Publications by authors named "Vijay Kumar"

1,277 Publications

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Influence of occlusal and proximal caries on outcome of full pulpotomy in posterior permanent teeth with partial irreversible pulpitis: A prospective study.

Int Endod J 2021 Jun 8. Epub 2021 Jun 8.

Division of Conservative Dentistry and Endodontics, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India.

Aim: To assess the influence of occlusal and proximal deep carious lesion on the outcome of full pulpotomy performed in mandibular teeth with pulpal diagnosis of symptomatic partial irreversible pulpitis.

Methodology: Eighty deep carious mandibular molar teeth with clinical and radiographic diagnosis of symptomatic partial irreversible pulpitis without periapical rarefaction from patients of either gender between the age of 16-35 years were included. Depending upon the location of deep carious lesion, the teeth were distributed equally into occlusal (n=40) and proximal caries groups (n=40). Full pulpotomy was performed under local anaesthesia and aseptic conditions. The pulp tissue was removed until the root canal orifices and 2.5% sodium hypochlorite (NaOCl) was applied to arrest pulpal bleeding. Mineral trioxide aggregate (MTA) was compacted over the radicular pulp. Teeth were restored with resin modified glass ionomer cement (RMGIC) and bulk-fill composite resin. Pre and post- operative pain was assessed at 24, 48 and 72 hours using a 11 point Numerical Rating Scale (NRS). Patients were followed at 6 and 12 months for clinical and radiographic evaluation. Asymptomatic teeth without any radiographic evidence of periapical rarefaction were considered successful. The data were analysed using the Shapiro-Wilk W test, Two-sample Wilcoxon rank-sum test, Pearson Chi-Square test, Fisher's exact test and Kappa coefficient. The significance level was predetermined at p<0.05.

Result: An intergroup comparison revealed that the pre and postoperative pain scores at 24, 48 and 72 hours were not significantly different (p>0.05). At the end of follow up period (12 months), success of full pulpotomy in occlusal and proximal caries group was 95% and 92.5% respectively (p=0.644). For both groups, the combined success rate of full pulpotomy was 93.75%.

Conclusion: The site of carious lesions (i.e. occlusal or proximal) did not affect the clinical and radiographic outcome of full pulpotomy performed in mature permanent mandibular teeth with partial irreversible pulpitis.
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http://dx.doi.org/10.1111/iej.13588DOI Listing
June 2021

Response of Helicobacter Pylori Eradication Treatment in Patients With Normal and Below-Normal Serum Vitamin D Levels.

Cureus 2021 Apr 30;13(4):e14777. Epub 2021 Apr 30.

Family Medicine, Jinnah Post Graduate Medical Center, Karachi, PAK.

Introduction  The infection of () is affected by the host immune system and the genetic makeup. It is postulated that deficiency of vitamin D may interfere in normal immunological response to infectious agents, including , and increase the risk of infection. This study aims to find the relationship between vitamin D status in the body and patient's response to eradication treatment. Methods  One hundred and fifty patients (n = 150) between the ages of 18 and 60 years of either gender, diagnosed with , were included in the study. After enrollment, patients were started on first-line eradication therapy, which included omeprazole, amoxicillin, and clarithromycin for 14 days. Patient's vitamin D levels were tested via laboratory. After 14 days, patients' stools were tested for presence of antigen.  Results  A total of 128 participants completed the study, out of which 92 (71.8%) participants showed no antigen in stool after 14 days and 36 (28.1%) participants still showed in their stool. The mean serum vitamin D level was significantly higher in participants who had successful treatment compared to those who had unsuccessful treatment (31.01 ± 7.8 ng/mL vs. 18.9 ± 5.6 ng/mL; p-value < 0.0001). Conclusion  Vitamin D levels may affect the response of eradication therapy. Further large-scale studies are needed in which vitamin D is given as an intervention to further study the association between vitamin D levels and treatment response.
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http://dx.doi.org/10.7759/cureus.14777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169094PMC
April 2021

Accuracy of Resolution of ST-Segment Elevation in Electrocardiogram to Determine the Patency of Infarct-Related Artery.

Cureus 2021 Apr 13;13(4):e14448. Epub 2021 Apr 13.

Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK.

Introduction:  There is very limited data comparing the accuracy of ECG to angiography in predicting reperfusion status. In this study, we will determine the accuracy of ECG change i.e. resolution of ST-segment elevation in predicting infarct-related artery (IRA) patency after thrombolysis in patients with ST-segment elevated myocardial infarction (STEMI), in comparison to angiography.

Methods: Three hundred and forty-one (n = 341) patients with acute STEMI received streptokinase, a thrombolytic agent within 12 hours of symptoms, and were enrolled in the study via consecutive convenient non-probability sampling. ECG was recorded as soon as the patient arrived in the emergency unit of cardiology. Subsequent ECG was recorded three hours after the administration of streptokinase to look for resolution of ST-segment elevation. ST-segment resolution was classified as greater/equal to 50% resolved or less than 50% resolved. Coronary angiography was performed within 24 hours of hospitalization and flow in the IRA was assessed.

