Publications by authors named "Ashish Kumar"

755 Publications

Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure.

Hepatol Int 2021 Jul 18. Epub 2021 Jul 18.

Department of Medicine, Ankara University School of Medicine, Ankara, Turkey.

Background: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.

Methods: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.

Results: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients.

Conclusions: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.
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http://dx.doi.org/10.1007/s12072-021-10221-7DOI Listing
July 2021

Comparison of supervised exercise therapy with or without revascularization for the management of intermittent claudication: SET in PAD.

Eur J Intern Med 2021 Jul 9. Epub 2021 Jul 9.

Section of Interventional Cardiology, Division of Cardiovascular Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.1016/j.ejim.2021.06.029DOI Listing
July 2021

Author sStatementAshish Kumar, Arpita Konar, Sukant Garg: Writing - Original Draft and Review.Supervision: Renu Wadhwa: Review and Editing.Sunil C Kaul, Renu Wadhwa: Funding Acquisition.Ashish Kumar, Arpita Konar, Sukant Garg, Sunil C Kaul, Renu Wadhwa: Reviewed the final version before submitting.Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs.

Neurochem Int 2021 Jul 7:105124. Epub 2021 Jul 7.

AIST-INDIA DAILAB, DBT-AIST International Center for Translationa l & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, 305 8565, Japan. Electronic address:

Brain and neuronal circuits constitute the most complex organ networks in human body. They not only control and coordinate functions of all other organs, but also represent one of the most-affected systems with stress, lifestyle and age. With global increase in aging populations, these neuropathologies have emerged as major concern for maintaining quality of life. Recent era has witnessed a surge in nutritional remediation of brain dysfunctions primarily by "nutraceuticals" that refer to functional foods and supplements with pharmacological potential. Specific dietary patterns with a balanced intake of carbohydrates, fatty acids, vitamins and micronutrients have also been ascertained to promote brain health. Dietary herbs and their phytochemicals with wide range of biological and pharmacological activities and minimal adverse effects have gained remarkable attention as neuro-nutraceuticals. Neuro-nutraceutical potentials of herbs are often expressed as effects on cognitive response, circadian rhythm, neuromodulatory, antioxidant and anti-inflammatory activities that are mediated by effects on gene expression, epigenetics, protein synthesis along with their turnover and metabolic pathways. Epidemiological and experimental evidence have implicated enormous applications of herbal supplementation in neurodegenerative and psychiatric disorders. The present review highlights the identification, experimental evidence and applications of some herbs including Bacopa monniera, Withania somnifera, Curcuma longa, Helicteres angustifolia, Undaria pinnatifida, Haematococcus pluvialis, and Vitis vinifera, as neuro-nutraceuticals.
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http://dx.doi.org/10.1016/j.neuint.2021.105124DOI Listing
July 2021

Pulsed laser assisted high-throughput intracellular delivery in hanging drop based three dimensional cancer spheroids.

Analyst 2021 Aug 9;146(15):4756-4766. Epub 2021 Jul 9.

Department of Engineering Design, Indian Institute of Technology Madras, Chennai 600036, India.

Targeted intracellular delivery of biomolecules and therapeutic cargo enables the controlled manipulation of cellular processes. Laser-based optoporation has emerged as a versatile, non-invasive technique that employs light-based transient physical disruption of the cell membrane and achieves high transfection efficiency with low cell damage. Testing of the delivery efficiency of optoporation-based techniques has been conducted on single cells in monolayers, but its applicability in three-dimensional (3D) cell clusters/spheroids has not been explored. Cancer cells grown as 3D tumor spheroids are widely used in anti-cancer drug screening and can be potentially employed for testing delivery efficiency. Towards this goal, we demonstrated the optoporation-based high-throughput intracellular delivery of a model fluorescent cargo (propidium iodide, PI) within 3D SiHa human cervical cancer spheroids. To enable this technique, nano-spiked core-shell gold-coated polystyrene nanoparticles (ns-AuNPs) with a high surface-to-volume ratio were fabricated. ns-AuNPs exhibited high electric field enhancement and highly localized heating at an excitation wavelength of 680 nm. ns-AuNPs were co-incubated with cancer cells within hanging droplets to enable the rapid aggregation and assembly of spheroids. Nanosecond pulsed-laser excitation at the optimized values of laser fluence (45 mJ cm), pulse frequency (10 Hz), laser exposure time (30 s), and ns-AuNP concentration (5 × 10 particles per ml) resulted in the successful delivery of PI dye into cancer cells. This technique ensured high delivery efficiency (89.6 ± 2.8%) while maintaining high cellular viability (97.4 ± 0.4%), thereby validating the applicability of this technique for intracellular delivery. The optoporation-based strategy can enable high-throughput single cell manipulation, is scalable towards larger 3D tissue constructs, and may provide translational benefits for the delivery of anti-cancer therapeutics to tumors.
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http://dx.doi.org/10.1039/d0an02432eDOI Listing
August 2021

Echocardiography, lung ultrasound, and cardiac magnetic resonance findings in COVID-19: A systematic review.

Echocardiography 2021 Jul 8. Epub 2021 Jul 8.

Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: The manifestations of COVID-19 as outlined by imaging modalities such as echocardiography, lung ultrasound (LUS), and cardiac magnetic resonance (CMR) imaging are not fully described.

Methods: We conducted a systematic review of the current literature and included studies that described cardiovascular manifestations of COVID-19 using echocardiography, CMR, and pulmonary manifestations using LUS. We queried PubMed, EMBASE, and Web of Science for relevant articles. Original studies and case series were included.

Results: This review describes the most common abnormalities encountered on echocardiography, LUS, and CMR in patients infected with COVID-19.
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http://dx.doi.org/10.1111/echo.15152DOI Listing
July 2021

Outcomes of Cardiac Arrest and Cardiopulmonary Resuscitation in Patients With Left Ventricular Assist Device; an Insight From a National Inpatient Sample.

Heart Lung Circ 2021 Jul 2. Epub 2021 Jul 2.

Department of Advanced Heart Failure and Transplant, Sands-Constellation Heart Institute, Rochester Regional Health, Rochester, NY, USA.

Background: Outcomes of patients with implanted left ventricular assist device (LVAD) implantation experiencing a cardiac arrest (CA) are not well reported. We aimed at defining the in-hospital outcomes of patients with implanted LVAD experiencing a CA.

Methods: The national inpatient sample (NIS) was queried using ICD9/ICD10 codes for patients older than 18 years with implanted LVAD and CA between 2010-2018. We excluded patients with orthotropic heart transplantation, biventricular assist device (BiVAD) implantation and do not resuscitate (DNR) status.

Results: A total of 93,153 hospitalisations between 2010 and 2018 with implanted LVAD were identified. Only 578 of these hospitalisations had experienced CA and of those, 173 (33%) hospitalisations underwent cardiopulmonary resuscitation (CPR). The mean age of hospitalisations that experienced a CA was 60.61±14.85 for non-survivors and 56.23±17.33 for survivors (p=0.14). The in-hospital mortality was 60.8 % in hospitalisations with CA and 74.33% in hospitalisations in whom CPR was performed. In an analysis comparing survivors with non-survivors, non-survivors had more diabetes mellitus (DM) (p=0.01), and ischaemic heart disease (IHD) (p=0.04). Age, female sex, peripheral vascular disease and history of coronary artery bypass graft (CABG) were independently associated with increased mortality in our cohort. Also, ventricular tachycardia (VT) and CPR were independently associated with in-hospital mortality. During the study period, there was a significantly decreasing trend in performing CPR in LVAD hospitalisations with CA.

Conclusion: In conclusion, age, female sex, peripheral vascular disease, history of CABG, VT and CPR were independently associated with in-hospital mortality in LVAD hospitalisations who experienced CA.
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http://dx.doi.org/10.1016/j.hlc.2021.05.096DOI Listing
July 2021

Particle-Scale Modeling to Understand Liquid Distribution in Twin-Screw Wet Granulation.

Pharmaceutics 2021 Jun 22;13(7). Epub 2021 Jun 22.

BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.

Experimental characterization of solid-liquid mixing for a high shear wet granulation process in a twin-screw granulator (TSG) is very challenging. This is due to the opacity of the multiphase system and high-speed processing. In this study, discrete element method (DEM) based simulations are performed for a short quasi-two-dimensional simulation domain, incorporating models for liquid bridge formation, rupture, and the effect of the bridges on inter-particular forces. Based on the knowledge gained from these simulations, the kneading section of a twin-screw wet granulation process was simulated. The time evolution of particle flow and liquid distribution between particles, leading to the formation of agglomerates, was analyzed. The study showed that agglomeration is a rather delayed process that takes place once the free liquid on the particle surface is well distributed.
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http://dx.doi.org/10.3390/pharmaceutics13070928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308998PMC
June 2021

Access-site complications in ultrasound-guided endovascular thrombectomy: a single-institution retrospective cohort study.

Neurosurg Focus 2021 Jul;51(1):E3

2Division of Neurosurgery, Department of Surgery, University of Toronto.

Objective: Mechanical endovascular thrombectomy (EVT) is an increasingly relied-on treatment for clot retrieval in the context of ischemic strokes, which otherwise are associated with significant morbidity and mortality. Despite several known risks associated with this procedure, there is a high degree of technical heterogeneity across both centers and operators. The most common procedural complications occur at the point of transfemoral access (the common femoral artery), and include access-site hematomas, dissections, and pseudoaneurysms. Other interventional fields have previously popularized the use of ultrasound to enhance the anatomical localization of structures relevant to vascular access and thereby reducing access-site complications. In this study, the authors aimed to describe the ultrasound-guided EVT technique performed at a large, quaternary neurovascular referral center, and to characterize the effects of ultrasound guidance on access-site complications.

Methods: A retrospective chart review of all patients treated with EVT at a single center between January 2013 and August 2020 was performed. Patients in this cohort were treated using a universal, unique, ultrasound-guided, single-wall puncture technique, which bears several theoretical advantages over the standard technique of arterial puncture via palpation.

