ali Razzaq Ingudam Bhupenchandra Aanandi Lal Jat Laishram Kanta Singh Amit Kumar

Planta 2022 Jun 29;256(2):24. Epub 2022 Jun 29.

ICAR-NationalOrganic Farming Research Institute, Tadong, Gangtok, Sikkim, 737 102, India.

Legumes, being angiosperm's third-largest family as well as the second major crop family, contributes beyond 33% of human dietary proteins. The advent of the global food crisis owing to major climatic concerns leads to nutritional deprivation, hunger and hidden hunger especially in developing and underdeveloped nations. Hence, in the wake of promoting sustainable agriculture and nutritional security, apart from the popular legumes, the inclusion of lesser-known and understudied local crop legumes called orphan legumes in the farming systems of various tropical and sub-tropical parts of the world is indeed a need of the hour. Despite possessing tremendous potentialities, wide adaptability under diverse environmental conditions, and rich in nutritional and nutraceutical values, these species are still in a neglected and devalued state. Therefore, a major re-focusing of legume genetics, genomics, and biology is much crucial in pursuance of understanding the yield constraints, and endorsing underutilized legume breeding programs. Varying degrees of importance to these crops do exist among researchers of developing countries in establishing the role of orphan legumes as future crops. Under such circumstances, this article assembles a comprehensive note on the necessity of promoting these crops for further investigations and sustainable legume production, the exploitation of various orphan legume species and their potencies. In addition, an attempt has been made to highlight various novel genetic, molecular, and omics approaches for the improvement of such legumes for enhancing yield, minimizing the level of several anti-nutritional factors, and imparting biotic and abiotic stress tolerance. A significant genetic enhancement through extensive research in 'omics' areas is the absolute necessity to transform them into befitting candidates for large-scale popularization around the globe.
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http://dx.doi.org/10.1007/s00425-022-03923-1DOI Listing
June 2022

Structure-based study to identify alkaloids as promising cytochrome P450 (CYP1A1) inhibitors: An in silico approach using virtual screening, molecular dynamic simulations, and binding free energy calculation.

Authors:
Ved Vrat Verma Lalit Bhargava Mohammad Sajid Amit Kumar Harpreet Singh Mausumi Bharadwaj

J Cell Biochem 2022 Jun 28. Epub 2022 Jun 28.

Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, India.

Carcinogens present in smokeless tobacco (SLT) like tobacco-specific nitrosamines can be metabolized by the cytochrome P450 (CYP450) enzyme. Functionally, the CYP450 enzyme resides in a heme pigment to perform the catalytic activity. The CYP1A1 is one of the main extrahepatic CYP450 enzymes known to detoxify toxic substances and activate carcinogens. The CYP1A1 inhibition by potential inhibitors reduce the chance of oral cancer. The current study aimed to explore more about the inhibitor binding site and identification of lead alkaloids, that could work as putative inhibitors against target CYP1A1. In respect, we have performed docking studies, virtual screening of alkaloids, and natural product libraries against CYP1A1 followed by molecular dynamic simulations and binding free energy calculations. Docking studies of tobacco-specific nitrosamine (TSNA) products and their similar carcinogen analogs revealed that the heme group is bound to the floor of the bowl-shaped cavity whereas carcinogens are bound to the roof of the rounded shape cavity. Furthermore, virtual screening and binding free energy calculations revealed Tomatidine as a putative inhibitor against CYP1A1. On the basis of altogether outcomes of the current study, we have concluded that the addition of lead-hit alkaloid Tomatidine and others in SLT products may be working as a supplement that could be able to reduce the expression of human CYP1A1 and suppresses carcinogenic by-products formations.
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http://dx.doi.org/10.1002/jcb.30302DOI Listing
June 2022

What India can learn from globally successful malaria elimination programmes.

Authors:
Sachin Sharma Reena Verma Bhawna Yadav Amit Kumar Manju Rahi Amit Sharma

BMJ Glob Health 2022 Jun;7(6)

ICMR-National Institute of Malaria Research, New Delhi, Delhi, India

India is targeting malaria elimination by 2030. Understanding and adopting the strategies employed by countries that have successfully eliminated malaria can serve as a crucial thrust in this direction for a geographically diverse country like India. This analysis is based on extensive literature search on malaria elimination policies, strategies and programmes adopted by nine countries (China, El Salvador, Algeria, Argentina, Uzbekistan, Paraguay, Sri Lanka, Maldives and Armenia) which have attained malaria-free status over the past decade. The key points which India can learn from their journey are mandatory time-bound response in the form of case reporting and management, rapid vector control response, continuous epidemiological and entomological surveillance, elevated community participation, more training and capacity building, private sector involvement, use of quality diagnostics, cross-border collaborations, inclusion of prevention of re-establishment programmes into the elimination plans, higher investment in research, and uninterrupted funds for successful implementation of malaria elimination programmes. These learnings would help India and other South Asian countries steer their programmes by devising tailor-made strategies for their own regions.
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http://dx.doi.org/10.1136/bmjgh-2022-008431DOI Listing
June 2022

Magnetic-Plasmonic Multimodular Hollow Nanoreactors for Compartmentalized Orthogonal Tandem Catalysis.

Authors:
Jongwon Lim Nitee Kumari Trimbak B Mete Amit Kumar In Su Lee

Nano Lett 2022 Jun 24. Epub 2022 Jun 24.

Creative Research Initiative Center for Nanospace-confined Chemical Reactions (NCCR) and Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.

In tandem catalytic systems, controlling the reaction steps and side reactions is extremely challenging. Here, we demonstrate a nanoreactor platform comprising magnetic- and plasmonic-coupled catalytic modules that synchronizes reaction steps at unconnected neighboring reaction sites via decoupled nanolocalized energy harvested using distinct antennae reactors while minimizing the interconflicting effects. As was desired, the course of the reaction and product yields can be controlled by a convenient remote operation of alternating magnetic field (AMF) and near-infrared light (NIR). Following this strategy, a tandem reaction involving [Pd]-catalyzed Suzuki-Miyaura C-C cross-coupling and [Pt]-catalyzed aerobic alcohol oxidation enabled an excellent yield of cinnamaldehyde (ca. 95%) by overcoming the risk of side reactions. The customization scope for using different catalytic metals (Pt, Pd, Ru, and Rh) with control over product release through remotely operable benign energy sources opens avenues for designing diverse catalytic schemes for targeted applications.
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http://dx.doi.org/10.1021/acs.nanolett.2c01817DOI Listing
June 2022

Clinical and Echocardiographic Profile of Congenital Heart Diseases in the 0-12-Year Age Group in a Tertiary Care Medical Institute in Eastern India: A Retrospective, Cross-Sectional Study.

Authors:
Sunil Kishore Manish Kumar Amit Kumar Anand Gupta Chandrabhanu Chandan Anshuman Anshuman Jayant Prakash Shalini Sinha Neeraj Kumar

Cureus 2022 Jun 20;14(6):e26114. Epub 2022 Jun 20.

Cardiology, Indira Gandhi Institute of Medical Sciences, Patna, IND.

