Publications by authors named "Akhilesh Kumar"

135 Publications

Agro-waste as a substrate for the production of pullulanase by Penicillium viridicatum under solid-state fermentation.

Sci Rep 2022 Jul 25;12(1):12661. Epub 2022 Jul 25.

Himalayan School of Biosciences, Swami Rama Himalayan University, Swami Rama Nagar, Jolly Grant, Dehradun, Uttarakhand, 248016, India.

One of the key enzymes utilized in the food industry is pullulanase. But its major drawbacks are its low yield and high production costs. In this regard, the current research aims to screen agro-waste substrates for optimal pullulanase production in solid-state fermentation. Of various agro-wastes used as a substrate, the maximum enzymic activity (9.74 U/gds) was observed in a medium based on 5 g of green gram husk and incubated for 3 days at 30 °C. The effects of 16 different nutrients on the yield of pullulanase production were studied using the Plackett-Burman experimental design. The incorporation of FeSO, MnSO, and MgSO into the pullulanase production medium significantly increased the yield and showed a 5.7-fold increase (56.25 U/gds) in comparison with the unoptimized media. The Box-Behnken experimental design was used to study the effect of interactions between Fe, Mg, and Mn on the production of pullulanase. Box-Behnken showed a 1.1-fold increase (62.1 U/gds) in pullulanase production. The total increase in yield after all optimization was 6.37-fold. The present study reports for the first time the applicability of green gram husk as a potent substrate for pullulanase production by Penicillium viridicatum.
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http://dx.doi.org/10.1038/s41598-022-16854-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314376PMC
July 2022

Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques.

Sci Rep 2022 Jul 19;12(1):12345. Epub 2022 Jul 19.

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53706, USA.

Allogeneic hematopoietic stem cell transplants (allo-HSCTs) dramatically reduce HIV reservoirs in antiretroviral therapy (ART) suppressed individuals. However, the mechanism(s) responsible for these post-transplant viral reservoir declines are not fully understood. Therefore, we modeled allo-HSCT in ART-suppressed simian-human immunodeficiency virus (SHIV)-infected Mauritian cynomolgus macaques (MCMs) to illuminate factors contributing to transplant-induced viral reservoir decay. Thus, we infected four MCMs with CCR5-tropic SHIV162P3 and started them on ART 6-16 weeks post-infection (p.i.), maintaining continuous ART during myeloablative conditioning. To prevent graft-versus-host disease (GvHD), we transplanted allogeneic MHC-matched α/β T cell-depleted bone marrow cells and prophylactically treated the MCMs with cyclophosphamide and tacrolimus. The transplants produced ~ 85% whole blood donor chimerism without causing high-grade GvHD. Consequently, three MCMs had undetectable SHIV DNA in their blood post-transplant. However, SHIV-harboring cells persisted in various tissues, with detectable viral DNA in lymph nodes and tissues between 38 and 62 days post-transplant. Further, removing one MCM from ART at 63 days post-transplant resulted in SHIV rapidly rebounding within 7 days of treatment withdrawal. In conclusion, transplanting SHIV-infected MCMs with allogeneic MHC-matched α/β T cell-depleted bone marrow cells prevented high-grade GvHD and decreased SHIV-harboring cells in the blood post-transplant but did not eliminate viral reservoirs in tissues.
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http://dx.doi.org/10.1038/s41598-022-16306-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296477PMC
July 2022

In vivo therapeutic efficacy of Curcuma longa extract loaded ethosomes on wound healing.

Vet Res Commun 2022 Jul 7. Epub 2022 Jul 7.

Biorefining and Advanced Materials Research Centre, Scotland's Rural College (SRUC), Kings Buildings, EH9 3JG, Edinburgh, UK.

Since ancient times, medicinal plants are widely accepted to promote the health and wellness of animals and mankind. The medicinal plant-based therapies have limitations of delayed onset of action, inconsistent absorption, low bioavailability, oxidation, and poor solubility. The encapsulation studies suggested improved efficacy. Therefore, the present study attempts to evaluate the efficacy of Curcuma longa extracts encapsulated in Ethosome on wound healing model compared to crude extract. The Curcuma longa extract swere prepared by cold percolation method and total curcuminoid content was determined by Reverse phase-HPLC. Three Ethosomal suspensions (ETS1, ETS2, and ETS3) were prepared and characterized for particle distribution, morphology, and absorption spectrum by Zetasizer, Scanning Electron Microscopy, and FTIR respectively. The Ethosomal suspension with the highest entrapment efficiency was applied topically at a varying concentrations (0.25, 0.5, and 1 g/cm) on the surgically created wounds in rats. The efficacy of wound healing was evaluated by clinical observation, macroscopic evaluation of granulation tissue, colour digital image processing, and histology. The methanolic extract of Curcuma longa showed better antibacterial potential than ethanolic and aqueous. The total Curcuminoid content in the Curcuma longa rhizome was 4.03%. The size, PDI, zeta potential, and viscosity of Ethosomal suspension ranged from 34.8 to 371 nm, 0.236-1.178, 15.6-36.8mV, and 0.8460-0.8510, respectively. The ETS3 was found the most optimum combination with the highest entrapment efficiency and the topical application at a dose rate of 0.5 g/cm and 1.0 g/cm resulted in comparable wound contracture, pain score, histopathological score as compared to control groups.It was concluded that the Curcuma longa encapsulation in Ethosome resulted in improved wound appearance, granulation tissue score, and appearance with a shortened period of wound resolution at the cellular level as compared to crude extract.
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http://dx.doi.org/10.1007/s11259-022-09952-1DOI Listing
July 2022

Fut9 Deficiency Causes Abnormal Neural Development in the Mouse Cerebral Cortex and Retina.