Results: There were 479 patients treated with EVT within the study period. Twenty patients in the cohort were identified as having experienced some form of access-site complication. Eight (1.67%) of these patients experienced minor access-site complications, all of which were groin hematomas and none of which were clinically significant, as defined by requiring surgical or interventional management or transfusion. The remaining 12 patients experienced arterial dissection (n = 5), arterial pseudoaneurysm (n = 4), retroperitoneal hematoma (n = 2), or arterial occlusion (n = 1), with only 1.04% (5/479) requiring surgical or interventional management or transfusion.

Conclusions: The authors found an overall reduction in total access-site complications as well as minor access-site complications in the study cohort compared with previously published randomized controlled trials and observational studies in the recent literature. The findings suggested that there may be a role for routine use of ultrasound-guided puncture techniques in EVT to decrease rates of complications.
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http://dx.doi.org/10.3171/2021.4.FOCUS2198DOI Listing
July 2021

Trigeminal Neuralgia from an Arteriovenous Malformation of the Trigeminal Root Entry Zone with a Flow-Related Feeding Artery Aneurysm: The Role of a Combined Endovascular and "Tailored" Surgical Treatment.

Neurol India 2021 May-Jun;69(3):744-747

Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, Uttar Pradesh, India.

Idiopathic trigeminal neuralgia (TN) due to an embedded arteriovenous malformation (AVM) on the trigeminal root entry zone (REZ) is rare but a potentially challenging condition to manage. Herein, we report such a case with an additional unruptured aneurysm on the feeding artery and highlight the role of a multimodality approach to their management. A 50-year-old female presented with drug-resistant right-sided trigeminal neuralgia for one year. The magnetic resonance imaging (MRI) suggested a possibility of AVM, the angiographic study showed an AVM nidus with feeders from the right anterior inferior cerebellar artery (AICA) and a dilated right intrinsic pontine artery, the latter showing a flow-related aneurysm towards its brainstem end. The flow-related aneurysm, as well as the dilated intrinsic pontine artery feeder, was embolized at first. During surgery, the AVM was found embedded inside the root entry zone. Parts of the AVM and its draining vein were partially coagulated followed by microvascular decompression of the AICA loop as well as a feeder emanating from it following which the patient recovered completely. She subsequently received gamma knife surgery (GKS) for the residual AVM and remained asymptomatic after 3.5 years of GKS. AVM-related TN are rare, and the additional presence of a feeding artery aneurysm increases the management complexity. Endovascular management of the aneurysm followed by microvascular decompression (MVD) and tailored AVM coagulation represent a prompt and effective means of pain control. Subsequent GKS is necessary to obliterate the AVM nidus.
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http://dx.doi.org/10.4103/0028-3886.319235DOI Listing
June 2021

Plagiarism: Injurious to the academic health of the researcher and research! (Part-II).

Authors:
Ashish Kumar

J Indian Soc Periodontol 2021 May-Jun;25(3):183

Editor, Journal of Indian Society of Periodontology, Professor and Head, Department of Periodontics, Dental College, Regional Institute of Medical Sciences, Lamphelpat, Imphal - 795 004, Manipur, India. E-mail:

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http://dx.doi.org/10.4103/jisp.jisp_183_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177175PMC
June 2021

Biogenesis, characterization, and functions of mirtrons.

Wiley Interdiscip Rev RNA 2021 Jun 21:e1680. Epub 2021 Jun 21.

Kusuma School of Biological Sciences, Indian Institute of Technology, Delhi, India.

MicroRNAs (miRNAs) are major post-transcriptional regulators of gene expression. They base pair with the complementary target mRNA at the 3'UTR and modulate cellular processes by repressing the mRNA translation or degrading the mRNA. There are well-documented mechanisms of biogenesis of miRNA; however, a sizeable number of miRNAs are also produced by non-canonical pathways. Mirtrons represent a predominant class of non-canonical miRNAs. Mirtrons originate from intronic regions and are produced in a splicing-dependent and Drosha-independent manner. Mirtrons constitute about 15% of all miRNAs produced in a human body and have caught attention of researchers worldwide due to their unconventional origin, sequence characteristics, evolutionary dynamics, ability to regulate variety of cellular processes and their immense potential in disease therapeutics. In this comprehensive review we collate the research done in the past decade including biogenesis, sequence characteristics, regulation, and emerging therapeutic roles of mirtrons. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.
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http://dx.doi.org/10.1002/wrna.1680DOI Listing
June 2021

Multifocal colorectal non-Hodgkin's lymphoma in a patient with ulcerative colitis: A case report.

Indian J Pathol Microbiol 2021 Jun;64(Supplement):S92-S94

Institute of Liver, Gastroenterology, and Panceatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India.

A case of multifocal non-Hodgkin's (Diffuse large B cell type) lymphoma of colon in a patient with ulcerative colitis is described. The patient was a 69-year old male treated with azathioprine and methotrexate for ulcerative colitis for 2 years. He was admitted with loose stools and hematochezia. Colonoscopy revealed two deep ulcers in ascending colon and a large ulcer in rectum. Biopsy from both the sites revealed atypical large lymphoid cells, which were CD20 positive. A whole body PET-CT scan showed disease localized to colon with bone marrow examination showing no evidence of lymphoma. The patient was given chemotherapy cycles and recovered well.
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http://dx.doi.org/10.4103/IJPM.IJPM_654_19DOI Listing
June 2021

Oxidant activated soluble adenylate cyclase of Leishmania donovani regulates the cAMP-PKA signaling axis for its intra-macrophage survival during infection.

