ABSTRACT
Vascular smooth muscle cell (VSMC) plasticity is fundamental in uterine spiral artery remodeling during placentation in Eutherian mammals. Our previous work showed that the invasion of trophoblast cells into uterine myometrium coincides with a phenotypic change of VSMCs. Here, we elucidate the mechanism by which trophoblast cells confer VSMC plasticity. Analysis of genetic markers on E13.5, E16.5, and E19.5 in the rat metrial gland, the entry point of uterine arteries, revealed that trophoblast invasion is associated with downregulation of MYOCARDIN, α-smooth muscle actin, and calponin1, and concomitant upregulation of Smemb in VSMCs. Myocardin overexpression or knockdown in VSMCs led to upregulation or downregulation of contractile markers, respectively. Co-culture of trophoblast cells with VSMCs decreased MYOCARDIN expression along with compromised expression of contractile markers in VSMCs. However, co-culture of trophoblast cells with VSMCs overexpressing MYOCARDIN inhibited their change in phenotype, whereas, overexpression of transactivation domain deleted MYOCARDIN failed to elicit this response. Furthermore, the co-culture of trophoblast cells with VSMCs led to the activation of NFκß signaling. Interestingly, despite producing IL-1ß, trophoblast cells possess only the decoy receptor, whereas, VSMCs possess the IL-1ß signaling receptor. Treatment of VSMCs with exogenous IL-1ß led to a decrease in MYOCARDIN and an increase in phosphorylation of NFκß. The effect of trophoblast cells in the downregulation of MYOCARDIN in VSMCs was reversed by blocking NFκß translocation to the nucleus. Together, these data highlight that trophoblast cells direct VSMC plasticity, and trophoblast-derived IL-1ß is a key player in downregulating MYOCARDIN via the NFκß signaling pathway.
Subject(s)
Interleukin-1beta , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , NF-kappa B , Nuclear Proteins , Signal Transduction , Trans-Activators , Trophoblasts , Animals , Trophoblasts/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/cytology , Trans-Activators/metabolism , Trans-Activators/genetics , Rats , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Signal Transduction/physiology , NF-kappa B/metabolism , Female , Myocytes, Smooth Muscle/metabolism , Interleukin-1beta/metabolism , Pregnancy , Coculture Techniques , Rats, Sprague-Dawley , Cells, Cultured , Cell Plasticity/physiology , CalponinsABSTRACT
BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.
Subject(s)
Breast Neoplasms , Registries , Humans , Female , India/epidemiology , Breast Neoplasms/mortality , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Middle Aged , Aged , Adult , Survival Analysis , Survival Rate , Aged, 80 and overABSTRACT
Supramolecular nanostructured based delivery systems are emerging as a meaningful approach in the treatment of cancer, offering controlled drug release and improved therapeutic efficacy. The self-assembled structures can be small molecules, polymers, peptides, or proteins, which can be used and functionalized to achieve tailored release and target specific cells, tissues, or organs. These structures can improve the solubility and stability of drugs having low aqueous solubility by encapsulating and protecting them from degradation. Alongside, peptides as natural biomolecules have gained increasing attention as potential candidates in cancer treatment because of their biocompatibility, low cytotoxicity, and high specificity toward tumor cells. The amino acid sequences in peptide molecules are tunable, efficiently controlling the morphology of peptide-based self-assembled nanosystems and offering flexibility to form supramolecular nanostructures (SNs). It is evident from the current literature that the supramolecular nanostructures based delivery of peptide for cancer treatment hold great promise for future cancer therapy, offering potential strategies for personalized medicine with improved patient outcomes. SIGNIFICANCE STATEMENT: This review focuses on fundamentals and various drug delivery mechanisms based on SNs. Different SN approaches and recent literature reviews on peptide delivery are also presented to the readers.