Neurochem Res 2022 Jun 26. Epub 2022 Jun 26.

Department of Integrative Physiology, Shiga University of Medical Science, Otsu, 520-2192, Japan.

α1,3-Fucosyltransferase 9 (Fut9) is responsible for the synthesis of Lewis X [Le, Galβ1-4(Fucα1-3)GlcNAc] carbohydrate epitope, a marker for pluripotent or multipotent tissue-specific stem cells. Although Fut9-deficient mice show anxiety-related behaviors, structural and cellular abnormalities in the brain remain to be investigated. In this study, using in situ hybridization and immunohistochemical techniques in combination, we clarified the spatiotemporal expression of Fut9, together with Le, in the brain and retina. We found that Fut9-expressing cells are positive for Ctip2, a marker of neurons residing in layer V/VI, and TLE4, a marker of corticothalamic projection neurons (CThPNs) in layer VI, of the cortex. A birthdating analysis using 5-ethynyl-2'-deoxyuridine at embryonic day (E)11.5, 5-bromo-2'-deoxyuridine at E12.5, and in utero electroporation of a GFP expression plasmid at E14.5 revealed a reduction in the percentage of neurons produced at E11.5 in layer VI/subplate of the cortex and in the ganglion cell layer of the retina in P0 Fut9 mice. Furthermore, this reduction in layer VI/subplate neurons persisted into adulthood, leading to a reduction in the number of Ctip2/Satb2 excitatory neurons in layer V/VI of the adult Fut9 cortex. These results suggest that Fut9 plays significant roles in the differentiation, migration, and maturation of neural precursor cells in the cortex and retina.
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http://dx.doi.org/10.1007/s11064-022-03651-8DOI Listing
June 2022

Convolutional neural network based CT scan classification method for COVID-19 test validation.

Smart Health (Amst) 2022 Sep 11;25:100296. Epub 2022 Jun 11.

Electronics and Communication Department, IES College of Technology, Bhopal, India.

Given the novel corona virus discovered in Wuhan, China, in December 2019, due to the high false-negative rate of RT-PCR and the time-consuming to obtain the results, research has proved that computed tomography (CT) has become an auxiliary One of the essential means of diagnosis and treatment of new corona virus pneumonia. Since few COVID-19 CT datasets are currently available, it is proposed to use conditional generative adversarial networks to enhance data to obtain CT datasets with more samples to reduce the risk of over fitting. In addition, a BIN residual block-based method is proposed. The improved U-Net network is used for image segmentation and then combined with multi-layer perception for classification prediction. By comparing with network models such as AlexNet and GoogleNet, it is concluded that the proposed BUF-Net network model has the best performance, reaching an accuracy rate of 93%. Using Grad-CAM technology to visualize the system's output can more intuitively illustrate the critical role of CT images in diagnosing COVID-19. Applying deep learning using the proposed techniques suggested by the above study in medical imaging can help radiologists achieve more effective diagnoses that is the main objective of the research. On the basis of the foregoing, this study proposes to employ CGAN technology to augment the restricted data set, integrate the residual block into the U-Net network, and combine multi-layer perception in order to construct new network architecture for COVID-19 detection using CT images. -19. Given the scarcity of COVID-19 CT datasets, it is proposed that conditional generative adversarial networks be used to augment data in order to obtain CT datasets with more samples and therefore lower the danger of overfitting.
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http://dx.doi.org/10.1016/j.smhl.2022.100296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188200PMC
September 2022

Essential role of Rnd1 in innate immunity during viral and bacterial infections.

Cell Death Dis 2022 Jun 2;13(6):520. Epub 2022 Jun 2.

Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, India.

Intracellular and cell surface pattern-recognition receptors (PRRs) are an essential part of innate immune recognition and host defense. Here, we have compared the innate immune responses between humans and bats to identify a novel membrane-associated protein, Rnd1, which defends against viral and bacterial infection in an interferon-independent manner. Rnd1 belongs to the Rho GTPase family, but unlike other small GTPase members, it is constitutively active. We show that Rnd1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms. Rnd1 counteracts intracellular calcium fluctuations by inhibiting RhoA activation, thereby inhibiting virus internalisation. On the other hand, Rnd1 also facilitates pro-inflammatory cytokines IL-6 and TNF-α through Plxnb1, which are highly effective against intracellular bacterial infections. These data provide a novel Rnd1-mediated innate defense against viral and bacterial infections.
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http://dx.doi.org/10.1038/s41419-022-04954-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161769PMC
June 2022

Up-regulation of Nrf2/HO-1 and inhibition of TGF-β1/Smad2/3 signaling axis by daphnetin alleviates transverse aortic constriction-induced cardiac remodeling in mice.