J Cell Biochem 2021 Jun 8. Epub 2021 Jun 8.

Department of Molecular Biology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India.

Adenosine 3',5'-cyclic monophosphate (cAMP) is a stress sensor molecule that transduces the cellular signal when Leishmania donovani moves from insect vector to mammalian host. At this stage, the parasite membrane-bound receptor adenylate cyclase predominantly produces cAMP to cope with the oxidative assault imposed by host macrophages. However, the role of soluble adenylate cyclase of L. donovani (LdHemAC) has not been investigated fully. In the present investigation, we monitored an alternative pool of cAMP, maintained by LdHemAC. The elevated cAMP effectively transmits signals by binding to Protein Kinase A (PKA) present in the cytosol and regulates antioxidant gene expression and phosphorylates several unknown PKA substrate proteins. Menadione-catalyzed production of reactive oxygen species (ROS) mimics host oxidative condition in vitro in parasites where cAMP production and PKA activity were found increased by ~1.54 ± 0.35, and ~1.78 ± 0.47-fold, respectively while expression of LdHemAC gene elevated by ~2.18 ± 0.17-fold. The LdHemAC sense these oxidants and became activated to cyclize ATP to enhance the cAMP basal level that regulates antioxidant gene expression to rescue parasites from oxidative stress. In knockdown parasites (LdHemAC-KD), the downregulated antioxidant genes expression, namely, Sod (2.30 ± 0.46), Pxn (2.73 ± 0.15), Tdr (2.7 ± 0.12), and Gss (1.57 ± 0.15) results in decreased parasite viability while in overexpressed parasites (LdHemAC-OE), the expression was upregulated by ~5.7 ± 0.35, ~2.57 ± 0.56, ~4.7 ± 0.36, and ~2.4 ± 0.83, respectively, which possibly overcomes ROS accumulation and enhances viability. Furthermore, LdHemAC-OE higher PKA activity regulates phosphorylation of substrate proteins (~56 kDs in membrane fraction and ~25 kDs in the soluble fraction). It reduced significantly when treated with inhibitors like DDA, Rp-cAMP, and H-89 and increased by ~2.1 ± 0.28-fold, respectively under oxidative conditions. The LdHemAC-KD was found less infective to RAW 264.7 macrophages and more prone to oxidative damage as compared to LdHemAC-OE and control parasites. Together, this study demonstrates mechanistic links among LdHemAC, cAMP, and PKA in parasite survival and invasion under host oxidative condition.
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http://dx.doi.org/10.1002/jcb.30018DOI Listing
June 2021

P2X7 receptor in multifaceted cellular signalling and its relevance as a potential therapeutic target in different diseases.

Eur J Pharmacol 2021 Sep 11;906:174235. Epub 2021 Jun 11.

Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela-769008, Odisha, India. Electronic address:

P2X7 receptor, a purinergic receptor family member, is abundantly expressed on many cells, including immune, muscle, bone, neuron, and glia. It acts as an ATP-activated cation channel that permits the influx of Ca, Na and efflux of K ions. The P2X7 receptor plays crucial roles in many physiological processes including cytokine and chemokine secretion, NLRP3 inflammasome activation, cellular growth and differentiation, locomotion, wound healing, transcription factors activation, cell death and T-lymphocyte survival. Past studies have demonstrated the up-regulation and direct association of this receptor in many pathophysiological conditions such as cancer, diabetics, arthritis, tuberculosis (TB) and inflammatory diseases. Hence, targeting this receptor is considered a worthwhile approach to lessen the afflictions associated with the disorders mentioned above by understanding the receptor architecture and downstream signalling processes. Here, in the present review, we have dissected the structural and functional aspects of the P2X7 receptor, emphasizing its role in various diseased conditions. This information will provide in-depth knowledge about the receptor and help to develop apt curative methodologies for the betterment of humanity in the coming years.
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http://dx.doi.org/10.1016/j.ejphar.2021.174235DOI Listing
September 2021

Microfluidic Based Physical Approaches towards Single-Cell Intracellular Delivery and Analysis.

Micromachines (Basel) 2021 May 28;12(6). Epub 2021 May 28.

Department of Engineering and System Science, National Tsing Hua University, Hsinchu 300044, Taiwan.

The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great interest. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. This review article aims to cover various microfluidic-based physical methods for single-cell intracellular delivery such as electroporation, mechanoporation, microinjection, sonoporation, optoporation, magnetoporation, and thermoporation and their analysis. The mechanisms of various physical methods, their applications, limitations, and prospects are also elaborated.
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http://dx.doi.org/10.3390/mi12060631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228766PMC
May 2021

Daratumumab for the management of autoimmune cytopenias in children and young adults: a case series.

Br J Haematol 2021 May 27. Epub 2021 May 27.

Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

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http://dx.doi.org/10.1111/bjh.17565DOI Listing
May 2021

Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents.

Curr Top Med Chem 2021 May 26. Epub 2021 May 26.

