In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis

Background: Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/Principal: Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings: The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/Significance: All experiments affirmed the efficacy of suramin against L. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL

Phytochemical Investigation and In Vitro Antioxidant Activity of Syzygium jambos Fruit and Its Seed

Background: Syzygium jambos (L.) Alston is part of the Myrtaceae family. The fruit of this plant is commonly known as “Rose apple”, “Malabar plum” and “Golap-jam” in West Bengal (India). This fruit and its seed have been used in the traditional medicinal system for a long time. Objective: The present study was carried out to investigate the phytochemical screening of different solvent extracts, total phenolic & flavonoid content and 13 different methods of in vitro antioxidant activity (DPPH, ABTS radical scavenging activity, site-specific & non-site-specific hydroxyl radical scavenging activity, superoxide radical scavenging, nitric oxide radical scavenging, PFRAP, FTC, total antioxidant capacity, hydrogen peroxide radical scavenging, TBARS, FRAP & CUPRAC) of Syzygium jambos fruit and its seed. Results: The preliminary phytochemical screening has revealed the presence of phenolics, flavonoids, alkaloids, tannin, saponin, and carbohydrates except for steroids and terpenoids. The total phenolic content & flavonoid content of Syzygium jambos fruit and its seed was found to be (S.jambos fruit -127.61 mg of GAE/100g, S.jambos seed - 217.34 mg of GAE/100g) & ( S.jambos fruit -8.64 mg of QE/100g, S.jambos seed- 15.97 mg of QE/100g) respectively. The fruit and its seed also showed significantly strong antioxidant activity in different in vitro methods. Conclusion: The Syzygium jambos fruit and its seed have an adequate quantity of phytochemicals that act as an antioxidant and scavenge free radicals efficiently. So, the fruit & its seed may be considered as effective in the prevention and treatment of oxidative stress-induced diseases like diabetes, cardiovascular diseases, cancer, arthritis, gout, neurodegenerative diseases, and respiratory tract infections.&nbsp

Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six-Year Observation

Background: HCV infection is very common in multi-transfused β-thalassemia patients who need regular blood transfusions. Aim: The study was conducted to determine the epidemiology of HCV in multi-transfused β-thalassemia patients in West Bengal, India. Methods: Over a span of six years, blood samples were collected from HCV sero-reactive β-thalassemia patients and processed for viral RNA isolation followed by nested RT-PCR for qualitative viremia detection. The HCV genotype was determined by amplifying the partial HCV core gene by nested RT-PCR followed by DNA sequencing and NCBI genotyping tools. Phylogenetic and phylogeographic studies were performed with MEGA-X and BEAST software, respectively. Results: Out of 917 multi-transfused HCV sero-reactive β-thalassemia patients, 598 (65.21%) were HCV RNA positive while 250 (41.80%) had spontaneously cleared the virus. A significant percentage of male patients from rural areas (p = 0.042) and economically backward class (p = 0.002) were at higher risk of HCV infection. Female thalassemia patients and individuals belonging to ages 11–15 years had higher chances of spontaneous clearance. The most prevalent circulatory HCV genotype was 3a (78.26%) followed by 1b (12.04%). Phylogeographic analyses revealed that the 3a strains share genomic similarities with strains from Pakistan, Sri Lanka, and Thailand, whereas the 1b strains share similarities with strains from Thailand, Vietnam, Russia, and China. Uncommon HCV subtypes 3g and 3i were also detected. Conclusion: The high prevalence of HCV infection among β-thalassemia patients of West Bengal, India indicates NAT-based assays should be implemented for HCV screening in donor blood to eliminate HCV by 2030

A novel nanohybrid for cancer theranostics: folate sensitized Fe2O3 nanoparticles for colorectal cancer diagnosis and photodynamic therapy

Organic–inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated Fe2O3 nanoparticles with excellent colloidal stability in water using a hydrothermal method for the theranostics applications. The attachment of FA to Fe2O3 was confirmed using various spectroscopic techniques including FTIR and picosecond resolved fluorescence studies. The nanohybrid (FA–Fe2O3) is a combination of two nontoxic ingredients FA and Fe2O3, showing remarkable photodynamic therapeutic (PDT) activity in human colorectal carcinoma cell lines (HCT 116) via generation of intracellular ROS. The light induced enhanced ROS activity of the nanohybrid causes significant nuclear DNA damage, as confirmed from the comet assay. Assessment of p53, Bax, Bcl2, cytochrome c (cyt c) protein expression and caspase 9/3 activity provides vivid evidence for cell death via an apoptotic pathway. In vitro magnetic resonance imaging (MRI) experiments in folate receptor (FR) overexpressed cancer cells (HCT 116) and FR deficient human embryonic kidney cells (HEK 293) reveal the target specificity of the nanohybrid towards cancer cells, and are thus pronounced MRI contrasting agents for the diagnosis of colorectal cance

The plant alkaloid chelerythrine binds to chromatin, alters H3K9Ac and modulates global gene expression

<p>Chelerythrine (CHL), a plant alkaloid, possesses antimicrobial, anti-inflammatory, and antitumor properties. Although CHL influences several key signal transduction pathways, its ability to interact directly with nucleoprotein complex chromatin, in eukaryotic cells has so far not been looked into. Here we have demonstrated its association with hierarchically assembled chromatin components, viz. long chromatin, chromatosome, nucleosome, chromosomal DNA, and histone H3 and the consequent effect on chromatin structure. CHL was found to repress acetylation at H3K9. It is more target-specific in terms of gene expression alteration and less cytotoxic compared to its structural analog sanguinarine.</p