Santosh Kumar

• PhD Student at Dr. Rajendra Prasad Central Agriculture University

Clinical study show that cervical cancer is the most frequently detected cancer in women living with human immunodeficiency virus (HIV) which has been defined as an acquired immunodeficiency syndrome (AIDS). Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervic...

Background/Objectives: HIV persists in central nervous system (CNS) reservoirs, where infected microglia and macrophages drive neuroinflammation, oxidative stress, and neuronal damage, contributing to HIV-associated neurocognitive disorder (HAND). Nanoparticle-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanopartic...

Scope: Inflammatory bowel disease (IBD) involves a range of immune-mediated disorders marked by systemic and local intestinal inflammation. We synthesized a novel compound DJ-X-025 and uncovered its anti-inflammatory properties using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro and a dextran sodium sulfate (DSS)-induced model of...

Background High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a p...

Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it i...

Although antiretroviral therapy (ART) can suppress peripheral HIV, patients still suffer from neuroHIV due to insufficient levels of ART drugs in the brain. Hence, this study focuses on developing a poly lactic-co-glycolic acid (PLGA) nanoparticle-based ART drug delivery system for darunavir (DRV) using an intranasal route that can overcome the lim...

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 75% of the world’s population still use plant-based medicinal compounds, indicating the ongoing significance of phytochemicals for hum...

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health...

Neurological disorders are a major global challenge, which counts for a substantial slice of disease burden around the globe. In these, the challenging landscape of central nervous system (CNS) diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and neuro-AIDS, demands innovative and novel therapeutic approaches. Curcu...

In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse model, we compared the biodistribution of EVG alone and in c...

The lymphatic network is pivotal for various physiological functions in the human body. Accumulated evidence supports the role of therapeutic lymphangiogenesis in the treatment of several pathologies. Endogenous gasotransmitter, hydrogen sulfide (H2S) has been extensively studied for its potential as a pro-angiogenic factor and vascular function mo...

In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse model, we compared the biodistribution of EVG alone and in c...

Objectives HIV suppression in brain viral reservoirs, especially macrophages, and microglia is critical to suppress HIV neuropathogenesis and subsequently HIV-associated neurocognitive disorders (HAND). Since most antiretroviral therapy (ART) drugs do not achieve optimal therapeutic concentrations in the brain and can cause neurotoxicity, an altern...

Background: TSP1 (thrombospondin-1)-a well-known angiogenesis inhibitor-mediates differential effects via interacting with cell surface receptors including CD36 and CD47. However, the role of TSP1 in regulating lymphangiogenesis is not clear. Our previous study suggested the importance of cell-specific CD47 blockade in limiting atherosclerosis. Fu...

The 27th Scientific Conference of the Society on Neuroimmune Pharmacology (SNIP) in New Delhi, India, on March 15–18, 2023 is a historic summit of experts from around the world. The four day conference provides insights into the latest and most advanced science in the intersecting areas of neuroscience, immunology, pharmacology, and its translation...

The beneficial effects of the polyphenolic compound piceatannol (PC) has been reported for metabolic diseases, antiproliferative, antioxidant, and anti-cancer properties. Despite its beneficial effects on inflammatory diseases, little is known about how PC regulates inflammatory responses and adipogenesis. Therefore, this study was designed to dete...

Despite the availability of combined antiretroviral therapy (cART), which reduces the HIV replication in chronically HIV-infected patients, HIV associated neurocognitive disorders (HAND) persists in the brain. The blood-brain barrier (BBB) is the major barrier for the penetration of drugs including antiretrovirals, limiting the drug penetration to...

Background Benzo(a)pyrene (BaP), an important polycyclic aromatic hydrocarbons (PAH) component of cigarette/tobacco smoking, is known to cause adverse health effects and is responsible for various life-threatening conditions including cancer. However, it is not yet clear whether BaP contributes to the macrophage- and astrocyte-mediated inflammatory...

Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or...

The 26 th Scientific Conference of the Society on NeuroImmune Pharmacology (SNIP) at the University of Tennessee Health Science Center in Memphis, Tennessee, June 1-3, 2022, is SNIP’s first full-fledged meeting in person since the onset of the coronavirus disease-19 pandemic. The three-day meeting encompasses a variety of activities that include a...

The lymphatic system is pivotal for immunosurveillance and the maintenance of tissue homeostasis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vessels, has both physiological and pathological roles. Recent advances in the molecular mechanisms regulating lymphangiogenesis have opened a new area of research on reparativ...

Obesity is a complex disease associated with various metabolic abnormalities, cardiovascular diseases, and low-grade chronic inflammation. Inflammation associated with T helper 1 (Th1) immune cells is dominant in adipose tissue (AT) and exerts metabolically deleterious impacts. The precise mechanism of alteration in AT immune system and its effect...

