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Abstract: Plant derived natural products have multifaceted beneficial roles in human pathophysiology. Plant secondary metabolites have been used as an adjunct medicine for a long time and β- Glucogallin is one such pharmaceutically important plant derived natural product. Β-glucogallin (1-O-galloyl-β-d-glucopyranose), a plant-derived polyphenolic ester, is regarded as the primary metabolite in the biosynthesis of hydrolyzable tannins. It is majorly found in amla, pomegranate, strawberry etc. Owing to its free radical scavenging properties, β-glucogallin (BG) is believed to protect against several diseases like diabetes and related complications like retinopathy, glaucoma, inflammation, hepatic damage, skin damage from UV, etc. Several semisynthetic derivatives of β-Glucogallin are being developed, which have better pharmacokinetic and pharmacodynamic parameters than β-glucogallin. Studies have shown the prophylactic role of β-Glucogallin in developing defence mechanisms against the advent and progression of certain diseases. β- glucogallin formulations have shown a positive effect as a neutraceutical. In this manuscript, we have discussed β-glucogallin, its natural sources, biosynthetic pathways, its semi-synthetic derivatives, and the plethora of its pharmacological activities like antioxidant-antiinflammatory, antidiabetic, cataract-preventing, anti glaucoma, and UV protectant. We have also highlighted various biological pathways, which are modulated by β-glucogallin. The manuscript will convey the importance of β-glucogallin as a compound of natural origin, having multifaceted health benefits.

Abstract: Homeopathy is a widely practiced alternate system of medicine around the world that employs small doses of various medicines to promote auto-regulation and self-healing. It is among the most commonly used alternative approaches in cancer and other diseases and alternative thera-peutic systems. It is widely used as palliative and as supportive therapy in cancer patients. Few cas-es have been reported on patients using homeopathy after surgery, radiotherapy, and chemotherapy, generally for overcoming side effects. The dose of Homoeopathic medicines and their mechanism of action in cancer has also been documented, while clinical trials on the effects of Homoeopathy in cancer treatment are rare. It is found that the anticancer potential of homeopathic medicines is re-ported for different cancer types, which show their efficacy through apoptosis and immune system modulation. Homeopathic treatment is an add-on to conventional therapy, with almost no interac-tion with the conventional drugs due to the small dose, and is largely attributed to improving lives by providing symptomatic relief, increasing survival time and boosting patient immunity. This re-view explores the accountability of the homeopathic system of medicine by highlighting some of the most commonly used homeopathic drugs for different types of cancers.

Abstract: Recent studies have shed light on the role of epigenetic marks in certain diseases like cancer, type II diabetes mellitus (T2DM), obesity, and cardiovascular dysfunction, to name a few. Epigenetic marks like DNA methylation and histone acetylation are randomly altered in the disease state. It has been seen that methylation of DNA and histones can result in down-regulation of gene expression, whereas histone acetylation, ubiquitination, and phosphorylation are linked to enhanced expression of genes. How can we precisely target such epigenetic aberrations to prevent the advent of diseases? The answer lies in the amalgamation of the efficient genome editing technique, CRISPR, with certain effector molecules that can alter the status of epigenetic marks as well as employ certain transcriptional activators or repressors. In this review, we have discussed the rationale of epigenetic editing as a therapeutic strategy and how CRISPR-Cas9 technology coupled with epigenetic effector tags can efficiently edit epigenetic targets. In the later part, we have discussed how certain epigenetic effectors are tagged with dCas9 to elicit epigenetic changes in cancer. Increased interest in exploring the epigenetic background of cancer and non-communicable diseases like type II diabetes mellitus and obesity accompanied with technological breakthroughs has made it possible to perform large-scale epigenome studies.

Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.

Visceral leishmaniasis (VL) is a serious public health concern in the Indian state of Bihar, which has been exacerbated by an increasing HIV/AIDS incidence that has resulted in poor clinical outcomes. So far, there has been no investigation into the knowledge, attitude, and practices (KAP) of people who have been subjected to hospital-based supervision for VL or HIV/VL co-infection. This study assessed the KAP toward VL infection among 210 VL-infected patients (126 participants with VL and 84 participants with HIV/VL) using a pretested standard questionnaire. The findings are summarized descriptively and KAP scores are classified dichotomously (good/poor). Multivariable logistic regression and bivariate correlation were used in the analysis. The study showed that both VL-infected and co-infected patients exhibited similar deficits in KAP scores toward VL. The HIV/VL participants who had a personal or family history of VL were more likely to have appropriate awareness of and preventive practices toward VL. The independent predictors of attitude index in HIV/VL participants were education, VL family history, and marital status. There was a weak but significant positive correlation between knowledge and practice (rs = 0.321, prs = 0.294, prs = 0.634, p