Free Radic Biol Med 2022 Jun 2;186:17-30. Epub 2022 May 2.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India. Electronic address:

Oxidative damage and accumulation of extracellular matrix (ECM) components play a crucial role in the adverse outcome of cardiac hypertrophy. Evidence suggests that nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) can modulate oxidative damage and adverse myocardial remodeling. Daphnetin (Daph) is a coumarin obtained from the plant genus Daphne species that exerts anti-oxidative and anti-inflammatory properties. Herein, we investigated the roles of Daph in transverse aortic constriction (TAC)-induced cardiac hypertrophy and fibrosis in mice. TAC-induced alterations in cardiac hypertrophy markers, histopathological changes, and cardiac function were markedly ameliorated by oral administration of Daph in mice. We found that Daph significantly reduced the reactive oxygen species (ROS) generation, increased the nuclear translocation of Nrf2, and consequently, reinstated the protein levels of NAD(P)H quinone dehydrogenase1 (NQO1), heme oxygenase-1 (HO-1), and other antioxidants in the heart. Besides, Daph significantly inhibited the TAC-induced accumulation of ECM components, including α-smooth muscle actin (α-SMA), collagen I, collagen III, and fibronectin, and interfered with the TGF-β1/Smad2/3 signaling axis. Further studies revealed that TAC-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive nuclei and the protein levels of Bax/Bcl2 ratio and cleaved caspase 3 were substantially decreased by Daph treatment. We further characterized the effect of Daph on angiotensin II (Ang-II)-stimulated H9c2 cardiomyoblast cells and observed that Daph markedly decreased the Ang-II induced increase in cell size, production of ROS, and proteins associated with apoptosis and fibrosis. Mechanistically, Daph alone treatment enhanced the protein levels of Nrf2, NQO1, and HO-1 in H9c2 cells. The inhibition of this axis by Si-Nrf2 transfection abolished the protective effect of Daph in H9c2 cells. Taken together, Daph effectively counteracted the TAC-induced cardiac hypertrophy and fibrosis by improving the Nrf2/HO-1 axis and inhibiting the TGF-β1/Smad2/3 signaling axis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.04.019DOI Listing
June 2022

Identification and Classification of Depressed Mental State for End-User over Social Media.

Comput Intell Neurosci 2022 21;2022:8755922. Epub 2022 Apr 21.

Department of Mining Engineering, College of Engineering and Technology, Bule Hora University, 144 Oromia Region, Blue Hora, Ethiopia.

In researching social network data and depression, it is often necessary to manually label depressed and non-depressed users, which is time-consuming and labor-intensive. The aim of this study is that it explores the relationship between social network data and depression. It can also contribute to detecting and identifying depression. Through collecting and analyzing college students' microblog social data, a preliminary screening algorithm for college students' suspected depression microblogs based on depression keywords, and semantic expansion is researched; a comprehensive lexical grammar was proposed. This research provided has a preliminary screening method based on depression keywords and semantic expansion for college students' suspected depression microblogs, with a screening accuracy. This method forms a depression keyword table by constructing the basic keyword table and the semantic expansion based on the word embedding learning model Word2Vec. Finally, the word table is used to calculate the semantic similarity of the tested microblogs and then identify whether it is a suspected depression microblog. The experimental results on the microblog dataset of college students show that the comprehensive lexical method is better than the SDS questionnaire segmentation method and the expert lexical method in terms of screening accuracy; the comprehensive lexical approach can quickly and automatically screen out a tiny proportion of suspected doubts from a large number of college students' microblogs. Depression Weibo can reduce the workload of experts' annotation, improve annotation efficiency, and provide a suitable data processing basis for the subsequent accurate identification (classification problem) of patients with depression.
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http://dx.doi.org/10.1155/2022/8755922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050301PMC
May 2022

Hemangioma of First Extensor Compartment of the Wrist- A Rare Case Report.

J Orthop Case Rep 2021 Jun;11(6):14-18

Department of Pathology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.

Introduction: Although upper extremity intramuscular hemangioma is a rare clinical entity, it poses considerable morbidity in the functional needs of an individual. The diagnosis of intramuscular hemangioma poses a diagnostic glitch. The combined radiological and histopathological assessment provides a complete understanding and diagnosis for the same. Every tumor follows an individualized protocol for its management.

Case Report: A 15-year-old female presented with swelling over dorsal aspect of distal 1/3rd right forearm, which was 3 cm away from the articular surface of the right wrist from the past 5 years. There was no history of trauma or infection over the right wrist. Finkelstein's test was negative, which rule out de Quervain's tenosynovitis. The movements of the right wrist were unrestricted without any distal neurovascular deficit. MRI of her right wrist and hand suggested the presence of low flow vascular malformation within the musculotendinous junction of APL and EPB muscles. The patient underwent excision biopsy of the hemangiomatous lesion in toto without any neurological complications. No recurrence was noted in the follow-up period for 6 months.

Conclusion: Being a benign vascular tumor, MRI provides the gateway to diagnose intramuscular hemangioma for early intervention to provide better functional results. The choice of definitive treatment for APL and EPB hemangioma was excision biopsy in toto which provided better functional results in our patient.
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http://dx.doi.org/10.13107/jocr.2021.v11.i06.2238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009473PMC
June 2021

Assessment of Safety and Immunogenicity of MHC homozygous iPSC-derived CD34+ Hematopoietic Progenitors in a NHP Model.

