CHEMOTHERAPEUTIC POTENTIAL OF NOVEL XANTHONE SOURCED FROM SWERTIA CHIRATA AGAINST SKIN CARCINOGENESIS

Objective: Swertia chirata forms a rich source of bio-active compounds, among which xanthones form an important part. Among the xanthones present in it, 1,5,8 Tri-hydroxy-3-methoxy xanthone (TMX) was found to be the most active. The present study aims to evaluate the chemotherapeutic potential of it against metastatic skin cancer cell lines. Methods: In this study, the antitumor activity of TMX (the active component of chirata plant) was evaluated in A431, SKMEL-5, and A375 cell line by using in-vitro assays such as cell viability assay, cell cycle analysis, caspase 3 activity assay, intracellular reactive oxygen species (ROS) level determination by dichlorofluorescein diacetate, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: In vitro studies showed that TMX from S. chirata exhibited significant antitumor activity by inducing apoptosis and restricting proliferation in both melanoma and non-melanoma skin cancer cell lines, but no such activity was seen in normal skin cancer cell line WS1. The qRT-PCR analysis revealed that in both the melanoma ad non-melanoma cell lines, TMX could exert its antitumor activity by downregulating c-Myc, cyclin-D1, and β-catenin and up-regulating Wnt antagonist gsk-3β, thereby suppressing wnt self-renewal pathway, but such regulation was absent in normal cell line. Conclusions: TMX from chirata could effectively inhibit the proliferation of metastatic skin cancer (both melanoma and non-melanoma) cell lines while being non-toxic to normal cell lines. The chemotherapeutic potential of TMX against metastatic skin cancer cell lines was achieved by downregulating several key regulatory genes enabling the suppression of the self-renewal pathway, the chief reason behind the invasiveness of cancer cells

Understanding the perspectives of frontline health workers (ASHAs, Anganwadi workers & ANMs) in Bundelkhand region to improve COVID-19 containment efforts

Community health workers (CHWs) have been the backbone of the fight against the COVID-19 pandemic in India. CHWs (such as ASHA workers, Anganwadi workers, and ANMs) have played a key role in preparing the national health system for the hyperbolic rise in COVID-19 cases and containing the spread of the virus at the ground level. Owing to their embeddedness in their communities, these CHWs can offer unique insight into our community-based COVID-19 responses. Despite this, the voices of health workers have been largely ignored in policy prescriptions and initiatives. In this short-term study, SRIJAN (Self Reliant Initiatives through Joint Action) aims to address this research gap. It covers the experiences and perspectives of CHWs fighting the COVID-19 pandemic in Bundelkhand, one of the poorest regions in rural India. In capturing the ground-reality in Bundelkhand, Stutilina Pal and Devanik Saha attempt to document the lessons learnt from the past year and incorporate them into future responses to health crises

Fabrication of 108^{108}Cd target for the astrophysical p-process studies

The detailed process of preparing enriched $^{108}$Cd targets on mylar and copper backing using the vacuum evaporation technique is described. These targets were employed in an experiment to measure the proton capture cross-section at energies significantly below the Coulomb barrier, for the astrophysical p-process studies. Due to the low melting point and high vapor pressure of cadmium, some adjustments were implemented in the Telemark multipocket e-beam setup. The target thickness was determined through the measurement of alpha particle energy loss from a triple alpha source and also by RBS measurements. The thickness of the $^{108}$Cd films varies between 290 to 660 $\mu$g/cm$^2$, with a non-uniformity of approximately 10$\%$. X-ray Photoelectron Spectroscopy (XPS) and X-ray Fluorescence (XRF) analyses were conducted to examine the presence of impurities and to assess surface morphology, phase, and chemical composition

Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to exhibit plant growth promoting activities and also have been reported to protect plants against invading pathogens. A yeast strain closely related to Rhodotorula mucilaginosa was isolated from the endosphere of Typha angustifolia collected from a Uranium mine. A microarray analysis was performed to investigate the early changes in rice shoot transcripts in response to this yeast (R. mucilaginosa JGTA-S1). Transcriptional changes were monitored in 6 h and 24 h treated rice plant shoots as compared to 0 h control. The microarray data has been submitted to the NCBI GEO repository under the accession number of GSE64321

Background gamma measurement for low energy astrophysical reaction at FRENA

The majority of astrophysical reactions have very low cross-sections (nanobarn to picobarn range) and significant error bars [1, 2]. Hence γ-ray background studies up to 3 MeV have been performed inside the Facility for Research in Experimental Nuclear Astrophysics (FRENA), Saha Institute of Nuclear Physics, Kolkata, India. A meticulous background calculation has been performed at different positions inside the accelerator hall and beam hall using two NaI(Tl) detectors [3]. An XPS measurement has been carried out to identify elements present in the FRENA wall concrete. Activity calculations done in [4] shows that neutrons produced by various experiments may combine with any nearby elements and form various radioactive isotopes with long half-lives, which may produce a γ-ray background