The fascinating discovery of the first giant virus, Acanthamoeba polyphaga mimivirus (APMV), belonging to the family Mimiviridae in 2008, and its associated virophage, Sputnik, have left the world of microbiology awestruck. To date, about 18 virophages have been isolated from different environmental sources. With their unique feature of resisting host cell infection and lysis by giant viruses, analogous to bacteriophage, they have been assigned under the family Lavidaviridae. Genome of T-27, icosahedral-shaped, non-enveloped virophages, consist of dsDNA encoding four proteins, namely, major capsid protein, minor capsid protein, ATPase and cysteine protease, which are essential in the formation and assembly of new virophage particles during replication. A few virophage genomes have been observed to contain additional sequences like PolB, ZnR and S3H. Another interesting characteristic of virophage is that Mimivirus lineage A is immune to infection by the Zamilon virophage through a phenomenon termed MIMIVIRE, resembling the CRISPR-Cas mechanism in bacteria. Based on the fact that giant viruses have been found in clinical samples of hospital-acquired pneumonia and rheumatoid arthritis patients, virophages have opened a novel era in the search for cures of various diseases. This article aims to study the prospective role of virophages in the future of human therapeutics.

The study of tropical diseases like leishmaniasis, a parasitic disease, has not received much attention even though it is the second-largest infectious disease after malaria. As per the WHO report, a total of 0.7–1.0 million new leishmaniasis cases, which are spread by 23 Leishmania species in more than 98 countries, are estimated with an alarming 26,000–65,000 death toll every year. Lack of potential vaccines along with the cost and toxicity of amphotericin B (AmB), the most common drug for the treatment of leishmaniasis, has raised the interest significantly for new formulations and drug delivery systems including nanoparticle-based delivery as anti-leishmanial agents. The size, shape, and high surface area to volume ratio of different NPs make them ideal for many biological applications. The delivery of drugs through liposome, polymeric, and solid-lipid NPs provides the advantage of high biocomatibilty of the carrier with reduced toxicity. Importantly, NP-based delivery has shown improved efficacy due to targeted delivery of the payload and synergistic action of NP and payload on the target. This review analyses the advantage of NP-based delivery over standard chemotherapy and natural product-based delivery system. The role of different physicochemical properties of a nanoscale delivery system is discussed. Further, different ways of nanoformulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite. The status of current nano-vaccines and the future potential of NP-based vaccine are elaborated here.

Herein, we develop a competitive screening method in which G-quadruplex DNA linked magnetic nanoparticles pull down selective ligands for a particular quadruplex topology from a series of small molecules. The screening strategy is first optimized with known G-quadruplex ligands and then used with a new series of G-quadruplex interactive bis-triazolyl ligands that are synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition. The assay enables the identification of c-MYC and BCL2 G-quadruplex selective bis-triazole ligands that specifically target promoter G-quadruplexes in cancer cells.

G-quadruplexes are well-known DNA secondary structures which can be formed both within the DNA and the RNA sequences of the human genome. While many functions of G-quadruplex during cell regulatory events are still unknown, a number of reports have established their role in finding new cancer therapies. In this report, we provide a detailed account of Thioflavin T (ThT) interacting with a promoter gene (c-Myc) which has relevance in several types of human cancers. Using a variety of spectroscopic techniques, we have shown that the binding of ThT is selective to c-Myc G-quadruplex only, having poor interactions with the duplex DNA sequences. UV–Visible titration experiments show that binding involves stacking interactions which were further corroborated by CD experiments. Fluorescence studies showed that the binding of ThT to c-Myc G-quadruplex results in a large increase in the fluorescence emission spectrum of c-Myc G-quadruplex while the same to duplex DNAs was much poor. Binding of ThT to c-Myc G-quadruplex results in thermal stabilization of the quadruplex DNA by up to 7.4 °C and Job plot experiments demonstrated the presence of 1:1 and 2:1 ligand to quadruplex complexes. Finally, the docking study suggested that ThT stacks with the guanine bases in one of the grooves which is in agreement with the CD studies. These results are expected to provide leads into the design of new ThT analogs and derivatives for enhancing the stability and selectivity of new G-quadruplex targeting ligands.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has emerged into a global health and economic menace. Amidst the COVID-19 turmoil, recent failures/uncertain outcomes in clinical trials involving the anti-malarial (hydroxychloroquine), anti-viral (remdesivir) or the combination of anti-malarial/antibiotic (hydroxychloroquine/azithromycin) regimens have predisposed the physicians to distrust these "highly-touted" drugs for COVID-19. In this milieu, immunotherapy might be a credible modality to target or modify specific/non-specific immune responses that interfere with the survival of intracellular pathogens. This scientific review throws light on the epidemiology of COVID-19, its pathogenesis and the current clinical scenario of immunotherapeutics including convalescent plasma (CP), type-1 interferons (IFN-I) and human monoclonal antibodies (mAbs) to combat COVID-19. The treatment outcomes underscore that immunotherapy might be a reliable tool to assuage COVID-19-associated immunopathology. However, specific patient pool studies are warranted to ascertain the precise (re)purposing of immunotherapeutics for COVID-19.