Subject(s)
Nanostructures , Neoplasms , Humans , Peptides/chemistry , Proteins , Nanostructures/chemistry , Drug Delivery Systems , Amino Acid Sequence , Pharmaceutical Preparations , Neoplasms/drug therapyABSTRACT
An effective strategy was employed for the rapid development of a supramolecular metallohydrogel of Mg(II) ion (i.e., Mg@PEHA) using pentaethylenehexamine (PEHA) as a low-molecular-weight gelator in aqueous medium under ambient conditions. The mechanical stability of the synthesized Mg@PEHA metallohydrogel was characterized by using rheological analysis, which showed its robustness across different angular frequencies and oscillator stress levels. The metallohydrogel exhibited excellent thixotropic behavior, which signifies that Mg@PEHA has a self-healing nature. Field emission scanning electron microscopy and transmission electron microscopy images were utilized to explore the rectangular pebble-like hierarchical network of the Mg@PEHA metallohydrogel. Elemental mapping through energy-dispersive X-ray spectroscopy analysis confirmed the presence of primary chemical constituents in the metallohydrogel. Fourier transform infrared spectroscopy spectroscopy provided insights into the possible formation strategy of the metallohydrogel. In this work, Schottky diode structures in a metal-semiconductor-metal geometry based on a magnesium(II) metallohydrogel (Mg@PEHA) were constructed, and the charge transport behavior was observed. Additionally, a resistive random access memory (RRAM) device was developed using Mg@PEHA, which displayed bipolar resistive switching behavior at room temperature. The researchers investigated the switching mechanism, which involved the formation or rupture of conduction filaments, to gain insights into the resistive switching process. The RRAM device demonstrated excellent performance with a high ON/OFF ratio of approximately 100 and remarkable endurance of over 5000 switching cycles. RRAM devices exhibit good endurance, meaning they can endure a large number of read and write cycles without significant degradation in performance. RRAM devices have shown promising reliability in terms of long-term performance and stability, making them suitable for critical applications that require reliable memory solutions. Significant inhibitory activity against the drug-resistant Klebsiella pneumonia strain and its biofilm formation ability was demonstrated by Mg@PEHA. The minimum inhibitory concentration value of the metallohydrogel was determined to be 3 mg/mL when it was dissolved in 1% DMSO. To study the antibiofilm activity, an MTT assay was performed, revealing that biofilm inhibition (60%) commenced at 1 mg/mL of Mg@PEHA when dissolved in 1% DMSO. Moreover, in the mouse excisional wound model, Mg@PEHA played a crucial role in preventing postoperative wound infections and promoting wound healing.
ABSTRACT
The expanding use of community science platforms has led to an exponential increase in biodiversity data in global repositories. Yet, understanding of species distributions remains patchy. Biodiversity data from social media can potentially reduce the global biodiversity knowledge gap. However, practical guidelines and standardized methods for harvesting such data are nonexistent. Following data privacy and protection safeguards, we devised a standardized method for extracting species distribution records from Facebook groups that allow access to their data. It involves 3 steps: group selection, data extraction, and georeferencing the record location. We present how to structure keywords, search for species photographs, and georeference localities for such records. We further highlight some challenges users might face when extracting species distribution data from Facebook and suggest solutions. Following our proposed framework, we present a case study on Bangladesh's biodiversity-a tropical megadiverse South Asian country. We scraped nearly 45,000 unique georeferenced records across 967 species and found a median of 27 records per species. About 12% of the distribution data were for threatened species, representing 27% of all species. We also obtained data for 56 DataDeficient species for Bangladesh. If carefully harvested, social media data can significantly reduce global biodiversity knowledge gaps. Consequently, developing an automated tool to extract and interpret social media biodiversity data is a research priority.