Background This study aimed to determine the clinical and echocardiography profile of congenital heart diseases (CHDs) among admitted children as well as patients presenting to the outpatient department of the Indira Gandhi Institute of Medical Sciences, Patna, which is a tertiary care and apex institute located in Bihar, India. Methodology A retrospective, cross-sectional study was conducted in a tertiary care hospital from January 2019 to January 2021. In total, 200 patients aged 0-12 were enrolled in the study. The study design was exploratory, with a proforma drafted to study patients with features suggestive of CHDs. All pediatric echocardiography was performed by a trained cardiologist. Records were obtained from the departmental record-keeping register, and reports were available for analyzing the data. For data collection, cardiology and pediatric department registers were reviewed and all CHD data were collected. Data analysis was done using SPSS software version 25.0 (IBM Corp., Armonk, NY, USA). Results Of the 200 children with CHDs, 142 were diagnosed to have acyanotic heart disease (ACHD), while 58 had cyanotic congenital heart disease (CCHD). Among 200 cases of CHD, ventricular septal defect (VSD) constituted 62 cases comprising 31% of the total CHD cases and 44% of all ACHD cases. Atrial septal defect (ASD) was the second most common CHD comprising 23% of all CHD cases. Tetralogy of Fallot (TOF) constituted 23 cases accounting for 11.5% of all CHD cases. It was the most common CCHD. Based on the age at the time of presentation, 90 (45%) cases were diagnosed below one year of age. Congestive heart failure (CHF) was most common in ACHD comprising 30% compared to CCHD in which only 7% of cases had CHF. This finding was statistically significant (p < 0.05). Analyzing the symptoms of different CHDs, of both ACHDs and CCHDs, the common symptoms were fast breathing (38%). Conclusions Among ACHD patients, 31% VSD and 21% ASD were noted. In CCHD, TOF was the most common with 11.5% of cases. Respiratory tract conditions were the most common comorbidities encountered. Because this is one of the first studies conducted in Bihar in the pediatric age group, it can help know the prevalence of CHDs in this region and will be useful for developing policies by stakeholders.
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http://dx.doi.org/10.7759/cureus.26114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208535PMC
June 2022

Influence of PWHT Parameters on the Mechanical Properties and Microstructural Behavior of Multi-Pass GTAW Joints of P92 Steel.

Authors:
Sachin Sirohi Amit Kumar Shiva Soni Gaurav Dak Sanjeev Kumar Aleksandra Świerczyńska Grzegorz Rogalski Dariusz Fydrych Chandan Pandey

Materials (Basel) 2022 Jun 7;15(12). Epub 2022 Jun 7.

Department of Mechanical Engineering, Indian Institute of Technology Jodhpur, N.H. 62, Nagaur Road, Jodhpur 342037, India.

The 9% Cr steels were developed for ultra-supercritical (USC) power plants to meet the requirements of high operating temperature and pressure. These steels are produced to operate at high temperatures where impact toughness is not a concern; however, it becomes important for the welded joints to have good impact toughness at room temperature for manufacturing. The present work investigates the effect of the post-weld heat treatment (PWHT) parameters, i.e., temperature and time, on the impact toughness of multi-pass gas tungsten arc welded (GTAW) joints of ferritic/martensitic grade P92 steel. The microstructural evolution in welded joints given varying post-weld temperatures and times was studied. The lath martensitic structure of the weld metal for the as-welded joints resulted in high hardness and low impact toughness. The weld fusion zone toughness was 12 J, which was lower than the minimum specified values of 41 J (ASME standards) and 47 J (EN ISO 3580:2017). The PWHT temperature and time were found to have a significant effect on the impact toughness of the weld metal. A drastic increase in the impact toughness of the weld metal was noticed, which was attributed to lath break-up, reduction in dislocation density and reduction in solid solution hardening. The maximum impact toughness of 124 J was measured for PWHT temperature and time of 760 °C and 120 min, respectively. The effect of PWHT parameters on tensile strength was also investigated, and test results showed that the joint was safe for USC boiler application as it failed from the region of the P92 base metal. The variation in microstructural evolution along the weldments resulted in hardness variation. PWHT led to homogeneity in microstructure and, ultimately, reduction in hardness value. According to the study, the optimum temperature and time for PWHT of a GTAW joint of P92 steel were found to be 760 °C and 120 min, respectively.
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http://dx.doi.org/10.3390/ma15124045DOI Listing
June 2022

A survey on ethnoveterinary medicines used by the tribal migratory shepherds of Northwestern Himalaya.

Authors:
Radha Suraj Prakash Niharika Sharma Amit Kumar Neeraj Kumari Sunil Puri Ashok Pundir Vijay Kumar Abhishek Kumar Sharma Nadeem Rais Abhijit Dey Jose M Lorenzo Mohamed Mekhemar Manoj Kumar

J Ethnopharmacol 2022 Jun 20:115467. Epub 2022 Jun 20.

Chemical and Biochemical Processing Division, ICAR - Central Institute for Research on Cotton Technology, Mumbai, 400019, India. Electronic address:

Ethnopharmacological Relevance: Tribal migratory shepherds (Gaddi) living in the Northwestern Himalayan region are well known for their nomadic lifestyle in which tribal migratory shepherds along with their livestock which mainly include sheep and goat migrate seasonally in the Northwestern Himalayan region from high hills to low hills for the survival of their livestock from cold winters and hot summer. Due to harsh environmental conditions, heavy snowfall, heavy rainfall, wild animal attacks, no medical facilities, no transportation, and no electricity facilities tribal migratory shepherds mostly rely on plant species mentioned for ethnoveterinary use to treat livestock disease.

Aim Of Study: The aim of our study is to conduct ethnoveterinary survey for the first time to document the contemporary oral ethnoveterinary knowledge of Gaddi shepherds living in Northwestern Himalayan region.

Methodology: The documentation of plant species mentioned for ethnoveterinary use was executed through extensive field surveys from 2017 to 2019. Data were collected through direct interviews by administrating questionnaire among tribal migratory shepherds.

Results: A total of 181 plant species mentioned for ethnoveterinary use belonging to the same or different families were documented during the seasonal migration of shepherds from Northwestern Himalayan region. Most frequently occurring family of plant species mentioned for ethnoveterinary was Poaceae, leaves and roots were reported to be the most frequently used plant parts. Most frequently documented plant species for ethnoveterinary use were Cynodon dactylon, Chenopodium album, Zanthoxylum armatum, Aloe vera, Azadirachta indica and Cannabis sativa. Chrysopogon serrulatus, Cynodon dactylon, and Vitex negundo were reported with high use reports. Some of the endemic species of Northwestern Himalayan region such as Elymus himalayanus and Euphorbia pilosa and one endangered species Picrorhiza kurrooa were reported in current study.

Conclusion: It is observed that there is a need to raise awareness among the tribal migratory shepherds about the sustainable use and conservation of some of the plant species mentioned for ethnoveterinary use. This study provided an inventory of plant species mentioned for ethnoveterinary use having significant ethnoveterinary potential, however there is need of scientific evaluations by in vitro, in vivo and clinical studies.
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http://dx.doi.org/10.1016/j.jep.2022.115467DOI Listing
June 2022

Ultra-High Carrier Mobilities in Ferroelectric Domain Wall Corbino Cones at Room Temperature.