Results: The most common site of myocardial infarction (MI) was the anterior wall (50.1%) and the commonest artery involved was the left anterior descending artery (44.2%). On ECG, ST-resolution of more than 50% was found in 242 (70.9%) participants. Thrombolysis in MI (TIMI) grade III flow in angiography was found in 211 (61.8%) participants. The sensitivity and specificity of ST-resolution to detect TIMI grade III flow was 94.79% and 67.69%, respectively, while accuracy was 84.46%.

Conclusion: ST-resolution on ECG after streptokinase can predict IRA patency on coronary angiography with moderate to good accuracy. ECG can assist in predicting the impact of streptokinase early in the course of management and give an option of monitoring patient prognosis with a non-invasive test in patients not comfortable with angiography.
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http://dx.doi.org/10.7759/cureus.14448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159311PMC
April 2021

Methylene Blue Dye Adsorption from Wastewater Using Hydroxyapatite/Gold Nanocomposite: Kinetic and Thermodynamics Studies.

Nanomaterials (Basel) 2021 May 26;11(6). Epub 2021 May 26.

Department of Physics, National Institute of Technology, Srinagar 190006, India.

The present work demonstrates the development of hydroxyapatite (HA)/gold (Au) nanocomposites to increase the adsorption of methylene blue (MB) dye from the wastewater. HA nanopowder was prepared via a wet chemical precipitation method by means of Ca(OH) and HPO as starting materials. The biosynthesis of gold nanoparticles (AuNPs) has been reported for the first time by using the plant extract of . Finally, the as-prepared HA nanopowder was mixed with an optimized AuNPs solution to produce HA/Au nanocomposite. The prepared HA/Au nanocomposite was studied by using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM) with Energy Dispersive X-Ray Analysis (EDX) analysis. Adsorption studies were executed by batch experiments on the synthesized composite. The effect of the amount of adsorbent, pH, dye concentration and temperature was studied. Pseudo-first-order and pseudo-second-order models were used to fit the kinetic data and the kinetic modeling results reflected that the experimental data is perfectly matched with the pseudo-first-order kinetic model. The dye adsorbed waste materials have also been investigated against , , and bacteria by the agar well diffusion method. The inhibition zones of dye adsorbed samples are more or less the same as compared to as-prepared samples. The results so obtained indicates the suitability of the synthesized sample to be exploited as an adsorbent for effective treatment of MB dye from wastewater and dye adsorbed waste as an effective antibacterial agent from an economic point of view.
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http://dx.doi.org/10.3390/nano11061403DOI Listing
May 2021

Thrombin impairs the angiogenic activity of extravillous trophoblast cells via monocyte chemotactic protein-1 (MCP-1): A possible link with preeclampsia.

Reprod Biol 2021 May 28;21(3):100516. Epub 2021 May 28.

Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, Rajasthan, 305817, India. Electronic address:

Cytokines' secretion from the decidua and trophoblast cells has been known to regulate trophoblast cell functions, such as Extravillous trophoblasts (EVTs) cell migration and invasion and remodeling of spiral arteries. Defective angiogenesis and spiral arteries transformation are mainly caused by proinflammatory cytokines and excessive thrombin generation during preeclampsia. Monocyte chemotactic protein-1 (MCP-1), a crucial cytokine, has a role in maintaining normal pregnancy. In this study, we explored whether thrombin regulates the secretion of MCP-1 in HTR-8/SVneo cells; if yes, what is its function? We used HTR-8/SVneo cells, developed from first trimester villous explants of early pregnancy, as the model of EVTs. MCP-1 gene silencing was performed using gene-specific siRNA. qPCR and ELISA were performed to estimate the expression and secretion of MCP-1. Here, we found that thrombin enhanced the secretion of MCP-1 in HTR-8/SVneo cells. Proteinase-activated receptor-1 (PAR-1) was found as the primary receptor, regulating MCP-1 secretion in these cells. Furthermore, MCP-1 secretion is modulated via protein kinase C (PKC) α, β, and Rho/Rho-kinase-dependent pathways. Thrombin negatively regulates HTR-8/SVneo cells' ability to mimic tube formation in an MCP-1 dependent manner. In conclusion, we propose that thrombin-controlled MCP-1 secretion may play an essential role in normal placental development and successful pregnancy maintenance. Improper thrombin production and MCP-1 secretion during pregnancy might cause inadequate vascular formation and transformation of spiral arteries, which may contribute to pregnancy disorders, such as preeclampsia.
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http://dx.doi.org/10.1016/j.repbio.2021.100516DOI Listing
May 2021

Association between retinal vascular caliber and brain structure in schizophrenia.

Asian J Psychiatr 2021 Jul 27;61:102707. Epub 2021 May 27.