Department of Chemistry, University of Delhi, North Campus, Delhi-110007, India.

Tetrahydroquinoline and isoquinoline scaffolds are important class heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinolines based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wide-ranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.
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http://dx.doi.org/10.2174/1568026621666210526164208DOI Listing
May 2021

Midodrine and albumin versus albumin alone for the secondary prophylaxis of acute kidney injury in a patient with cirrhosis and ascites.

Eur J Gastroenterol Hepatol 2021 May 21. Epub 2021 May 21.

Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India.

Background: Acute kidney injury (AKI) in a patient with cirrhosis has high short-term mortality. Midodrine has shown promising results in the treatment of AKI-hepatorenal syndrome (HRS-AKI).

Aims: To compare midodrine and albumin versus albumin alone for the secondary prophylaxis of HRS-AKI.

Patients And Method: Open labeled, nonrandomized, pilot study. Patients with a diagnosis of HRS-AKI were recruited after complete recovery. Patients were given midodrine daily (15 mg) and injection albumin infusion 20 g weekly in group-A (Gp-A) and injection albumin 20 g weekly with no midodrine in group-B (Gp-B). The primary endpoint was the recurrence of AKI-HRS, and the secondary endpoint was ascites tap in 2-month period.

Results: A total of 42 patients were enrolled in Gp-A, n = 22, and Gp-B, n = 20. There was no significant difference between the groups (Gp-A vs. Gp-B) in terms of age, model stage liver disease, Child-Turcotte-Pugh score and serum creatinine at inclusion (1.27 ± 0.1 vs. 1.22 ± 0.2 mg/dL). During follow up ten patients (50%) in Gp-B and four patients (18%) in Gp-A develop HRS-AKI (P = 0.04). The mean number of ascites tap was significantly higher in Gp-B compared to Gp-A (2.6 ± 0.5 vs. 1.9 ± 0.5) in 2 months. There was a significant increase in mean arterial pressure in Gp-A compared to Gp-B on days 7, 15, 30, 45 and 60. There was a significant difference in mean arterial pressure at day 7 in patients who developed HRS-AKI versus those who did not develop HRS-AKI [(n = 14, 65.5 ± 5.5) vs. (n = 28,74.6 ± 9.2 mm Hg), P = 0.02].

Conclusions: Midodrine along with albumin infusion, is helpful in the secondary prophylaxis of HRS-AKI and reduces the number of ascites tap. However, a large randomized study is required for further validation.
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http://dx.doi.org/10.1097/MEG.0000000000002154DOI Listing
May 2021

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

J Clin Exp Hepatol 2021 May-Jun;11(3):354-386. Epub 2020 Oct 9.

Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, 110060, Delhi, India.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.
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http://dx.doi.org/10.1016/j.jceh.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103529PMC
October 2020

Gram-scale synthesis of ZnS/NiO core-shell hierarchical nanostructures and their enhanced H production in crude glycerol and sulphide wastewater.

Environ Res 2021 08 12;199:111323. Epub 2021 May 12.

Nanocatalysis and Solar Fuels Research Laboratory, Department of Materials Science & Nanotechnology, Yogi Vemana University, Kadapa, 516005, Andhra Pradesh, India. Electronic address:

Design and development of the efficient and durable photocatalyst that generates H fuel utilizing industrial wastewater under solar light irradiation is a sustainable process. Innumerable photocatalysts have been reported for efficient H production, but their large-scale production with the same efficiency of H production is a challenging task. In this study, a few gram-scale syntheses of ZnS wrapped with NiO hierarchical core-shell nanostructure via the surfactant-mediated process has been reported. Morphology and crystal structure analysis of ZnS/NiO showed spherical shaped hierarchical core-shell with cubic and face-centered cubic crystal structures. The surface examination confirmed the presence of Zn, S, Ni and O ions in the nanocomposite. The photocurrent and photoluminescence studies of pristine and nanocomposites revealed that core-shell material is non-corrosive with a prolonged life-time of photo-excitons. Parametric studies on photocatalytic H generation in lab-scale photoreactor using crude glycerol in water recorded a high rate of H generation of 9.3 mmol h.g of catalyst under the simulated solar light irradiation. Optimized reaction parameters are extended to a demonstrative photoreactor containing aqueous crude glycerol produced 18.5 mmol h of H generation under the natural solar light irradiation. The same nanostructures were further tested with the simulated sulfide wastewater and the optimized catalyst showed H production of 350 mL h. The experimental results of time-on stream and catalytic stability demonstrated that ZnS/NiO hierarchical core-shell nanostructures can be recyclable and reusable for the continuous photocatalytic H generation.
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http://dx.doi.org/10.1016/j.envres.2021.111323DOI Listing
August 2021

Minimally invasive intrathecal spinal cord imaging with optical coherence tomography.

J Biomed Opt 2021 May;26(5)

University of Toronto, Sunnybrook Hospital, Division of Neurosurgery, Toronto, Ontario, Canada.

Significance: Imaging of the spinal cord is challenging due to the surrounding bony anatomy, physiologic motion, and the small diameter of the spinal cord. This precludes the use of non-invasive imaging techniques in assessing structural changes related to trauma and evaluating residual function.