Authors:
Conor J McCluskey Matthew G Colbear James P V McConville Shane J McCartan Jesi R Maguire Michele Conroy Kalani Moore Alan Harvey Felix Trier Ursel Bangert Alexei Gruverman Manuel Bibes Amit Kumar Raymond G P McQuaid J Marty Gregg

Adv Mater 2022 Jun 22:e2204298. Epub 2022 Jun 22.

School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, UK.

Recently, electrically conducting heterointerfaces between dissimilar band-insulators (such as lanthanum aluminate and strontium titanate) have attracted considerable research interest. Charge transport has been thoroughly explored and fundamental aspects of conduction firmly established. Perhaps surprisingly, similar insights into conceptually much simpler conducting homointerfaces, such as the domain walls that separate regions of different orientations of electrical polarisation within the same ferroelectric band-insulator, are not nearly so well-developed. Addressing this disparity, we herein report magnetoresistance in approximately conical 180° charged domain walls, which occur in partially switched ferroelectric thin film single crystal lithium niobate. This system is ideal for such measurements: firstly, the conductivity difference between domains and domain walls is extremely and unusually large (a factor of at least 10 ) and hence currents driven through the thin film, between planar top and bottom electrodes, are overwhelmingly channelled along the walls; secondly, when electrical contact is made to the top and bottom of the domain walls and a magnetic field is applied along their cone axes (perpendicular to the thin film surface), then the test geometry mirrors that of a Corbino disc, which is a textbook arrangement for geometric magnetoresistance measurement. Our data imply carriers at the domain walls with extremely high room temperature Hall mobilities of up to ∼ 3,700cm V s . This is an unparalleled value for oxide interfaces (and for bulk oxides too) and is most comparable to mobilities in other systems typically seen at cryogenic, rather than at room, temperature. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204298DOI Listing
June 2022

Protective effects of novel diazepinone derivatives in snake venom induced sterile inflammation in experimental animals.

Authors:
M I Alam Huma Quasimi Amit Kumar Aftab Alam Saumya Bhagat M Sarwar Alam G A Khan Abhijeet Dhulap Mairaj Ahmad Ansari

Eur J Pharmacol 2022 Jun 18:175095. Epub 2022 Jun 18.

Department of Biotechnology, Jamia Hamdard, New Delhi, India.

Snake envenomation leads to the formation of damage-associated molecular patterns (DAMPs), which are mediated by endogenous intracellular molecules. These are recognized by pattern-recognition receptors (PRRs) and can induce sterile inflammation.

Aims: In the present study, we aim at understanding the mechanisms involved in DAMPs induced sterile inflammation to unravel the novel therapeutic strategies for treating snake bites. The potential of benzodiazepinone derivatives to act against snake venom induced inflammation has been explored in the present investigation.

Main Methods: Three compounds VA 17, VA 43 and PA 03 were taken from our library of synthetic compounds. Oxidative stress markers such as lipid peroxidation, superoxide and nitric oxide were measured along with the analysis of DAMPs (IL6, HMGB1, vWF, S100b and HSP70). These compounds have been docked using molecular docking against the snake venom PLA structure (PDB code: 1OXL).

Key Findings: The compounds have been found to effectively neutralize viper and cobra venoms induced lethal activity both ex vivo and in vivo. The compounds have also neutralized the viper venom induced hemorrhagic, coagulant, anticoagulant reactions as well as inflammation. The fold of protection have always been found to be higher in case of ex vivo than in in vivo. These compounds have neutralized the venom induced DAMPs as exhibited by IL6, HMGB1, vWF, S100b and HSP70. The fold of neutralization is found to be higher in VA 43.

Significance: The identified compounds could be used as potential candidates for developing treatment of snakebites in areas where antiserums are not yet available.
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http://dx.doi.org/10.1016/j.ejphar.2022.175095DOI Listing
June 2022

Solid-State Reaction Synthesis of Nanoscale Materials: Strategies and Applications.

Authors:
Amit Kumar Soumen Dutta Seonock Kim Taewan Kwon Santosh S Patil Nitee Kumari Sampathkumar Jeevanandham In Su Lee

Chem Rev 2022 Jun 17. Epub 2022 Jun 17.

Creative Research Initiative Center for Nanospace-confined Chemical Reactions (NCCR) and Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.

Nanomaterials (NMs) with unique structures and compositions can give rise to exotic physicochemical properties and applications. Despite the advancement in solution-based methods, scalable access to a wide range of crystal phases and intricate compositions is still challenging. Solid-state reaction (SSR) syntheses have high potential owing to their flexibility toward multielemental phases under feasibly high temperatures and solvent-free conditions as well as their scalability and simplicity. Controlling the nanoscale features through SSRs demands a strategic nanospace-confinement approach due to the risk of heat-induced reshaping and sintering. Here, we describe advanced SSR strategies for NM synthesis, focusing on mechanistic insights, novel nanoscale phenomena, and underlying principles using a series of examples under different categories. After introducing the history of classical SSRs, key theories, and definitions central to the topic, we categorize various modern SSR strategies based on the surrounding solid-state media used for nanostructure growth, conversion, and migration under nanospace or dimensional confinement. This comprehensive review will advance the quest for new materials design, synthesis, and applications.
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http://dx.doi.org/10.1021/acs.chemrev.1c00637DOI Listing
June 2022

Implication of methylselenocysteine in combination chemotherapy with gemcitabine for improved anticancer efficacy.

Authors:
Chittaranjan Behera Kamalpreet Kaur Sandha Nagma Banjare Sumera Banoo Malik Misbah Tabassum Rajesh Kumar Amit Kumar Dilip M Mondhe Prem N Gupta

Eur J Pharm Sci 2022 Jun 14:106238. Epub 2022 Jun 14.

PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India. Electronic address:

The limitations associated with cancer monotherapy including dose dependent toxicity and drug resistance can be addressed by combination chemotherapy. The combination of antineoplastic agents improves the cytotoxic activity in comparison to the single-agent based therapy in a synergistic or additive mode by reducing tumor growth as well as metastatic ability. In the present investigation, we explored the potential of methylselenocysteine (MSC) in combination chemotherapy with gemcitabine (GEM). The cytotoxic activity of GEM and MSC was determined in various cell lines and based on the activity, A549 cells were explored for the mechanistic studies including DAPI staining, measurement of oxidative stress, mitochondrial membrane potential loss, nitric oxide level, western blotting, cell migration and colony formation assays. A549 cells in combination treatment with MSC and GEM demonstrated enhanced cytotoxicity with more irregular cellular morphology as well as chromatin condensation and nuclear blebbing. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, and alleviated cell migration potential and clonogenic propensity of A549 cells. Also, caspase-3 and PARP mediated apoptosis was observed in the combination treated cells. MSC based drug combination could offer the attributes of improved drug delivery and there was a 6-folds dose reduction of GEM in combination. Further, antitumor study in Ehrlich solid tumor model showed the efficacy of MSC combination with GEM for the enhanced antitumor activity. The proposed combination demonstrated the potential for further translational studies.
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http://dx.doi.org/10.1016/j.ejps.2022.106238DOI Listing
June 2022

Visible-light driven dual heterojunction formed between g-CN/[email protected] for the effective degradation of tetracycline.