Objective: The objective of this study is to introduce short stories and motivational messages on soft skills in pharmacy didactic courses to improve classroom engagement. Methods: Surveys were then conducted on the impact of students’ understanding of soft skills and their impact on classroom engagement. Results: The survey results from the two cl...

Background: Opioid Use Disorder (OUD) has been linked to dopamine and the neurological reward centers. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the production of many neurotransmitters such as dopamine. As such, MTHFR variants that lead to decreased production of neurotransmitters may play a role in OUD. However, lacunae...

Simple Summary In this review, we discuss the potential use of extracellular vesicles (EVs) to deliver dietary supplements to the brain to reduce brain complications associated with HIV, COVID-19, and other brain disorders. Brain-related complications affect people with HIV and COVID-19 alike. Moreover, since HIV patients are at a higher risk of co...

Traumatic brain injury is a sudden trauma or blow on the head, and severe traumatic brain injury is a major cause of death and disability worldwide. The acute and chronic consequences following traumatic brain injury can lead to progressive secondary neurodegenerative changes and cognitive dysfunction. To date, there is no effective pharmaceutical...

This guest commentary introduces “The Neuroimmune Pharmacology of SARS-CoV-2,” a special theme issue for The Journal of Neuroimmune Pharmacology led by the Society on NeuroImmune Pharmacology. The issue builds on the Society’s Virtual Workshop on COVID-19 held April 9, 2021. Graphical abstract Top row from left: Drs. Santosh Kumar, Sowmya Yelamanc...

In the current study, correlation among specific capsular types, sequence types and specific hosts were observed. Study proves high diversity with respect to small ruminant isolates belonging to capsular type A. Higher sharing of sequence types among small ruminant, porcine and avian hosts indicate the close association of these isolates getting ad...

The infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and resultant coronavirus diseases-19 (COVID-19) disproportionally affects minorities, especially African Americans (AA) compared to the Caucasian population. The AA population is disproportionally affected by COVID-19, in part, because they have high prevalence of underl...

In this study, we investigated whether intravenously self-administered nicotine with menthol and audiovisual cue modulates nicotine-metabolizing CYP2A6, oxidative stress modulators, and cytokines/chemokines in plasma extracellular vesicles (EVs) in rats. We assigned rats to self-administered nicotine with: (a) audiovisual cue (AV), (b) menthol, and...

Background PLWHA commonly suffer from chronic pain that is often treated with opioids, leading to subsequent opiate use disorders. As the majority of Americans live in close proximity to a pharmacy, community pharmacists are well equipped to interact with PLWHA. Few data quantify the needs of PLWHA with OUD, or how they utilize community pharmacist...

Chemodietary agents are emerging as promising adjuvant therapies in treating various disease conditions. However, there are no adjuvant therapies available to minimize the neurotoxicity of currently existing antiretroviral drugs (ARVs). In this study, we investigated the anti-HIV effect of a chemodietary agent, Cucurbitacin-D (Cur-D), in HIV-infect...

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is u...

Over the last two decades, the United States (U.S.) has experienced an opioid crisis that has had a significant negative societal and economic impact. Due to the high utilization of opioids in Persons Living with HIV and AIDS (PLWHA), there is a need for a qualitative literature review that presents opioid-use related problems in this population. T...

Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for use as drug delivery systems for the c...

The coronavirus disease-19 (COVID-19) pandemic has affected individuals of all categories, irrespective of their geographical locations, professions, gender, or race. As a result of full or partial lock-down and stay-at-home orders, the well-being and productivity of individuals were severely affected. Since basic science research requires laborato...

Introduction Extracellular vesicles (EVs) are a family of natural nanosize vesicles that transport biological cargos, including DNA, RNA, protein, and lipids. In recent years, EVs have attracted a lot of attention for their capability to function as a drug delivery system (DDS). While clinical trials have been conducted, the techniques to formulate...

The opioid epidemic has had a significant, negative impact in the United States, and people living with HIV/AIDS (PLWHA) represent a vulnerable sub-population that is at risk for negative sequela from prolonged opioid use or opioid use disorder (OUD). PLWHA are known to suffer from HIV-related pain and are commonly treated with opioids, leading to...

Though alcoholic liver injury plays the primary role in direct alcohol-related morbidity, alcohol consumption is also interlinked with many other diseases in extra-hepatic tissues/organs. The mechanism of alcoholic tissue injury is well documented, however the mechanisms that affect extra-hepatic tissues have not yet been well defined. Extracellula...

Abuse of alcohol and tobacco could exacerbate HIV pathogenesis by transferring materials through exosomes (small nanovesicles). Exosomes present a stable and accessible source of information concerning the health and/or disease status of patients, which can provide diagnostic and prognostic biomarkers for myriad conditions. Therefore, we aimed to s...

