Publications by authors named "Sachin Kumar"

407 Publications

Defeating the Devil in the Waste: Remediation of Infectious Covid-19 Waste.

Acta Sci Neurol 2020 Aug 30;3(8):37-38. Epub 2020 Jul 30.

Principal Investigator/DBT Welcome Trust India Alliance Fellow, Laboratory of Neurogenetics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.

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http://dx.doi.org/10.31080/ASNE.2020.03.0207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611303PMC
August 2020

Energy optimization from a binary mixture of non-edible oilseeds pyrolysis: Kinetic triplets analysis using Thermogravimetric Analyser and prediction modeling by Artificial Neural Network.

J Environ Manage 2021 Jul 17;297:113253. Epub 2021 Jul 17.

Department of Chemical Engineering, Indian Institute of Technology, Guwahati, 781039, India. Electronic address:

Pyrolysis kinetics and thermodynamic parameters of two non-edible seeds, Pongamia pinnata (PP) and Sapindus emarginatus (SE), and their blend in the ratio of 1:1 (PS) were studied using the thermogravimetric analyzer. Kinetic triplets were determined using both model-free [Starink (STR), Friedman (FRM), Iterative Kissinger-Akahira-Sunose (IT-KAS), Iterative Ozawa-Flynn-Wall (IT-OFW), Vyazovkin (VYZ), and Master plot (MP)] and model fitting Coats-Redfern (CR) methods at three different heating rates 10, 30 and 50 °C/min. Activation energies were 192.66, 179.44, and 163.25 kJ/mol for PP, SE, and PS, respectively. It was found that the blend of the two-biomass (PS) showed promising results with lower activation energy compared to the individual biomass. Thermodynamic parameters (ΔG, ΔS, and ΔH) were obtained using the model-free isoconversional method. The three hidden layers of complex neuron topology are well fitted to the experimental DTG curves by artificial neural network (ANN). The study confirmed that the heating rate had a significant impact on the kinetics and thermodynamic parameters. The reaction mechanism was also in consonance with the experimental data. The study suggests that the PP and SE seeds can be an appropriate feed for pyrolysis, and their blend (PS) can be a viable alternative in optimizing the entire process.
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http://dx.doi.org/10.1016/j.jenvman.2021.113253DOI Listing
July 2021

Prevalence of and Factors Associated with Sleep-Wake Abnormalities in Patients with Cirrhosis.

J Clin Exp Hepatol 2021 Jul-Aug;11(4):453-465. Epub 2020 Oct 24.

Department of Hepatology and Liver Transplantation, New Delhi, India.

Background & Aims: Sleep-wake abnormalities [poor nighttime sleep and excessive daytime sleepiness (EDS)] are common in patients with cirrhosis. The aim of this study was to assess the prevalence of sleep-wake abnormalities and clinical factors associated with these abnormalities in a group of patients with cirrhosis.

Methods: 1098 patients with cirrhosis [Child Turcotte Pugh (CTP) class A, 22.2%; CTP class B, 29.2% and CTP class C, 48.6%], with either no ascites or mild ascites controlled on diuretics, and no history of or current overt hepatic encephalopathy were included in the study.

Results: Poor nighttime sleep and EDS were found in 569 (51.8%) and 489 (44.5%) patients respectively. On multivariate analysis, factors associated with poor nighttime sleep were CTP class C (vs. class A), presence of minimal hepatic encephalopathy (MHE), intermediate or evening type of diurnal preference category (vs. morning type), high risk for obstructive sleep apnea (OSA), diuretic use, presence of major depression, and presence of generalized anxiety disorder (GAD). Factors associated with EDS on multivariate analysis were CTP class B and C (vs. class A), intermediate or evening type of diurnal preference category (vs. morning type), high risk for OSA, presence of major depression, and presence of GAD.

Conclusions: Sleep-wake abnormalities are common in patients with cirrhosis. CTP status, diurnal preference chronotype, risk of OSA, major depression and GAD are associated with both poor nighttime sleep and EDS. MHE and diuretic use are associated with poor nighttime sleep, but not with EDS.
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http://dx.doi.org/10.1016/j.jceh.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267360PMC
October 2020

Sulfonium-based liposome-encapsulated antibiotics deliver a synergistic antibacterial activity.

RSC Med Chem 2021 Jun 24;12(6):1005-1015. Epub 2021 May 24.