Authors:
Gaurav Sharma Amit Kumar Shweta Sharma Mu Naushad Dai-Viet N Vo Mohd Ubaidullah Sabry M Shaheen Florian J Stadler

Environ Pollut 2022 Jun 13:119597. Epub 2022 Jun 13.

College of Materials Science and Engineering, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, Nanshan District Key Lab. for Biopolymers and Safety Evaluation, Shenzhen University, Shenzhen, 518060, PR China.

In the present study, we have successfully formulated a dual heterojunction of g-CN/[email protected] (GCBM) which was found to be highly active in the visible region. GCBM was found to be highly efficient for the degradation of an antibiotic, tetracycline (TC) as compared to the individual constituting units; g-CN and BiOCl. Maximum of 97% TC degradation rate was obtained within 90 min of visible light irradiation for initial concentration of 10 mg/L of TC. Optical analysis exhibited that the synthesized heterojunction showed high absorption in the complete spectrum. The reactive species specified by the scavenger study showed that the major involvement of O and OH radicals. The charge transfer mechanism showed that 2 schemes were majorly involvement in which Z-scheme was formed between g-CN and BiOCl and Schottky junction was formed between g-CN and Mxene-TiC. The formation of Schottky junction helped in inhibiting the back transfer of photogenerated charges and thus, helped in reducing the recombination rate. The synthesized photocatalyst was found to be highly reusable and was studied for consecutive 5 cycles that generalized the high proficiency even after repetitive cycles.
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http://dx.doi.org/10.1016/j.envpol.2022.119597DOI Listing
June 2022

Initial Immunomodulation and Outcome of Children with Multisystem Inflammatory Syndrome Related to COVID-19: A Multisite Study from India.

Authors:
Narendra Kumar Bagri M Khan R M Pandey Rakesh Lodha S K Kabra Suresh Kumar Angurana Shally Awasthi Harshita Bamnawat Javeed Iqbal Bhat Tsultem D Bhutia Bashir Ahmad Charoo Abhijit Choudhary Bharat Choudhary Rashmi Ranjan Das Bhagirathi Dwibedi Sanajit Ghosh Meenakshi Girish Krishna Mohan Gulla Jagdish Prasad Goyal Prakriti Gupta Shivanand I Atul Jindal Joseph John Preetha Joshi Ravleen Kaur Daisy Khera Amit Kumar Pradeep Kumar Prawin Kumar

Indian J Pediatr 2022 Jun 14. Epub 2022 Jun 14.

Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Objective: To determine the outcomes in children with MIS-C receiving different immunomodulatory treatment.

Methods: In this multicentric, retrospective cohort study, data regarding treatment and outcomes of children meeting the WHO case definition for MIS-C, were collected. The primary composite outcome was the requirement of vasoactive/inotropic support on day 2 or beyond or need of mechanical ventilation on day 2 or beyond after initiation of immunomodulatory treatment or death during hospitalization in the treatment groups. Logistic regression and propensity score matching analyses were used to compare the outcomes in different treatment arms based on the initial immunomodulation, i.e., IVIG alone, IVIG plus steroids, and steroids alone.

Results: The data of 368 children (diagnosed between April 2020 and June 2021) meeting the WHO case definition for MIS-C, were analyzed. Of the 368 subjects, 28 received IVIG alone, 82 received steroids alone, 237 received IVIG and steroids, and 21 did not receive any immunomodulation. One hundred fifty-six (42.39%) children had the primary outcome. On logistic regression analysis, the treatment group was not associated with the primary outcome; only the children with shock at diagnosis had higher odds for the occurrence of the outcome [OR (95% CI): 11.4 (5.19-25.0), p < 0.001]. On propensity score matching analysis, the primary outcome was comparable in steroid (n = 45), and IVIG plus steroid (n = 84) groups (p = 0.515).

Conclusion: While no significant difference was observed in the frequency of occurrence of the primary outcome in different treatment groups, data from adequately powered RCTs are required for definitive recommendations.
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http://dx.doi.org/10.1007/s12098-022-04254-5DOI Listing
June 2022

A STING agonist preconditions against ischaemic stroke via an adaptive antiviral Type 1 interferon response.

Authors:
Nandini Kundu Amit Kumar Carlo Corona Yingxin Chen Sonia Seth Saravanan S Karuppagounder Rajiv R Ratan

Brain Commun 2022 24;4(3):fcac133. Epub 2022 May 24.

Burke Neurological Institute and Brain and Mind Research Institute, Weill Cornell Medicine, 785 Mamaroneck Ave, White Plains, NY, USA.

Converging lines of inquiry have highlighted the importance of the Type I antiviral response not only in defending against viruses but also in preconditioning the brain against ischaemic stroke. Despite this understanding, treatments that foster brain resilience by driving antiviral interferon responses have yet to be developed for human use. Studies from our laboratory showed that tilorone, the first human antiviral immunomodulatory agent to be developed, robustly preconditioned against stroke in mice and rats. Tilorone is a DNA intercalator; therefore, we hypothesized that it stabilizes cytosolic DNA (released from the mitochondria or the nucleus), thereby activating cyclic GMP-AMP synthase, a homeostatic DNA sensor, and its downstream pathway. This pathway involves imulator of erferon enes (STING), tank-binding kinase 1 (TBK1), and nterferon egulatory rotein-3 and culminates in a protective Type I interferon response. We tested this hypothesis by examining the ability of structurally diverse small-molecule agonists of STING to protect against oxygen/glucose deprivation in mouse cortical cultures and against transient ischaemia in mice. The STING agonists significantly reduced cell death both and failed to do so in STING knockout mice. As expected, STING agonist-induced protection was associated with the induction of interferon related genes and the effects could be abrogated by a TBK1 inhibitor. Taken together, these findings in mice identify STING as a therapeutic target for preconditioning the brain against ischaemic stroke and . Moreover, they suggest that clinically approved STING agonists such as Ganciclovir or α-Mangostin are candidate drugs that could be tested in humans as a prophylactic treatment to alleviate brain injury associated with ischaemic stroke.
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http://dx.doi.org/10.1093/braincomms/fcac133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175192PMC
May 2022

Efficacy of digital nasoalveolar molding in reducing severity of cleft lip or palate malformation in infants: a systematic review protocol.

Authors:
Prabhat Kumar Chaudhari Kunaal Dhingra Harnoor Dhillon Edlira Zere Jitender Sharan Amit Kumar Mohammad Khursheed Alam Anand Marya

JBI Evid Synth 2022 Jun 10. Epub 2022 Jun 10.

Division of Orthodontics and Dentofacial Deformities, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India Periodontics Division, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India Orthodontic and Craniofacial Department, School of Graduate Dentistry, Rambam Health Care Campus, Technion, Faculty of Medicine, Haifa, Israel Unit of Orthodontics and Dentofacial Orthopedics, Department of Dentistry, All India Institute of Medical Sciences, Bhubaneshwar, Odisha, India Laboratory Medicine, Rajendra Institute of Medical Sciences, Ranchi, India Orthodontic Department, College of Dentistry, Jouf University, KSA Department of Orthodontics, University of Puthisastra, Phnom Penh, Cambodia.