Blood Adv 2022 Apr 11. Epub 2022 Apr 11.

University of Wisconsin, Madison, Wisconsin, United States.

Administration of ex vivo expanded somatic myeloid progenitors has been explored as a way to facilitate a more rapid myeloid recovery and improve overall survival following myeloablation. Recent advances in induced pluripotent stem cell (iPSC) technologies have created alternative platforms for supplying off-the-shelf immunologically compatible myeloid progenitors, including cellular products derived from major histocompatibility complex (MHC) homozygous "superdonors", potentially increasing the availability of MHC- matching cells and maximizing the utility for stem cell banking. However, it is unclear the teratogenic and tumorigenic potential of iPSC-derived progenitor cells and whether they will induce alloreactive antibodies upon transfer. Here, we evaluated the safety and efficacy of using CD34+CD45+ hematopoietic progenitors derived from MHC homozygous iPSCs (iHPs) for treating cytopenia following myeloablative HSC transplants in a Mauritian cynomolgus macaque (MCM) nonhuman primate (NHP) model. We demonstrated that infusing iHPs is well-tolerated and safe, observing no teratomas or tumors in the MCMs up to one year after HSC transplant and iHP infusion. Importantly, the iHPs also did not induce significant levels of alloantibodies in MHC-matched or -mismatched immunocompetent MCMs, even after increasing MHC expression on iHPs with IFNγ. These results suggest feasibility of iHP use in the setting of myeloablation and that iHP products pose a low risk of inducing alloreactive antibodies.
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http://dx.doi.org/10.1182/bloodadvances.2022006984DOI Listing
April 2022

Generation of SIV-resistant T cells and macrophages from nonhuman primate induced pluripotent stem cells with edited CCR5 locus.

Stem Cell Reports 2022 04 31;17(4):953-963. Epub 2022 Mar 31.

Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA. Electronic address:

Adoptive therapies with genetically modified somatic T cells rendered HIV resistance have shown promise for AIDS therapy. A renewable source of HIV-resistant human T cells from induced pluripotent stem cells (iPSCs) would further facilitate and broaden the applicability of these therapies. Here, we report successful targeting of the CCR5 locus in iPSCs generated from T cells (T-iPSCs) or fibroblasts (fib-iPSCs) from Mauritian cynomolgus macaques (MCM), using CRISPR-Cas9 technology. We found that CCR5 editing does not affect hematopoietic and T cell differentiation potentials of fib-iPSCs. However, T-iPSCs with edited CCR5 lost their capacity to differentiate into CD4CD8 T cells while maintaining myeloid differentiation potential. T cells and macrophages produced from CCR5-edited MCM iPSCs did not support replication of the CCR5-tropic simian immunodeficiency viruses SIVmac239 (T cell tropic) and SIVmac316 (macrophage-tropic). Overall, these studies provide a platform for further exploration of AIDS therapies based on gene-edited iPSCs in a nonhuman primate model.
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http://dx.doi.org/10.1016/j.stemcr.2022.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023799PMC
April 2022

The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.

Dev Cell 2022 03 4;57(5):654-669.e9. Epub 2022 Mar 4.

Department of Molecular & Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA. Electronic address:

The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.
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http://dx.doi.org/10.1016/j.devcel.2022.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957288PMC
March 2022

Case Report: Delayed Diffuse Alveolar Hemorrhage in Echis sochureki Envenoming, Jodhpur, India.

Am J Trop Med Hyg 2022 01 31;106(3):967-969. Epub 2022 Jan 31.

Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, India.

Snakebite envenoming is a common occupational hazard in the tropics. Venom-induced consumption coagulopathy and acute kidney injury are the most frequently encountered complications of viper bites. Diffuse alveolar hemorrhage (DAH) is an unusual presentation reported rarely in the literature. Our case report highlights the uncommon presentation of delayed pulmonary hemorrhage after snakebite envenoming. A 40-year-old healthy man presented to our emergency department after 6 hours of Echis sochureki (a saw-scaled viper subspecies) bite. He had abnormal coagulation parameters and thrombocytopenia with no signs of acute kidney injury. Transfusion protocols were initiated because of active bleeding and a rapid decrease in hemoglobin levels over next few days. Around day 10, his coagulation profile and hemoglobin were corrected, but he developed hemoptysis with rapidly progressive respiratory distress. Computed tomography of the chest was suggestive of DAH and the patient was started on plasma exchange with pulse methylprednisolone. After the initial worsening, he had rapid symptomatic improvement and radiological resolution. The patient had persistent hypofibrinogenemia, which resolved, and was discharged and remained healthy at the 60-day follow-up. This case highlights a presentation with an initial phase of venom-induced consumption coagulopathy followed by delayed DAH in saw-scaled viper envenoming that was treated successfully with immunosuppressants and plasma exchange.
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http://dx.doi.org/10.4269/ajtmh.21-1187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922478PMC
January 2022

Assessment of antidiabetic effect of 4-HIL in type 2 diabetic and healthy Sprague Dawley rats.