Aim: The purpose of our research was to apply endovascular technology and techniques and construct a preclinical animal model of intrathecal spinal cord imaging using optical coherence tomography (OCT).

Approach: Five animals (2 Yorkshire Swine and 3 New Zealand Rabbits) were utilized. Intrathecal access was gained using a 16-guage Tuohy, and an OCT catheter was advanced under roadmap technique into the cervical canal. The OCT catheter has a motorized pullback, and a total length of 54 mm of the spinal canal is imaged.

Results: Image acquisition was successful for all animals. There were no instances of difficult catheter navigation, enabling OCT imaging rostrally to C2. The thecal sac provided excellent thoroughfare for the OCT catheter. The clear cerebrospinal fluid also provided an excellent medium for image acquisition, with no detectable artifact from the contents of the cerebrospinal fluid. The anatomical space of the spinal canal could be readily appreciated including: dural lining of the thecal sac, epidural veins, pial lining of the spinal cord, arachnoid bands, dentate ligaments, and nerve rootlets/roots.

Conclusion: Minimally invasive intrathecal imaging using endovascular OCT was feasible in this preclinical animal study. The repurposing of an endovascular device for spinal imaging comes with limitations, and a spine-specific device is necessary.
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http://dx.doi.org/10.1117/1.JBO.26.5.056002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118064PMC
May 2021

Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis.

Front Cell Infect Microbiol 2021 26;11:641985. Epub 2021 Apr 26.

Department of Molecular Biology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, India.

secretes over 151 proteins during cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in infection. Visceral Leishmaniasis is a persistent infection, caused by in Indian subcontinent. This persistence is partly due to phagocytosis and evasion of host immune response. The underlying mechanism involves secretory proteins of parasite; however, related studies are meagre. We have identified a novel secretory glycoprotein, Mevalonate kinase (MVK), and shown its importance in parasite internalization and immuno-modulation. In our studies, MVK was found to be secreted maximum after 1 h temperature stress at 37°C. Its secretion was increased by 6.5-fold in phagolysosome-like condition (pH ~5.5, 37°C) than at pH ~7.4 and 25°C. Treatment with MVK modulated host immune system by inducing interleukin-10 and interleukin-4 secretion, suppressing host's ability to kill the parasite. Peripheral blood mononuclear cell (PBMC)-derived macrophages infected with mevalonate kinase-overexpressing parasites showed an increase in intracellular parasite burden in comparison to infection with vector control parasites. Mechanism behind the increase in phagocytosis and immunosuppression was found to be phosphorylation of mitogen-activated protein (MAP) kinase pathway protein, Extracellular signal-regulated kinases-1/2, and actin scaffold protein, cortactin. Thus, we conclude that Mevalonate kinase aids in parasite engulfment and subvert the immune system by interfering with signal transduction pathways in host cells, which causes suppression of the protective response and facilitates their persistence in the host. Our work elucidates the involvement of in the process of phagocytosis which is thought to be dependent largely on macrophages and contributes towards better understanding of host pathogen interactions.
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http://dx.doi.org/10.3389/fcimb.2021.641985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110032PMC
July 2021

Validating and implementing cardiac telemetry for continuous QTc monitoring: A novel approach to increase healthcare personnel safety during the COVID-19 pandemic.

J Electrocardiol 2021 Apr 27;67:1-6. Epub 2021 Apr 27.

Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Electronic address:

Background: Minimizing direct patient contact among healthcare personnel is crucial for mitigating infectious risk during the coronavirus disease 2019 (COVID-19) pandemic. The use of remote cardiac telemetry as an alternative to 12‑lead electrocardiography (ECG) for continuous QTc monitoring may facilitate this strategy, but its application has not yet been validated or implemented.

Methods: In the validation component of this two-part prospective cohort study, a total of 65 hospitalized patients with simultaneous ECG and telemetry were identified. QTc obtained via remote telemetry as measured by 3 independent, blinded operators were compared with ECG as assessed by 2 board-certified electrophysiologists as the gold-standard. Pearson correlation coefficients were calculated to measure the strength of linear correlation between the two methods. In a separate cohort comprised of 68 COVID-19 patients treated with combined hydroxychloroquine and azithromycin, telemetry-based QTc values were compared at serial time points after medication administration using Friedman rank-sum test of repeated measures.

Results: Telemetry-based QTc measurements highly correlated with QTc values derived from ECG, with correlation coefficients of 0.74, 0.79, 0.85 (individual operators), and 0.84 (mean of all operators). Among the COVID-19 cohort, treatment led to a median QTc increase of 15 milliseconds between baseline and following the 9th dose (p = 0.002), with 8 (12%) patients exhibiting an increase in QTc ≥ 60 milliseconds and 4 (6%) developing QTc ≥ 500 milliseconds.

Conclusions: Cardiac telemetry is a validated clinical tool for QTc monitoring that may serve an expanding role during the COVID-19 pandemic strengthened by its remote and continuous monitoring capability and ubiquitous presence throughout hospitals.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076730PMC
April 2021

Impact of nanochitosan and spp. on health, productivity and defence response in under field condition.