Objective: This review will compare the efficacy of nasoalveolar molding plates fabricated using a digital workflow and compare these with conventional fabrication methods or no intervention in infants with cleft lip or palate.

Introduction: Nasoalveolar molding reduces the severity of the orofacial defect in infants with cleft lip or palate using a series of adaptable plates for the maxillary arch. The conventional method needs multiple patient visits at short intervals for treatment. A digital workflow can be used to fabricate multiple plates in one appointment. This eliminates human error, reduces the number of appointments, and allocates more time for patient care than appliance fabrication.

Inclusion Criteria: This review will consider clinical studies that report the results of digital nasoalveolar molding in individuals with cleft lip or palate and compare it to conventional methods or to no treatment.

Methods: This review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases including PubMed, Embase, Cochrane Oral Health Group Trial Register, and ClinicalTrials.gov will be searched using appropriate keywords. Publications in English will be considered. Screening based on titles and abstracts will be done after de-duplication, followed by full-text reading for selection based on the inclusion criteria. Data extracted from the studies will be tabulated and assessed for risk of bias. If applicable, a meta-analysis of the pooled data will be done.

Systematic Review Registration Number: PROSPERO (CRD42020186452).
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http://dx.doi.org/10.11124/JBIES-21-00345DOI Listing
June 2022

The Impact of Unilateral Sensorineural Hearing Loss on Quality of Life of Sub-Himalayan Population.

Authors:
Rachit Sood Saurabh Varshney Kartikesh Gupta Nongthombam Surjalata Devi Narendra Kumar Amit Kumar Tyagi Amit Kumar

Int J Otolaryngol 2022 31;2022:8304639. Epub 2022 May 31.

Department of ENT, AIIMS, Rishikesh, Uttarakhand, India.

Introduction: Unilateral Sensorineural Hearing Loss (USNHL) is an age-old known entity. Patients with USNHL lack the merits of binaural hearing, i.e., temporal summation, sound localization, and speech recognition in a noisy environment. The lack of binaural hearing affects such individuals' quality of life (QOL). The present study is the most extensive Indian series related to QOL in USNHL patients.

Objectives: This study aims to assess the impact of USNHL on the QOL of patients in the state of Uttarakhand.

Methods: A cross-sectional study was carried out at a tertiary care center in Uttarakhand over a period of 18 months, from January 2018 to July 2019. A total of 115 patients with pure USNHL were evaluated using a validated questionnaire-Hearing Handicap Inventory for Adults-Hindi (HHIA-H).

Results: In our study, patients with higher HHIA-H scores were male, young adults (age group 18-30 years), students, and laborers. Most of our patients (64%) had significant handicaps, followed by moderate handicaps in 25%. However, no significant correlation of degree of handicap was seen with age, duration, and degree of hearing loss.

Conclusion: USNHL can lead to a significant handicap that can severely affect the emotional and social aspects of life. Thus, early diagnosis and rehabilitation are essential to prevent handicap and uplift QOL in patients with USNHL. This trial is registered with Clinical Trials Registry of India (CTRI reg. no. CTRI/2018/06/014396).
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http://dx.doi.org/10.1155/2022/8304639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174010PMC
May 2022

Allosteric Binding Sites of Aβ Peptides on the Acetylcholine Synthesizing Enzyme ChAT as Deduced by In Silico Molecular Modeling.

Authors:
Anurag Tk Baidya Amit Kumar Rajnish Kumar Taher Darreh-Shori

Int J Mol Sci 2022 May 28;23(11). Epub 2022 May 28.

Division of Clinical Geriatric, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, NEO, 141 52 Stockholm, Sweden.

The native function of amyloid-β (Aβ) peptides is still unexplored. However, several recent reports suggest a prominent role of Aβ peptides in acetylcholine homeostasis. To clarify this role of Aβ, we have reported that Aβ peptides at physiological concentrations can directly enhance the catalytic efficiency of the key cholinergic enzyme, choline acetyltransferase (ChAT), via an allosteric interaction. In the current study, we further aimed to elucidate the underlying ChAT-Aβ interaction mechanism using in silico molecular docking and dynamics analysis. Docking analysis suggested two most probable binding clusters on ChAT for Aβ and three for Aβ. Most importantly, the docking results were challenged with molecular dynamic studies of 100 ns long simulation in triplicates (100 ns × 3 = 300 ns) and were analyzed for RMSD, RMSF, RoG, H-bond number and distance, SASA, and secondary structure assessment performed together with principal component analysis and the free-energy landscape diagram, which indicated that the ChAT-Aβ complex system was stable throughout the simulation time period with no abrupt motion during the evolution of the simulation across the triplicates, which also validated the robustness of the simulation study. Finally, the free-energy landscape analysis confirmed the docking results and demonstrated that the ChAT-Aβ complexes were energetically stable despite the unstructured nature of C- and N-terminals in Aβ peptides. Overall, this study supports the reported in vitro findings that Aβ peptides, particularly Aβ, act as endogenous ChAT-Potentiating-Ligand (CPL), and thereby supports the hypothesis that one of the native biological functions of Aβ peptides is the regulation of acetylcholine homeostasis.
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http://dx.doi.org/10.3390/ijms23116073DOI Listing
May 2022

A Tandem Semipinacol Rearrangement/Aldehyde Arylation or Alkylation of Trisubstituted 2,3-Epoxy Alcohols with Grignard Reagents for Functionalized 1,3-Diols.

Authors:
Amit Kumar Gaurav Sharma Sanjeev K Shukla Gautam Panda

J Org Chem 2022 Jun 9;87(12):7696-7711. Epub 2022 Jun 9.

Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, UP, India.

A tandem semipinacol rearrangement/aldehyde arylation or alkylation reaction leading to formation of functionalized 1,3-diols bearing three consecutive tertiary stereocenters is identified from the reaction of various new trisubstituted 2,3-epoxy alcohols with numerous Grignard reagents. This reaction is useful for stereoselective construction of three consecutive tertiary stereocenters. The observed 1,3-diols exist in the configuration, which is confirmed by two-dimensional nuclear Overhauser effect spectroscopy, the crystal structure of acetonide of 1,3-diol analogue , and further density functional theory studies.
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http://dx.doi.org/10.1021/acs.joc.2c00267DOI Listing
June 2022

Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III Non-Small-Cell Lung Cancer: Results of KINDLE-Vietnam Cohort.

Authors:
Tu Van Dao Tuan Bao Diep Tri Le Phuong Reto Huggenberger Amit Kumar

Front Oncol 2022 23;12:842296. Epub 2022 May 23.

Medical Affairs, AstraZeneca India, Bangalore, India.

Objective: KINDLE-Vietnam was a part of a real-world KINDLE study with an aim to characterise treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC).

Materials And Methods: Retrospective data from patients diagnosed with stage III NSCLC (American Joint Committee on Cancer, 7 edition) between January 2013 and December 2017 with at least 9 months of follow-up were collected from 2 centres in Vietnam. Descriptive statistics were used to summarise demographics, disease characteristics and treatment modalities. Kaplan-Meier methodology evaluated survival estimates; 2-sided 95% confidence intervals (CIs) were computed. Inferential statistics were used to correlate clinical and treatment variables with median progression-free survival (mPFS) and median overall survival (mOS).