Introduction While considerable progress has been made in the fight against HIV/AIDS, to date there has not been a cure, and millions of people around the world are currently living with HIV/AIDS. eople living with HIV/AIDS have substance abuse disorders at higher rates than non-infected individuals, which puts them at an increased risk of drug dru...

Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from...

The rice crop is affected by various biotic and abiotic stresses. The fungal diseases come under major biotic stress, among fungal diseases sheath blight of rice is one of the major threat for cultivation of rice crops. The sheath blight pathogen (Rhizoctonia solani Kühn) is being affected by different sources of nutrients. In this regards, six car...

The diagnosis of neurocognitive disorders associated with HIV infection, alcohol, and tobacco using CSF or neuroimaging are invasive or expensive methods, respectively. Therefore, extracellular vesicles (EVs) can serve as reliable noninvasive markers due to their bidirectional transport of cargo from the brain to the systemic circulation. Hence, ou...

Even with an efficient combination of antiretroviral therapy (ART), which significantly decreases viral load in human immunodeficiency virus type 1 (HIV-1)-positive individuals, the occurrence of HIV-1-associated neurocognitive disorders (HAND) still exists. Microglia have been shown to have a significant role in HIV-1 replication in the brain and...

Smoking, which is highly prevalent in HIV-infected populations, has been shown to exacerbate HIV replication, in part via the cytochrome P450 (CYP)-induced oxidative stress pathway. Recently, we have shown that extracellular vesicles (EVs), derived from tobacco- and/or HIV-exposed macrophages, alter HIV replication in macrophages by cell-cell inter...

n January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome se...

In the last two decades, the mortality rate in people living with HIV/AIDS (PLWHA) has decreased significantly, resulting in an almost normal longevity in this population. However, a large portion of this population still endures a poor quality of life, mostly due to an increased inclination for substance abuse, including tobacco smoking. The preva...

The use of antiretroviral therapy (ART) has remarkably decreased the morbidity associated with HIV-1 infection, however, the prevalence of HIV-1-associated neurocognitive disorders (HAND) is still increasing. The blood-brain barrier (BBB) is the major impediment for penetration of antiretroviral drugs, causing therapeutics to reach only suboptimal...

In the current study, we hypothesized that extracellular vesicles (EVs) secreted from human papilloma virus (HPV)-infected cervical cancer cells exacerbate human immunodeficiency virus (HIV)-1 replication in differentiated U1 cell line through an oxidative stress pathway. To test the hypothesis, we treated an HIV-1-infected macrophage cell line (U1...

The cytochrome P450 (CYP) family of enzymes is known to metabolize the majority of xenobiotics. Hepatocytes, powerhouses of CYP enzymes, are where most drugs are metabolized into non-toxic metabolites. Additional tissues/cells such as gut, kidneys, lungs, blood, and brain cells express selective CYP enzymes. Extrahepatic CYP enzymes, especially in...

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HA...

Introduction: Antiretroviral therapy (ART) has led to a significant reduction in HIV-1 morbidity and mortality. Many antiretroviral drugs (ARVs) are metabolized by cytochrome P450 (CYP) pathway, and majority of these drugs are also either CYP inhibitors or inducers and few possess both activities. These CYP substrates, when used for HIV treatment i...

Cellular CYP2E1 is well-known to mediate alcohol- (ALC) and acetaminophen- (APAP) induced toxicity in hepatic and extra-hepatic cells. Although exosomes have been gaining importance in understanding mechanism of intra- and inter-cellular communication, the functional role of drug metabolizing cytochrome P450 (CYP) enzymes in human plasma exosomes a...

Introduction: Drugs used in HIV treatment; all protease inhibitors, some non-nucleoside reverse transcriptase inhibitors, and pharmacoenhancers ritonavir and cobicistat can inhibit cytochrome P450 (CYP) enzymes. CYP inhibition can cause clinically significant drug-drug interactions (DDI), leading to increased drug exposure and potential toxicity. A...

Background Cigarette smoking increases systemic oxidative stress, inflammation, and viral replication in individuals with HIV. Macrophages are infected during HIV infection and serve as an important reservoir throughout the process. Macrophages exist in two phenotypes, the classically acti-vated M1 macrophage and alternatively activated M2 macropha...

Our goal was to design nanocarriers that specifically target and deliver therapeutics to polarized macrophages. Mannose receptors are highly overexpressed on polarized macrophages. In this study, we constructed Pluronic® -F127 polymer and tannic acid (TA) based nanoparticles (F127-TA core nanoparticles) with varying mannose densities. The particle...

