Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

Background: Leishmania contains a concatenated mitochondrial DNA, kDNA. Universal minicircle sequence binding protein (UMSBP), a mitochondrial protein, initiates kDNA replication by binding with a conserved universal minicircle sequence (UMS) of kDNA. Here, we describe first time in L. donovani the regulation of DNA binding activity of UMSBP and the role of UMSBP in virulence. Methods: Insilco and EMSA study were performed to show UMS-binding activity of UMSBP. Tryparedoxin(TXN)-tryparedoxin peroxidase(TXNPx) assay as well as co-overexpression of cytochrome-b5 reductase-like protein (CBRL) and tryparedoxin in L. donovani were done to know the regulation of DNA binding activity of UMSBP. Knockout and episomal-expression constructs of UMSBP were transfected in L. donovani . The cell viability assay and immunofluorescence study to know the status of kDNA were performed. Macrophages were infected with transfected parasites. mRNA level of cytochrome b, activity of complex-III, intracellular ATP level of both transfected promastigotes and amastigotes as well as ROS concentration and the level of apoptosis of transfected promastigotes were measured. Level of oxidative phosphorylation of both transfected and un-transfected amastigotes were compared. Burden of transfected amastigotes in both macrophages and BALB/c mice were measured. Results: L. donovani UMSBP is capable of binding with UMS, regulated by redox through mitochondrial enzymes, TXN, TXNPx and CBRL. Depletion of UMSBP (LdU ^−/− ) caused kDNA loss, which decreased cytochrome-b expression [component of complex-III of electron transport chain (ETC)] and leads to the disruption of complex-III activity, decreased ATP generation, increased ROS level and promastigotes exhibited apoptosis like death. Interestingly, single knockout of UMSBP (LdU ^−/+ ) has no effect on promastigotes survival. However, single knockout in intracellular amastigotes demonstrate loss of mRNA level of cytochrome-b, disruption in the activity of complex-III and reduced production of ATP in amastigotes than wild type. This process interfere with the oxidative-phosphorylation and thereby completely inhibit the intracellular proliferation of LdU ^−/+ amastigotes in human macrophages and in BALB/c mice. Amastigotes proliferation was restored as wild type after episomal expression of LdUMSBP in LdU ^−/+ parasites (LdU ^−/+ AB). Conclusion: The LdUMSBP regulates leishmanial mitochondrial respiration and pathogenesis. So, LdUMSBP may be an attractive target for rational drug designing and LdU ^−/+ parasites could be considered as a live attenuated vaccine candidate against visceral leishmaniasis.

Lipid metabolism plays a decisive role in host-pathogen interactions and immune regulation, with apolipoproteins (Apo) being central to this process. However, their role in leishmaniasis remains unexplored. Herein, we deliberate the immunoregulatory function of ApoA1 during Leishmania donovani infection using THP-1-derived macrophages alone and in combination with T lymphocytes derived from human PBMC. We found low serum ApoA1 levels in active VL and PKDL than in healthy controls. It was shown that direct interaction of ApoA1 with ABCA1 (ATP-binding cassette transporter A1) on macrophages promotes cholesterol efflux, reflected by increased HDL levels and reduced total cellular cholesterol. This phenomenon was associated with reduced Leishmania infectivity and its downstream signaling in macrophages, i.e., downregulation of PPAR-γ and the endoplasmic reticulum-stress marker CHOP. Additionally, ApoA1 in the presence of extracellular HDL slightly promoted macrophage polarization towards M1, as indicated by increased expression of IL-12 and iNOS2 or nitric oxide production, alongside reduced expression of M2 phenotype-associated markers, including IL-10 and arginase. In co-culture with PBMC-derived T-cells, ApoA1-primed macrophages facilitated Th1 polarization, as demonstrated by increased IFN-γ and STAT1, and indirectly by reduced expression of Th2-specific markers (GATA-3 and IL-4). Overall, these results implicate ApoA1 as a vital immunomodulatory factor and potential therapeutic target in leishmaniasis.