Indian Institute of Technology Guwahati, Centre for the Environment Guwahati Assam India

The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics. In this prospect, liposomal delivery systems have been employed in improving the efficacy of the antibacterial agents. The liposome-based antibiotics enhance the therapeutic potential of the new or existing antibiotics and reduce their adverse effects. The current study describes the development of sulfonium-based antibacterial lipids that demonstrate the delivery of existing antibiotics. The presence of cationic sulfonium moieties and inherent membrane targeting abilities of the lipids could help reduce the antibiotic resistance abilities of the bacteria and deliver the antibiotics to remove the infectious pathogens electively. The transmission electron microscopic images and dynamic light scattering analyses revealed the liposome formation abilities of the sulfonium-based amphiphilic compounds in the aqueous medium. The effectiveness of the compounds was tested against the Gram-negative and Gram-positive bacterial strains. The viability of the bacterial cells was remarkably reduced in the presence of the compounds. The sulfonium-based compounds with pyridinium moiety and long hydrocarbon chains showed the most potent antibacterial activities among the tested compounds. Mechanistic studies revealed the membrane-targeted bactericidal activities of the compounds. The potent compound also showed tetracycline and amoxicillin encapsulation and sustained release profiles in the physiologically relevant medium. The tetracycline and amoxicillin-encapsulated lipid showed much higher antibacterial activities than the free antibiotics at similar concentrations, emphasizing the usefulness of the synergistic effect of sulfonium-based lipid and the antibiotics, signifying that the sulfonium lipid penetrated the bacterial membrane and increased the cellular uptake of the antibiotics. The potent lipid also showed therapeutic potential, as it is less toxic to mammalian cells (like HeLa and HaCaT cells) at concentrations higher than their minimum inhibitory concentration values against , , and MRSA. Hence, the sulfonium-based lipid exemplifies a promising framework for assimilating various warheads, and provides a potent antibacterial material.
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http://dx.doi.org/10.1039/d1md00091hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221259PMC
June 2021

Effect of ageing on microstructure and fracture behavior of cortical bone as determined by experiment and Extended Finite Element Method (XFEM).

Med Eng Phys 2021 Jul 1;93:100-112. Epub 2021 Jun 1.

Indian Institute of Technology Ropar, Rupnagar, Punjab, 140001, India. Electronic address:

Bone fracture is a severe health concern; therefore, understanding the causes of bone fracture are crucial. This paper investigates the microstructure and fracture behaviour of cadaveric cortical bone of two different groups (Young, n= 6; Aged, n=7). The microstructure is obtained from µ-CT images, and the material parameters are measured with nanoindentation. Fracture behaviour in transverse and longitudinal orientations is investigated experimentally and numerically. The results show that the Haversian canal (HC) size increases and the osteon wall thickness (OWT) decreases significantly in the aged group, whereas a nonsignificant difference is found in tissue properties. The crack initiation (J) and crack growth (J) toughness of the aged group are found to be significantly lower (p<0.01) than the young group in the transverse orientation; however, for the longitudinal orientation, only the value of J in the aged group is found significantly lower. Further, a 4-phase XFEM (based on micro-CT image) model is developed to investigate the crack propagation behaviour in both orientations. For the transverse orientation, results show that in the aged group, the crack initially follows the cementline and then penetrates the osteon, whereas, in the young group, it propagates along the cementline. These results are in agreement with experimental results where the decrease in J is more significant than the J in the aged group. This study suggests that ageing leads to a larger HC and reduced OWT, which weakens the crack deflection ability and causes fragility fracture. Further, the XFEM results indicate that the presence of a small microcrack in the vicinity of a major crack tip causes an increase in the critical stress intensity factor.
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http://dx.doi.org/10.1016/j.medengphy.2021.05.021DOI Listing
July 2021

Potential environmental toxicant exposure, metabolizing gene variants and risk of PCOS-A systematic review.

Reprod Toxicol 2021 Aug 11;103:124-132. Epub 2021 Jun 11.

Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India. Electronic address:

Exposure of environmental toxicants such as potentially toxic metals and pesticides have largely been attributed to produce adverse effects on general women's health and to be more precise on the reproductive system. In order to explore exposure of toxicants and metabolizing gene variants as risk factor for polycystic ovarian syndrome (PCOS), literature search was carried out using the databases PubMed, Central Cochrane Library, Google Scholar, Science Direct with appropriate keywords upto 6 December 2020. While most of the studies indicate higher serum Cu concentration and lower concentration of Mn as risk factor, studies also report presence of higher pesticide concentration in PCOS women. Genes such as MTHFR, CYPs participate in the metabolism of toxicants and may show different response due to underlying genetic variants. Thus, toxicant exposure are to some extent responsible for the pathogenesis of syndrome through oxidative stress and endocrine disruption, but the susceptibility may vary due to the underlying genetic polymorphism of the exposed population.
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http://dx.doi.org/10.1016/j.reprotox.2021.06.005DOI Listing
August 2021

Polymyxin B accelerates the α-synuclein aggregation.