Hum Exp Toxicol 2022 Jan-Dec;41:9603271211061873

Division of Toxicology and Experimental Medicine, 226031CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, India.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and insulin resistance. 4-hydroxyisoleucine (4-HIL) is a non-proteinogenic amino acid isolated from the fenugreek seeds and has enormous pharmacological activities. The present study was undertaken to investigate the antihyperglycemic effect of 4-HIL in streptozotocin (STZ)-induced diabetic rats. Moreover, its toxicity was evaluated in vitro and in vivo employing human embryonic kidney cells (HEK-293) and healthy rats, respectively. In experiment 1, STZ-induced diabetic male rats were subjected to an oral treatment of 4-HIL (100 mg/kg), while experiment 2 deals with the effects of 4-HIL on healthy male and female rats following oral administration. The treatment (experiment 1) declined the elevated blood glucose level, feed intake, and increased body weight(s). Additionally, blood glucose impairment was improved as observed by OGTT and IPGT tests. Pancreatic histopathology revealed mild changes in the 4-HIL group. Moreover, experiment 2 showed increased body weight, normal blood glucose levels (male-106.06 ± 7.49 mg/dl and female-100.06 ± 14.69 mg/dL), hematological parameters, and histopathological profiles in the treatment group. 4-HIL did not affect the viability of HEK-293 cells, and no signs of toxicity were observed in healthy rats. Therefore, the study concludes that 4-HIL has potential antihyperglycemic activity without any toxic effects.
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http://dx.doi.org/10.1177/09603271211061873DOI Listing
March 2022

Innate immune sensing of influenza A viral RNA through IFI16 promotes pyroptotic cell death.

iScience 2022 Jan 31;25(1):103714. Epub 2021 Dec 31.

Department of Biological Sciences, Laboratory of Immunology and Infectious Disease Biology, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal 462066, MP, India.

Programmed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus (IAV) infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for the influenza A virus by interacting with genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). On the contrary, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. Collectively, these results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
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http://dx.doi.org/10.1016/j.isci.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762390PMC
January 2022

Patients' perspective about speech, swallowing and hearing status post-SARS-CoV-2 (COVID-19) recovery: E-survey.

Eur Arch Otorhinolaryngol 2022 May 21;279(5):2523-2532. Epub 2022 Jan 21.

School of Communication Sciences and Disorders, University of Memphis, Memphis, TN, USA.

Objective: The present study investigates the COVID-19 survivors' perspective on speech, swallowing, and hearing-related issues post-COVID-19. We further investigate the recovery duration for speech, swallowing, and hearing-related symptoms post-COVID.

Design: Survey study; E-survey.

Methodology: A total of 78 subjects (35.78 years ± 11.93) participated in the survey. All the participants were diagnosed with the RTPCR method. To understand the recovery duration for the speech, swallowing and hearing issues post-COVID-19, we conducted a three-phase study.

Results: In the first phase of the survey, 68 subjects reported symptoms related to speech, swallowing, and hearing issues 15 days of post-COVID recovery. A total of 76.4% of subjects reported only swallowing-related issues, 4.41% only speech-related issues, whereas 1.47% reported the problem in speech and hearing functions. The 2nd phase of the study was conducted after the first phase of the study. Only 22 subjects reported the presence of swallowing, speech and hearing-related issues from the 68 subjects. During the last phase, only 12 subjects reported speech, swallowing, and hearing issues. All subjects recovered from the olfaction and gustation impairment, whereas 50% of subjects reported the presence of xerostomia.

Conclusion: From the present study, we conclude that the SARC-CoV-2 virus directly affects the respiratory system and affects the aero-digestive system and laryngeal system physiology. Individuals with comorbid conditions admitted in ICU during COVID-19 treatment and prolonged hospital stay were at higher risk of developing speech, swallowing, and hearing-related issues post-COVID-19. The present study indicated that all COVID-19 survivors should be screened for speech, swallowing, and hearing-related issues for early rehabilitation if needed.
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http://dx.doi.org/10.1007/s00405-021-07217-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776384PMC
May 2022

Effects of Spirulina (Arthrospira platensis) as a drinking water supplement during cyclical chronic heat stress on broiler chickens: Assessing algal composition, production, stress, health and immune-biochemical indices.

J Therm Biol 2022 Jan 20;103:103100. Epub 2021 Sep 20.

Division of Avian Physiology and Reproduction, ICAR-Central Avian Research Institute, Izatnagar, 243122, U.P, India.

Spirulina, the blue green algae is considered to exhibit multifaceted benefits on both human health and animal production. Three hundred sixty day old unsexed broiler chicks of CARIBROVISHAL strain were assigned to five treatment groups each comprising nine replicates of 8 chicks. The experiment was carried out during the hot humid summer season (Mid-April to May) under deep litter rearing system with uniform managemental conditions. Birds were administered orally with Spirulina through drinking water in the morning (06:00-12:00 PM) on daily basis throughout the experimental period at 5, 10, 15 and 20 gL concentration. Spirulina supplementation neither improved nor compromised production performance of broilers reared during hot climatic condition. Results based on one way analysis of variance indicated a significant effect on haemoglobin and total red blood cell count. Serum lipid content and transaminases were reduced, while serum protein concentration was higher (P < 0.01) in the groups administered with 15 and 20 gL of Spirulina. The extent of imparting shank pigmentation was improved in all the supplemented groups. Cell mediated and humoral immunity against Phytoheamagglutunin-P and Newcastle disease vaccination respectively were maximized (P < 0.05) at 20 gL. These findings provide direct evidence of dose-related modulation of production, physiological and immunological attributes by Spirulina engendering its further investigation as a potential source of drinking water supplement for stress alleviation in broilers. From the results, it may concluded that Spirulina can be incorporated at 15 or 20 gL for achieving optimal improvement of health and welfare attributes in broilers reared during hot summer without compromising production.
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http://dx.doi.org/10.1016/j.jtherbio.2021.103100DOI Listing
January 2022

Masson's Hemangioma of Knee: A Rare Case Report.