Results: A total of 150 patients (median age: 60 years [range 26-82]) were enrolled; 75.3% were male, 62.0% had smoking history, 56.4% had stage IIIB disease and 62.5% had adenocarcinoma. The majority of the cases (97.3%) were not discussed at a multidisciplinary team meeting. Overall, chemotherapy alone (43.3%), radiotherapy alone (17.0%), sequential chemoradiation (13.5%) and concurrent chemoradiation (12.8%) were preferred as initial therapy. Surgery-based treatment was administered in limited patients (stage IIIA, 10%; stage IIIB, 1.3%). Palliative therapy was the most commonly administered treatment upon relapse in the second-and third-line setting. The mPFS and mOS for the Vietnam cohort were 8.7 months (95% CI, 7.59-9.72) and 25.7 months (95% CI, 19.98-42.61), respectively. The mPFS and mOS for stage IIIA were 11.9 months (95% CI, 8.64-14.95) and 28.2 months (95% CI, 24.15-not-calculable) and for stage IIIB were 7.8 months (95% CI, 6.64-8.71) and 20.0 months (95% CI, 13.01-42.61).

Conclusions: KINDLE-Vietnam offers insights into the clinical findings of stage III NSCLC. There is a high unmet need for identifying patients in the early stages of NSCLC. Strategies for improving clinical outcomes in this patient population include physician education, multidisciplinary management and catering to increased access to novel agents like immunotherapy and targeted therapy.
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http://dx.doi.org/10.3389/fonc.2022.842296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169691PMC
May 2022

Deposition of trace metals associated with atmospheric particulate matter: Environmental fate and health risk assessment.

Authors:
Meththika Vithanage Pasan Chinthana Bandara Luís A B Novo Amit Kumar Balram Ambade G Naveendrakumar Manjula Ranagalage Dhammika N Magana-Arachchi

Chemosphere 2022 Sep 4;303(Pt 3):135051. Epub 2022 Jun 4.

Molecular Biology and Human Diseases Project, National Institute of Fundamental Studies, Kandy, Sri Lanka.

Anthropogenic and natural sources influence trace metals (TMs) bound to different sized particulate matter (PM) in dry and wet atmospheric deposition, which can create ecosystem and human health issues in the long run. Limited reviews are available summarizing worldwide concentrations in TMs in atmospheric PMs, their sources and pathways. Simultaneously, quantitative assessment of the potential human and ecosystem health risks imposed by the atmospheric particulate matter has not been adequately reviewed. Addressing this gap, here we review, the concentration of TMs in dry deposition mainly varies with the responsible sources, whereas, in wet deposition, it depends on the solubility of TMs. Other than deposition on impervious surfaces, the TMs incorporated PM can be deposited on biological agents. Health risk assessments show that ingestion and dermal contact pathways are more likely to cause health issues, however, the probability of occurring ingestion and dermal contact pathways is limited. Attention must be paid to the contribution from non-exhaust and exhaust vehicular emissions for TMs in atmospheric deposition, understanding their impact on stormwater management and urban agriculture. Behaviors of TMs in the atmosphere depends on many complex factors including origin, wind patterns, and weather conditions. Therefore, future research needs to be carried to model and predict the fate and transfer of TMs once they are generated through natural and anthropogenic sources. We believe that such research would allow establishing pollution control policies and measures in urban environments which will be critical to reduce the levels of TMs associated with atmospheric deposition in the environment.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135051DOI Listing
September 2022

A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors.

Authors:
Amit Kumar Kiran Siwach Claudiu T Supuran Pawan K Sharma

Bioorg Chem 2022 Sep 1;126:105920. Epub 2022 Jun 1.

Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119, India. Electronic address:

Human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII are well established anticancer drug targets and their selective inhibition is highly desired for the proper treatment of cancer. Lack of isoform-selectivity in current clinically used CA inhibitors (CAIs) is a major concern as it leads to undesired side effects, associated with off-target inhibition. Thus, there is need to explore alternative approaches for the design of isoform-selective inhibitors and the leading promising approach for the design of isoform-selective CAIs is "the tail-approach". Virtually, most drug design studies in the last decade were done by considering the tail-approach reported in 1999. The past decade of 2010-2020 witnessed progressive maturation of this approach as a large number of CAIs have been designed and synthesised based on it, many of which turned out to be effective as well as selective hCA IX and hCA XII inhibitors. This review covers the past decade (2010-2020) research, considering selective as well as potent inhibitors of tumor associated isoforms, hCA IX and hCA XII, which include newer generation inhibitors containing sulfonamides or their bioisosteres, non-classical inhibitors (including carboxylic acid/ester, coumarin and sulfocoumarin classes) and various other novel classes of inhibitors belonging to newly identified chemotypes/scaffolds.
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http://dx.doi.org/10.1016/j.bioorg.2022.105920DOI Listing
September 2022

Improvement of Hand Hygiene Compliance Using the Plan-Do-Study-Act Method: Quality Improvement Project From a Tertiary Care Institute in Bihar, India.

Authors:
Amit Kumar Rakesh Kumar Anand K Gupta Sunil Kishore Manish Kumar Rizwan Ahmar Jayant Prakash Shambhavi Sharan

Cureus 2022 Jun 2;14(6):e25590. Epub 2022 Jun 2.

Pediatrics, Indira Gandhi Institute of Medical Sciences, Patna, IND.

Background Hospital-acquired infections (HAIs) are the most severe complications of intensive care stay, especially in pediatric patients. Proper hand hygiene (HH) is the cheapest, simplest, but often neglected method to prevent HAIs. The World Health Organization (WHO) has formulated and promoted a standardized recommendation for HH. Both the WHO and the Centers for Disease Control and Prevention (CDC) recommend the use of soap and water for handwashing whenever there is visible dirt on the hands. In all other situations, an alcohol-based hand rub is an effective alternative. The quality improvement (QI) methodology has been widely followed in many countries to improve basic and advanced healthcare systems. The QI strategy follows the plan-do-study-act (PDSA) method. Methodology This quasi-experimental (pre- and post-intervention), prospective, QI study was conducted at the neonatal intensive care unit and pediatric intensive care unit of the pediatrics department in a tertiary care hospital in Bihar, India. A QI team was formed. The study was divided into four phases. WHO charts for assessing HH compliance were used for observation and data collection. The EQUATOR Checklist (Squire Checklist) was used to accurately report the QI work. Epi Info™ (version 7.2.5) was used for statistical analysis. The chi-square test was used to measure the statistical difference between pre- and post-intervention HH compliance (proportions). Results In the pre-intervention phase, a total of 106 HH opportunities were observed. The HH compliance at this stage was 40.6%. The QI team conducted several meetings, and a root cause analysis was performed with the help of the Fishbone diagram. It was decided to target three probable causes, namely, (a) less awareness, (b) inconvenient locations of hand rub dispensers, and (c) forgetfulness. The QI team decided to run three PDSA cycles. In the last phase, 212 HH opportunities were observed with a compliance percentage of 69.8%. There was a significant improvement when data of pre- and post-intervention HH compliance were compared in all categories of healthcare workers (HCWs), except doctors, where the improvement was not statistically significant. When the cumulative data of all subtypes of HCWs were analyzed, there was a significant improvement (p < 0.0001). Run charts and box plots were used for the easy depiction of the results. Conclusions Adopting proper HH methods remains the most effective way of preventing nosocomial infections, especially in intensive care units. We used the WHO model of HH in our study. The pre-intervention HH compliance was 40.6%. QI methodology using root cause analysis and implementation of three PDSA cycles were used to increase the HH compliance percentage. Post-intervention HH compliance increased to 69.8% and the effect was sustained. The study highlights the usefulness of the QI methodology in bringing small but important changes in clinical practice for better patient care.
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http://dx.doi.org/10.7759/cureus.25590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162031PMC
June 2022

How Did the Lockdown Imposed Due to COVID-19 Affect Patients With Cerebral Palsy?