Un protocolo para recolectar datos sobre biodiversidad en Facebook Resumen El uso creciente de plataformas de ciencia comunitaria ha causado un incremento exponencial de los datos sobre biodiversidad en los repositorios mundiales. Sin embargo, el conocimiento sobre la distribución de las especies todavía está incompleto. Los datos sobre biodiversidad obtenidos de las redes sociales tienen el potencial para disminuir el vacío de conocimiento sobre la biodiversidad mundial. No obstante, no existe una guía práctica o un método estandarizado para recolectar dichos datos. Seguimos los protocolos de privacidad y protección de datos para diseñar un método estandarizado para extraer registros de la distribución de especies de grupos en Facebook que permiten el acceso a sus datos. El método consta de tres pasos: selección del grupo, extracción de datos y georreferenciación de la localidad registrada. También planteamos cómo estructurar las palabras clave, buscar fotografías de especies y georreferenciar las localidades de dichos registros. Además, resaltamos algunos retos que los usuarios pueden enfrentar al extraer los datos de distribución de Facebook y sugerimos algunas soluciones. Aplicamos nuestro marco de trabajo propuesto a un estudio de caso de la biodiversidad en Bangladesh, un país tropical megadiverso en el sureste de Asia. Reunimos casi 45,000 registros georreferenciados únicos para 967 especies y encontramos una media de 27 registros por especie. Casi el 12% de los datos de distribución correspondió a especies amenazadas, que representaban el 27% de todas las especies. También obtuvimos datos para 56 especies deficientes de datos en Bangladesh. Si los datos de las redes sociales se recolectan con cuidado, éstos pueden reducir de forma significativa el vacío de conocimiento para la biodiversidad mundial. Como consecuencia, es una prioridad para la investigación el desarrollo de una herramienta automatizada para extraer e interpretar los datos sobre biodiversidad de las redes sociales.
Subject(s)
Biodiversity , Conservation of Natural Resources , Social Media , Conservation of Natural Resources/methods , Bangladesh , Endangered SpeciesABSTRACT
Citizen science plays a crucial role in helping monitor biodiversity and inform conservation. With the widespread use of smartphones, many people share biodiversity information on social media, but this information is still not widely used in conservation. Focusing on Bangladesh, a tropical megadiverse and mega-populated country, we examined the importance of social media records in conservation decision-making. We collated species distribution records for birds and butterflies from Facebook and Global Biodiversity Information Facility (GBIF), grouped them into GBIF-only and combined GBIF and Facebook data, and investigated the differences in identifying critical conservation areas. Adding Facebook data to GBIF data improved the accuracy of systematic conservation planning assessments by identifying additional important conservation areas in the northwest, southeast, and central parts of Bangladesh, extending priority conservation areas by 4,000-10,000 km2 . Community efforts are needed to drive the implementation of the ambitious Kunming-Montreal Global Biodiversity Framework targets, especially in megadiverse tropical countries with a lack of reliable and up-to-date species distribution data. We highlight that conservation planning can be enhanced by including available data gathered from social media platforms.
Registros de las redes sociales para guiar la planeación de la conservación Resumen La ciencia ciudadana es importante para monitorear la biodiversidad e informar la conservación. Con el creciente uso de los teléfonos inteligentes, muchas personas comparten información de la biodiversidad en redes sociales, pero todavía no se usa ampliamente en la conservación. Analizamos la importancia de los registros de las redes sociales para las decisiones de conservación enfocados en Bangladesh, un país tropical megadiverso y mega poblado. Cotejamos los registros de distribución de especies de aves y mariposas en Facebook y Global Biodiversity Information Facility (GBIF), las agrupamos en datos sólo de GBIF o datos combinados de Facebook y GBIF e investigamos las diferencias en la identificación de las áreas de conservación críticas. La combinación de los datos de Facebook con los de GBIF mejoró la precisión de las evaluaciones de la planeación de la conservación sistemática al identificar otras áreas importantes de conservación en el noroeste, sureste y centro de Bangladesh, extendiendo así las áreas prioritarias de conservación en unos 4,000-10,000 km2 . Se requieren esfuerzos comunitarios para impulsar la implementación de los objetivos ambiciosos del Marco Global de Biodiversidad Kunming-Montreal, especialmente en países tropicales que carecen de datos confiables y actuales sobre la distribución de las especies. Destacamos que la planeación de la conservación puede mejorarse si se incluye información tomada de las redes sociales.
