Browsing by Author "Saroj Kumar"

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A review on ferulic acid and analogs based scaffolds for the management of Alzheimer's disease
(Elsevier Masson s.r.l., 2021) Yash Pal Singh; Himanshu Rai; Gourav Singh; Gireesh Kumar Singh; Sunil Mishra; Saroj Kumar; S. Srikrishna; Gyan Modi
Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and impaired motor activity, resulting in the brain's cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-β (Aβ) peptides to form Aβ plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Aβ aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Aβ aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD. © 2021 Elsevier Masson SAS
Design, synthesis and biological evaluation of novel piperic acid and benzylpiperazine hybrid molecules for improvement of memory impairment via cholinesterase inhibitory activity
(Springer Science and Business Media Deutschland GmbH, 2025) Jitendra Kumar; Gauri Shankar; S. Dasaratha Kumar; Gourav Singh; T. A. Gajendra; Sanskriti Rai; Upesh Mandloi; Saripella Srikrishna; Saroj Kumar; Amit Kumar Singh; Pradeep Harish Kumar; Kavindra Nath Tiwari; Sairam Krishnamurthy; Gyan Prakash Modi; Sunil Kumar Mishra
In this paper, we have developed a series of piperic acid (PA) derivatives to overcome the inherent constraints linked to PA for Alzheimer's disease (AD) management. We have carried out a comprehensive study to investigate the structure–activity relationship (SAR) of PAanalogs to enhance their inhibitory properties towards cholinesterase enzymes. Compound 3m exhibited notable inhibition against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) among all developed analogs (BChE (µM), 1.03 ± 0.011; AChE (µM), 4.26 ± 0.13 respectively) over PA (AChE% inhibition at 20 µM, 7.14 ± 0.98; BChE% inhibition at 20 µM, 5.87 ± 0.76). Compound 3m was chosen for further biological investigations based on these encouraging outcomes. 3 m demonstrated a binding affinity for AChE’s peripheral anionic site, indicating its interaction with this specific enzyme region. Additionally, it also possesses favorable permeability across the blood–brain barrier, with a Pe (permeability coefficient) value of 5.79 ± 1.12. The molecular docking investigations unveiled the ability of 3mto intricately engage with AChE and BChE.In cell-based cytotoxicity tests, compound 3m displayed cell-friendly characteristics across different tested concentrations. Notably, 3m exhibited the ability to counteract scopolamine-induced memory impairmentin mice, enhancing both spatial and cognitive memories. These results strongly suggest that 3m can behave as a potential compound for AD management. © The Author(s), under exclusive licence to the Institute of Chemistry, Slovak Academy of Sciences 2024.
Design, synthesis and biological evaluation of novel piperic acid and benzylpiperazine hybrid molecules for improvement of memory impairment via cholinesterase inhibitory activity
(Springer Science and Business Media Deutschland GmbH, 2024) Jitendra Kumar; Gauri Shankar; Sunil Kumar; Gourav Singh; T.A. Gajendra; Sanskriti Rai; Upesh Mandloi; Saripella Srikrishna; Saroj Kumar; Amit Kumar Singh; Pradeep Kumar; Kavindra Nath Tiwari; Sairam Krishnamurthy; Gyan Modi; Sunil Kumar Mishra
In this paper, we have developed a series of piperic acid (PA) derivatives to overcome the inherent constraints linked to PA for Alzheimer's disease (AD) management. We have carried out a comprehensive study to investigate the structure–activity relationship (SAR) of PAanalogs to enhance their inhibitory properties towards cholinesterase enzymes. Compound 3m exhibited notable inhibition against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) among all developed analogs (BChE (µM), 1.03 ± 0.011; AChE (µM), 4.26 ± 0.13 respectively) over PA (AChE% inhibition at 20 µM, 7.14 ± 0.98; BChE% inhibition at 20 µM, 5.87 ± 0.76). Compound 3m was chosen for further biological investigations based on these encouraging outcomes. 3 m demonstrated a binding affinity for AChE’s peripheral anionic site, indicating its interaction with this specific enzyme region. Additionally, it also possesses favorable permeability across the blood–brain barrier, with a Pe (permeability coefficient) value of 5.79 ± 1.12. The molecular docking investigations unveiled the ability of 3mto intricately engage with AChE and BChE.In cell-based cytotoxicity tests, compound 3m displayed cell-friendly characteristics across different tested concentrations. Notably, 3m exhibited the ability to counteract scopolamine-induced memory impairmentin mice, enhancing both spatial and cognitive memories. These results strongly suggest that 3m can behave as a potential compound for AD management. Graphical abstract: (Figure presented.) © The Author(s), under exclusive licence to the Institute of Chemistry, Slovak Academy of Sciences 2024.
