Browsing by Author "Kushawaha, Pramod Kumar"

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    Bilayer fixed-dose combination tablet for curcumin microparticles and piroxicam and i n vitro evaluation
    (Newlands Press Ltd, 2023-02-07T00:00:00) Handa, Mayank; Kumar, Kamlesh; Garabadu, Debapriya; Kushawaha, Pramod Kumar; Shukla, Rahul
    Aim: In the present work, fixed-dose combination of bilayer tablets for piroxicam as and curcumin as immediate-release and sustained-release layer (SRL) respectively for management of inflammatory response. Materials & methods: The SRL include Curcumin polycaprolactone microparticles from spray drying. The tablet layers include Pearlitol 200SD, Microcrystalline cellulose PH101, Aerosil 200, talc each layer. Results: SEM studies confirm spherical microparticles. PXRD and DSC studies confirm the amorphous microparticles. In vitro studies exhibit, an immediate release and sustained release for Piroxicam and Curcumin after 2 h. Cellular uptake studies on RAW 264.7 cells confirm the complete internalization of microparticles. Conclusion: Therefore, it was concluded that microparticles can be formulated into a unit dosage form for the management of inflammation. � 2023 Newlands Press.
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    Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism
    (Springer Science and Business Media Deutschland GmbH, 2023-10-26T00:00:00) Om, Hari; Chand, Umesh; Kushawaha, Pramod Kumar
    Introduction: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy. Key findings: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment. Significance: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients. Graphical abstract: [Figure not available: see fulltext.]. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism
    (Springer Science and Business Media Deutschland GmbH, 2023-10-26T00:00:00) Om, Hari; Chand, Umesh; Kushawaha, Pramod Kumar
    Introduction: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy. Key findings: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment. Significance: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients. Graphical abstract: [Figure not available: see fulltext.]. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Interferon inducible guanylate binding protein 1 restricts the growth of Leishmania donovani by modulating the level of cytokines/chemokines and MAP kinases
    (Academic Press, 2022-05-09T00:00:00) Kumar, Ravindra; Kushawaha, Pramod Kumar
    Visceral Leishmaniasis (VL) is a zoonotic chronic endemic infectious disease caused by Leishmania donovani infection and a well-studied model for intracellular parasitism. Guanylate binding proteins (GBPs) are induced by interferons (IFNs), and play a crucial role in cell autonomous immunity and the regulation of inflammation. Guanylate-binding protein 1 (GBP1) has been shown vital for the host immune response against various pathogens. However, the role of GBP1 during VL is undefined. In the present study, we have investigated the role of GBP1 in Leishmania donovani infection using in vitro model. For that, knock down of the Gbp1 gene was carried out in both PMA differentiated human monocyte cell line THP-1 and mouse macrophages RAW264.7 cell line using siRNA based RNA interference. Infection of these cell lines revealed a high parasite load in knock down cells at 24 and 48h post infection as compared to control cells. A significant increase was observed in the level of different cytokines (IL-4, IL-10, IL-12b, IFN-?, TNF-?) and chemokines (CXCL9, CXCL 10, and CXCL 11) in GBP1 knock down cell lines after post-infection. In GBP1 knock down cells the expression level of IFN effector molecules (iNOS and PKR) was found to be elevated in THP1 cells and remained almost unchanged in RAW264.7 cells after Leishmania donovani infection as compared to the control cells. Moreover, interestingly, the level of MAPK activated ERK1/2, and p38 MAPK were considerably induced by the parasite in knock down cells as compared to control after 24 h post-infection. This study, first time reported the involvement of GBP1 in Leishmania donovani infection by modulating the level of important cytokines, chemokines, IFN effector molecules, and MAP kinases. � 2022 Elsevier Ltd
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    Interferon inducible guanylate binding protein 1 restricts the growth of Leishmania donovani by modulating the level of cytokines/chemokines and MAP kinases
    (Academic Press, 2022-05-09T00:00:00) Kumar, Ravindra; Kushawaha, Pramod Kumar