3 Biotech 2021 May 25;11(5):237. Epub 2021 Apr 25.

Department of Microbiology, College of Basic Sciences and Humanities, G.B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand India.

The role of plant growth-promoting rhizobacteria along with nanochitosan on maize productivity remains unexplored. In the present study we report the effect of nanochitosan and PGPR on growth, productivity and mechanism(s) involved in defence response in under field conditions. Application of nanochitosan (50 mg L) along with plant growth-promoting rhizobacteria enhanced seed germination, plant height, root length, leaf area, fresh and dry weight of shoot and root, chlorophyll, carotenoids, total sugar and protein content upto 1.5-2 fold over control in maize after 60 days of the field experiment. Treated maize plants also showed enhanced level of defence-related biomolecules like phenolic compounds (103%), catalase (60.09%), peroxidase (81.57%) and superoxide dismutase (76.50%) over control. Level of phenols and sugar content in maize plants enhanced which was analysed by GC-MS (Gas chromatography-mass spectrometry). Significant increase in cob length, cob weight/plot, grain yield/plot and 100 grain weight was observed in treated maize plants over control. As per the results, the combination of nanochitosan and plant growth-promoting rhizobacteria was reported to improve the health and yield of maize. The interaction can be further studied in field trials for improvement in agriculture production.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02790-z.
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http://dx.doi.org/10.1007/s13205-021-02790-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071787PMC
May 2021

Intracoronary brachytherapy for the treatment of recurrent drug-eluting stent in-stent restenosis: A systematic review and meta-analysis.

World J Cardiol 2021 Apr;13(4):95-102

Department ofInternal Medicine, University of Nevada Reno School of Medicine, Reno, NV 89509, United States.

Background: We performed a meta-analysis on observational studies since randomized control trials are not available. We studied intracoronary brachytherapy (ICBT) and recurrent drug eluting stent in-stent restenosis (DES-ISR) to evaluate the procedural success, target lesion revascularization (TLR), incidence of myocardial infarction (MI) and all-cause mortality at 2 years follow-up.

Aim: To perform meta-analysis for patients undergoing ICBT for recurrent DES-ISR.

Methods: We performed a systematic search of the PubMed/MEDLINE, Cochrane and DARE databases to identify relevant articles. Studies were excluded if intra-coronary brachytherapy was used as a treatment modality for initial ISR and studies with bare metal stents. We used a random-effect model with DerSimonian & Laird method to calculate summary estimates. Heterogeneity was assessed using statistics.

Results: A total of 6 observational studies were included in the final analysis. Procedural angiographic success following intra-coronary brachytherapy was 99.8%. Incidence of MI at 1-year was 2% and 4.1% at 2-years, respectively. The incidence of TLR 14.1% at 1-year and 22.7% at 2-years, respectively. All-cause mortality at 1- and 2-year follow-up was 3% and 7.5%, respectively.

Conclusion: Given the observational nature of the studies included in the analysis, heterogeneity was significantly higher for outcomes. While there are no randomized controlled trials or definitive guidelines available for recurrent ISR associated with DES, this analysis suggests that brachytherapy might be the alternative approach for recurrent DES-ISR. Randomized controlled trials are required to confirm results from this study.
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http://dx.doi.org/10.4330/wjc.v13.i4.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069516PMC
April 2021

Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19.

Cells 2021 04 6;10(4). Epub 2021 Apr 6.

Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249203, India.

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10-20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5' end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/cells10040821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067447PMC
April 2021

Electrochemical sensing of pioglitazone hydrochloride on N-doped r-GO modified commercial electrodes.

Analyst 2021 Jun 29;146(11):3578-3588. Epub 2021 Apr 29.

School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, UP, India.

In this paper, we explain the electrochemical sensing of commercially available pioglitazone hydrochloride (PIOZ) tablets on a nitrogen (N) doped r-GO (Nr-GO) modified commercial glassy carbon electrode (GCE) and a commercial screen printed graphite electrode (SPGE). Nr-GO is synthesized by the chemical reduction of graphene oxide (GO) and simultaneous insertion of an N-dopant by hydrazine monohydrate. Pristine GO itself is prepared by chemical exfoliation of bulk graphite. Upon chemical reduction, the exfoliated GO sheets restack together leaving behind the doped N-atom as evidenced by XRD and Raman spectroscopy. The N-atom exists in the pyrrolinic and pyridinic form at the edge of graphitic domains which is confirmed by XPS. The as-synthesized Nr-GO is used for the preparation of electro-active electrodes with the help of the GCE and SPGE. These electrodes have the capability to oxidize PIOZ by a diffusion dominated process as evidenced by the impedance spectroscopic technique. The differential pulse voltammetric responses of different concentrations of PIOZ are assessed over the Nr-GO modified GCE and SPGE, which exhibit better limits of detection (LODs) of 67 nM and 29 nM, respectively, compared to those from earlier reports. These assays exhibit non-interfering capability in the presence of various body interferents at pH = 7.0.
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http://dx.doi.org/10.1039/d1an00224dDOI Listing
June 2021

TLR4 and TLR9 polymorphism: Probable role in susceptibility among the population of Bihar for Indian visceral leishmaniasis.

Innate Immun 2021 Apr 28:1753425920965658. Epub 2021 Apr 28.