Authors:
Amit Kumar Asir John Samuel

Pediatr Phys Ther 2022 May 25. Epub 2022 May 25.

Department of Pediatric and Neonatal Physiotherapy Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation Maharishi Markandeshwar (Deemed to be University) Mullana, Haryana, India.

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http://dx.doi.org/10.1097/PEP.0000000000000934DOI Listing
May 2022

Molecular response of Sargassum vulgare to acidification at volcanic CO vents: Insights from proteomic and metabolite analyses.

Authors:
Amit Kumar Simona Nonnis Immacolata Castellano Hamada AbdElgawad Gerrit T S Beemster Maria Cristina Buia Elisa Maffioli Gabriella Tedeschi Anna Palumbo

Mol Ecol 2022 May 30. Epub 2022 May 30.

Stazione Zoologica Anton Dohrn, Department of Biology and Evolution of Marine Organisms, Naples, Italy.

Ocean acidification is impacting marine life all over the world. Understanding how species can cope with the changes in seawater carbonate chemistry represents a challenging issue. We addressed this topic using underwater CO vents that naturally acidify some marine areas off the island of Ischia. In the most acidified area of the vents, having a mean pH value of 6.7, comparable to far-future predicted acidification scenarios (by 2300), the biomass is dominated by the brown alga Sargassum vulgare. The novelty of the present study is the characterization of the S. vulgare proteome together with metabolite analyses to identify the key proteins, metabolites, and pathways affected by ocean acidification. A total of 367 and 387 proteins were identified in populations grown at pH that approximates the current global average (8.1) and acidified sites, respectively. Analysis of their relative abundance revealed that 304 proteins are present in samples from both sites: 111 proteins are either higher or exclusively present under acidified conditions, whereas 120 proteins are either lower or present only under control conditions. Functionally, under acidification, a decrease in proteins related to translation and post-translational processes and an increase of proteins involved in photosynthesis, glycolysis, oxidation-reduction processes, and protein folding were observed. In addition, small-molecule metabolism was affected, leading to a decrease of some fatty acids and antioxidant compounds under acidification. Overall, the results obtained by proteins and metabolites analyses, integrated with previous transcriptomic, physiological, and biochemical studies, allowed us to delineate the molecular strategies adopted by S. vulgare to grow in future acidified environments, including an increase of proteins involved in energetic metabolism, oxidation-reduction processes, and protein folding at the expense of proteins involved in translation and post-translational processes.
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http://dx.doi.org/10.1111/mec.16553DOI Listing
May 2022

Secondary metabolites produced by Macrophomina phaseolina, a fungal root endophyte of Brugmansia aurea, using classical and epigenetic manipulation approach.

Authors:
Gurpreet Singh Amit Kumar M K Verma Prasoon Gupta Meenu Katoch

Folia Microbiol (Praha) 2022 May 27. Epub 2022 May 27.

Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.

Endophytic fungi are rich sources of structurally complex chemical scaffolds with interesting biological activities. However, their metabolome is still unknown, making them appealing for novel compound discovery. To maximize the number of secondary metabolites produced from a single microbial source, we used the "OSMAC (one strain-many compounds) approach." In potato dextrose medium, M. phaseolina produced phomeolic acid (1), ergosterol peroxide (2), and a volatile compound 1,4-benzene-diol. Incorporating an epigenetic modifier, sodium valproate, affected the metabolite profile of the fungus. It produced 3-acetyl-3-methyl dihydro-furan-2(3H)-one (3) and methyl-2-(methyl-thio)-butyrate (4), plus volatile chemicals: butylated hydroxy toluene (BHT), di-methyl-formamide, 3-amino-1-propanol, and 1,4-benzenediol, 2-amino-1-(O-methoxyphenyl) propane. The structure of compounds 1-4 was established with the help of spectroscopic data. This study revealed first-time compounds 1-4 in the fungus M. phaseolina using a classical and epigenetic manipulation approach.
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http://dx.doi.org/10.1007/s12223-022-00976-3DOI Listing
May 2022

Selective inhibition of carbonic anhydrase IX by sulphonylated 1,2,3-triazole incorporated benzenesulphonamides capable of inducing apoptosis.

Authors:
Kiran Siwach Amit Kumar Harish Panchal Rajiv Kumar Jitender Kumar Bhardwaj Andrea Angeli Claudiu T Supuran Pawan K Sharma

J Enzyme Inhib Med Chem 2022 Dec;37(1):1454-1463

Department of Chemistry, Kurukshetra University, Kurukshetra, India.

In search of selective carbonic anhydrase (CA) IX inhibitors endowed with apoptotic inducing properties, we designed and synthesised two subsets of 4- and 3-(5-aryl-(4-phenylsulphonyl)-1-1,2,3-triazol-1-yl)benzenesulphonamides. All compounds were assayed for human carbonic anhydrase (hCA) isoforms I, II, IV, and IX inhibition. Isoforms hCA I and hCA IV were weakly inhibited by most of the synthesised compounds. Many four-substituted benzenesulphonamides displayed low nanomolar inhibition against isoform hCA II, unlike the three-substituted analogues. All target compounds exhibited good inhibition profile with K values ranging from 16.4 to 66.0 nM against tumour-associated isoform hCA IX. Some selective and potent inhibitors of hCA IX were assayed for apoptotic induction in goat testicular cells. Compounds and showed interesting apoptotic induction potential. The present study may provide insights into a strategy for the design of novel anticancer agents based on hCA inhibitors endowed with apoptotic interference.
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http://dx.doi.org/10.1080/14756366.2022.2077333DOI Listing
December 2022

Identifying the Novel Inhibitors Against the Mycolic Acid Biosynthesis Pathway Target "mtFabH" of .

Authors:
Niranjan Kumar Rakesh Srivastava Raj Kumar Mongre Chandra Bhushan Mishra Amit Kumar Rosy Khatoon Atanu Banerjee Md Ashraf-Uz-Zaman Harpreet Singh Andrew M Lynn Myeong-Sok Lee Amresh Prakash

Front Microbiol 2022 6;13:818714. Epub 2022 May 6.

Amity Institute of Integrative Sciences and Health, Amity University, Gurugram, India.