Design, Synthesis, and Biological Evaluation of Ferulic Acid Template-Based Novel Multifunctional Ligands Targeting NLRP3 Inflammasome for the Management of Alzheimer’s Disease
(American Chemical Society, 2024) Gourav Singh; Gauri Shankar; Samir Ranjan Panda; Sunil Kumar; Sanskriti Rai; Himanshu Verma; Prabhat Kumar; Prasanta Kumar Nayak; V.G.M. Naidu; Saripella Srikrishna; Saroj Kumar; Gyan Modi
Alzheimer’s disease (AD) is the most common cause of dementia, which arises due to low levels of acetyl and butyrylcholines, an increase in oxidative stress, inflammation, metal dyshomeostasis, Aβ and tau aggregations. The currently available drugs for AD treatment can provide only symptomatic relief without interfering with pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multifunctional molecules for AD, systematic SAR studies on EJMC-4e were caried out to improve its multifunctional properties. The rigorous medicinal efforts led to the development of 12o, which displayed a 15-fold enhancement in antioxidant properties and a 2-fold increase in the activity against AChE and BChE over EJMC-4e. Molecular docking and dynamics studies revealed the binding sites and stability of the complex of 12o with AChE and BChE. The PAMPA-BBB assay clearly demonstrated that 12o can easily cross the blood-brain barrier. Interestingly, 12o also expresses promising metal chelation activity, while EJMC-4e was found to be devoid of this property. Further, 12o inhibited metal-induced or self Aβ1-42 aggregation. Observing the neuroprotection ability of 12o against H2O2-induced oxidative stress in the PC-12 cell line is noteworthy. Furthermore, 12o also inhibited NLRP3 inflammasome activation and attenuated mitochondrial-induced ROS and MMP damage caused by LPS and ATP in HMC-3 cells. In addition, 12o is able to effectively reduce mitochondrial and cellular oxidative stress in the AD Drosophila model. Finally, 12o could reverse memory impairment in the scopolamine-induced AD mice model, as evident through in vivo and ex vivo studies. These findings suggest that this compound may act as a promising candidate for further improvement in the management of AD. © 2024 American Chemical Society.
Design, Synthesis, and Biological Evaluation of Ferulic Acid-Piperazine Derivatives Targeting Pathological Hallmarks of Alzheimer’s Disease
(American Chemical Society, 2024) Gourav Singh; Sunil Kumar; Samir Ranjan Panda; Prabhat Kumar; Sanskriti Rai; Himanshu Verma; Yash Pal Singh; Saroj Kumar; Saripella Srikrishna; V.G.M. Naidu; Gyan Modi
Alzheimer’s disease (AD) is the most prevalent cause of dementia and is characterized by low levels of acetyl and butyrylcholine, increased oxidative stress, inflammation, accumulation of metals, and aggregations of Aβ and tau proteins. Current treatments for AD provide only symptomatic relief without impacting the pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multitarget molecules for AD, through extensive medicinal chemistry efforts, we have developed 13a, harboring the key functional groups to provide not only symptomatic relief but also targeting oxidative stress, able to chelate iron, inhibiting NLRP3, and Aβ1-42 aggregation in various AD models. 13a exhibited promising anticholinesterase activity against AChE (IC50 = 0.59 ± 0.19 μM) and BChE (IC50 = 5.02 ± 0.14 μM) with excellent antioxidant properties in DPPH assay (IC50 = 5.88 ± 0.21 μM) over ferulic acid (56.49 ± 0.62 μM). The molecular docking and dynamic simulations further corroborated the enzyme inhibition studies and confirmed the stability of these complexes. Importantly, in the PAMPA-BBB assay, 13a turned out to be a promising molecule that can efficiently cross the blood-brain barrier. Notably, 13a also exhibited iron-chelating properties. Furthermore, 13a effectively inhibited self- and metal-induced Aβ1-42 aggregation. It is worth mentioning that 13a demonstrated no symptom of cytotoxicity up to 30 μM concentration in PC-12 cells. Additionally, 13a inhibited the NLRP3 inflammasome and mitigated mitochondrial-induced reactive oxygen species and mitochondrial membrane potential damage triggered by LPS and ATP in HMC-3 cells. 13a could effectively reduce mitochondrial and cellular reactive oxygen species (ROS) in the Drosophila model of AD. Finally, 13a was found to be efficacious in reversing memory impairment in a scopolamine-induced AD mouse model in the in vivo studies. In ex vivo assessments, 13a notably modulates the levels of superoxide, catalase, and malondialdehyde along with AChE and BChE. These findings revealed that 13a holds promise as a potential candidate for further development in AD management. © 2024 American Chemical Society.
Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer's disease
(Elsevier Masson s.r.l., 2025) Gauri Shankar; Prabhat Kumar; Sanskriti Rai; Aparajita Ghosh; Tanmaykumar Varma; Mushtaq Ahmad Wani; Sunil N. Kumar; Upesh Mandloi; Gireesh Kumar Singh; Prabha Garg; Onkar Prakash Kulkarni; Saripella Srikrishna; Saroj Kumar; Gyan Prakash Modi
Contemporary research evidence has corroborated a gradual loss of central cholinergic neurons in Alzheimer's Disease (AD). This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death in the disease. The approved drugs for AD treatment can only offer relief from symptoms without addressing the underlying pathological hallmarks of the disease. To address the limitations associated with rivastigmine (RIV), a marketed drug for AD, a series of tryptamine derivatives was designed, synthesized, and evaluated in various in-vitro and in-vivo AD models. Enzyme inhibition studies identified compounds 6d and 6e as the lead molecules with potent inhibitors against AChE (6d, IC50: 0.99 ± 0.009 nM and 6e IC50: 7.97 ± 0.016 nM and BChE (6d, IC50: 27.79 ± 0.21 nM and 6e, IC50: 0.79 ± 0.005 nM), compared to the marketed drug Riv (AChE, IC50: 6630 ± 0.76 nM, BChE IC50 = 91 ± 0.40 nM). The molecular docking and dynamics studies corroborated the enzyme inhibition studies. The PAMPA assay strongly suggested the BBB crossing ability of the lead molecules. Further, 6d and 6e demonstrated the capability to counteract oxidative stress and Aβ1-42 in various in-vitro studies. Compound 6e exhibited remarkable radical scavenging activity in the DPPH assay (IC50: 22.91 ± 1.73 μM) compared to rivastigmine (% radical scavenging activity: 3.71 ± 0.09 at 200 μM). Interestingly, 6d and 6e exhibited promising activity in the AD Drosophila model by protecting eye phenotypes from degeneration induced by Aβ1-42 toxicity and reduced mitochondrial and cellular oxidative stress in this model. Furthermore, upon oral administration, 6d and 6e could reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice at 0.3 and 0.5 mg/kg compared to rivastigmine at 3 mg/kg and were found to have potent ex-vivo anti-ChEs properties, which are correlated with the observed pro-cognitive effects in the Morris Water Maze, likely mediated through the inhibition of both cholinesterases. The expression of various neuroprotection markers, such as BDNF and TRKB, was significantly overexpressed compared to the disease control group. © 2024 Elsevier Masson SAS
Drug-induced reactive oxygen species–mediated inhibitory effect on growth of Trypanosoma evansi in axenic culture system
(Springer Science and Business Media Deutschland GmbH, 2020) Rajender Kumar; Ruma Rani; Saroj Kumar; Khushboo Sethi; Shikha Jain; Kanisht Batra; Sanjay Kumar; B.N. Tripathi
Trypanosoma evansi, an extracellular haemoflagellate, has a wide range of hosts receptive and susceptible to infection, in which it revealed highly inconsistent clinical effects. Drugs used for the treatment of trypanosomosis have been utilized for more than five decades and have several problems like local and systemic toxicity. In the present investigation, imatinib and sorafenib were selected as drugs as they are reported to have the potential to cause reactive oxygen species (ROS)–mediated effect in cancer cells. Both have also been reported to have potential against T. brucei, T. cruzi and Leishmania donovani. To date, imatinib and sorafenib have not evaluated for their growth inhibitory effect against T. evansi. Imatinib and sorafenib showed significant (p < 0.001) inhibition on parasite growth and multiplication with IC50 (50% inhibitory concentration) values 6.12 μM and 0.33 μM respectively against T. evansi. Both the drug molecules demonstrated for the generation of ROS in T. evansi and were found up to 65% increased level of ROS as compared with negative control in the axenic culture system. Furthermore, different concentrations of imatinib and sorafenib were found non-toxic on horse peripheral blood mononuclear cells and Vero cell lines. Also, in conclusion, our results demonstrated that imatinib- and sorafenib-induced generation of ROS contributed inhibitory effect on the growth of Trypanosoma evansi in an axenic culture system. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Exploration of Neuroprotective Properties of a Naturally Inspired Multifunctional Molecule (F24) against Oxidative Stress and Amyloid β Induced Neurotoxicity in Alzheimer’s Disease Models