Background Alcohol consumption is considered to be a major health problem among people living with HIV/AIDS. Our previous reports have shown that ethanol reduced intracellular concentrations of antiretroviral drugs elvitegravir and darunavir in the HIV-1-infected U1 cell line. Ethanol also increased HIV-1 replication despite the presence of elviteg...

Human immunodeficiency virus (HIV) infection, despite great advances in antiretroviral therapy, remains a lifelong affliction. Though current treatment regimens can effectively suppress viral load to undetectable levels and preserve healthy immune function, they cannot fully alleviate all symptoms caused by the presence of the virus, such as HIV-as...

Smoking aggravates HIV‐1 pathogenesis and leads to decreased responses to antiretroviral therapy. However, the exact mechanism by which smoking enhances HIV‐1 pathogenesis is unknown. Benzo(a)pyrene (BaP) is a major carcinogen in cigarette smoke. It requires metabolic activation through cytochrome P450s (CYPs) to exert its toxic effects. We hypothe...

Introduction Alcohol consumption is negatively associated with antiretroviral therapy (ART) adherence ¹ . Maintenance of optimal ART levels in monocytes and/or macrophages, the known HIV viral reservoirs, is essential to suppress HIV viral replication. Previously, we reported ethanol mediated alterations in metabolism of elvitegravir (EVG) in human...

Introduction: Combination antiretroviral therapy (ART) reduces viral load to under the limit of detection, successfully decreasing HIV-related morbidity and mortality. Due to viral mutations, complex drug combinations and different patient response, there is an increasing demand for individualized treatment options for patients. Areas covered: This...

Cytokines and chemokines circulate in plasma and may be transferred to distant sites, via exosomes. HIV infection is associated with dysregulation of cytokines and chemokines, which subsequently contribute to the pathogenesis of HIV. Alcohol and tobacco exposure, which are prevalent in HIV-infected individuals, may induce changes in the expression...

Cytokine and chemokine levels in plasma and exosomes of HIV-neagtive non-drug abusers (Healthy), HIV-positive non-drug abusers (HIV), HIV-negative alcohol drinkers (alcohol), HIV-positive alcohol drinkers (HIV+alcohol), HIV-negative smokers (smoker), and HIV-positive smokers (HIV+smokers). (XLSX)

Introduction HIV-1-infected smokers are at risk of oxidative damage to neuronal cells in the central nervous system by both HIV-1 and cigarette smoke. Since neurons have a weak antioxidant defense system, they mostly depend on glial cells, particularly astrocytes, for protection against oxidative damage and neurotoxicity. Astrocytes augment the neu...

Smoking aggravates HIV-1 pathogenesis and leads to decreased responses to antiretroviral therapy.In this study, we aim to fnd a molecular mechanism that would explain smoking-induced HIV-1 replication. Benzo(a)pyrene (BaP), a major carcinogen in cigarette, requires metabolic activation through cytochrome P450s (CYPs) to exert its toxic efects. We h...

Pasteurella multocida is responsible for diseases, which are endemic and economically important in India, still comparative investigations on phylogenetic relations of Indian P. multocida isolates are scarce. Therefore, present study was undertaken to understand the phylogenetic relationship of several isolates belonging to different host, place of...

HIV-infected smokers are at relatively higher risk of cancer than HIV-infected non-smokers. HIV weakens the immune system and renders infected individuals more vulnerable to the carcinogenic effects of smoking. HIV-infected smokers suffer more aggressive forms of cancers than do non-smokers because of the cumulative effects of the virus and cigaret...

Introduction: Hepatitis C is a disease with a significant global impact. Over the last several years, the treatment of the disease has been revolutionized. Therapy has transformed over the last several years with the approval of second generation direct acting antivirals, and currently utilized medications for the treatment of hepatitis C are signi...

Diallyl sulfide (DAS) has been shown to prevent xenobiotic (e.g. ethanol, acetaminophen) induced toxicity and disease (e.g. HIV-1) pathogenesis. DAS imparts its beneficial effect by inhibiting CYP2E1-mediated metabolism of xenobiotics, especially at high concentration. However, DAS also causes toxicity at relatively high dosages and with long expos...

Introduction Macrophages play an important role in HIV, where they are a cellular reservoir. Macrophages are polarized into two phenotypes: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which may have altered expression of drug efflux transporters, including BCRP and MRP1. These differences may result in subtherapeutic conce...

Smoking is known to exacerbate HIV-1 pathogenesis, especially in monocytes, through the oxidative stress pathway. Exosomes are known to alter HIV-1 pathogenesis through inter-cellular communication. However, the role of exosomes in smoking-mediated HIV-1 pathogenesis is unknown. In this study, we investigated the effect of cigarette smoke condensat...