J Orthop Case Rep 2021 Aug;11(8):79-83

Department of Pathology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.

Introduction: Intrasynovial hemangioma, a rare benign vascular lesion of joint cavities, is also called intrasynovial papillary endothelial hyperplasia or Masson's hemangioma (MH). These lesions are characterized by abnormal proliferation of endothelial cells with mild atypia with an organized thrombus. MH follows an individualized protocol for its management.

Case Report: A 22-year-old male gave a 10-year history of the diagnosed and operated (arthroscopically) case of synovial hemangioma of the left knee and presented with similar complaints. There was no history of trauma or infection over the left knee. The movements of the left knee were normal except with terminal restriction of movements. MRI of the left knee suggested intrasynovial low flow vascular malformation within the substance of the synovium. The patient underwent synovectomy of the hemangiomatous lesion in toto without any recurrence in the follow-up period for 8 months. Histopathology confirmed the diagnosis of intravascular papillary endothelial hyperplasia/MH.

Conclusion: Although intrasynovial hemangioma is a very rare clinical entity, Orthopedic surgeons should have a high index of suspicion for MH, when a long-standing pain and hemarthrosis of the knee joint is being encountered in the clinical practice.
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http://dx.doi.org/10.13107/jocr.2021.v11.i08.2376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686491PMC
August 2021

Design, Synthesis, and Biological Evaluation of Densely Substituted Dihydropyrano[2,3-]pyrazoles a Taurine-Catalyzed Green Multicomponent Approach.

ACS Omega 2021 Nov 2;6(45):30734-30742. Epub 2021 Nov 2.

Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India.

An efficient taurine-catalyzed green multicomponent approach has been described for the first time to synthesize densely substituted therapeutic core dihydropyrano[2,3-]pyrazoles. Applications of the developed synthetic strategies and technologies revealed the synthesis of a series of newly designed 1,4-dihydropyrano[2,3-]pyrazoles containing isonicotinamide, spirooxindole, and indole moieties. Detailed analysis of the synthesized analogues revealed their potential to bind wild-type and antibiotic-resistant variants of dihydrofolate reductase, a principal drug target enzyme for emerging antibiotic-resistant pathogenic strains. Hence, the synthesized dihydropyrano[2,3-]pyrazole derivatives presented herein hold immense promise to develop future antistaphylococcal therapeutic agents.
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http://dx.doi.org/10.1021/acsomega.1c04773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600639PMC
November 2021

Aloin alleviates pathological cardiac hypertrophy via modulation of the oxidative and fibrotic response.

Life Sci 2022 Jan 18;288:120159. Epub 2021 Nov 18.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, PIN-781101, Assam, India. Electronic address:

Aims: Pathological cardiac hypertrophy is a characteristic feature in many cardiovascular diseases (CVDs). Aloin is an anthraquinone glycoside from Aloe species, and the effect of aloin on cardiac hypertrophy and associated fibrotic changes have not been elucidated. This study investigated the effect of aloin against the isoproterenol (ISO)-induced cardiac hypertrophy in rats.

Main Methods: Cardiac hypertrophy experimental model was induced in rats by subcutaneous injection of ISO for 14 days. Meanwhile, the animals were administered orally with aloin at doses of 25 and 50 mg/kg/day. On the 15th day, cardiac echocardiography was performed, the heart was collected and subjected for histopathological, gene expression, and immunoblot studies. Additionally, the effect of aloin on ISO-induced hypertrophic changes in H9c2 cells was investigated.

Key Findings: Aloin markedly alleviated ISO-induced heart injury, reduced cardiac hypertrophy, improved cardiac function, and histological alterations in the heart. Mechanistically, aloin attenuated ISO-induced fibrosis via inhibition of the levels of collagen I, α-smooth muscle actin (α-SMA), fibronectin, transforming growth factor-β (TGF-β) and pSmad2/3 proteins in the heart. Aloin alleviated ISO-induced myocardial oxidative damage and up-regulated the levels of antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Moreover, aloin treatment attenuated ISO-induced hypertrophic changes and the generation of reactive oxygen species (ROS) in H9c2 cells in vitro.

Significance: Our findings demonstrated that aloin alleviated ISO-induced cardiac hypertrophy and fibrosis via inhibiting TGF-β/pSmad2/3 signaling and restoring myocardial antioxidants, and therefore has promising therapeutic potential against cardiac hypertrophy and fibrosis.
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http://dx.doi.org/10.1016/j.lfs.2021.120159DOI Listing
January 2022

Evaluation and management of "low" anorectal malformation in male children: an observational study.