    Visceral Leishmaniasis (VL) is a zoonotic chronic endemic infectious disease caused by Leishmania donovani infection and a well-studied model for intracellular parasitism. Guanylate binding proteins (GBPs) are induced by interferons (IFNs), and play a crucial role in cell autonomous immunity and the regulation of inflammation. Guanylate-binding protein 1 (GBP1) has been shown vital for the host immune response against various pathogens. However, the role of GBP1 during VL is undefined. In the present study, we have investigated the role of GBP1 in Leishmania donovani infection using in vitro model. For that, knock down of the Gbp1 gene was carried out in both PMA differentiated human monocyte cell line THP-1 and mouse macrophages RAW264.7 cell line using siRNA based RNA interference. Infection of these cell lines revealed a high parasite load in knock down cells at 24 and 48h post infection as compared to control cells. A significant increase was observed in the level of different cytokines (IL-4, IL-10, IL-12b, IFN-?, TNF-?) and chemokines (CXCL9, CXCL 10, and CXCL 11) in GBP1 knock down cell lines after post-infection. In GBP1 knock down cells the expression level of IFN effector molecules (iNOS and PKR) was found to be elevated in THP1 cells and remained almost unchanged in RAW264.7 cells after Leishmania donovani infection as compared to the control cells. Moreover, interestingly, the level of MAPK activated ERK1/2, and p38 MAPK were considerably induced by the parasite in knock down cells as compared to control after 24 h post-infection. This study, first time reported the involvement of GBP1 in Leishmania donovani infection by modulating the level of important cytokines, chemokines, IFN effector molecules, and MAP kinases. � 2022 Elsevier Ltd
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    Nano-immunomodulators: prospective applications to combat drug resistant bacterial infections and related complications
    (Taylor and Francis Ltd., 2023-11-08T00:00:00) Chand, Umesh; Kushawaha, Pramod Kumar
    Antimicrobial resistance (AMR) is a growing problem in our healthcare sector, it can make infections more difficult and expensive to treat and lead to treatment failure and increased risk of death. Currently, at least 700,000 people worldwide die each year from AMR. Alternative methods for mitigating drug-resistant bacterial infections are desperately needed because of the unacceptably low rate of conventional antibiotic discovery. Therefore, the implementation of various therapeutic strategies is necessary to deal with drug-resistant bacteria and immunomodulation is one of them which is highly encouraged through various studies. Immunomodulators are different biological or synthetic substances that possess the capability of inducing, suppressing, or overall modulating the innate and adaptive immune system. Some phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, peptides, synthetic molecules, and synthetic biomaterials, can play a crucial role in the fight against bacterial infections directly or indirectly by enhancing the activity of existing antibiotics or by boosting immunity. Nanotechnology can be used to modulate immune responses through various fabrication methods and strategies of design and for drug formulation by encapsulating potential compounds/molecules in the form of nanoparticles and by surface modification or capping of nanomaterials. This approach can improve drug solubility, stability, and bioavailability, reduce toxicity, and help to increase the effectiveness of drugs against resistant microorganisms. This review aims to provide current developments in the field of immunomodulators of different origins that can be combined with nanotechnology and exploited as potential future drugs or adjuvants to fight drug-resistant bacterial pathogens. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Nano-immunomodulators: prospective applications to combat drug resistant bacterial infections and related complications
    (Taylor and Francis Ltd., 2023-11-08T00:00:00) Chand, Umesh; Kushawaha, Pramod Kumar
    Antimicrobial resistance (AMR) is a growing problem in our healthcare sector, it can make infections more difficult and expensive to treat and lead to treatment failure and increased risk of death. Currently, at least 700,000 people worldwide die each year from AMR. Alternative methods for mitigating drug-resistant bacterial infections are desperately needed because of the unacceptably low rate of conventional antibiotic discovery. Therefore, the implementation of various therapeutic strategies is necessary to deal with drug-resistant bacteria and immunomodulation is one of them which is highly encouraged through various studies. Immunomodulators are different biological or synthetic substances that possess the capability of inducing, suppressing, or overall modulating the innate and adaptive immune system. Some phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, peptides, synthetic molecules, and synthetic biomaterials, can play a crucial role in the fight against bacterial infections directly or indirectly by enhancing the activity of existing antibiotics or by boosting immunity. Nanotechnology can be used to modulate immune responses through various fabrication methods and strategies of design and for drug formulation by encapsulating potential compounds/molecules in the form of nanoparticles and by surface modification or capping of nanomaterials. This approach can improve drug solubility, stability, and bioavailability, reduce toxicity, and help to increase the effectiveness of drugs against resistant microorganisms. This review aims to provide current developments in the field of immunomodulators of different origins that can be combined with nanotechnology and exploited as potential future drugs or adjuvants to fight drug-resistant bacterial pathogens. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Staphylococcus aureus vaccine strategy: Promise and challenges
    (Elsevier GmbH, 2023-03-13T00:00:00) Chand, Umesh; Priyambada, Pragnya; Kushawaha, Pramod Kumar