Subject(s)
Butterflies , Social Media , Humans , Animals , Conservation of Natural Resources , Biodiversity , BirdsABSTRACT
OBJECTIVES: To compare the efficacy of laparoscopic transabdominal cerclage (TAC) pre-pregnancy and laparoscopic TAC in pregnancy in treating cervical insufficiency. METHOD: A retrospective analytical study comparing outcomes of laparoscopic TAC pre-pregnancy with laparoscopic TAC in pregnancy. A total of 178 patients who underwent laparoscopic TAC at our hospital were enrolled in the study. In total, 122 patients underwent interval cerclage, and 56 patients underwent cerclage during pregnancy. RESULTS: A total of 178 patients who met the inclusion criteria were included in the analysis. Second-trimester abortions decreased by 50%, with an overall increase in full-term live births (32.53%) in patients undergoing laparoscopic TAC pre-pregnancy. The fetal survival rate was around 90% and 85% with laparoscopic TAC pre-pregnancy and laparoscopic TAC in pregnancy, respectively. Although the obstetric outcomes of laparoscopic TAC pre-pregnancy and in pregnancy were comparable, laparoscopic TAC pre-pregnancy was safer than laparoscopic TAC in pregnancy due to the complications associated with the procedure during pregnancy. CONCLUSIONS: Laparoscopic TAC pre-pregnancy yielded better reproductive outcomes than laparoscopic TAC in pregnancy and was associated with fewer perioperative complications.
Subject(s)
Cerclage, Cervical , Laparoscopy , Uterine Cervical Incompetence , Pregnancy , Female , Humans , Pregnancy Outcome , Retrospective Studies , Cerclage, Cervical/methods , Laparoscopy/methods , Term Birth , Uterine Cervical Incompetence/surgeryABSTRACT
In this paper, we evaluate the uniqueness of a hypothetical iris recognition system that relies upon a nonlinear mapping of iris data into a space of Gaussian codewords with independent components. Given the new data representation, we develop and apply a sphere packing bound for Gaussian codewords and a bound similar to Daugman's to characterize the maximum iris population as a function of the relative entropy between Gaussian codewords of distinct iris classes. As a potential theoretical approach leading toward the realization of the hypothetical mapping, we work with the auto-regressive model fitted into iris data, after some data manipulation and preprocessing. The distance between a pair of codewords is measured in terms of the relative entropy (log-likelihood ratio statistic is an alternative) between distributions of codewords, which is also interpreted as a measure of iris quality. The new approach to iris uniqueness is illustrated using two toy examples involving two small datasets of iris images. For both datasets, the maximum sustainable population is presented as a function of image quality expressed in terms of relative entropy. Although the auto-regressive model may not be the best model for iris data, it lays the theoretical framework for the development of a high-performance iris recognition system utilizing a nonlinear mapping from the space of iris data to the space of Gaussian codewords with independent components.
ABSTRACT
Background and Aims: Squint surgery is a risk factor for postoperative vomiting (POV) in children. This study was designed to compare the incidence of POV in children undergoing strabismus surgery under balanced anesthesia with sevoflurane versus intravenous anesthesia with propofol. Material and Methods: In this prospective randomized controlled study conducted in a tertiary care ophthalmology hospital, 70 ASA I-II children aged 1-12 years undergoing strabismus surgery were randomized to two groups -Group S (sevoflurane-based anesthesia) and Group P (propofol-based anesthesia) for maintenance. The surgical details, intraoperative hemodynamic parameters, recovery characteristics, and emergence delirium were recorded. Any episode of postoperative vomiting in the 0-2 hours, 2-6 hours, and 6-24 hours period was noted. Rescue antiemetic was administered if there was more than one episode of vomiting. Results: Both the groups were similar with respect to demographic and surgical details. The average duration of surgery was 118.2 ± 41.88 min in group S and 137.32 ± 39.09 min in group P (P = .05). Four children in group S (11.4%) and one child in group P (2.9%) had POV in the first 24 hours but this was not statistically significant (P = .36). The median time to discharge from post anesthesia care unit was significantly less (P = .02) in the P group (50 min) than in the S group (60 min). Conclusion: Propofol-based anesthesia does not offer advantage over sevoflurane, in reducing POV after squint surgery, when dual prophylaxis with dexamethasone and ondansetron is administered. It, however, reduces the duration of stay in the post anesthesia care unit.