(American Chemical Society, 2022) Yash Pal Singh; Navneet Kumar; Khushbu Priya; Brijesh Singh Chauhan; Gauri Shankar; Saroj Kumar; Gireesh Kumar Singh; Saripella Srikrishna; Prabha Garg; Gourav Singh; Geeta Rai; Gyan Modi
The pathological hallmarks of Alzheimer’s disease (AD) are manifested as an increase in the level of oxidative stress and aggregation of the amyloid-β protein. In vitro, in vivo, and in silico experiments were designed and carried out with multifunctional cholinergic inhibitor, F24 (EJMC-7a) to explore its neuroprotective effects in AD models. The neuroprotection ability of F24 was tested in SH-SY5Y cells, a widely used neuronal cell line. The pretreatment and subsequent co-treatment of SH-SY5Y cells with different doses of F24 was effective in rescuing the cells from H2O2 induced neurotoxicity. F24 treated cells were found to be effective in the reduction of cellular reactive oxygen species, DNA damage, and Aβ1–42 induced neurotoxicity, which validated its neuroprotective effectiveness. F24 exhibited efficacy in an in vivo Drosophila model by rescuing eye phenotypes from degeneration caused by Aβ toxicity. Further, computational studies were carried out to monitor the interaction between F24 and Aβ1–42 aggregates. The computational studies corroborated our in vitro and in vivo studies suggesting Aβ1–42 aggregation modulation ability of F24. The brain entry ability of F24 was studied in the parallel artificial membrane permeability assay. Finally, F24 was tested at doses of 1 and 2.5 mg/kg in the Morris water maze AD model. The neuroprotective properties shown by F24 strongly suggest that multifunctional features of this molecule provide symptomatic relief and act as a disease-modifying agent in the treatment of AD. The results from our experiments strongly indicated that natural template-based F24 could serve as a lead molecule for further investigation to explore multifunctional therapeutic agents for AD management. © 2021 American Chemical Society
Exploring the potential of invariable surface glycoprotein (ISG65) as promising antigen for diagnosis of Trypanosoma evansi infection
(Elsevier B.V., 2023) Rajender Kumar; Khushboo Sethi; Kanisht Batra; Saroj Kumar; Shikha Jain; Sanjay Kumar
Trypanosoma evansi, a hemoflagellate protozoan, leads to wasting disease, surra in livestock animals causing huge economic losses. Currently, the preferred assay for surra diagnosis is whole cell lysate (WCL) based ELISA, which requires the use of rodents for WCL preparation. To avoid use of laboratory animals, we used recombinant DNA technology to express T. evansi invariable surface glycoprotein (ISG) in E. coli. The potential of recombinant ISG65 (rISG65) as a diagnostic antigen was investigated in immunoblot and indirect ELISA using experimentally infected equine serum samples from 0 to 84 days post infection. The results indicated that rISG65 reacted with horse T. evansi positive serum giving two bands of approximately 48 kDa and 96 kDa. T. evansi-specific antibodies were detected as early as 10 and 14 days post infection using immunoblot and indirect ELISA, respectively using rISG65 antigen. No cross-reactivity was observed in ELISA and immunoblot with different serum samples of equines positive for Equine herpesvirus 1, Burkholderia mallei, and Theileria equi infections. Several immunoreactive regions were observed between 30 and 100 kDa in T. evansi isolate of horse origin indicating the existence of multiple copies of ISG protein in a single trypanosome. The recombinant ISG has proven to be good candidate antigen to be used in ELISA for serodiagnosis of T. evansi infection in different animals. © 2023 Elsevier B.V.