National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Objective: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging.

Method: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis.

Results: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex.

Discussion: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.
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http://dx.doi.org/10.1016/j.ajp.2021.102707DOI Listing
July 2021

miRNA-149 targets PARP-2 in endometrial epithelial and stromal cells to regulate the trophoblast attachment process.

Mol Hum Reprod 2021 May 29. Epub 2021 May 29.

Female Reproductive Biology Laboratory, Division of Endocrinology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.

Embryo implantation is a highly complex process involving many regulatory factors, including several micro RNAs (miRNAs/miRs). One miRNA present in the stromal cells of normal endometrium is miR-149, which targets poly [ADP-ribose] polymerase 2 (PARP-2), a gene involved in endometrial receptivity for trophoblast implantation. However, the precise role of miR-149 in the endometrial receptivity during blastocyst implantation is still unknown. We studied miR-149 dependent PARP-2 regulation during trophoblast attachment to endometrial epithelial cells. Using FISH, we found that miR-149 is expressed in mouse endometrial epithelial and stromal cells at implantation and inter-implantation sites. Endometrial receptivity for embryo implantation and attachment is inhibited by the upregulation of miR-149 in endometrium. Our RT-PCR analysis revealed downregulation of miR-149 in the implantation region of the uterus during the receptive stage (day 5, 0500 h, p.c.) in mouse. Under in vitro conditions, miR-149 overexpression inhuman endometrial epithelial cells (hEECs) abrogated the human trophoblastic cells spheroid and mouse blastocyst attachment. Subsequently, miR-149 also regulates human endometrial stromal cell (hESCs) decidualization by downregulating PARP-2 and upregulating caspase-8 proteins. Overexpression of miR-149 in human hEECs and transformed human endometrial stromal cells (T-HESCs) downregulated PARP-2 protein expression, reconfirming that PARP-2 is a downstream target of miR-149 in endometrial cells as well. miR-149 is also able to alter the expression of caspase-8, another PARP-2 regulator. In conclusion, our data indicates that miR-149 is one of regulators of endometrial receptivity and decidualization for trophoblast implantation, and it exert the effects by acting on the downstream targets PARP-2 and caspase-8.
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http://dx.doi.org/10.1093/molehr/gaab039DOI Listing
May 2021

Eosinophilic gastroenteritis: Clinical characteristics and management.

Indian J Gastroenterol 2021 Jun 28;40(3):338-343. Epub 2021 May 28.

Institute of Digestive and Hepatopancreatobiliary Sciences, Sakra World Hospital, Sy No. 52/2 & 52/3, Devarabeesanahalli, Bangalore, 560 103, India.

There is paucity of published data related to eosinophilic gastroenteritis (EGE). We aimed to study the clinical characteristics, management, and follow-up of EGE. From March 2014 to December 2018, patients with gastrointestinal (GI) symptoms suspected to have EGE were investigated. This is a retrospective study. Complete blood count, upper GI endoscopy (UGIE), and biopsy were done. Contrast-enhanced computed tomography (CECT) abdomen was done when intestinal obstruction was suspected. Laparoscopic small bowel resection or stricturoplasty and full-thickness biopsy were obtained. EGE was diagnosed if the biopsies showed eosinophilic infiltration of one or more regions of the GI tract (> 30 eosinophils per high power field [HPF]). Patients were treated with immunosuppressive therapy and if indicated surgery. Clinical response to therapy was assessed and patients were followed up for 1 year. Forty-one patients (mean age 34.8 years, median age 32, range 25-70 years, 29 males) had EGE. Upper abdominal pain was the most common symptom. Peripheral eosinophilia was present in 82.9% patients. On UGIE, duodenal lesions were observed in 75% patients. EGE was confirmed in 37 patients by endoscopic duodenal biopsies, in 2 patients by jejunal mucosal biopsies using enteroscopy, and in 2 patients by full thickness surgical biopsies. Forty-one patients were treated with oral corticosteroids inclusive of 4 patients who underwent surgery. Of the 37 patients, 6 were lost to follow-up; 31 patients were followed up for a period of 1 year. All the patients who were treated with corticosteroids responded to initial therapy. Over a follow-up period one case had frequent relapses. EGE should be suspected in patients with upper abdominal pain. Peripheral eosinophilia occurs in the majority. Tissue diagnosis showing eosinophilic infiltration is diagnostic. Oral corticosteroid therapy is highly effective and relapse is rare.
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http://dx.doi.org/10.1007/s12664-021-01160-0DOI Listing
June 2021

Biotechnological interventions and genetic diversity assessment in Swertia sp.: a myriad source of valuable secondary metabolites.

Appl Microbiol Biotechnol 2021 Jun 26;105(11):4427-4451. Epub 2021 May 26.

Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, India.