Biophys Chem 2021 Jun 3;277:106628. Epub 2021 Jun 3.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781 039, India. Electronic address:

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons. It is characterised by the deposition of insoluble α-synuclein aggregates in the brain. Constipation is a common PD-associated condition, and the treatment of constipation with certain antibiotics seem to improve the PD symptoms. Polymyxin B, a last resort drug in treating the life-threatening Gram-negative bacterial infections, is one such antibiotic. The administration of polymyxin B in PD patients is known to alleviate the movement disorder symptoms; the mechanism of action, however, remains unclear. We, therefore, wondered if polymyxin B could modulate the aggregation of α-synuclein. We find that the polymyxin B catalyses the aggregation of α-synuclein into amyloid fibrils. At equimolar polymyxin B concentration, the lag phase was reduced to around one-third of that in the absence of polymyxin B.
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http://dx.doi.org/10.1016/j.bpc.2021.106628DOI Listing
June 2021

WheatQTLdb: a QTL database for wheat.

Mol Genet Genomics 2021 Jun 11. Epub 2021 Jun 11.

Department of Genetics and Plant Breeding, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, 250004, India.

During the last three decades, QTL analysis in wheat has been conducted for a variety of individual traits, so that thousands of QTL along with the linked markers, their genetic positions and contribution to phenotypic variation (PV) for concerned traits are now known. However, no exhaustive database for wheat QTL is currently available at a single platform. Therefore, the present database was prepared which is an exhaustive information resource for wheat QTL data from the published literature till May, 2020. QTL data from both interval mapping and genome-wide association studies (GWAS) have been included for the following classes of traits: (i) morphological traits, (ii) N and P use efficiency, (iii) traits for biofortification (Fe, K, Se, and Zn contents), (iv) tolerance to abiotic stresses including drought, water logging, heat stress, pre-harvest sprouting and salinity, (v) resistance to biotic stresses including those due to bacterial, fungal, nematode and insects, (vi) quality traits, and (vii) a variety of physiological traits, (viii) developmental traits, and (ix) yield and its related traits. For the preparation of the database, literature was searched for data on QTL/marker-trait associations (MTAs), curated and then assembled in the form of WheatQTLdb. The available information on metaQTL, epistatic QTL and candidate genes, wherever available, is also included in the database. Information on QTL in this WheatQTLdb includes QTL names, traits, associated markers, parental genotypes, crosses/mapping populations, association mapping panels and other useful information. To our knowledge, WheatQTLdb prepared by us is the largest collection of QTL (11,552), epistatic QTL (107) and metaQTL (330) data for hexaploid wheat to be used by geneticists and plant breeders for further studies involving fine mapping, cloning, and marker-assisted selection (MAS) during wheat breeding.
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http://dx.doi.org/10.1007/s00438-021-01796-9DOI Listing
June 2021

Role of vitamins and minerals as immunity boosters in COVID-19.

Inflammopharmacology 2021 Aug 10;29(4):1001-1016. Epub 2021 Jun 10.

Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, 06511, USA.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19.
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http://dx.doi.org/10.1007/s10787-021-00826-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190991PMC
August 2021

The flail elbow: Every surgeon's nightmare.

J Clin Orthop Trauma 2021 Aug 20;19:154-167. Epub 2021 May 20.

Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3NE, UK.

A flail elbow joint has an excessive or abnormal degree of mobility resulting in loss of function. Such a situation can arise from structural damage or loss of neuromuscular control. Structural damage may be in terms of loss of integrity of bony, ligamentous, or both components, and this is commonly caused by trauma, failed arthroplasty, infections - either in the native joint or associated with the above, or inflammatory arthritides. Arm paralysis from any cause may also leads to a loss of muscle control making the elbow flail. The management of the condition varies according to etiology; and concurrent issues like infection and instability need to be addressed in addition to the structural problems. Treatment can be non-surgical with the use of orthotics to support the elbow, and maybe more appropriate in certain circumstances. Surgical treatment can involve fixation, repair or reconstruction. Often the deficiency is not amenable to these methods and arthroplasty has to be considered. The situation becomes more fraught in case of failure of arthroplasty and/or infection, where reconstruction can be challenging. In this review we have considered diverse clinical scenarios that fall under this broad umbrella, with a focus on those encountered commonly in practice.
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http://dx.doi.org/10.1016/j.jcot.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165553PMC
August 2021

Rice bran, an off-shoot to newer therapeutics in neurological disorders.

Biomed Pharmacother 2021 Aug 4;140:111796. Epub 2021 Jun 4.

Department of Pharmacy, Faculty of Pharmacy, University of Oradea, Romania.