IL-18 immunoadjuvanted xenogeneic canine MMP-7 DNA vaccine overcomes immune tolerance and supresses the growth of murine mammary tumor
(Elsevier B.V., 2020) Pavan Kumar Yadav; Shishir Kumar Gupta; Saroj Kumar; Mayukh Ghosh; Brijesh Singh Yadav; Dinesh Kumar; Ajay Kumar; Mohini Saini; Meena Kataria
The development of the tumorigenesis and angiogenesis through proteolytic cleavage of extracellular matrix protein and basement membranes is promoted by Matrix metelloproteinases-7 (MMP-7). Consequently, MMP-7 is presumed as potential target for mammary cancer immunotherapy. However, MMP-7 is an endogenous tumor associated antigen (TAA); therefore, immunization is challenging. In current study, a potent anti-tumor immune response has been elicited through recombinant bivalent plasmid pVIVO2.IL18.cMMP7 which subside the highly metastatic 4 T1 cell line induced mammary tumors and efficiently negate the existing challenge of using MMP-7 as immunotherapeutic target. Balb/c mice were immunized with canine MMP-7 (cMMP-7) using interleukine-18 (IL-18), as an immunoadjuvant, to explore the potential of the combination regarding elicitation of a potent anti-tumor immune response. Mice vaccinated with pVIVO2.IL18.cMMP7 DNA plasmid reduced the tumor growth significantly along with augmentation of the immune response to fight against tumor antigen as depicted by substantial enrichment of CD4+ and CD8+ population in splenocytes, infiltration of immune system cells in tumor tissue and enhanced survival time of mice. Further, splenocyte supernatant examination of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were remarkably up-regulated demonstrating the stimulation of cell-mediated immune response. Thus the current observations vividly portray that administration of xenogeneic MMP-7 DNA vaccine bypasses the tolerance barrier. © 2020 Elsevier B.V.
MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice
(Springer, 2021) Pavan Kumar Yadav; Shishir Kumar Gupta; Saroj Kumar; Mayukh Ghosh; Brijesh Singh Yadav; Dinesh Kumar; Ajay Kumar; Mohini Saini; Meena Kataria
Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8+ cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide32-40 and Peptide175-183) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8+ T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP-7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
New D-π-A-Based Coumarin- Derived Fluorescent Theranostic Probes With Broad-Spectrum Antimicrobial Activity
(John Wiley and Sons Inc, 2025) Himanshu Rai; Atul Kumar Tiwari; Aishwarya Nikhil; Ankit Tiwari; Prahalad Singh Bharti; Suresh Kumar Maury; Munesh Kumar Gupta; Sundaram Singh; Saroj Kumar; Gyan Prakash Modi
Understanding how multidrug-resistant (MDR) bacteria and fungi defy the existing antimicrobial agents requires innovative tools and techniques for real-time, in situ exploration of bacterial responses to antibiotics. Fluorescence-tagged antibiotics or dyes with inherent antimicrobial activity can provide a profound understanding of the molecular biology underlying antibiotic action and resistance mechanisms. Cutting-edge research highlights the pursuit of benzo-α-pyrone (coumarin) derivatives due to their excellent pharmacokinetics, diverse pharmacological activities, and innovative fluorescence molecular probes. In this study, donor-π-acceptor-based coumarin dyes were designed and evaluated for antimicrobial efficacy against fungal strains (Candida albicans), Gram-negative pathogens (Escherichia coli), and Gram-positive bacteria (Staphylococcus aureus). I-6 exhibited notable antimicrobial activity against S. aureus and C. albicans compared with E. coli. Conversely, I-9, a congener of I-6, showed a comparable affinity for S. aureus but found poor activity against the remaining tested strains. Mechanistic investigative studies unveiled that the inhibitory efficacy of I-6 can be attributed to its capacity to generate high reactive oxygen species (ROS) formation. Despite the evident antimicrobial potential of I-6 in the data, our future prospects, including real-time visualization to study physiological processes like uptake, distribution, and mechanism of action through fluorescence-based imaging modalities, could enhance the applicability of these probes. © 2025 Deutsche Pharmazeutische Gesellschaft.