The genus Swertia (Family: Gentianaceae) has cosmopolitan distribution which is present in almost all the continents except South America and Australia. Swertia genus has been renowned as one of the potent herbal drugs in the British, American, and Chinese Pharmacopeias as well as well-documented in the Indian traditional medicinal systems, viz. Ayurveda, Siddha, and Unani. Many species of this genus have therapeutic properties and have been used traditionally in the treatment of a number of health ailments viz. hepatitis, diabetes, inflammation, bacillary dysentery, cancer, malaria, fever etc. This genus is industrially important medicinal plant that has been used as a principal component in numerous marketed herbal/ polyherbal formulations. Medicinal usage of Swertia is endorsed to the miscellaneous compounds viz. xanthones, irridoids, seco-irridoids, and triterpenoids. A chain of systematic isolation of bio-active compounds and their diverse range of pharmacological effects during last 15-20 years proved this genus as industrially important plant. Due to the various practices of the Swertia species, annual demand is more than 100 tons per year for this important herb which is continuously increasing 10% annually. The market value rises 10% by the year as there is increased demand in national and international market resulted in adulteration of many Swertia spp. due to paucity of agricultural practices, exomorphological, phytochemical, and molecular characterization. Thus, efficient biotechnology methods are prerequisite for the mass production of authentic species, sustainable production of bio-active compounds and ex situ conservation. A chain of systematic biotechnological interventions in Swertia herb during last 20 years cover the assessment of genetic diversity, in vitro sustainable production of bio-active compounds and mass propagation of elite genotypes via direct and indirect organogenesis. This review attempts to present the comprehensive assessment on biotechnological process made in Swertia over the past few years. KEY POINTS: • Critical and updated assessment on biotechnological aspects of Swertia spp. • In vitro propagation and genetic diversity assessment in Swertia spp. • Biosynthesis and sustainable production of secondary metabolites in Swertia spp.
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http://dx.doi.org/10.1007/s00253-021-11345-4DOI Listing
June 2021

Risk mitigation with the use of clozapine - Quo vadimus.

Asian J Psychiatr 2021 Jul 19;61:102693. Epub 2021 May 19.

National Institute of Mental Health and Neurosciences, India.

The risk of neutropenia decreases significantly after the first year of clozapine initiation, and indefinite hematological monitoring is increasingly questioned. Despite comparable risks of neutropenia, the guidelines for antithyroid drugs - carbimazole and propylthiouracil do not recommend routine hematological monitoring. Assuming a similar pathogenic mechanism, data from antithyroid drugs indicate that neutropenia develops rapidly, and indefinite hematological monitoring misses a large majority of cases in the pre-symptomatic phase. Hence, a more pragmatic strategy of intensive hematological monitoring in the first year of clozapine initiation followed by selective haematological monitoring in case of febrile illnesses or pharyngitis needs to be explored.
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http://dx.doi.org/10.1016/j.ajp.2021.102693DOI Listing
July 2021

Necessity of regulatory guidelines for the development of amyloid based biomaterials.

Biomater Sci 2021 May 21. Epub 2021 May 21.

Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, UP-208016, India.

Amyloid diseases are caused due to protein homeostasis failure where incorrectly folded proteins/peptides form cross-β-sheet rich amyloid fibrillar structures. Besides proteins/peptides, small metabolite assemblies also exhibit amyloid-like features. These structures are linked to several human and animal diseases. In addition, non-toxic amyloids with diverse physiological roles are characterized as a new functional class. This finding, along with the unique properties of amyloid like stability and mechanical strength, led to a surge in the development of amyloid-based biomaterials. However, the usage of these materials by humans and animals may pose a health risk such as the development of amyloid diseases and toxicity. This is possible because amyloid-based biomaterials and their fragments may assist seeding and cross-seeding mechanisms of amyloid formation in the body. This review summarizes the potential uses of amyloids as biomaterials, the concerns regarding their usage, and a prescribed workflow to initiate a regulatory approach.
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http://dx.doi.org/10.1039/d1bm00059dDOI Listing
May 2021

Anaesthetic Challenges and Transesophageal Echocardiography-Guided Perioperative Management in a Patient with Uncorrected Adult Congenital Heart Disease Presenting for Emergency Laparoscopic Hysterectomy.

Turk J Anaesthesiol Reanim 2021 Apr 24;49(2):169-174. Epub 2020 Dec 24.

Clinical Fellow in Anaesthesia, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool, United Kingdom.

Anaesthetic management of a patient with adult congenital heart disease with a single ventricle physiology presenting for an emergency laparoscopic surgery is challenging. The importance of a multidisciplinary approach, astute understanding of the pathophysiology and optimisation of intraoperative hemodynamic goals cannot be overemphasised. The present report describes the anaesthetic challenges and the role of transoesophageal echocardiography in perioperative management of a patient with uncorrected tetralogy of Fallot with pulmonary atresia, who successfully underwent an emergency laparoscopic hysterectomy under general anaesthesia.
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http://dx.doi.org/10.5152/TJAR.2020.373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098740PMC
April 2021

Molecular Oncology of Gall Bladder Cancer.