Normal brain functioning involves the interaction of interconnected molecular and cellular activities, which appear to alter normal to abnormal brain functioning when worsened, contributing to the emergence of neurological disorders. There are currently millions of people who are living with brain disorders globally and this will rise if suitable prevention strategies are not explored. Nutraceutical intended to treat numerous health goals with little adverse effect possible together can be more beneficial than pharmaceutical monotherapy for fostering balanced brain functioning. Nutraceutical provides a specific composition of effective macronutrients and micronutrients that are difficult to synthesize in the laboratory. Numerous elements of rice fibers in rice bran are characterized as natural anti-oxidant and having potential anti-inflammatory activity. The rice bran captures interest among the researchers as it is widespread, affordable, and rich in nutrients including protein, fat, carbohydrates, bioactive components, and dietary fiber. This review covers the neuroprotective multiplicity of rice bran and its constituents to deter pathological conditions of the brain and to facilitate balanced brain functioning at the same time.
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http://dx.doi.org/10.1016/j.biopha.2021.111796DOI Listing
August 2021

Production of first- and second-generation ethanol for use in alcohol-based hand sanitizers and disinfectants in India.

Biomass Convers Biorefin 2021 May 27:1-18. Epub 2021 May 27.

Biochemical Conversion Division, Sardar Swaran Singh National Institute of Bio-Energy, Jalandhar-Kapurthala Road, Wadala Kalan, Kapurthala, Punjab 144601 India.

Emergence of "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" causing "COVID-19" or "coronavirus disease 19" as pandemic has got worldwide attention towards hygiene as the first line of defense for the infection control. It is first line of defense not only from COVID-19 but also from other infectious diseases caused by deadly pathogens such as cholera, hepatitis, tuberculosis, polio, etc. Absence of any particular vaccine or treatment let World Health Organization (WHO) recommend to the public to maintain social distancing along with regularly washing their hands with soap, sanitize their hands (where washing is not possible), and disinfect their belongings and buildings to avoid the infection. Out of various formulations available in the market, WHO has recommended alcohol-based hand sanitizers, which mainly comprise of ethanol, isopropyl alcohols, and hydrogen peroxides in different combinations due to their high potential to kill the broad range of pathogens including bacterial, viral, fungal, helminthes, etc. Therefore, alcohol-based sanitizers are in high demand since centuries to prevent infection from pathogenic diseases. Ethanol is the most common and popular alcohol in terms of vanishing wide range of pathogens, convenient to use and its production. Ethanol is produced worldwide and is used in various sectors, e.g., beauty and cosmetics, food and beverages, and as the most demanding gasoline additive. The present review is focused on the ethanol production in India, its diversified applications emphasizing hand sanitizers with discussions on formulation of sanitizer and disinfectants, and viability of lignocellulosic and food grain-based ethanol. The review article also emphasizes on the technological details of 1G and 2G ethanol production, their associated challenges, and inputs for the improved ethanol yields so as to strengthen the supply chain of ethanol in India, and making "Atmanirbhar Bharat" (Self-reliant India) campaign of Indian government successfully viable.
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http://dx.doi.org/10.1007/s13399-021-01553-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155184PMC
May 2021

Chemical Characterization and Anti-Inflammatory Activity of Phytoconstituents from .

Plants (Basel) 2021 May 31;10(6). Epub 2021 May 31.

Faculty of Pharmacy, AIMST University, Kedah 08100, Malaysia.

C.B Clarke (Gentianaceae) is a well-reported plant in the traditional system of medicine. The present study was intended to isolate the phytoconstituents from the ethanolic extract of the aerial parts of ; and evaluate for in vitro COX-1/COX-2 inhibition activity, in vivo anti-inflammatory and ulcerogenic activity. Phytoisolation involved partitioning of ethanolic extract into petroleum ether and chloroform soluble fractions using silica gel-based column chromatography. The isolation afforded two phytoisolates, namely oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). Phytoisolates structures were established by melting point, ultraviolet (UV), attenuated total reflection-Fourier-transform infrared (ATR-FTIR), nuclear magnetic resonance (1H-NMR, 13C-NMR and HMBC) and mass spectrometry. Phytoisolates were further evaluated for in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity. The study revealed SA-4 (COX-1/COX-2 inhibition activity of 104/61.68 µM with % inhibition of 61.36) to be more effective than SA-1 (COX-1/COX-2 inhibition activity of 128.4/87.25 µM, with % inhibition of 47.72). SA-1 and SA-4, when subjected to ulcerogenic study, exhibited significant gastric tolerance. The current study reports chromatographic isolation and spectrometric characterization of SA-1 and SA-4. The present study concludes that compound SA-4 possess significant anti-inflammatory activity and less irritant property over gastric mucosa with no significant ulcerogenicity in comparison to indomethacin.
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http://dx.doi.org/10.3390/plants10061109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229181PMC
May 2021

Estrogen suppresses HOXB2 expression via ERα in breast cancer cells.

