Sunny Kumar - Academia.edu (original) (raw)

Papers by Sunny Kumar

Cureus

Introduction: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have... more Introduction: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome. Methods: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States). Results: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%). Conclusion: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals' attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Goat is the most important source of income for the rural populace. Goat health and production&lt... more Goat is the most important source of income for the rural populace. Goat health and production depends upon environmental factors. The present study aims to understand the influence of different altitudes on the morphology, biochemical, and antioxidant parameters changes in goats. The rectal temperature (RT), body length (BL), body height (BH), tail length (TL), horn length (HL), ear length (EL), and head width (HW) were measured as the morpho-physiological parameters. Glucose, total protein, albumin, triglyceride, creatinine, urea, uric acid, alanine aminotransferase, and aspartate aminotransferase were analyzed for biochemical parameters. Whereas, FRAP, DPPH, and ABTS were measured as the antioxidant parameters. Results showed that significantly (p<0.05) higher BL, BH, and significantly lower HL. All the biochemical parameters were within the range of normal levels, as suggested by a diffe...

Additional file 1: Figure S1. IMS-088 reduced levels of phospho-TDP43 in the brain of hTDP-43A315... more Additional file 1: Figure S1. IMS-088 reduced levels of phospho-TDP43 in the brain of hTDP-43A315T mice. The anti-phospho-TDP-43 antibody (pSer410, Sigma-Aldrich, USA) was used for immunodetection (n = 3 independent experiments).

Objective: The study aims to assess the effect of extended thromboprophylaxis with non-vitamin K ... more Objective: The study aims to assess the effect of extended thromboprophylaxis with non-vitamin K antagonist oral anticoagulant (NOAC) on the risk of stroke and major bleeding among patients hospitalized with an acute medical illness based on data from randomized controlled trials. Background: Among acutely ill hospitalized medical patients, treatment with NOAC for 30–42 days is effective in preventing symptomatic deep vein thrombosis or pulmonary embolism compared with standard-of-care enoxaparin for 6–14 days. The risk-benefit profile of NOAC on stroke prophylaxis has not been studied in this setting. Design/Methods: We performed a systematic literature search in MEDLINE, Embase, and ClinicalTrials.gov for randomized controlled trials comparing the effect of extended-duration NOAC with standard-duration enoxaparin on the stroke and bleeding endpoint. Three Phase III studies were identified: ADOPT (NCT00457002), MAGELLAN (NCT00571649), and APEX (NCT01583218). The relative risk of st...

International Journal of Recycling of Organic Waste in Agriculture, 2020

Purpose In the current scenario, food wastage is a significant concern throughout the world. This... more Purpose In the current scenario, food wastage is a significant concern throughout the world. This food wastage may convert to compost, and that compost may apply in the agriculture field for the better yield of crops. In this context, a field study conducted on the effects of compost prepared from food wastage on the yield of cabbage, cauliflower, and radish. Methods The experiment consisted of twelve treatments and twelve control plants of all the plants. Field soil of both control and treatment plots were analyzed by standard methods. Standard methods took different morphological and chemical parameters of all the plants. Results Results indicated that compost from food waste increased soil fertility. The application of manure was significantly (p < 0.01) superior over the morphological and biochemical properties of the control group plants. The application of compost increased leaf relative water content and decreased the electrolyte leakage in all the plants. The yield of cab...

In this article, the mass-energy equivalence is analyzed based on the total energy content & iner... more In this article, the mass-energy equivalence is analyzed based on the total energy content & inertia of a body. The analysis included quantum energy formalization with relativity. The finding suggested that photons have absolute mass to justify their momentum.

In this article, the mass-energy equivalence is analyzed based on the total energy content & iner... more In this article, the mass-energy equivalence is analyzed based on the total energy content & inertia of a body. The analysis included quantum energy formalization with relativity. The finding suggests that photons have absolute mass to justify their momentum.

Acta Neuropathologica Communications, 2020

To test the hypothesis that the cerebrospinal fluid (CSF) could provide a spreading route for pat... more To test the hypothesis that the cerebrospinal fluid (CSF) could provide a spreading route for pathogenesis of amyotrophic lateral sclerosis (ALS), we have examined the effects of intraventricular infusion during 2 weeks of pooled CSF samples from sporadic ALS patients or control CSF samples into transgenic mice expressing human TDP43WT which do not develop pathological phenotypes. Infusion of ALS-CSF, but not of control CSF, triggered motor and cognitive dysfunction, as well as ALS-like pathological changes including TDP43 proteinopathy, neurofilament disorganization and neuroinflammation. In addition, the neuron-specific translational profiles from peptide analyses of immunoprecipitated ribosomes revealed dysregulation of multiple protein networks in response to ALS-CSF altering cytoskeletal organization, vesicle trafficking, mitochondrial function, and cell metabolism. With normal mice, similar ALS-CSF infusion induced mild motor dysfunction but without significant TDP43 pathology...

