Oleuropein (OLP) holds promise as a therapeutic candidate for both Plasmodium falciparum infection and cancer. It modulates the phosphoinositide 3-kinase (PI3K)-Akt1 signaling pathway to regulate inflammation and restore immune homeostasis. Moreover, it influences the cell death/autophagy axis, along with increasing the antimalarial efficacy of artemisinin.
View Article and Find Full Text PDFBreast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character.
View Article and Find Full Text PDFDrug resistance in presents a formidable challenge to the humanity. And, unavailability of an effective vaccine worsens the situation further. Autophagy is one of the mechanisms employed by parasite to evade drug pressure to survive.
View Article and Find Full Text PDFThe suboptimal efficacies of existing anti-malarial drugs attributed to the emergence of drug resistance dampen the clinical outcomes. Hence, there is a need for developing novel drug and drug targets. Recently silver nanoparticles (AgNPs) constructed with the leaf extracts of Euphorbia cotinifolia were shown to possess antimalarial activity.
View Article and Find Full Text PDFThe anti-inflammatory activity of a phytocompound (oleuropein [OLP]) in the lipopolysaccharide (LPS)-mimicked macrophage model of inflammation demonstrates the importance of PI3K-Akt1 signaling in establishing "immune homeostasis." Here, we present a protocol for the cultivation of in vitro cultures of P. falciparum for carrying out drug sensitivity assays.
View Article and Find Full Text PDFAntimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis.
View Article and Find Full Text PDFBackground: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events.
Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively.
Poly(I:C) and R848, synthetic ligands that activate Toll-like receptor 3 (TLR3) and TLR7/8 respectively, have been well-established for their ability to stimulate the immune system and induce antigen-specific immune responses. These ligands are capable of inducing the production of cytokines and chemokines, and hence support the activation and differentiation of B and T cells. We saw the long-lasting and perdurable immune responses by these adjuvants essentially required for an efficacious subunit vaccine.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is an inflammatory, autoimmune and connective-tissue arthropathy. The methotrexate (MTX) and aceclofenac (ACL) combination drug regimen is known to regulate the immunological pathways. Also, RA-elicited inflammation is decreased by the combination drug treatment.
View Article and Find Full Text PDFImmunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink".
View Article and Find Full Text PDFThe innate lymphoid cell (ILC) system comprising of the circulating and tissue-resident cells is known to clear infectious pathogens, establish immune homeostasis as well as confer antitumor immunity. Human natural killer cells (hNKs) and other ILCs carry out mopping of the infectious pathogens and perform cytolytic activity regulated by the non-adaptive immune system. The NK cells generate immunological memory and rapid recall response tightly regulated by the adaptive immunity.
View Article and Find Full Text PDFInterferon-γ (IFN-γ)-producing natural killer (NK) cells and innate lymphoid cells (ILCs) activate the adaptive system's B and T cells in response to pathogenic invasion; however, how these cells are activated during infections is not yet fully understood. In recent years, a new lymphocyte population referred to as "natural killer-like B (NKB) cells", expressing the characteristic markers of innate NK cells and adaptive B cells, has been identified in both the spleen and mesenteric lymph nodes during infectious and inflammatory pathologies. NKB cells produce IL-18 and IL-12 cytokines during the early phases of microbial infection, differentiating them from conventional NK and B cells.
View Article and Find Full Text PDFDevelopment of resistance by the malaria parasite, a systemic inflammatory and infectious pathogen, has raised the need for novel efficacious antimalarials. Plant-derived natural compounds are known to modulate the immune response and eradicate the infectious pathogens. Therefore we carried out experiments with swertiamarin to dissect its anti-inflammatory and immunomodulatory potential.
View Article and Find Full Text PDFAceclofenac (ACE), a cyclooxygenase-2 inhibitor, is the derivative of the diclofenac group that has been in use for the symptomatic treatment of systemic inflammatory autoimmune disease, rheumatoid arthritis (RA). Partial solubility, high lipophilic nature, and stability challenge its use in developing topical formulations. Hence, we developed and characterized nanostructured lipid carrier (NLC)-based ACE (ACE-NLC) hydrogel for an efficient transdermal delivery.
View Article and Find Full Text PDFCrohn's disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response.
View Article and Find Full Text PDFExtensive research conducted on mouse-human chimeras has advanced our understanding on infectious diseases including the human-malaria parasite, . culture of asexual-blood stage infection of does not answer all questions related to parasitology, pharmacology and immunology, and complex life cycle, complicated genome, evolution of drug resistance and poor diagnosis makes it difficult to understand the patho-biology of parasite. Unavailability of effective-vaccine and issues of drug resistance advocates the use of human cell/tissues reconstituted immunodeficient-mice to A number of immunodeficient-strains (TK/NOG, FRG/NOD, NOD/SCID/IL-2 receptor γ chain , NOD severe combined immunodeficiency gamma [NSG] mouse and NOD.
View Article and Find Full Text PDFThe present study was designed to develop pH-sensitive lipid polymer hybrid nanoparticles (pHS-LPHNPs) for specific cytosolic-delivery of docetaxel (DTX). The pHS-LPHNPs-DTX formulation was prepared by self-assembled nano-precipitation technique and characterized for zeta potential, particle size, entrapment efficiency, polydispersity index (PDI), and in vitro drug release. In vitro cytotoxicity of pHS-LPHNPs-DTX was assessed on breast cancer cells (MDA-MB-231 and MCF-7) and compared with DTX-loaded conventional LPHNPs and bare DTX.
View Article and Find Full Text PDFRegulatory T (T) cells are essential to maintain immune homeostasis in the intestine and T cell dysfunction is associated with several inflammatory and autoimmune disorders including inflammatory bowel disease (IBD). Efforts using low-dose (LD) interleukin-2 (IL-2) to expand autologous T cells show therapeutic efficacy for several inflammatory conditions. Whether LD IL-2 is an effective strategy for treating patients with IBD is unknown.
View Article and Find Full Text PDFTransdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (MSP-Fu) of exhibited improved immunogenic responses.
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