Indian J Surg Oncol 2021 Apr 16;12(Suppl 1):57-64. Epub 2019 Nov 16.

Department of Surgical Oncology, King George's Medical University, Lucknow, Uttar Pradesh 226003 India.

Gall bladder carcinoma (GBC) is a worldwide problem, with a higher incidence in areas of the world where cholelithiasis is common. As GBC is usually diagnosed in an advanced stage, the mortality is high. An understanding of the molecular pathways of carcinogenesis and the mutations involved in the development and progression of GBC could be useful in early diagnosis. Understanding molecular markers of prognosis as well as predictors of outcome could also potentially benefit patients undergoing treatment. New therapies targeting major molecular pathways and immunotherapy are exciting novel therapeutic options. This review focuses on the current understanding of the molecular oncology of GBC.
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http://dx.doi.org/10.1007/s13193-019-01008-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119519PMC
April 2021

Single-Cell Transcriptomics: Current Methods and Challenges in Data Acquisition and Analysis.

Front Neurosci 2021 22;15:591122. Epub 2021 Apr 22.

Department of Computer Sciences, Baba Ghulam Shah Badshah University, Rajouri, India.

Rapid cost drops and advancements in next-generation sequencing have made profiling of cells at individual level a conventional practice in scientific laboratories worldwide. Single-cell transcriptomics [single-cell RNA sequencing (SC-RNA-seq)] has an immense potential of uncovering the novel basis of human life. The well-known heterogeneity of cells at the individual level can be better studied by single-cell transcriptomics. Proper downstream analysis of this data will provide new insights into the scientific communities. However, due to low starting materials, the SC-RNA-seq data face various computational challenges: normalization, differential gene expression analysis, dimensionality reduction, etc. Additionally, new methods like 10× Chromium can profile millions of cells in parallel, which creates a considerable amount of data. Thus, single-cell data handling is another big challenge. This paper reviews the single-cell sequencing methods, library preparation, and data generation. We highlight some of the main computational challenges that require to be addressed by introducing new bioinformatics algorithms and tools for analysis. We also show single-cell transcriptomics data as a big data problem.
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http://dx.doi.org/10.3389/fnins.2021.591122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100238PMC
April 2021

Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis.

Curr Hypertens Rep 2021 05 7;23(5):28. Epub 2021 May 7.

Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA.

Purpose Of Review: To review the current knowledge on interactions between dietary factors and microRNAs (miRNAs) in essential hypertension (EH) pathogenesis.

Recent Findings: There exists an integration of maintenance signals generated by genetic, epigenetic, immune, and environmental (e.g., dietary) factors that work to sustain balance in the gut-liver axis. It is well established that an imbalance in this complex, intertwined system substantially increases the risk for EH. As such, pertinent research has been taken to decipher how each signal operates in isolation and together in EH progression. Recent literature indicates that both macro- and micronutrients interrupt regulatory miRNA expressions and thus, alter multiple cellular processes that contribute to EH and its comorbidities. We highlight how carbohydrates, lipids, proteins, salt, and potassium modify miRNA signatures during EH. The disruption in miRNA expression can negatively impact communication systems such as over activating the renin-angiotensin-aldosterone system, modulating the vascular smooth muscle cell phenotype, and promoting angiogenesis to favor EH. We also delineate the prognostic value of miRNAs in EH and discuss the pros and cons of surgical vs dietary prophylactic approaches in EH prevention. We propose that dietary-dependent perturbation of the miRNA profile is one mechanism within the gut-liver axis that dictates EH development.
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http://dx.doi.org/10.1007/s11906-021-01142-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105193PMC
May 2021

Association of Total Sarnat Score with brain injury and neurodevelopmental outcomes after neonatal encephalopathy.

Arch Dis Child Fetal Neonatal Ed 2021 May 5. Epub 2021 May 5.

Centre for Perinatal Neuroscience, Brain Sciences Department, Imperial College of Science Technology and Medicine, London, UK.

We examined the association of Total Sarnat Score (TSS) with brain injury on neonatal magnetic resonance (MR) and adverse neurodevelopmental outcome (NDO) (death or moderate or severe disability) at 2 years of age in 145 infants undergoing therapeutic hypothermia for neonatal encephalopathy. TSS was associated with basal ganglia/thalamic injury on conventional MR (p=0.03) and thalamic N-acetyl aspartate on MR spectroscopy (R=0.16, p=0.004) at 2 weeks of age, and Bayley Composite Cognitive (R=0.18, p=0.01), Motor (R=0.15, p=0.02) and Language (R=0.11, p=0.01) Scores at 2 years of age after adjustment for seizures at the time of neurological assessment. The accuracy of TSS (area under the curve (AUC)=0.71) for predicting adverse NDO was similar to the modified Sarnat staging (AUC=0.72). TSS of >12 within 6 hours of birth indicated high risk of adverse NDO, while TSS of <4 indicated intact survival and was reassuring of a good outcome among cooled infants.
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http://dx.doi.org/10.1136/archdischild-2020-321164DOI Listing
May 2021

Smad2 and Smad3 differentially modulate chordin transcription via direct binding on the distal elements in gastrula Xenopus embryos.