Pediatr Surg Int 2022 Feb 27;38(2):337-343. Epub 2021 Oct 27.

Department of Pediatric Surgery, King George's Medical University, Lucknow, UP, 226003, India.

Purpose: ARM with perineal fistula has been traditionally defined as low ARM (LARM). This study was conducted to evaluate LARM in male patients with an emphasis on the role of various factors on the outcome and follow-up of them.

Materials And Methods: It was a retrospective cohort study. The clinical presentation, associated anomalies, and complications were assessed. The operative procedures included cutback anoplasty and others. The patients were followed in the outpatient department. The complications were assessed and managed accordingly.

Results: During the study period of 8 years, 301 patients were admitted. The complaints included absent or abnormal anal opening, abdominal distension, constipation, and peritonitis. Most of the children (n = 214) presented in the neonatal period. The most common clinical presentation was the perineal fistula. The most common associated anomaly was urologic. Fourteen patients were referred from other centers after complications. The most common problem in follow-up was constipation.

Conclusion: LARM in male patients may have a diverse presentation. The associated anomalies need proper assessment. Awareness may avoid delayed presentation and unwanted complications. When managed by an expert, the condition can be effectively managed. Regular follow-up is important.
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http://dx.doi.org/10.1007/s00383-021-05035-5DOI Listing
February 2022

Land gradient and configuration effects on yield, irrigation amount and irrigation water productivity in rice-wheat and maize-wheat cropping systems in Eastern India.

Agric Water Manag 2021 Sep;255:107036

International Rice Research Institute (IRRI), Los Baños, Laguna, The Philippines.

Laser land levelling is expanding rapidly in the rice-wheat (RW) and maize-wheat (MW) systems of the Indo-Gangetic Plains of India and Pakistan. Current practice is to level to zero (0%) gradient, whereas a small gradient (e.g. 0.1%) is typically used in developed countries. Therefore, experiments were conducted in farmers' plots (~15 m x 40 m) in the Eastern Gangetic Plains to evaluate laser levelling with a 0.1% gradient in comparison with 0% and farmer levelling practice (FL). The study was conducted over two years in RW and MW systems. In the MW system, raised beds in plots lasered with 0% and 0.1% gradients were also evaluated. Laser levelling with 0% gradient significantly reduced irrigation amount and/or increased irrigation water productivity (WPi) in all crops/systems grown on the flat compared to FL except for wheat in the MW system. While there was a consistent trend for higher yield with a 0% gradient compared with FL, the differences were not significant in any crop/system. For the RW system, the results suggest no to marginal benefits in irrigation amount and WPi from levelling with a 0.1% gradient in comparison with 0% gradient. In that system, by far the bigger gains were from changing from FL to laser levelling with 0% gradient. This resulted in substantial reductions in irrigation amount, which greatly increased WPi in both crops (by ~40%), while yield was not affected. Rice grown with FL was not profitable, but lasering with 0% gradient significantly increased gross margin for rice, wheat and the total RW system. As for the RW system, levelling to 0% with a flat configuration significantly increased WPi of both crops in the MW system compared to FL, but by a lesser proportion. Raised beds significantly increased yield of maize by 8% (0.5 t ha), reduced irrigation amount by 20% (40 mm) and increased WPi by 34% (1.0 kg m) in comparison with the laser levelled flat plots. Gross margin of the MW system on beds was 17-20% higher than FL, and gross margin with beds on a 0.1% gradient was significantly higher than either gradient on the flat. The results suggest that the gains from levelling with a 0.1% gradient compared to 0% are marginal; however, this may change if the goal of consolidation of small farmer plots into larger fields becomes a reality provided there is a proportionate increase in irrigation flow rates, and ability to drain.
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http://dx.doi.org/10.1016/j.agwat.2021.107036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363937PMC
September 2021

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart.

Int J Mol Sci 2021 Aug 23;22(16). Epub 2021 Aug 23.

Space Biosciences Division, NASA Ames Research Center, Mail Stop 288-2, Moffett Field, CA 94035, USA.

Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, , upregulated and downregulated , suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated () and cell cycle/apoptosis-related gene , and downregulated the inflammatory response gene . There were no changes in apoptosis-related genes such as . Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress.
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http://dx.doi.org/10.3390/ijms22169088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396460PMC
August 2021

Angiotensin-converting Enzyme Inhibitors: Can it be a Potential Treatment of Infantile Hemangioma.

J Indian Assoc Pediatr Surg 2021 Jul-Aug;26(4):234-239. Epub 2021 Jul 12.

Department of Pediatric Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India.

Aims: The aim of the sudy was to evaluate potential role of oral captopril, an angiotensin-converting enzyme (ACE) inhibitor, and in treatment of infantile hemagioma (IH) and report our preliminary results.

Methods: This prospective study included 18 children with IH admitted in the department of pediatric surgery with no history of prior treatment of any type. Baseline blood pressure (BP), electrocardiogram, two-dimensional echocardiography, serum electrolytes, and renal function test (RFT) were noted. Oral captopril was started as first-line drug at a dose of 0.1 mg/kg orally 12 h with gradually increase of dosage up to 2.0 mg/kg 12 h over the period of 10 days with monitoring of BP, serum electrolytes, RFT, and occurrence of any side effect. If no side effects were noted and patients were stable, they were discharged and followed up until 6 months after stopping treatment. During follow-up, response to treatment was documented clinically and photographically. Development of any side effect was also noted.