Post-Coronavirus Disease-2019-associated Multisystem Inflammatory Syndrome in Adults: A Case from India
(Journal of Association of Physicians of India, 2025) Anju Dinkar; Jitendra P. Singh; J. Bhavya; Saroj Kumar
Multisystem inflammatory syndrome in adults (MIS-A) is a postacute hyperinflammatory condition associated with prior SARS-CoV-2 infection. While predominantly reported in children (MIS-C), MIS-A is increasingly recognized in adults and is characterized by multiorgan dysfunction, elevated inflammatory markers, and evidence of recent COVID-19. Timely diagnosis remains challenging due to clinical overlap with other infectious and inflammatory conditions. We report a case of a 36-year-old previously healthy male from Bihar, India, who presented with severe epigastric pain, progressive dyspnea, and systemic symptoms. Clinical examination revealed tachypnea, hypotension, pedal edema, ascites, and hemorrhagic rashes over the abdomen. Laboratory evaluation showed leukocytosis, thrombocytopenia, acute kidney injury, transaminitis, coagulopathy, markedly elevated inflammatory markers, and cardiac biomarkers. Chest imaging revealed bilateral subpleural opacities and mild pleural effusions, indicating pulmonary involvement. Despite a negative SARS-CoV-2 RT-PCR result, high antibody titers confirmed a recent COVID-19 infection. Imaging of the abdomen confirmed acute interstitial edematous pancreatitis. Extensive evaluation excluded tropical, autoimmune, and other infectious etiologies. The present case was managed with high-dose corticosteroids, vasopressors, mechanical ventilation, anticoagulation, and supportive therapy. He showed gradual improvement and was discharged after 6 weeks. MIS-A should be considered in patients with recent SARS-CoV-2 exposure presenting with systemic inflammation, including respiratory and extrapulmonary organ dysfunction. Early recognition and immunomodulatory therapy are essential for favorable outcomes. © The Author(s).
Quantification of Eimeria necatrix, E. acervulina and E. maxima genomes in commercial chicken farms by quantitative real time PCR
(Springer, 2020) Krishnendu Kundu; Saroj Kumar; Partha Sarathi Banerjee; Rajat Garg
Advent of quantitative polymerase chain reaction and its variants have enabled identification and quantification of seven known Eimeria species of poultry in biological samples. Attempts were made in the present study to identify and quantify three important pathogenic Eimeria species responsible for intestinal coccidiosis in domestic farmed chicken, E. necatrix, E. acervulina and E. maxima in droppings collected from thirty one poultry farms of North Indian states of Haryana, Punjab, Uttar Pradesh and Uttarakhand. The study included broiler, layer and backyard rearing units. Overall occurrence of E. necatrix, E. maxima and E. acervulina was 64.5%. E. necatrix was detected in 55% (11/20) broiler farms, 66.7% (4/6) layer farms and 100% (5/5) backyard rearing units studied. Thus, occurrence of E. necatrix was detected in 64.5% (20/31) farms studied. E. maxima and E. acervulina were detected in droppings of 65% (13/20) broiler farms, 66.7% (4/6) layer farms and 60% (3/5) back yard rearing units. Genome counts of each Eimeria species revealed maximum parasite load of E. necatrix followed by E. acervulina in broiler farms and least in layer farms. The mean parasite load (genome) copies for these parasite species were intermediate for backyard units while E. maxima had the lowest number of genome copies in droppings. Mean E. maxima counts were highest in boiler farms, while it was similar for layer and back yard units. However, statistically no significant differences were observed for parasite load existing either between the broiler, layer or back yard units or between the genome counts of E. necatrix, E. acervulina or E. maxima. © 2020, Indian Society for Parasitology.
Rhodanine composite fluorescence probes to detect pathological hallmarks in Alzheimer's disease models
(Elsevier B.V., 2024) Himanshu Rai; Rishabh Singh; Prahalad Singh Bharti; Prabhat Kumar; Sanskriti Rai; Tanmaykumar Varma; Brijesh Singh Chauhan; Aishwarya Srikant Nilakhe; Joy Debnath; Renu Dhingra; Vijay N. Mishra; Sarika Gupta; Sairam Krishnamurthy; Jian Yang; Prabha Garg; Saripella Srikrishna; Saroj Kumar; Gyan Modi
Amyloid fibrils and hyperphosphorylated tau tangles are widely acceptable histological and biochemical pathogenic markers in Alzheimer's Disease (AD). Detecting these markers at an early stage could be beneficial for differentiating AD from other neuronal anomalies. Herein, a series of rhodanine (acceptor) based dyes in conjugation with a coumarin or carbostyril (donor) were synthesized and tested their ability to detect these biomarkers. The lead probe 19 displayed staining affinity for Aβ fibrils and tau tangles with little or no interaction with abundant plasma protein (BSA). Minimal cytotoxicity, brain accessibility, biocompatibility, and fluorescence sustainability across physiological pHs rendering it suitable for in-vivo imaging. Dual staining of histological samples validated affinity of probe 19 for Aβ plaques and tau tangles in AD brain tissue specimens via immunofluorescence, ThT (aggregated Aβ specific dye), and Tau-1 (tau filament-specific dye). Moreover, live in-vivo fluorescence imaging in mice and ocular labeling of Aβ in AD Drosophila models extend the preclinical applicability of probe 19 for screening purposes. On behalf of the following data, we assume that probe 19 can successfully detect pathological AD biomarkers in investigational studies. © 2024 Elsevier B.V.