Biochem Biophys Res Commun 2021 Jun 1;559:168-175. Epub 2021 May 1.

Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Gangwon-Do, 24252, Republic of Korea. Electronic address:

Transforming growth factor (TGF)β/activin superfamily regulates diverse biological processes including germ layer specification and axis patterning in vertebrates. TGFβ/activin leads to phosphorylation of Smad2 and Smad3, followed by regulation of their target genes. Activin treatment also induces the essential organizer gene chordin (chrd). The involvement of Smad2/3 in chrd expression has been unclear as to whether Smad2/3 involvement is direct or indirect and whether any cis-acting response elements for Smad2/3 are present in the proximal or distal regions of its promoter. In the present study, we isolated the -2250 bps portion of the chrd promoter, showing that it contained Smad2/3 direct binding sites at its distal portion, separate from the proximal locations of other organizer genes, goosecoid and cerberus. The pattern of transcription activation for the promoter (-2250 bps) was indistinguishable from that of the endogenous chrd in gastrula Xenopus embryos. Reporter gene assays and site-directed mutagenesis analysis of the chrd promoter mapped two active activin/Smad response elements (ARE1 and ARE2) for Smad2 and Smad3. For a differential chrd induction, Smad2 acted on both ARE1 and ARE2, but Smad3 was only active for ARE2. Collectively, the results demonstrate that the distal region of chrd promoter contains the direct binding cis-acting elements for Smad2 and Smad3, which differentially modulate chrd transcription in gastrula Xenopus embryos.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.048DOI Listing
June 2021

Effect of Adjuvant Metronomic Capecitabine on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer.

JAMA 2021 05;325(17):1792-1793

Department of Surgical Oncology, King George's Medical University, Lucknow, India.

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http://dx.doi.org/10.1001/jama.2021.2783DOI Listing
May 2021

ACRAL GANGRENE: UGLY COUSIN OF "COVID TOES" IN MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN ASSOCIATED WITH SARS-COV-2?

Pediatr Infect Dis J 2021 May 3. Epub 2021 May 3.

From the Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India Pediatric Intensive Care Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. DOI: 10.1097/INF.0000000000003181.

A spectrum of dermatologic manifestations has been reported in multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. We report 2 patients with multisystem inflammatory syndrome in children and severe cardiovascular dysfunction who developed acral gangrene. Both responded well to therapy and recovered in the follow-up.
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http://dx.doi.org/10.1097/INF.0000000000003181DOI Listing
May 2021

A γ-lactam siderophore antibiotic effective against multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp.

Eur J Med Chem 2021 Aug 8;220:113436. Epub 2021 Apr 8.

Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, 44106, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA; Geriatric Research, Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA; Departments of Pharmacology, Molecular Biology & Microbiology, And Proteomics & Bioinformatics, Case Western Reserve University, Cleveland, OH, 44106, USA; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, 44106, USA. Electronic address:

Serious infections caused by multidrug-resistant (MDR) organisms (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) present a critical need for innovative drug development. Herein, we describe the preclinical evaluation of YU253911, 2, a novel γ-lactam siderophore antibiotic with potent antimicrobial activity against MDR Gram-negative pathogens. Penicillin-binding protein (PBP) 3 was shown to be a target of 2 using a binding assay with purified P. aeruginosa PBP3. The specific binding interactions with P. aeruginosa were further characterized with a high-resolution (2.0 Å) X-ray structure of the compound's acylation product in P. aeruginosa PBP3. Compound 2 was shown to have a concentration >1 μg/ml at the 6 h time point when administered intravenously or subcutaneously in mice. Employing a meropenem resistant strain of P. aeruginosa, 2 was shown to have dose-dependent efficacy at 50 and 100 mg/kg q6h dosing in a mouse thigh infection model. Lastly, we showed that a novel γ-lactam and β-lactamase inhibitor (BLI) combination can effectively lower minimum inhibitory concentrations (MICs) against carbapenem resistant Acinetobacter spp. that demonstrated decreased susceptibility to 2 alone.
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http://dx.doi.org/10.1016/j.ejmech.2021.113436DOI Listing
August 2021

Can proteomics-based approaches further help COVID-19 prevention and therapy?

Authors:
Vijay Kumar

Expert Rev Proteomics 2021 04 16;18(4):241-245. Epub 2021 May 16.

Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center (UTHSC), Memphis, TN, USA.

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http://dx.doi.org/10.1080/14789450.2021.1924684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127169PMC
April 2021

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity.

Cells 2021 Apr 24;10(5). Epub 2021 Apr 24.

Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center (UTHSC), 881 Madison Avenue, Memphis, TN 38103, USA.

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.
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http://dx.doi.org/10.3390/cells10051004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147115PMC
April 2021

Comment on: "Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation".

Clin Pharmacokinet 2021 Apr 26. Epub 2021 Apr 26.

Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

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http://dx.doi.org/10.1007/s40262-021-01021-1DOI Listing
April 2021

Black pepper and piperine induce anticancer effects on leukemia cell line.

Toxicol Res (Camb) 2021 Mar 18;10(2):169-182. Epub 2021 Feb 18.

Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

The black pepper, most commonly used in Indian cuisines for ages, is considered as "king of spices." The present study evaluates the anticancer potential of black pepper and its main constituent, i.e. alkaloid piperine, against human leukemia cell line, K-562 cells. Gas chromatography-mass spectrometry (GC-MS) analysis confirmed the presence of piperine in black pepper extract. The methanolic extract of black pepper (BP-M) and pure piperine (PIP) showed a strong cytotoxic effect against this cell line. Both BP-M and PIP generated apoptotic bodies in K-562 cells and caused nuclear condensation as visualized by fluorescent microscopy, which was further confirmed by flow cytometry analysis. BP-M and PIP also generated reactive oxygen species in K-562 cells as established by flow cytometry. The translation of Bax, caspase-3 and caspase-9 genes was found to be upregulated with subsequent downregulation of Bcl-2 gene. The anti-proliferative effect of both BP-M and PIP was also observed by trypan blue staining and was further confirmed by the downregulated expression of proliferating cell nuclear antigen (PCNA). The molecular docking studies showed the binding of PIP with PCNA and Bcl-2 and supported the findings. The docking studies also proposed the binding of PIP to ADP binding pocket of Apaf-1 protein. Taken together, these findings signify the anticancer potential of both black pepper and PIP, thus proposing black pepper as a potent nutraceutical for preventing the progression of chronic myeloid leukemia.
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http://dx.doi.org/10.1093/toxres/tfab001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045589PMC
March 2021

Identification patterns of Trichoderma strains using morphological characteristics, phylogenetic analyses and lignocellulolytic activities.

Mol Biol Rep 2021 Apr 20;48(4):3285-3301. Epub 2021 Apr 20.

Biotechnology Research Institute, Universiti Malaysia Sabah, Jln UMS, 88400, Kota Kinabalu, Sabah, Malaysia.

Trichoderma is a genus of soil-borne fungus with an abundance of reports of its economic importance in the agriculture industry. Thus, the correct identification of Trichoderma species is necessary for its commercial purposes. Globally, Trichoderma species are routinely identified from micro-morphological descriptions which can be tedious and prone to errors. Thus, we emphasize that the accurate identification of Trichoderma strains requires a three-pronged approach i.e. based on its morphological characteristics, multilocus gene sequences of the rDNA [internal transcribed spacer (ITS) 1 and 2 regions], translation elongation factor 1-α (TEF-1α), Calmodulin (CAL) and its lignocellulolytic activities. We used this approach to identify a total of 53 Trichoderma strains which were isolated from a wet paddy field located at Tuaran, Sabah, Malaysia. The 53 strains were positively identified as belonging to three Trichoderma species, namely T. asperellum (43 strains), T. harzianum (9 strains), and T. reesei (one strain) on the basis of its morphological characteristics and multilocus gene sequences. Phylogenetic trees constructed based on the UPGMA method of the ITS 1 and 2 regions of the rDNA, TEF-1α and CAL revealed three distinct groups with the T. asperellum, T. harzianum and T. reesei strains placed under the section of Trichoderma, Pachybasium and Longibrachiatum, respectively. In addition, the lignocellulolytic activities of the isolates were measured based on the diameters of the halo zones produced when degrading cellulose, lignin, and starch, respectively. This diagnostic assay can be used to identify Trichoderma as it produces polyphenol oxidase when Tannic Acid Media is used for the lignin test, endoglucanases when Jensen media is used for cellulose, and it hydrolyzes starch to glucose when the modified Melin-Nokrans media is used for the starch test. Accurate identification of Trichoderma species is needed as these strains can potentially be used as a biocontrol agent to prevent diseases and to increase yield in agriculture crops.
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http://dx.doi.org/10.1007/s11033-021-06321-0DOI Listing
April 2021

Reply to letter to editor "Cancer patients should be considered as a high-risk priority target in the COVID-19 vaccination process".

J Surg Oncol 2021 Apr 20. Epub 2021 Apr 20.

Department of Gynecology and Obstetrics, King George's Medical University, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.1002/jso.26507DOI Listing
April 2021

Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042).

J Med Chem 2021 05 19;64(9):5323-5344. Epub 2021 Apr 19.

Research and Development, Bayer AG, Pharmaceuticals, Aprather Weg 18a, 42113 Wuppertal, Germany.