Gene 2021 Aug 29;794:145746. Epub 2021 May 29.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India. Electronic address:

The expression of HOXB2, a homeobox transcription factor, is altered in a variety of solid tumors. Using an in vivo screen to identify regulators of breast tumor growth in murine mammary fat pads, Boimel and co-workers recently identified HOXB2 as a tumor suppressor. However, the mechanistic underpinnings of its role in breast cancer is not understood. Given the emerging interaction of estrogen-regulated gene expression and altered HOX gene expression network in the pathophysiology of breast cancer, this study addressed the relationship between estrogen signaling and HOXB2 expression. Using a mouse model and human breast cancer cell lines, we show that estrogen suppresses HOXB2 expression. Suppression of HOXB2 by PPT, a known ERα agonist, in MCF-7 and T47D cells indicated the involvement of ERα, which was confirmed by siRNA-mediated ERα knockdown experiments. In-silico analysis of the upstream promoter region revealed the presence of three putative EREs. Chromatin immunoprecipitation experiments showed that upon estrogen binding, ERα engaged with EREs in the 5' upstream region of HOXB2 in MCF-7 and T47D cells. Future investigations should address the implications of estrogen-mediated suppression on the proposed tumor suppressor function of HOXB2.
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http://dx.doi.org/10.1016/j.gene.2021.145746DOI Listing
August 2021

Triazole analogues as potential pharmacological agents: a brief review.

Futur J Pharm Sci 2021 25;7(1):106. Epub 2021 May 25.

Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana 136119 India.

Background: A large number of studies have recently reported that, because of their significant biological and pharmacological properties, heterocyclic compounds and their derivatives have attracted a strong interest in medicinal chemistry. The triazole nucleus is one of the most important heterocycles which has a feature of natural products as well as medicinal agents. Heterocyclic nitrogen is abundantly present in most medicinal compounds. The derivatization of triazole ring is based on the phenomenon of bio-isosteres in which substituted the oxygen atom of oxadiazole nucleus with nitrogen triazole analogue.

Main Text: This review focuses on recent synthetic procedure of triazole moiety, which comprises of various pharmacological activities such as antimicrobial, anticonvulsant, anti-inflammatory, analgesic, antitubercular, anthelmintic, antioxidant, antimalarial, antiviral, etc..

Conclusion: This review highlights the current status of triazole compounds as different multi-target pharmacological activities. From the literature survey, triazole is the most widely used compound in different potential activities.
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http://dx.doi.org/10.1186/s43094-021-00241-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148872PMC
May 2021

Prediction of mechanical properties of trabecular bone in patients with type 2 diabetes using damage based finite element method.

J Biomech 2021 06 5;123:110495. Epub 2021 May 5.

Department of Mechanical Engineering, Indian Institute of Technology Ropar, Rupnagar, Punjab 140001, India. Electronic address:

Type-2 diabetic (T2D) and osteoporosis (OP) suffered patients are more prone to fragile fracture though the nature of alteration in areal bone mineral density (aBMD) in these two cases are completely different. Therefore, it becomes crucial to compare the effect of T2D and OP on alteration in mechanical and structural properties of femoral trabecular bone. This study investigated the effect of T2D, OP, and osteopenia on bone structural and mechanical properties using micro-CT, nanoindentation and compression test. Further, a nanoscale finite element model (FEM) was developed to predict the cause of alteration in mechanical properties. Finally, a damage-based FEM was proposed to predict the pathological related alteration of bone's mechanical response. The obtained results demonstrated that the T2D group had lower volume fraction (-18.25%, p = 0.023), young's modulus (-23.47%, p = 0.124), apparent modulus (-37.15%, p = 0.02), and toughness (-40%, p = 0.001) than the osteoporosis group. The damage-based FE results were found in good agreement with the compression experiment results for all three pathological conditions. Also, nanoscale FEM results demonstrated that the elastic and failure properties of mineralised collagen fibril decreases with increase in crystal size. This study reveals that T2D patients are more prone to fragile fracture in comparison to OP and osteopenia patients. Also, the proposed damage-based FEM can help to predict the risk of fragility fracture for different pathological conditions.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110495DOI Listing
June 2021

Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer.

Sci Rep 2021 May 14;11(1):10323. Epub 2021 May 14.

Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India.

MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.
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http://dx.doi.org/10.1038/s41598-021-89388-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121812PMC
May 2021

Detection of retinal and blood Aβ oligomers with nanobodies.

Alzheimers Dement (Amst) 2021 6;13(1):e12193. Epub 2021 May 6.

School of Medicine Western Sydney University Campbelltown New South Wales Australia.

Introduction: Abnormal retinal changes are increasingly recognized as an early pathological change in Alzheimer's disease (AD). Although amyloid beta oligomers (Aβo) have been shown to accumulate in the blood and retina of AD patients and animals, it is not known whether the early Aβo deposition precedes their accumulation in brain.