ABSTRACT
Citizen science programs are becoming increasingly popular among naturalists but remain heavily biased taxonomically and geographically. However, with the explosive popularity of social media and the near-ubiquitous availability of smartphones, many post wildlife photographs on social media. Here, we illustrate the potential of harvesting these data to enhance our biodiversity understanding using Bangladesh, a tropical biodiverse country, as a case study. We compared biodiversity records extracted from Facebook with those from the Global Biodiversity Information Facility (GBIF), collating geospatial records for 1013 unique species, including 970 species from Facebook and 712 species from GBIF. Although most observation records were biased toward major cities, the Facebook records were more evenly spatially distributed. About 86% of the Threatened species records were from Facebook, whereas the GBIF records were almost entirely Of Least Concern species. To reduce the global biodiversity data shortfall, a key research priority now is the development of mechanisms for extracting and interpreting social media biodiversity data.
ABSTRACT
In the quest to synthesize high-performing insensitive high-energy density materials (HEDMs), the main challenge is establishing an equilibrium between energy and stability. For this purpose, we explored 4-hydroxy-3,5-dinitropyrazole- and tetrazole-based energetic scaffolds connected via a N-methylene-C bridge. The hydroxy functionality between nitro groups on the pyrazole ring promotes physical stability via inter- and intramolecular hydrogen bonding and contributes to oxygen balance, supporting better energetic performance. Due to two acidic sites (OH and NH) with different reactivities, a series of monocationic and dicationic salts were synthesized, and their overall performance was compared. All compounds synthesized in this study have high physical stability with impact sensitivity >40 J and friction sensitivity >360 N. Monocationic salts were generally found to have better thermal stability with respect to their corresponding dicationic energetic salts, which showed better energetic performance. The salt formation strategy effectively improved the thermal stability of 2 (Td = 168 °C), where most energetic salts have decomposition temperatures higher than 220 °C. All of the compounds were characterized through IR, multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), and elemental analysis. The structure-property relationship was studied using Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies.
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BACKGROUND: There is a large and growing unmet need for rehabilitation - a diverse category of services that aim to improve functioning across the life course - particularly in low- and middle-income countries. Yet despite urgent calls to increase political commitment, many low- and middle-income country governments have dedicated little attention to expanding rehabilitation services. Existing policy scholarship explains how and why health issues reach the policy agenda and offers applicable evidence to advance access to physical, medical, psychosocial, and other types of rehabilitation services. Drawing from this scholarship and empirical data on rehabilitation, this paper proposes a policy framework to understand national-level prioritization of rehabilitation in low- and middle-income countries. METHODS: We conducted key informant interviews with rehabilitation stakeholders in 47 countries, complemented by a purposeful review of peer-reviewed and gray literature to achieve thematic saturation. We analyzed the data abductively using a thematic synthesis methodology. Rehabilitation-specific findings were triangulated with policy theory and empirical case studies on the prioritization of other health issues to develop the framework. RESULTS: The novel policy framework includes three components which shape the prioritization of rehabilitation on low- and middle-income countries' national government's health agendas. First, rehabilitation lacks a consistent problem definition, undermining the development of consensus-driven solutions which could advance the issue on policy agendas. Second, governance arrangements are fragmented within and across government ministries, between the government and its citizens, and across national and transnational actors engaged in rehabilitation service provision. Third, national legacies - particularly from civil conflict - and weaknesses in the existing health system influences both rehabilitation needs and implementation feasibility. CONCLUSIONS: This framework can support stakeholders in identifying the key components impeding prioritization for rehabilitation across different national contexts. This is a crucial step for ultimately better advancing the issue on national policy agendas and improving equity in access to rehabilitation services.