Herein we describe the discovery, mode of action, and preclinical characterization of the soluble guanylate cyclase (sGC) activator runcaciguat. The sGC enzyme, via the formation of cyclic guanosine monophoshphate, is a key regulator of body and tissue homeostasis. sGC activators with their unique mode of action are activating the oxidized and heme-free and therefore NO-unresponsive form of sGC, which is formed under oxidative stress. The first generation of sGC activators like cinaciguat or ataciguat exhibited limitations and were discontinued. We overcame limitations of first-generation sGC activators and identified a new chemical class via high-throughput screening. The investigation of the structure-activity relationship allowed to improve potency and multiple solubility, permeability, metabolism, and drug-drug interactions parameters. This program resulted in the discovery of the oral sGC activator runcaciguat (compound , BAY 1101042). Runcaciguat is currently investigated in clinical phase 2 studies for the treatment of patients with chronic kidney disease and nonproliferative diabetic retinopathy.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02154DOI Listing
May 2021

Cooling in mild encephalopathy: Costs and perils of therapeutic creep.

Semin Fetal Neonatal Med 2021 Jun 9;26(3):101244. Epub 2021 Apr 9.

Centre of Perinatal Neuroscience, Department of Brain Sciences, Imperial College, London, UK. Electronic address:

Increasing confidence in therapeutic hypothermia and ambiguity of cooling guidelines has led to many clinicians extending its use to untested populations like mild encephalopathy, or even no encephalopathy. Poor quality clinical neurological examination for encephalopathy staging coupled with a fear of litigation if a baby with mild encephalopathy progress to moderate or severe encephalopathy appears to be the primary driver for this therapeutic creep. Recent data suggesting increased apoptosis with cooling uninjured brains, and lack of hypothermic neuroprotection in partial prolonged hypoxia, implies that such therapeutic creeps may cause more harm than benefit. Currently available preclinical and clinical data do not support the clinical use of therapeutic hypothermia for mild encephalopathy, although phase II clinical trials are ongoing. We recommend that until further evidence from adequately powered randomised controlled trials are available, cooling in mild encephalopathy need to be considered experimental and parental consent should be obtained before providing this therapy.
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http://dx.doi.org/10.1016/j.siny.2021.101244DOI Listing
June 2021

Evaluation of Role of Arterialization of Venous Flaps in Abdomen in Rats.

Indian J Plast Surg 2021 Jan 10;54(1):69-74. Epub 2021 Mar 10.

Department of Plastic Surgery, King George Medical College, Lucknow, Uttar Pradesh, India.

 Reconstruction forms the primary tenet in plastic surgery. Venous flaps are a known option but the survival is limited. Arterialization of venous flap can enhance its survival. While various techniques of arterialization of venous flaps are described, there are very few studies comparing them.  The current study was conducted among 34 rats weighing 160 to 200 grams. The rats were divided into four groups. Group I-islanded epigastric flap was raised with superficial caudal epigastric vessels as pedicle. Group II-arterialized flow through venous flap was raised with superficial caudal epigastric vein (SCEV) as afferent and lateral thoracic vein as drainage vein. Side-to-side anastomosis was done between femoral artery and vein, lateral to the origin of superficial caudal epigastric artery. Group III-after raising the flap, as in group II, femoral vein was ligated proximal to superficial caudal epigastric vessels. Group IV-an arterialized flow through venous flap was raised with superficial caudal epigastric vein as afferent and lateral thoracic vein as drainage vein. End-to-side anastomosis was done between femoral artery and superficial caudal epigastric vein. Animals that died before completion of the study were excluded. The color changes of flaps were noted. Flap survival was expressed as a percentage of the total flap surface area. The patency of anastomosis was seen on postoperative day 5.  There was no total flap failure. On statical analysis, the flap survival area on day 5 between Group I and Group IV was not significant ( value 0.431). The survival area in Group I (78.85 ± 10.54%) was comparable to Group IV (65.71 ± 20.70%). Group II and III had poor results as compared with Group I. In four rats, thrombosis of arteriovenous anastomosis was noted with flap survival area of 30 to 33%.  It was noted that epigastric venous flaps with end-to-side anastomosis between femoral artery and superficial caudal epigastric vein (group IV) have survival area comparable to islanded flaps.
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http://dx.doi.org/10.1055/s-0041-1725227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012788PMC
January 2021

SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration.

Biochem Biophys Res Commun 2021 05 24;554:94-98. Epub 2021 Mar 24.

Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, UP, 201303, India. Electronic address:

The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Moreover, heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. In this paper, we have shown that the SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. These interactions suggests that the heparin-binding site on the S1 protein might assist the binding of amyloid proteins to the viral surface and thus could initiate aggregation of these proteins and finally leads to neurodegeneration in brain. The results will help us to prevent future outcomes of neurodegeneration by targeting this binding and aggregation process.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988450PMC
May 2021