Use of recombinant calflagin protein as a potential candidate for diagnosis of Trypanosoma evansi infection
(Elsevier B.V., 2022) Rajender Kumar; Khushboo Sethi; Deepak Kumar Gaur; Sachin Kumar Goyal; Saroj Kumar; Shikha Jain; Sanjay Kumar
Serodiagnosis of surra, caused by Trypanosoma evansi, is still based on native antigens purified from bloodstream form of T. evansi grown in rodents. In order to investigate prospective diagnostic possibilities as an alternative for native antigens, we cloned, expressed 26 kDa calflagin protein containing 218 amino acids from T. evansi (Indian Strain) in Escherichia coli. The potential of recombinant calflagin (rCLF) protein as diagnostic antigen was evaluated in immunoblot and indirect ELISA using experimentally infected equine serum samples from 0 to 84 days post infection. The antibodies against T. evansi were detected with rCLF antigen in serum samples of experimentally infected equines as early as 10 days and 14 days post infection, using immunoblot and ELISA respectively. No cross-reactivity was observed with rCLF antigen in ELISA with different serum samples of equines positive for Equine herpesvirus 1, Burkholderia mallei, and Theileria equi infections. Several immunoreactive regions ranging from 10 to 28 kDa were detected using distinct T. evansi isolates (pony, cattle, donkey and camel origin) indicating presence of multiple calflagin family members in a single trypanosome. Indirect immunofluorescence antibody test with anti-CLF rabbit hyperimmune serum showed localisation of native immunogenic protein near attachment of flagellum. The rCLF protein was found to be a potential diagnostic candidate for distinguishing T. evansi positive and negative equine serum sample, suggesting that it could be used for serological surveys in animals for surra. In addition, it could be used with other potential diagnostic candidates to improve the diagnostic efficiency. © 2022 Elsevier B.V.
Vancomycin-Conjugated Polyethyleneimine-Stabilized Gold Nanoparticles Attenuate Germination and Show Potent Antifungal Activity against Aspergillus spp.
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Aishwarya Nikhil; Atul Kumar Tiwari; Ragini Tilak; Saroj Kumar; Prahlad Singh Bharti; Prem C. Pandey; Roger J. Narayan; Munesh Kumar Gupta
Antifungal drug resistance in filamentous fungi, particularly Aspergillus species, is increasing worldwide. Therefore, new antifungal drugs or combinations of drugs are urgently required to overcome this public health situation. In the present study, we examined the antifungal activity of vancomycin-functionalized AuNPs. These functionalized AuNPs were characterized, and their antifungal activity and associated killing mechanism were investigated using conventional methodologies against the conidia of A. fumigatus and A. flavus. The differential antifungal activity of vancomycin-functionalized Au-NPs against the conidia of Aspergillus species is dependent on structural differences in the conidial cell wall. The results demonstrated potent fungicidal activity against A. fumigatus, with a MIC value of 4.68 µg/mL, 93% germination inhibition, and 38.4% killing rate within 8 h of exposure. However, the activity against A. flavus was fungistatic; a MIC value of 18.7 µg/mL and 35% conidial germination inhibition, followed by 28.4% killing rate, were noted under similar conditions. Furthermore, endogenous reactive oxygen species (ROS) accumulation was 37.4 and 23.1% in conidial populations of A. fumigatus and A. flavus, respectively. Raman spectroscopy analysis confirmed the possible (but not confirmed) binding of functionalized AuNPs with the chitin and galactomannan components of the cell wall. A potential strategy that involves the exploration of antibacterial drugs using AuNPs as efficient drug carriers may also be appropriate for countering emerging drug resistance in filamentous fungi. © 2024 by the authors.