Journal of Environmental Science & Engineering, 2021

Background: TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases in... more Background: TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile remains unknown. Methods: Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used a Ribotag approach combined with microarray and proteomic analyses to investigate the neuronal translational profiles in mouse model of ALS/FTD. Results: Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-ĸB) essential modulator (NEMO), induces autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive im...

ACS applied materials & interfaces, Jan 26, 2018

Targeting dendritic cells (DCs) either ex-vivo (Ex. Sipuleucel-T) or in-vivo, for stimulating cel... more Targeting dendritic cells (DCs) either ex-vivo (Ex. Sipuleucel-T) or in-vivo, for stimulating cellular immunity has been a leading approach for cancer vaccines. We have rationally engineered a nanoparticulate based delivery system for vaccines (InAc-NPs) to target DCs by using a plant polymer-based Toll-like receptor-4 (TLR4) agonist inulin acetate (InAc) as a biomaterial. The material and the antigen-encapsulated InAc-NPs (~190 nm in diameter) were characterized for their physicochemical properties. As a potent vaccine adjuvant, InAc-NPs activated TLR4 on multiple immune cells including DCs and primary swine and human cells to secret various cytokines as detected by ELISA and quantitative-PCR. In addition, InAc-NPs promoted the maturation of DCs as observed by a decreased phagocytic ability and enhanced capability to activate various maturation markers (MHC-I, MHC-II, CD40, and CD80) quantified using flow-cytometry. In mice, the InAc-NPs produced strong serum antibody titers (total...

Medical hypotheses, 2018

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antit... more The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Journal of controlled release : official journal of the Controlled Release Society, Sep 29, 2017

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, ... more New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1...

International Journal of Pharmaceutics, 2016

Micellization offers several advantages for the delivery of water insoluble drugs including a nan... more Micellization offers several advantages for the delivery of water insoluble drugs including a nanoparticulate &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;core-shell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; delivery system for drug targeting. Recently, hydrophobically modified polysaccharides (HMPs) are gaining recognition as micelle forming polymers to encapsulate hydrophobic drugs. In this manuscript, for the first time, we have evaluated the self-assembling properties of a lauryl carbamate derivative of the poly-fructose natural polymer inulin (Inutec SP1(®) (INT)) to form paclitaxel (PTX) loaded micelles. INT self-assembled into well-defined micellar structures in aqueous environment with a low critical micellar concentration of 27.8μg/ml. INT micelles exhibited excellent hemocompatibility and low toxicity to cultured cells. PTX loaded INT micelles exhibited a mean size of 256.37±10.45nm with excellent drug encapsulation efficiency (95.66±2.25%) and loading (8.69±0.22%). PTX loaded micelles also displayed sustained release of PTX and enhanced anti-cancer efficacy in-vitro in mouse melanoma cells (B16F10) compared to Taxol formulation with Cremophor EL as solvent. In addition, PTX loaded INT micelles exhibited comparable in-vivo antitumor activity in B16F10 allograft mouse model at half the dose of Taxol. In conclusion, INT offers safe, inexpensive and natural alternative to widely used PEG-modified polymers for the formulation of micellar delivery systems for paclitaxel.

Advanced Healthcare Materials, 2016

Skin-penetrating peptides (SPPs) are attracting increasing attention as a noninvasive strategy fo... more Skin-penetrating peptides (SPPs) are attracting increasing attention as a noninvasive strategy for transdermal delivery of therapeutics. The identifi cation of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affi nity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfi de-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affi nity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identifi ed SPP SPACE TM. An octameric peptide (ACNAHQARSTCG) yielded signifi cantly higher delivery of CsA compared to heptameric SPPs. The safety profi le of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents. reduces both risk of infections and discomfort in patients. [ 1 ] Drug permeation into and across skin, however, still poses serious challenges, mainly related to the natural imperviousness of this tissue. [ 2 ] Among the various skin layers, the stratum corneum (SC) is particularly important in protecting underlying organs from foreign agents, such as pathogens and toxins. [ 3 ] SC comprises keratin-rich cells embedded in multiple lipid bilayers. [ 4 ] The hydrophobicity and the densely packed structure of this layer limit the permeation of even small therapeutically active ingredients. [ 5 ] To increase drug permeation across the tissue, chemical permeation enhancers (CPEs) have been proposed, including small synthetic chemicals (azone derivatives, fatty acids, alcohols, esters, sulfoxides, pyrrolidones, glycols, surfactants, and terpenes) and peptides. [ 6 ] We have discovered and extensively characterized a number of small (1000-1500 Da) skin penetrating peptides for the transdermal delivery of highly relevant drug models, such as siRNA, hyaluronic acid, and cyclosporine A (CsA). [ 7 ] In a recent study, we described several fundamental aspects underlying the mechanism of skin permeation enhancement by peptides. [ 8 ] Our fi ndings, obtained based on studies of fi ve sequences (skin penetrating and cell entering (SPACE TM), TD-1, poly-R, dermis localizing peptide (DLP), and LP-12) with different physicochemical properties, strongly indicate that skin penetrating peptides' (SPPs) action occurs mainly through the keratin domain of the skin. This is supported by experimental observations of the structural alteration by SPPs of the proteins of the stratum corneum , as well as by affi nity binding studies that indicate an affi nity between SPPs and keratin, the most abundant skin protein. Further, the studies evidenced a strong correlation between the strength of the ternary complex formed between keratin, a model therapeutic CsA and SPP and the ability of CsA to permeate into the skin. We therefore contend that the noncovalent binding (affi nity) of SPPs to keratin enables their migration across the skin through a progressively penetrating protein binding mechanism, while the affi nity for CsA enables the concurrent transport of the drug along with the SPPs. These observations suggest a simple strategy for the de novo design of SPPs for transdermal delivery of a desired drug,