Subject(s)
Health Policy , Policy Making , Humans , Government Programs , GovernmentABSTRACT
Myo-inositol oxygenase (MIOX), the only catabolic enzyme of the inositol pathway, catalyzes conversion of myo-inositol to D-GlcA (glucuronic acid). The present study encompasses bioinformatic analysis of MIOX gene across phylogenetically related plant lineages and representative animal groups. Comparative motif analysis of the MIOX gene(s) across various plant groups suggested existence of abiotic- stress related cis-acting elements such as, DRE, MYB, MYC, STRE, MeJa among others. A detailed analysis revealed a single isoform of MIOX gene, located in chromosome 6 of indica rice (Oryza sativa) with an open reading frame of 938 bp coding for 308 amino acids producing a protein of ~ 35 kD. Secondary structure prediction of the protein gave the predicted number of 144 alpha helices and 154 random coils. The three-dimensional structure suggested it to be a monomeric protein with a single domain. Bacterial overexpression of the protein, purification and enzyme assay showed optimal catalytic activity at pH 7.5-8 at an optimal temperature of 37 °C with Michaelis constant of 40.92 mM. The range of Km was determined as 22.74-28.7 mM and the range of Vmax was calculated as 3.51-3.6 µM/min, respectively. Four salt-tolerant and salt-sensitive rice cultivars displayed differential gene expression of OsMIOX at different time points in different tissues under salinity and drought stress as observed from qRT-PCR data, microarray results and protein expression profile in immunoblot analysis. Gel volumetric analysis confirmed a very high expression of MIOX in roots and leaves on 7th day following germination. Microarray data showed high expression of MIOX at all developmental stages including seedling growth and reproduction. These data suggest that OsMIOX might have a role to play in rice abiotic stress responses mediated through the myo-inositol oxidation pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01340-6.
ABSTRACT
We have shown solvent- and substrate-dependent chiral inversion of a few glycoconjugate supramolecules. (Z)-F-Gluco, in which d-glucosamine has been attached chemically to Cbz-protected l-phenylalanine at the Câ terminus, forms a self-healing hydrogel through intertwining of the nanofibers wherein the gelators undergo lamellar packing in the ß-sheet secondary structures with a single chiral handedness. Dihybrid (Z)-F-gluco nanocomposite gel was prepared by in-situ formation of silver nanoparticles AgNPs in the gel; this enhances the mechanical properties of the composite gel through physical crosslinking without altering the packing pattern. In contrast, (Z)-L-gluco bearing an l-leucine moiety does not form a hydrogel but an organogel. Interestingly, the chiral handedness of the aggregates of (Z)-L-gluco can be reversed by choosing suitable solvents. In addition to self-healing behavior, (Z)-L-gluco gel revealed shape persistency. Further, (Z)-F-gluco hydrogel is benign, nontoxic, non-immunogenic, and non-allergenic in animal cells. AgNP-loaded (Z)-F-gluco hydrogel showed antibacterial activity against both Gram-positive and Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Solvents/chemistry , Silver/chemistry , Metal Nanoparticles/chemistry , Gram-Negative Bacteria , Gram-Positive Bacteria , Hydrogels/chemistry , Glycoconjugates/pharmacologyABSTRACT
BACKGROUND: NOSTRIN, abundantly expressed in colon, was reported to be anti-angiogenic, anti-invasive and anti-inflammatory. NOSTRIN expression was inversely related to survival of pancreatic ductal adeno-carcinoma patients. Yet its function and regulatory mechanism in CRC remains elusive. METHODS: NOSTRIN's influence on EMT of CRC cells were analysed using realtime PCR array containing the functional EMT-transcriptome followed by western blotting. Regulation of oncogenic potential of CRC cells by NOSTRIN was elucidated using soft agar colony formation, trans-well invasion, wound healing and colonosphere formation assays. Biochemical assays were used to reveal mechanism of NOSTRIN function. Human CRC tissue array was used to test NOSTRIN mark in control and CRC disease stages. RESULTS: We showed here that CRC cell lines with less NOSTRIN expression has more invasive and migratory potential. NOSTRIN affected EMT-associated transcriptome of CRC cells by down regulating 33 genes that were functionally annotated to transcription factors, genes important for cell growth, proliferation, migration, cell