Methods And Results: Using nanobodies targeting Aβ and Aβ oligomers we were able to detect Aβ oligomers in the retina and blood but not in the brain of 3-month-old APP/PS1 mice. Furthermore, Aβ plaques were detected in the brain but not the retina of 3-month-old APP/PS1 mice.

Conclusion: These results suggest that retinal accumulation of Aβo originates from peripheral blood and precedes cognitive decline and Aβo deposition in the brain. This provides a very strong basis to develop and implement an "eye test" for early detection of AD using nanobodies targeting retinal Aβ.
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http://dx.doi.org/10.1002/dad2.12193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101010PMC
May 2021

Retraction notice to "Corrigendum to "Evaluation of imidazole and its derivative against Newcastle disease virus infection in chicken: A drug repurposing approach"" [Virus Res. (2020) 278 197859].

Virus Res 2021 07 6;300:198372. Epub 2021 May 6.

Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam, 781039, India. Electronic address:

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http://dx.doi.org/10.1016/j.virusres.2021.198372DOI Listing
July 2021

Microbial Fabricated Nanosystems: Applications in Drug Delivery and Targeting.

Front Chem 2021 20;9:617353. Epub 2021 Apr 20.

Department of Biochemistry and Biotechnology, Sardar Bhagwan Singh University, Dehradun, India.

The emergence of nanosystems for different biomedical and drug delivery applications has drawn the attention of researchers worldwide. The likeness of microorganisms including bacteria, yeast, algae, fungi, and even viruses toward metals is well-known. Higher tolerance to toxic metals has opened up new avenues of designing microbial fabricated nanomaterials. Their synthesis, characterization and applications in bioremediation, biomineralization, and as a chelating agent has been well-documented and reviewed. Further, these materials, due to their ability to get functionalized, can also be used as theranostics i.e., both therapeutic as well as diagnostic agents in a single unit. Current article attempts to focus particularly on the application of such microbially derived nanoformulations as a drug delivery and targeting agent. Besides metal-based nanoparticles, there is enough evidence wherein nanoparticles have been formulated using only the organic component of microorganisms. Enzymes, peptides, polysaccharides, polyhydroxyalkanoate (PHA), poly-(amino acids) are amongst the most used biomolecules for guiding crystal growth and as a capping/reducing agent in the fabrication of nanoparticles. This has promulgated the idea of complete green chemistry biosynthesis of nano-organics that are most sought after in terms of their biocompatibility and bioavailability.
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http://dx.doi.org/10.3389/fchem.2021.617353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093762PMC
April 2021

Retraction notice to "Evaluation of imidazole and its derivative against Newcastle disease virus infection in chicken: A drug repurposing approach" [Virus Res. (2019) 260 114-122].

Virus Res 2021 Jul 30;299:198373. Epub 2021 Apr 30.

Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam, 781039, India. Electronic address:

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http://dx.doi.org/10.1016/j.virusres.2021.198373DOI Listing
July 2021

Dynamic analysis of the role of innate immunity in SEIS epidemic model.

Eur Phys J Plus 2021 23;136(4):439. Epub 2021 Apr 23.

Department of Mathematics, University of Delhi, Delhi, New Delhi 110007 India.

Consideration of every important aspect while modeling a disease makes the model more precise and the disease eradication strategy more powerful. In the present paper, we analyze the importance of innate immunity on SEIS modeling. We propose an SEIS model with Holling type II and type III functions representing innate immunity. We find the existence and stability conditions for the equilibria. When innate immunity is in the form of Holling type II function, the disease-free equilibrium exists for reproduction number less than unity and is locally asymptotically stable, and supercritical transcritical (forward) as well as subcritical transcritical (backward) bifurcation may occur where the contact rate acts as the bifurcation parameter. Hence, disease-free equilibrium need not be globally stable. For reproduction number greater than unity unique endemic equilibrium exists which is locally asymptotically stable. The global stability conditions for the same are deduced with the help of Lozinski measure. When innate immunity is considered a Holling type III function, the disease-free equilibrium point exists for reproduction number less than unity and is locally as well as globally stable. The existence of either unique or multiple endemic equilibria is found when reproduction number is greater than unity, and there exists at least one locally asymptotically stable equilibrium point and bistability can also be encountered. The conditions for the existence of Andronov-Hopf bifurcation are deduced for both cases. Moreover, we observe that ignoring innate immunity annihilates the possibility of Andronov-Hopf bifurcation. Numerical simulation is performed to validate the mathematical findings. Comparing the obtained results to the case when innate immunity is ignored, it is deduced that ignoring it ends the possibility of backward bifurcation, Andronov-Hopf bifurcation as well as the existence of multiple equilibria, and it also leads to the prediction of higher infection than the actual which may deflect the accuracy of the model to a high extent. This would further lead to false predictions and inefficient disease control strategies which in turn would make disease eradication a difficult and more expensive task.
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http://dx.doi.org/10.1140/epjp/s13360-021-01390-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064703PMC
April 2021

Traumatic respiratory failure and veno-venous extracorporeal membrane oxygenation support.