European Journal of Pharmaceutical Sciences, 2016

Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several... more Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several chronic diseases in animal models. However, this success is yet to be translated to humans mainly because of its poor oral bioavailability caused by extremely low water solubility. This manuscript demonstrates that water insoluble curcumin (~1μg/ml) forms highly aqueous soluble complexes (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2mg/ml) with a safe pH sensitive polymer, poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) when precipitated together in water. The complexation process was optimized to enhance curcumin loading by varying several formulation factors. Acetone as a solvent and polyvinyl alcohol as a stabilizer with 1:2 ratio of drug to polymer yielded complexes with relatively high loading (~280μg/ml) and enhanced solubility (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2mg/ml). The complexes were amorphous in solid and were soluble only in buffers with pHs less than 5.0. Hydrogen bond formation and hydrophobic interactions between curcumin and the polymer were recorded by infrared spectroscopy and nuclear magnetic resonance spectroscopy, respectively. Molecular complexes of curcumin were more stable at various pHs compared to unformulated curcumin. In mice, these complexes increased peak plasma concentration of curcumin by 6 times and oral bioavailability by ~20 times. This is a simple, economic and safer strategy of enhancing the oral bioavailability of curcumin.

Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement, 2015

The skin is the largest organ in the human body and constitutes a potential site for local and sy... more The skin is the largest organ in the human body and constitutes a potential site for local and systemic drug delivery. However, the impermeable nature of the outermost layer of the skin called stratum corneum (SC) ensures a stringent barrier for transport of hydrophilic molecules and macromolecules into and across the skin. Hence, only small (<500 Da) and lipophilic (Log P = 1–3) molecules can be passively delivered through the skin. In particular, it is challenging to deliver hydrophilic drugs and macromolecules, such as proteins and nucleic acids, into and across the skin. To address these limitations, several physical and chemical skin penetration enhancement techniques have been proposed. Recently, peptides have emerged as successful skin penetration enhancers for both small molecular weight drugs and macromolecules. These peptides are called skin penetration enhancement peptides (SPEPs). Currently, majority of the SPEPs have been discovered from already-established cell-penetrating peptides, pore-forming antimicrobial peptides, or by screening random peptide displayed phage libraries. In this chapter, we have discussed the discovery of various classes of SPEPs and their mechanism of skin permeation enhancement.

Journal of controlled release : official journal of the Controlled Release Society, Jan 2, 2015

The immune system has evolved to recognize and respond to a wide variety of pathogens and produce... more The immune system has evolved to recognize and respond to a wide variety of pathogens and produce distinct immune responses against diverse pathogenic structures. Despite remarkable advances, the general mechanisms by which the immune system differentiates the structure of antigen presenting particulates have yet to be elucidated. Using particles of various sizes and shapes, we assessed the role of morphological features of particles in antigen presentation and subsequent processing by the immune cells. Ovalbumin was used as a model antigen. Spherical polystyrene particles of 193nm and 521nm diameters were successfully stretched to form rod-shaped particles of 376nm and 1530nm in length, respectively. Ovalbumin conjugation to these different particle types was optimized to achieve ~50μg of ovalbumin conjugation per mg of particle. In vivo immunization study results revealed that small spherical particles (193nm in diameter) produced a Th1-biased response whereas rod-shaped particles...

Journal of Controlled Release, 2015

Nucleic acids (NAs) hold significant potential for the treatment of several diseases. Topical del... more Nucleic acids (NAs) hold significant potential for the treatment of several diseases. Topical delivery of NAs for the treatment of skin diseases is especially advantageous since it bypasses the challenges associated with systemic administration which suffers from enzymatic degradation, systemic toxicity and lack of targeting to skin. However, the skin's protective barrier function limits the delivery of NAs into skin after topical application. Here, we highlight strategies for enhancing delivery of NAs into skin, and provide evidence that translation of topical NA therapies could have a transformative impact on the treatment of skin diseases.