Cancer Awareness and Stigma in Rural Assam India: Baseline Survey of the Detect Early and Save Her/Him (DESH) Program.

BACKGROUND: India has an estimated incidence of more than one million cancers annually. Breast, oral, and cervical cancers account for over one-third of newly diagnosed cases. With the introduction of pilot cancer screening programs in India, little is known about current sociocultural barriers that may hinder acceptance of screening and treatment. We sought to identify knowledge gaps, misconceptions, and stigmas surrounding cancer diagnosis. PATIENTS AND METHODS: A baseline survey was conducted in Assam, India, as part of the Detect Early and Save Her/Him program, a mobile screening program for breast, oral, and cervical cancer. Data were collected on participants' cancer knowledge, and attitudes towards screening, diagnosis, and treatment. RESULTS: Of the 923 residents who participated, a large majority (92.9%; n = 858) were neither aware of cancer screening availability nor had prior screening. Low-medium awareness was demonstrated regarding the carcinogenic effects of betel nuts (n = 433, 47%). Only one-third of participants recognized oral ulcers and dysphagia as cancer symptoms. Approximately 10% of respondents had misconceptions about cancer etiologies, and 42-57% endorsed statements reflecting a negative stigma towards cancer, including its long-term detrimental effects on personal, occupational, and familial life. However, the majority (68-96%) agreed with statements endorsing positive community support and medical care for cancer patients. CONCLUSIONS: This study identifies actionable targets for intervention in cancer education and awareness within a large rural Indian population. Education to address preventable causes of cancer and to correct misconceptions and stigma is a critical component in ensuring the successful implementation of cancer screening programs.

Exploring the Binding Affinity of Novel Syringic Acid Analogues and Critical Determinants of Selectivity as Potent Proteasome Inhibitors.

Syringic acid, a known plant phenolic compound and its analogues are known to possess high proteasome inhibitory activity. In the current work, we describe synthesis, characterization, DFT, docking of syringic acid (SA) and analogues (SAA1 and SAA2) and biological effects were studied. Syringic acid and its analogues were docked for the first time with the crystal structures of ß5 proteasome of diverse eukaryotic organisms. Among all proteasomes, the humanoid proteasome showed the highest degree of docking conformation and low inhibition constant (Ki). SAA2 specifically displayed binding to the N-terminal Thr1 residue in the S1 pocket of Mus musculus ß5 proteasome along with threonine, lysine and arginine; conventionally involved major amino acid residues in ligand binding. The geometrical properties (B3LYP/6- 31g (d, p)) and electrostatic potentials of molecules were computed using DFT calculations. A detailed molecular picture of the compounds and its interactions was obtained from NBO analysis. SA-analogues elucidated potent antioxidant activities and good antibacterial activity. In-vitro DNA binding studies revealed that all molecules had strong binding at the major groove of dsDNA. In the view of medical applicability, proteasome inhibition is an important therapeutic strategy for various types of cancers. Therefore, current discoveries may encourage the rational design and development of new chemical entities of syringic acid based chemotherapeutics.

Comprehensive structural and functional characterization of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (Mtb-MurA) and prediction of its accurate binding affinities with inhibitors.

Tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death in the world. One third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structure model of Mtb-MurA enzyme has been developed for the first time by homology modeling and molecular dynamics simulation techniques. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E. coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structure model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives showed the best interaction compared to other inhibitors. We also designed new efficient analogs of T6361 and T6362 which showed even better interaction with Mtb-MurA than the parental 5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing a more specific inhibitor for Mtb-MurA enzyme.