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

Altered expression of protein coding gene (PCG) and long non-coding RNA (lncRNA) have been identified in SARS-CoV-2 infected cells and tissues from COVID-19 patients. The functional role and mechanism (s) of transcriptional regulation of deregulated genes in COVID-19 remain largely unknown. In the present communication, reanalyzing publicly available gene expression data, we observed that 66 lncRNA and 5491 PCG were deregulated in more than one experimental condition. Combining our earlier published results and using different publicly available resources, it was observed that 72 deregulated lncRNA interacted with 3228 genes/proteins. Many targets of deregulated lncRNA could also interact with SARS-CoV-2 coded proteins, modulated by IFN treatment and identified in CRISPR screening to modulate SARS-CoV-2 infection. The majority of the deregulated lncRNA and PCG were targets of at least one of the transcription factors (TFs), interferon responsive factors (IRFs), signal transducer, and activator of transcription (STATs), NFκB, MYC, and RELA/p65. Deregulated 1069 PCG was joint targets of lncRNA and TF. These joint targets are significantly enriched with pathways relevant for SARS-CoV-2 infection indicating that joint regulation of PCG could be one of the mechanisms for deregulation. Over all this manuscript showed possible involvement of lncRNA and mechanisms of deregulation of PCG in the pathogenesis of COVID-19

Tobacco-induced carcinogenesis and chemoprevention by some natural products

Tobacco habit is one of the main etiological factors responsible for cancer in body's multiple organs due to the presence of numerous carcinogens. In different animal models, it was evident that the carcinogens could induce carcinogenesis in multiple organs depending on its route of exposure site (e.g., skin, oral cavity, and lung), metabolism (e.g., liver and lung), and excretion (e.g., lung and kidney). It was evident that the active carcinogen metabolites could induce cellular reactive oxygen species (ROS) level, bind to DNA/RNA/proteins, thereby transforming the stem cell of the specific organs toward neoplasm. Different epidemiological studies including our own showed few natural compounds might reduce the risk of tobacco-induced carcinogenesis. The anticarcinogenic roles of crude extract as well as active compounds of such natural dietary ingredients were also evaluated by several in vivo animal models. Most of the active components have potential antioxidative, anti-inflammatory, and anticarcinogenic roles. For better understanding, the roles of three different types of compounds were selected for this review 1. Tea polyphenols from Camellia sinensis: epigallocatechin gallate and theaflavin; 2. amarogentin from Swertia chirata; and 3. Eugenol from Syzygium aromaticum. Studies showed that three types of compounds could restrict the carcinogenesis in different organs at premalignant stages. This might be due to antioxidation and activation of detoxification system, inhibition of cancer initiating stem cell population, modulation of multiple cellular pathways associated with cell cycle, cell proliferation, and survival which ultimately lead to restrict tumor development at initiation/promotion stage

Study for the long-lived gamma background due to neutron emitting calibration reactions

In this article, a detailed theoretical investigation has been done on the long-lived gamma background due to neutron emitting reactions. It mainly focused on the experiments that will be used to calibrate energy with the terminal voltage of an upcoming Facility for Research in Experimental Nuclear Astrophysics (FRENA). Many reactions like (p, n), (p, γ) have been utilized in various accelerator facilities around the globe for energy calibration purposes. Neutron emitting reactions like 7Li(p, n), 13C(p, n), 19F(p, n), 27Al(p, n), etc. have been very commonly used. For such reactions, a significant number of neutrons produced from such experiments can interact with surrounding elements like copper, tantalum, stainless steel (SS304 and SS316), concrete materials,etc. These interactions may create long-lived gamma activity in the vicinity of the accelerator and detection area. Background gammas from these radioactive isotopes can interfere with gamma measurements in future experiments. The present study has been done to investigate those possibilities of gamma background which may occur due to the calibration study by neutron emitting experiments. Here 7Li(p, n), 13C(p, n), 19F(p, n) and 27Al(p, n) reactions having neutron threshold energies 1.8803, 3.2355, 4.2351, 5.8036 MeV respectively are chosen keeping in mind the proton energy available at the facility

Differential alterations in metabolic pattern of the spliceosomal UsnRNAs during pre-malignant lung lesions induced by benzo(a)pyrene: modulation by tea polyphenols

The differential alterations of the spliceosomal UsnRNAs (U1, U2, U4, U5, and U6) were reported to be associated with cellular proliferation and development. The attempt was made in this study to analyze the metabolic pattern of the spliceosomal UsnRNAs during the development of pre-malignant lung lesions induced in experimental mice model system by benzo(a)pyrene (BP) and also to see how tea polyphenols, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), modulate the metabolism of these UsnRNAs during the lung carcinogenesis. No significant changes in the level of the UsnRNAs were seen in the inflammatory lung lesions at 9th week due to treatment of BP. However, there was significant increase in the level of U1 ( approximately 2.5 fold) and U5 ( approximately 47%) in the hyperplastic lung lesions at 17th week. But in the mild dysplastic lung lesions at 26th week, the level of UsnRNAs did not change significantly. Whereas, in the dysplastic lung lesions at 36th week there was significant increase in the level of the U2 ( approximately 2 fold), U4 ( approximately 2.5 fold) and U5 ( approximately 2 fold). Due to the EGCG and ECG treatment the lung lesions at 9th week appeared normal and in the 17th, 26th, and 36th week it appeared as hyperplasia. The level of the UsnRNAs was significantly low in the lung lesions at 9th week (only U2 and U4 by EGCG), at 17th week (only U1 by EGCG/ECG), at 26th week (U1 by ECG; U2, U4 and U5 by EGCG/ECG) and at 36th week (U1 by ECG, U2 and U4 by EGCG/ECG). Whereas, there was significant increase in the level of U5 (by EGCG/ECG) and U6 (by EGCG only) in the lung lesions at 36th and 26th week respectively. This indicates that the metabolism of the spliceosomal UsnRNAs differentially altered during the development of pre-malignant lung lesions by BP as well as during the modulation of the lung lesions by the tea polyphenols