Immunotherapy and immunochemotherapy in combating visceral leishmaniasis.

Visceral leishmaniasis (VL), a vector-borne disease, is caused by an obligate intramacrophage, kinetoplastid protozoan parasite of the genus Leishmania. Globally, VL is construed of diversity and complexity concerned with high fatality in tropics, subtropics, and Mediterranean regions with ~50,000-90,000 new cases annually. Factors such as the unavailability of licensed vaccine(s), insubstantial measures to control vectors, and unrestrained surge of drug-resistant parasites and HIV-VL co-infections lead to difficulty in VL treatment and control. Furthermore, VL treatment, which encompasses several problems including limited efficacy, emanation of drug-resistant parasites, exorbitant therapy, and exigency of hospitalization until the completion of treatment, further exacerbates disease severity. Therefore, there is an urgent need for the development of safe and efficacious therapies to control and eliminate this devastating disease. In such a scenario, biotherapy/immunotherapy against VL can become an alternative strategy with limited side effects and no or nominal chance of drug resistance. An extensive understanding of pathogenesis and immunological events that ensue during VL infection is vital for the development of immunotherapeutic strategies against VL. Immunotherapy alone or in combination with standard anti-leishmanial chemotherapeutic agents (immunochemotherapy) has shown better therapeutic outcomes in preclinical studies. This review extensively addresses VL treatment with an emphasis on immunotherapy or immunochemotherapeutic strategies to improve therapeutic outcomes as an alternative to conventional chemotherapy.

Naringenin-Functionalized Gold Nanoparticles and Their Role in α-Synuclein Stabilization.

Misfolding and self-assembly of several intrinsically disordered proteins into ordered ß-sheet-rich amyloid aggregates emerged as hallmarks of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Here we show how the naringenin-embedded nanostructure effectively retards aggregation and fibril formation of α-synuclein, which is strongly associated with the pathology of Parkinson's-like diseases. Naringenin is a polyphenolic compound from a plant source, and in our current investigation, we reported the one-pot synthesis of naringenin-coated spherical and monophasic gold nanoparticles (NAR-AuNPs) under optimized conditions. The average hydrodynamic diameter of the produced nanoparticle was ∼24 nm and showed a distinct absorption band at 533 nm. The zeta potential of the nanocomposite was ∼-22 mV and indicated the presence of naringenin on the surface of nanoparticles. Core-level XPS spectrum analysis showed prominent peaks at 84.02 and 87.68 eV, suggesting the zero oxidation state of metal in the nanostructure. Additionally, the peaks at 86.14 and 89.76 eV were due to the Au-O bond, induced by the hydroxyl groups of the naringenin molecule. The FT-IR analysis further confirmed strong interactions of the molecule with the gold nanosurface via the phenolic oxygen group. The composite surface was found to interact with monomeric α-synuclein and caused a red shift in the nanoparticle absorption band by ∼5 nm. The binding affinity of the composite nanostructure toward α-synuclein was in the micromolar range (Ka∼ 5.02 × 106 M-1) and may produce a protein corona over the gold nanosurface. A circular dichroism study showed that the nanocomposite can arrest the conformational fluctuation of the protein and hindered its transformation into a compact cross-ß-sheet conformation, a prerequisite for amyloid fibril formation. Furthermore, it was found that naringenin and its nanocomplex did not perturb the viability of neuronal cells. It thus appeared that engineering of the nanosurface with naringenin could be an alternative strategy in developing treatment approaches for Parkinson's and other diseases linked to protein conformation.