Perfusion 2021 Apr 30:2676591211012840. Epub 2021 Apr 30.

Department of Advanced Cardiopulmonary Therapies and Transplantation, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.

Background: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation.

Study Design: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed.

Results: Fifteen patients from a large Level I trauma center met the criteria. The median PaO/FiO ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%).

Conclusions: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.
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http://dx.doi.org/10.1177/02676591211012840DOI Listing
April 2021

Synbiotic formulation of Cichorium intybus root powder with Lactobacillus acidophilus NCDC15 and Lactobacillus reuteri BFE7 improves growth performance in Murrah buffalo calves via altering selective gut health indices.

Trop Anim Health Prod 2021 Apr 28;53(2):291. Epub 2021 Apr 28.

Animal Nutrition Division, ICAR-National Dairy Research Institute, Karnal, Haryana, 132001, India.

The objective of this study was to evaluate the effects of synbiotic formulation of Cichorium intybus root powder (C) with Lactobacillus acidophilus NCDC15 (LA) and Lactobacillus reuteri BFE7 (LR) on growth performance in Murrah buffalo calves via monitoring selective gut health indices. Twenty-four Murrah buffalo calves of 5-7 days old and 33 ± 2.0 kg of body weight were distributed randomly into three groups adopting complete randomized design (CRD) as follows: (1) group I served as control (CON) provided with a basal diet alone; (2) group II supplemented with synbiotic formulation of 200 mL L. acidophilus NCDC15 fermented milk with 8 g of Cichorium intybus root powder (LAC) along with basal diet; (3) group III supplemented with synbiotic formulation of 200 mL L. reuteri BFE7 fermented milk with 8 g of Cichorium intybus root powder (LRC) along with basal diet. The final body weight (BW), average dry matter intake (DMI) and structural body measurements were significantly increased (P < 0.05) in LAC and LRC groups by synbiotic as compared to the CON. No effect was registered on apparent nutrient digestibility coefficient of various nutrients in supplemented groups. Faecal score was reduced by the supplementation of synbiotic being lowest in LRC followed by LAC and CON. Calves supplemented synbiotic showed lower (P < 0.05) faecal pH and ammonia with a concomitant increase in faecal lactate levels and faecal short chain fatty acids (SCFA) as compared to control. The faecal Lactobacillus and Bifidobacterium population was increased (P < 0.05) in synbiotic fed groups as compared to control. Additionally, coliform and clostridia count was decreased (P < 0.05) in treatment groups compared to CON. Overall, it may be concluded that synbiotic supplementation was effective in improving the growth performance in Murrah buffalo calves via altering selective gut health indices.
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http://dx.doi.org/10.1007/s11250-021-02733-zDOI Listing
April 2021

Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer.

Biochim Biophys Acta Rev Cancer 2021 Apr 21;1876(1):188552. Epub 2021 Apr 21.

Dept. of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. Electronic address:

Small cell lung cancer (SCLC), a smoking-related highly aggressive neuroendocrine cancer, is characterized by rapid cell proliferation, early metastatic dissemination, and early relapse due to chemoresistance to first-line platinum-doublet chemotherapy. Genomically, SCLC tumors show nearly universal loss of TP53 and RB1 tumor suppressor genes, while gene expression signature classifies them into 4 distinct subgroups based on the expression patterns of lineage transcription factors - ASCL1/ASH1, NEUROD1, YAP-1, and POU2F3. Due to the lack of targetable molecular alterations and clinically useful diagnostic, prognostic and predictive biomarker, there is insignificant progress in the therapeutic management of SCLC patients. Numerous studies have shown a significant involvement of non-coding RNAs in the regulation of cell proliferation, invasion and migration, apoptosis, metastasis, and chemoresistance in various human cancers. In this review, we comprehensively discuss the role of microRNAs (miRNAs) in regulating the aforementioned biological process in SCLC. For this, we searched the scientific literature and selected studies that have evaluated the role of miRNAs in the disease pathogenesis or as a cancer biomarker in SCLC. Our review suggests that several miRNAs are involved in the pathogenesis of SCLC mainly by regulating cell proliferation, metastasis, and chemoresistance. Few studies have also demonstrated the clinical utility of miRNAs in monitoring response to chemotherapy as well as in predicting survival outcomes. However, more in-depth mechanistic studies utilizing in vivo models and multicentric studies with larger patient cohorts are needed before the applications of miRNAs as therapeutic targets or as biomarkers are translated from the laboratory into clinics.
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http://dx.doi.org/10.1016/j.bbcan.2021.188552DOI Listing
April 2021

Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics.

