Drug repositioning: current scenario and future prospective for rewriting saga of drug development

Drug development is a process that demands huge investment of resources and time with only 1 drug candidate successful in reaching market among 10,000 screened taking time duration of 10-15 years and millions of dollars. This high attrition rates discourage investors and researchers. The pharmaceutical industry is shifting its attention away from de novo drug research and towards discovering novel targets and indications for already-approved drugs. In order to accelerate the drug development process with reduced risk of failure and relatively lower costs, pharmaceutical companies have adopted drug repositioning as an alternative. Therefore, a good strategy for drug development would be drug repositioning or drug repurposing, which is to identify, investigate, and exploit new therapeutic uses of already-available, on-market drugs, as well as those that have been withdrawn due to toxicities or that remain on shelves in various stages of development. The outbreak of SARS-COV-19 shows that humanity is constantly vulnerable to epidemics and new microbial attacks and that there is no time to create disease-specific therapies. Consequently, it would seem advantageous to use what is already accessible. Novel therapeutic indications that have previously been approved by the market can reduce investment costs significantly in terms of money, resources, and most importantly, time, as long as they meet PKPD and toxicity standards. Sponsors and pharmaceutical corporations get enthusiastic about additional investments and initiatives related to drug development as a consequence. The upcoming therapeutic revolution, especially with the aid of artificial intelligence, is indicated by the successful applications of several already-available drugs against COVID-19 and the various phases of repurposed drugs against TB, colorectal cancer, Alzheimer’s disease, cervical cancer, and Parkinsonism

Biocompatibility and Bioimaging Application of Carbon Nanoparticles Synthesized by Phosphorus Pentoxide Combustion Method

Carbon nanoforms have emerged as a versatile bioimaging tool. In this work, we have synthesized four different carbon nanoparticles of different dimensions (10–100 nm) and variable fluorescence quantum efficiency (0.007 to 0.37) from four different carbon sources by phosphorus pentoxide-mediated combustion. The fluorescence quantum efficiency of the resulting self-passivated nanoparticles has been empirically correlated to the molecular weight and viscosity of the respective carbon source used in the synthesis. The carbon nanoparticles have been found to be significantly biocompatible as observed in the MTS assay. We have applied these biocompatible luminescent carbon nanoparticles as high brightness fluorescent probes for staining human blood platelets with very high target specificity

Two neutrino positron double beta decay of 106^{106}Cd for 0+→0+0^+ \to 0^+ transition

The two neutrino positron double beta decay of $^{106}$Cd for 0$^{+} \to$ 0$^{+}$ transition has been studied in the Hartree-Fock-Bogoliubov model in conjunction with the summation method. In the first step, the reliability of the intrinsic wave functions of $^{106}$Cd and $^{106}$Pd nuclei has been tested by comparing the theoretically calculated results for yrast spectra, reduced $B(E2$:$0^{+}\to 2^{+})$ transition probabilities, quadrupole moments $Q(2^{+})$ and gyromagnetic factors $g(2^{+})$ with the available experimental data. In the second step, the nuclear transition matrix element $M_{2\nu}$ and the half-life $T_{1/2}^{2\nu}$ for 0$^{+}\to$ 0$^{+}$ transition have been calculated with these wave functions. Moreover, we have studied the effect of deformation on nuclear transition matrix element M$_{2\nu}.$Comment: 20 page

Successfully treated synchronous double malignancy of the breast and esophagus: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of multiple primary cancers is reported to be between 0.3% and 4.3%. The second primary lesion is identified either simultaneously with the primary lesion (synchronous) or after a period of time (metachronous). Few cases of metastasis of breast carcinoma to the esophagus and vice versa have been reported in the past.</p> <p>Case presentation</p> <p>We report an extremely rare case of a 55-year-old Indian woman who had carcinomas in both the esophagus and the breast simultaneously. She was treated successfully using combined modalities of surgery, chemotherapy and radiation therapy.</p> <p>Conclusion</p> <p>Cases of synchronous double malignancies can be treated by dealing with the malignancy in the two sites as independent carcinomas. We have to take into consideration the total dose of radiation to a critical organ as well as the effect of the total dose of toxic chemotherapeutic drugs on our patient.</p