    Staphylococcus aureus (S. aureus) is a leading and crucial infectious threat to global public health due to the widespread emergence of antibiotic-resistant strains such as Methicillin-Resistant S. aureus (MRSA). MRSA infects immunocompromised patients and healthy individuals and has rapidly spread from the healthcare setting to the outside community. The development of flawless vaccines become a medical need worldwide against multi-drug resistant S. aureus. Therefore, protection by an immune-based strategy may provide valuable measures to contain the spread of invasive S. aureus infections. Several vaccine candidates have been prepared which are either in the preclinical phase or in the early clinical phase, whereas several candidates have failed to show a protective efficacy in human subjects. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Several approaches have also been made to the development of monoclonal or polyclonal antibodies for passive immunization to protect against S. aureus infections. In recent years, a multi-epitope vaccine has emerged as a novel platform for subunit vaccine design by using computational approaches. Therefore, in this review, we have summarized and discussed the mechanistic overview of different strategies used to develop potential vaccine candidates and passive interventions which are in different stages of clinical trials to fight multi-drug resistant S. aureus infections. � 2023 Elsevier GmbH
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    Staphylococcus aureus vaccine strategy: Promise and challenges
    (Elsevier GmbH, 2023-03-13T00:00:00) Chand, Umesh; Priyambada, Pragnya; Kushawaha, Pramod Kumar
    Staphylococcus aureus (S. aureus) is a leading and crucial infectious threat to global public health due to the widespread emergence of antibiotic-resistant strains such as Methicillin-Resistant S. aureus (MRSA). MRSA infects immunocompromised patients and healthy individuals and has rapidly spread from the healthcare setting to the outside community. The development of flawless vaccines become a medical need worldwide against multi-drug resistant S. aureus. Therefore, protection by an immune-based strategy may provide valuable measures to contain the spread of invasive S. aureus infections. Several vaccine candidates have been prepared which are either in the preclinical phase or in the early clinical phase, whereas several candidates have failed to show a protective efficacy in human subjects. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Several approaches have also been made to the development of monoclonal or polyclonal antibodies for passive immunization to protect against S. aureus infections. In recent years, a multi-epitope vaccine has emerged as a novel platform for subunit vaccine design by using computational approaches. Therefore, in this review, we have summarized and discussed the mechanistic overview of different strategies used to develop potential vaccine candidates and passive interventions which are in different stages of clinical trials to fight multi-drug resistant S. aureus infections. � 2023 Elsevier GmbH
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    Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in�vitro cellular studies
    (Taylor and Francis Ltd., 2023-03-05T00:00:00) Reddy, Gayathri Aparnasai; Handa, Mayank; Garabadu, Debapriya; Kumar, Ravindra; Kushawaha, Pramod Kumar; Shukla, Rahul
    Purpose: Complicated intra-abdominal infection (cIAI) management involves administering antibiotics that destroy the cell wall and the genesis of bacterial lipopolysaccharide (LPS). During the infectious state, the expression of transferrin receptors upregulates on the intestinal epithelial cells, which are considered the site of infection. In the present research, transferrin decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulated moxifloxacin (MOX) were developed for possible targeting of the receptors in the colon. Significance: This study will explore more about the incorporation of transferrin as effective coating material in targeted drug delivery. Methods: Nanoparticles were prepared using nano-emulsification and surface modification with transferrin was done by layer-by-layer methodology and evaluated by powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), FTIR, SEM, antibacterial activity, and cellular uptake studies. Results: The formulated NPs exhibit a size of ?170 nm, PDI�?�0.25, zeta potential�??4.0 mV, drug loading�?�6.8%, and entrapment efficiency of 82%. Transferrin-decorated NPs exhibit tailored release for almost 12 h and in�vitro antibacterial activity for 14 h. The cellular uptake studies were done on a RAW264.7 cell line for better determination of transferrin uptake of fabricated NPs. Conclusion: The above study circumvents around the preparation of transferrin decorated PLGA encumbered MOX NPs intended for cIAI-induced sepsis. PLGA NPs provide tailored release of MOX with primary burst and followed by sustained release. These observations confines with antibacterial activity studies. The prepared transferrin-coated NPs were stable and effectively uptaken by RAW264.7 cells. However, future studies include the preclinical investigation of these NPs in sepsis-induced murine models. � 2023 Informa UK Limited, trading as Taylor & Francis Group.