Elife 2021 Apr 8;10. Epub 2021 Apr 8.

Divisions of Experimental Hematology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United States.

Innate immune cellular effectors are actively consumed during systemic inflammation, but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here, we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NF-κB independent, Traf6/IκB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205/CD172a conventional dendritic cells type 2 and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation.
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http://dx.doi.org/10.7554/eLife.66190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137144PMC
April 2021

Genomic Variations in SARS-CoV-2 Genomes From Gujarat: Underlying Role of Variants in Disease Epidemiology.

Front Genet 2021 19;12:586569. Epub 2021 Mar 19.

Gujarat Biotechnology Research Centre (GBRC), Department of Science & Technology (DST), Gandhinagar, India.

Humanity has seen numerous pandemics during its course of evolution. The list includes several incidents from the past, such as measles, Ebola, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), etc. The latest edition to this is coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of August 18, 2020, COVID-19 has affected over 21 million people from 180 + countries with 0.7 million deaths across the globe. Genomic technologies have enabled us to understand the genomic constitution of pathogens, their virulence, evolution, and rate of mutation, etc. To date, more than 83,000 viral genomes have been deposited in public repositories, such as GISAID and NCBI. While we are writing this, India is the third most affected country by COVID-19, with 2.7 million cases and > 53,000 deaths. Gujarat is the 11th highest affected state with a 3.48% death rate compared to the national average of 1.91%. In this study, a total of 502 SARS-CoV-2 genomes from Gujarat were sequenced and analyzed to understand its phylogenetic distribution and variants against global and national sequences. Further variants were analyzed from diseased and recovered patients from Gujarat and the world to understand its role in pathogenesis. Among the missense mutations present in the Gujarat SARS-CoV-2 genomes, C28854T (Ser194Leu) had an allele frequency of 47.62 and 7.25% in deceased patients from the Gujarat and global datasets, respectively. In contrast, the allele frequency of 35.16 and 3.20% was observed in recovered patients from the Gujarat and global datasets, respectively. It is a deleterious mutation present in the nucleocapsid (N) gene and is significantly associated with mortality in Gujarat patients with a -value of 0.067 and in the global dataset with a -value of 0.000924. The other deleterious variant identified in deceased patients from Gujarat (-value of 0.355) and the world (-value of 2.43E-06) is G25563T, which is located in Orf3a and plays a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct clusters under the GH clade of GISAID. This study will shed light on the viral haplotype in SARS-CoV-2 samples from Gujarat, India.
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http://dx.doi.org/10.3389/fgene.2021.586569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017293PMC
March 2021

CT chest analysis of 2019 novel coronavirus pneumonia: An Indian perspective.

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S154-S160. Epub 2021 Jan 23.

Department of Radiology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India.

Context: Since its outbreak, the COVID-19 pneumonia pandemic is rapidly spreading across India; although computed tomography of chest (CT chest) is not recommended as a screening tool, there is a rapid surge in the CT chest performed in suspected cases. We should be aware of the imaging features among the Indian population.

Aim: To analyze the CT chest features in Indian COVID-19 patients.

Settings And Design: Retrospective study.

Subjects And Methods: CT chest of 31 polymerase chain reaction (PCR) verified patients of COVID-19 was assessed for ground-glass opacities (GGO), consolidations, bronchiectasis, pleural effusions, vascular enlargement, crazy paving, and reverse halo sign.

Statistical Analysis Used: The data was analyzed in Microsoft Excel 2019.

Results: Only one patient showed a normal scan. Multilobar involvements with parenchymal abnormalities were seen in all the patients with bilateral involvement in 74.1%. 42.5% of the lung parenchymal abnormalities were pure GGOs, while 41.6% had GGOs mixed with consolidation. Peripheral and posterior lung field involvement was seen in 70.5% and 65.5%, respectively; 56.8% had well-defined margins. Pure GGOs were seen in all six patients, who underwent CT in the first 2 days of onset of symptoms. Seventeen patients scanned between 3 and 6 days of the illness showed GGOs mixed with consolidation and pure consolidations 76%. Vascular enlargement, crazy paving, and reverse halo sign were seen in 70%, 53%, and 35% of the patients, respectively. Patients scanned after 1 week of symptoms showed traction bronchiectasis along with GGOs and or consolidations.

Conclusions: COVID-19 pneumonia showed multifocal predominantly subpleural basal posteriorly located GGOs and/or consolidations which were predominantly well defined. "Crazy paving" was prevailing in the intermediate stage while early traction bronchiectasis among the patients presented later in the course of illness.
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http://dx.doi.org/10.4103/ijri.IJRI_367_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996674PMC
January 2021