Nuclear deformation and the two neutrino double-\beta decay in ^{124,126}Xe,^{128,130}Te, ^{130,132}Ba and ^{150}Nd isotopes

The two neutrino double beta decay of $^{124,126}$Xe,$^{128,130}$Te, $^{130,132}$Ba and $^{150}$Nd isotopes is studied in the Projected Hartree-Fock-Bogoliubov (PHFB) model. Theoretical 2$\nu$ $\beta^{-}\beta ^{-}$ half-lives of $^{128,130}$Te, and $^{150}$Nd isotopes, and 2$\nu \beta^{+}\beta^{+}$, 2$\nu$ $\beta^{+}EC$ and 2$\nu$ $ECEC$ for $^{124,126}$Xe and $^{130,132}$Ba nuclei are presented. Calculated quadrupolar transition probabilities B(E2: $0^+\to 2^+$), static quadrupole moments and $g$ factors in the parent and daughter nuclei reproduce the experimental information, validating the reliability of the model wave functions. The anticorrelation between nuclear deformation and the nuclear transition matrix element $M_{2\nu}$ is confirmed.Comment: 19 page

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

How to reduce household costs for people with tuberculosis : a longitudinal costing survey in Nepal

The aim of this study was to compare costs and socio-economic impact of tuberculosis (TB) for patients diagnosed through active (ACF) and passive case finding (PCF) in Nepal. A longitudinal costing survey was conducted in four districts of Nepal from April 2018 to October 2019. Costs were collected using the WHO TB Patient Costs Survey at three time points: intensive phase of treatment, continuation phase of treatment and at treatment completion. Direct and indirect costs and socio-economic impact (poverty headcount, employment status and coping strategies) were evaluated throughout the treatment. Prevalence of catastrophic costs was estimated using the WHO threshold. Logistic regression and generalized estimating equation were used to evaluate risk of incurring high costs, catastrophic costs and socio-economic impact of TB over time. A total of 111 ACF and 110 PCF patients were included. ACF patients were more likely to have no education (75% vs 57%, P = 0.006) and informal employment (42% vs 24%, P = 0.005) Compared with the PCF group, ACF patients incurred lower costs during the pretreatment period (mean total cost: US$55 vs US$87, P < 0.001) and during the pretreatment plus treatment periods (mean total direct costs: US$72 vs US$101, P < 0.001). Socio-economic impact was severe for both groups throughout the whole treatment, with 32% of households incurring catastrophic costs. Catastrophic costs were associated with ‘no education’ status [odds ratio = 2.53(95% confidence interval = 1.16–5.50)]. There is a severe and sustained socio-economic impact of TB on affected households in Nepal. The community-based ACF approach mitigated costs and reached the most vulnerable patients. Alongside ACF, social protection policies must be extended to achieve the zero catastrophic costs milestone of the End TB strategy

Phytoremediation of heavy metal-contaminated sites: Eco-environmental concerns, field studies, sustainability issues and future prospects

Environmental contamination due to heavy metals (HMs) is of serious ecotoxicological concern worldwide because of their increasing use at industries. Due to non-biodegradable and persistent nature, HMs cause serious soil/water pollution and severe health hazards in living beings upon exposure. HMs can be genotoxic, carcinogenic, mutagenic, and teratogenic in nature even at low concentration. They may also act as endocrine disruptors and induce developmental as well as neurological disorders and thus, their removal from our natural environment is crucial for the rehabilitation of contaminated sites. To cope with HM pollution, phytoremediation has emerged as a low-cost and eco-sustainable solution to conventional physico-chemical cleanup methods that require high capital investment and labor alter soil properties and disturb soil microflora. Phytoremediation is a green technology wherein plants and associated microbes are used to remediate HM-contaminated sites to safeguard the environment and protect public health. Hence, in view of the above, the present paper aims to examine the feasibility of phytoremediation as a sustainable remediation technology for the management of metals-contaminated sites. Therefore, this paper provides an in-depth review on both the conventional and novel phytoremediation approaches, evaluate their efficacy to remove toxic metals from our natural environment, explore current scientific progresses, field experiences and sustainability issues and revise world over trends in phytoremediation research for its wider recognition and public acceptance as a sustainable remediation technology for the management of contaminated sites in 21st century