Department of Microbiology, All India Institute of Medical Sciences, Patna, India.

Genetic variations in the host TLRs genes play an important role in susceptibility and/or resistance to visceral leishmaniasis by altering the host-pathogen interaction. In this study, we investigated the association between polymorphisms of TLR4 (Asp299Gly, Thr399Ile) and TLR-9 (T-1237C), with susceptibility to visceral leishmaniasis. A bi-directional PCR amplification of specific alleles technique was used to characterize the distribution of TLR4 (Asp299Gly and Thr399Ile) and TLR9 (T-1237C) polymorphisms. A total of 60 samples were randomly selected from confirmed visceral leishmaniasis patients and 24 endemic healthy volunteers. The samples were genotyped and allele frequencies were determined. We observed that TLR4 Asp299Gly and Thr399Ile genotypes were more frequent in visceral leishmaniasis patients (10% and 15% respectively) compared to controls (4.2% and 8.3% respectively). However, the differences were not significant in TLR4 Asp299Gly and Thr399Ile alleles and genotypes. In the case of TLR9, we observed the frequency of T1237C genotype was higher in visceral leishmaniasis patients (43.3%) than in healthy controls (33.3%). Statistically significant differences were observed in TLR9 T1237C alleles and genotypes. We concluded that TLR9 T1237C, but not TLR4, gene polymorphisms can be regarded as contributors to visceral leishmaniasis susceptibility among the Indian population of Bihar state.
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http://dx.doi.org/10.1177/1753425920965658DOI Listing
April 2021

LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for Mixed Lineage Leukemia-Rearranged acute leukemia.

Haematologica 2021 Apr 29. Epub 2021 Apr 29.

Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA; Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, 45229.

Although great advances have been made in understanding the pathobiology of MLL-rearranged (MLL-r) leukemias, therapies for this leukemia have remained limited, and clinical outcomes remain bleak. To identify novel targets for immunotherapy treatments, we compiled a lineage-independent MLL-r leukemia gene signature using publicly available data sets. Data from large leukemia repositories were filtered through the In-silico Human Surfaceome, providing a list of highly predicted cell surface proteins overexpressed in MLL-r leukemias. LAMP5, a lysosomal associated membrane protein, is expressed highly and specifically in MLL-r leukemia. We found that LAMP5 is a direct target of the oncogenic MLL-fusion protein. LAMP5 depletion significantly inhibited leukemia cell growth in vitro and in vivo. Functional studies showed that LAMP-5 is a novel modulator of innateimmune pathways in MLL-r leukemias. Downregulation of LAMP5 led to inhibition of NF-κB signaling and increased activation of type-1 interferon signaling downstream of Toll-like Receptor/Interleukin 1 Receptor activation. These effects were attributable to the critical role of LAMP-5 in transferring the signal flux from Interferon Signaling Endosomes to Pro-Inflammatory Signaling Endosome. Depletion of IRF7 was able to partially rescue the cell growth inhibition upon LAMP5 downregulation. Lastly, LAMP-5 was readily detected on the surface of MLL-r leukemia cells. Targeting surface LAMP-5 using an antibody-drug conjugate leads to significant cell viability decrease specifically on MLL-r leukemias. Overall, based on the limited expression throughout human tissues, we postulate that LAMP-5 could potentially serve as an immunotherapeutic target with a wide therapeutic window to treat MLL-r leukemias.
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http://dx.doi.org/10.3324/haematol.2020.257451DOI Listing
April 2021

Efficacy of modified coronally advanced flap in the treatment of multiple adjacent gingival recessions: a systematic review and meta-analysis.

Acta Odontol Scand 2021 Apr 26:1-11. Epub 2021 Apr 26.

Department of Periodontics and Implantology, Post Graduate Institute of Dental Sciences, Rohtak, India.

Objective: This systematic review (SR) aims to evaluate the efficacy of modified coronally advanced flap (mCAF) on clinical and patient-reported outcomes in the treatment of multiple adjacent gingival recessions (MAGRs).

Materials And Methods: Randomized controlled trials (RCTs), case-series and prospective clinical studies on treatment of Miller class I/II or RT1 MAGRs with ≥ 6 months follow-up were identified from the electronic databases and hand-searched journals. Complete root coverage (CRC) was the primary outcome variable. To evaluate treatment effects, meta-analysis was conducted, wherever appropriate.

Results: A total of 1395 recessions in 408 patients were evaluated in SR and meta-analysis was performed for four RCTs. Overall CRC achieved with mCAF was 70% and mean root coverage (MRC) ranged from 51.58 to 97.27%. Meta-analysis showed that combination of mCAF with connective tissue graft (CTG) or collagen matrix (CM) demonstrated significantly higher CRC% and recession reduction than mCAF alone. Limited evidence is available to support the use of platelet rich fibrin or enamel matrix derivative or acellular dermal matrix graft along with mCAF to further enhance its efficacy.

Conclusions: mCAF is an effective procedure for treating MAGRs and in terms of achieving CRC and MRC. Additional use of CTG or CM further enhances treatment outcomes.
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http://dx.doi.org/10.1080/00016357.2021.1908594DOI Listing
April 2021