Results: Excellent response to captopril was noticed in nine patients over 16-18 months. Four patients showed good response. Oral propranolol had to be administered alternatively in one patient showing fair response during the initial 4 months but no response afterward and in four patients showing no response at all. One patient developed an allergic reaction to propranolol and was started oral corticosteroid. These five patients had near complete resolution of lesion for the next 8-10 months.

Conclusions: ACE inhibitors might have a role, though slow, in the involution of IHs. Therefore, these may have the potential to emerge as an alternative treatment for IH in future after confirmation with randomized studies with propranolol.
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http://dx.doi.org/10.4103/jiaps.JIAPS_112_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323578PMC
July 2021

Regulatory safety pharmacology and toxicity assessments of a standardized stem extract of Cassia occidentalis Linn. in rodents.

Regul Toxicol Pharmacol 2021 Jul 19;123:104960. Epub 2021 May 19.

Pharmaceutics & Pharmacokinetics, CSIR-CDRI, Lucknow, 226 031, India. Electronic address:

Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.
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http://dx.doi.org/10.1016/j.yrtph.2021.104960DOI Listing
July 2021

The wandering ventriculoperitoneal shunt and the scope of its salvage.

Childs Nerv Syst 2021 08 8;37(8):2613-2618. Epub 2021 May 8.

Department of Pediatric Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: Distal shunt tube migration following ventriculoperitoneal (VP) shunt placement in children is mostly managed by an initial shunt diversion/removal and subsequent replacement. Lately, shunt salvage is being used as an alternative in certain conditions. We have focused on the situations where one can consider or disregard shunt salvage in such cases.

Method: A retrospective study of children treated for distal shunt migration following VP shunt placement between January 2013 and December 2019.

Result: Seventeen children were managed for over 7 years. These included cutaneous extrusions (n = 4), hollow viscus perforation (n = 6), inguinal hernias (n = 5), and umbilical extrusion (n = 2). The surgical treatment varied from a cutaneous wound closure (with a tube in situ), temporary external shunt diversion, and laparotomy with shunt reposition into the peritoneal cavity. Shunt salvage was possible in three cases, whereas in 2 cases even though shunt salvage was possible, it was not feasible due to a short residual shunt length.

Conclusion: VP shunt salvage is possible in certain cases of distal shunt migration with a functional uninfected shunt. Small cutaneous extrusions can be covered by a local skin flap. Also, one should consider the residual intraperitoneal shunt length before its salvage in small children.
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http://dx.doi.org/10.1007/s00381-021-05198-5DOI Listing
August 2021

ert entities of current worldwide pandemic.

Int Rev Immunol 2021 ;40(1-2):1-4

Laboratory of Immunology and Infectious Disease Biology, Indian Institute of Science Education and Research (IISER), Bhopal, India.

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http://dx.doi.org/10.1080/08830185.2021.1884375DOI Listing
October 2021

3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration.

Cell Stem Cell 2021 05 29;28(5):846-862.e8. Epub 2021 Mar 29.

Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA; Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA; Center for Visual Science, University of Rochester, Rochester, NY 14620, USA; UR Stem Cell and Regenerative Medicine Center, Rochester, NY 14620, USA. Electronic address:

The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromised in age-related macular degeneration (AMD) and related macular dystrophies (MDs), yet in vitro models of RPE-CC complex that enable investigation of AMD/MD pathophysiology are lacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix, we developed a 3D RPE-CC model that recapitulates key features of both healthy and AMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CC model, we demonstrated that both RPE- and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature. Our data show that choroidal neovascularization (CNV) and CC atrophy occur in the absence of endothelial cell dysfunction and are not necessarily secondary to drusen deposits underneath RPE cells, and CC atrophy and/or CNV can be initiated systemically by patient serum or locally by mutant RPE-secreted factors. Finally, we identify FGF2 and matrix metalloproteinases as potential therapeutic targets for AMD/MDs.
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http://dx.doi.org/10.1016/j.stem.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520418PMC
May 2021

Generation of T cells from Human and Nonhuman Primate Pluripotent Stem Cells.

Bio Protoc 2020 Jul 5;10(13):e3675. Epub 2020 Jul 5.

Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.

Pluripotent stem cells (PSCs) have the potential to provide homogeneous cell populations of T cells that can be grown at a clinical scale and genetically engineered to meet specific clinical needs. OP9-DLL4, a stromal line ectopically expressing the Notch ligand Delta-like 4 (DLL4) is used to support differentiation of PSCs to T-lymphocytes. This article outlines several protocols related to generation of T cells from human and non-human primate (NHP) PSCs, including initial hematopoietic differentiation of PSC on OP9 feeders or defined conditions, followed by coculture of the OP9-DLL4 cells with the PSC-derived hematopoietic progenitors (HPs), leading to efficient differentiation to T lymphocytes. In addition, we describe a protocol for robust T cell generation from hPSCs conditionally expressing ETS1. The presented protocols provide a platform for T cell production for disease modeling and evaluating their use for immunotherapy in large animal models.
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http://dx.doi.org/10.21769/BioProtoc.3675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842311PMC
July 2020
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