Mycolic acids are the key constituents of mycobacterial cell wall, which protect the bacteria from antibiotic susceptibility, helping to subvert and escape from the host immune system. Thus, the enzymes involved in regulating and biosynthesis of mycolic acids can be explored as potential drug targets to kill (Mtb). Herein, Kyoto Encyclopedia of Genes and Genomes is used to understand the fatty acid metabolism signaling pathway and integrative computational approach to identify the novel lead molecules against the mtFabH (β-ketoacyl-acyl carrier protein synthase III), the key regulatory enzyme of the mycolic acid pathway. The structure-based virtual screening of antimycobacterial compounds from ChEMBL library against mtFabH results in the selection of 10 lead molecules. Molecular binding and drug-likeness properties of lead molecules compared with mtFabH inhibitor suggest that only two compounds, ChEMBL414848 (C1) and ChEMBL363794 (C2), may be explored as potential lead molecules. However, the spatial stability and binding free energy estimation of thiolactomycin (TLM) and compounds C1 and C2 with mtFabH using molecular dynamics simulation, followed by molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) indicate the better activity of C2 (ΔG = -14.18 kcal/mol) as compared with TLM (ΔG = -9.21 kcal/mol) and C1 (ΔG = -13.50 kcal/mol). Thus, compound C1 may be explored as promising drug candidate for the structure-based drug designing of mtFabH inhibitors in the therapy of Mtb.
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http://dx.doi.org/10.3389/fmicb.2022.818714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121832PMC
May 2022

HSc70 interactome reveal major role of macroautophagy and minor role of chaperone mediated autophagy in K-Ras G12V cell proliferation and survival.

Authors:
Vipin Kumar Yadav Poorwa Awasthi Rachna Behl Amit Kumar

J Proteomics 2022 Jul 18;264:104614. Epub 2022 May 18.

Genome & Cell Integrity Laboratory, CSIR- Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh 226001, India; CSIR- Institute of Microbial Technology, Chandigarh 160036, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India. Electronic address:

Constitutively active K-Ras oncogene mutation at G12V changes the proteome of cells and activates macroautophagy for cell advantage. Inhibition of macroautophagy impairs K-Ras mediated tumor progression to a limited extent with increase of spontaneous tumors due to poorly understood mechanisms. Here, we show that inhibition of macroautophagy in K-Ras G12V mouse embryonic fibroblasts (MEFs) hyper activates chaperon mediated autophagy (CMA). Quantitative identification of CMA substrates through co-immunoprecipitation of CMA component heat shock cognate 70 (Hsc70) demonstrates a shift of proteins from macroautophagy to CMA mediated degradation. However, macroautophagy impairment show significant inhibition on proliferation and CMA hyper activation provides a basal support to macroautophagy-inhibited MEFs for survival. On the other hand, K-Ras G12V MEFs impaired of CMA reduces number of Hsc70 clients but activated macroautophagy significantly compensated CMA loss. Nonetheless, co-inhibition of CMA and macroautophagy had a synergistic detrimental effect on both proliferation and survival of MEFs expressing K-Ras G12V mutant. Our results point to K-Ras G12V MEFs dependency on macroautophagy and CMA partly compensates its loss for survival but not hyper-proliferation; implicating that targeting both macroautophagy and CMA as a promising therapeutic target in G12V mutation associated K-Ras cancers. SIGNIFICANCE: The present study provides a framework of Hsc70 interacting proteins, which differentially interact with Hsc70 in response to autophagy alterations. The role of proteins accumulation and induced proteo-toxicity could be underlying factor in macroautophagy and CMA co-inhibited K-Ras G12V MEFs phenotype. Our study provides rational for adaptive mechanisms in K-Ras tumors inhibited with different autophagy pathways and also supports targeting both macroautophagy and CMA simultaneously as therapeutic target. At the same time current study will help in characterizing the underlying cellular processes that may play a role in escaping tutor suppressor role CMA and macroautophagy in cancers harboring K-Ras G12V mutation that may be further utilized to identify molecular targets for K-Ras-driven cancers.
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http://dx.doi.org/10.1016/j.jprot.2022.104614DOI Listing
July 2022

Design and Fabrication of a Dual Protein-Based Trilayered Nanofibrous Scaffold for Efficient Wound Healing.

Authors:
Vinay Kumar Amit Kumar Narendra Singh Chauhan Govind Yadav Mayank Goswami Gopinath Packirisamy

ACS Appl Bio Mater 2022 Jun 20;5(6):2726-2740. Epub 2022 May 20.

Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee Roorkee 247667, Uttarakhand, India.

Chronic wound healing is a major threat all over the world. There are currently a plethora of biomaterials-based wound dressings available for wound healing applications. In this study, a dual protein-based (silk fibroin and sericin) nanofibrous scaffold from a natural source ( silkworm cocoons) with antibacterial and antioxidative properties for wound healing was investigated. An electrospun layer-by-layer silk protein-based nanofibrous scaffold was fabricated with a top layer of hydrophobic silk fibroin protein blended with polyvinyl alcohol (PVA), a middle layer of waste protein silk sericin loaded with silver(I) sulfadiazine as an antibacterial agent, and a bottom layer using silk fibroin blended with polycaprolactone (PCL). The trilayered nanofibrous scaffold with a smooth and bead-free morphology demonstrated excellent wettability, slow in vitro degradation, controlled drug release, and potent antibacterial and antioxidant properties. In vitro, the scaffold also demonstrated excellent hemocompatibility and biocompatibility. Furthermore, in vivo wound contraction, histological, and micro-CT investigations show complete wound healing and the formation of new skin tissue in a male Balb/c mouse model treated with the scaffold. The antioxidant properties of the sericin protein and SSD-based triple-layered nanofibrous scaffold protect the wound from bacterial infection and improve wound healing in a mouse model. The current study develops a dual protein-based nanofibrous scaffold with antibacterial and antioxidant properties as a promising wound dressing material.
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http://dx.doi.org/10.1021/acsabm.2c00200DOI Listing
June 2022

Neuroprotective Effect of N-acetylcysteine Against Monocrotophos-Induced Oxidative Stress in Different Brain Regions of Rats.

Authors:
Twinkle Dhillon Amit Kumar Vijay Kumar

Appl Biochem Biotechnol 2022 May 19. Epub 2022 May 19.

Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India.

Monocrotophos (MCP) is systemic organophosphate insecticide used against crop pests. It is reported to cause mammalian toxicity through both acute and chronic exposure. In the present study, we have shown the protective role of N-acetylcysteine (NAC) against MCP-induced oxidative stress in frontal cortex, corpus striatum and hippocampus brain regions of rats. Male Albino Wistar rats were divided into control, NAC-treated, MCP and NAC + MCP-treated groups. An oral dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. Results showed an increase in lipid peroxidation (LPO) and protein oxidation followed by decreased antioxidant enzymes after 28 days of MCP exposure. Histopathological analysis showed that monocrotophos exposure caused neurodegenerative changes as evident by neurons with dystrophic changes in the form of shrunken hyperchromatic nuclei in all the regions of the rat brain. N-acetylcysteine supplementation to MCP-treated rats showed a reduction in oxidative stress and ameliorated cellular alterations in all of the three regions. The results of the study indicate that N-acetylcysteine offers neuroprotection by improving antioxidant response and decreasing oxidative stress in different regions of the rat brain.
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http://dx.doi.org/10.1007/s12010-022-03967-9DOI Listing
May 2022
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