adhesion and cytoskeleton regulators in CRC cells. NOSTRIN over-expression significantly reduced soft agar colony formation, wound healing and cell invasion. In line with this, RNA interference of Nostrin enhanced metastatic potential of CRC cells. Furthermore, stable overexpression of NOSTRIN in CRC cell line not only curtailed its ability to form colonosphere but also decreased expression of stemness markers CD133, CD44 and EpCAM. NOSTRIN's role in inhibiting self-renewal was further confirmed using BrdU incorporation assay. Interestingly, NOSTRIN formed immune-complex with Cdk1 in CRC cells and aided in increase of inhibitory Y15 and T14 phosphorylation of Cdk1 that halts cytokinesis. These ex vivo findings were substantiated using human colon cancer tissue array containing cDNAs from patients' samples with various stages of disease progression. Significant decrease in NOSTRIN expression was found with initiation and progression of advanced colon cancer disease stages. CONCLUSION: We illustrate function of a novel molecule, NOSTRIN in curtailing EMT and maintenance of CRC cell stemness. Our data validates importance of NOSTRIN mark during onset and disease progression of CRC indicating its diagnostic potential.
Subject(s)
Adaptor Proteins, Signal Transducing , Colonic Neoplasms , DNA-Binding Proteins , Pancreatic Neoplasms , Adaptor Proteins, Signal Transducing/genetics , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , DNA-Binding Proteins/genetics , Disease Progression , Epithelial-Mesenchymal Transition , Humans , Neoplastic Stem Cells , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , TranscriptomeABSTRACT
Microscopes, bright-field (BF) and fluorescence microscopes, in particular, are ubiquitous for clinical diagnostics, cellular and microbiological investigations and in research laboratories. However, the size, cost, fragility and need for skilled personnel to operate these tools restrict their use in resource-limited settings. As an alternative platform, herein, we report a flexible multimodal imaging system that operates in BF and fluorescence modes using a smartphone. Our device utilizes the inbuilt primary camera of phones, and with the aid of easily available optical components, the designed platform is transformed into a high-throughput microscopic device that performs on par with that of a laboratory-grade microscope. The designed platform operates at three different optical magnifications and yields a lateral resolution of 1.21 µm over an acceptable field-of-view (FoV) of diameter â¼4530 µm. The versatility of the device has been demonstrated through imaging of standard microbeads and human blood samples both in BF and fluorescence modes of imaging. Furthermore, the designed imaging platform is equipped with an on-board cell recognition feature which has been obtained through developing a smartphone application for automatic cell counting with high precision.
Subject(s)
Smartphone , Humans , Microscopy, Fluorescence/methodsABSTRACT
Background & objectives: Information on recent cancer statistics is important for planning, monitoring and evaluating cancer control activities. This article aims to provide an update on the cancer incidence estimates in India by sex, age groups and anatomical sites for the year 2022. Methods: The National Cancer Registry Programme Report 2020, reported the cancer incidence from 28 Population-Based Cancer Registries (PBCRs) for the years 2012-2016. This was used as the basis to calculate cancer estimates in India. Information pertaining to the population at risk was extracted from the Census of India (2001 and 2011) for the estimation of age-sex stratified population. PBCRs were categorised into the respective State and regions of the country to understand the epidemiology of cancer. The age-specific incidence rate for each specific anatomical site of cancer was applied to the estimated population to derive the number of cancer cases in India for 2022. Results: The estimated number of incident cases of cancer in India for the year 2022 was found to be 14,61,427 (crude rate:100.4 per 100,000). In India, one in nine people are likely to develop cancer in his/her lifetime. Lung and breast cancers were the leading sites of cancer in males and females, respectively. Among the childhood (0-14 yr) cancers, lymphoid leukaemia (boys: 29.2% and girls: 24.2%) was the leading site. The incidence of cancer cases is estimated to increase by 12.8 per cent in 2025 as compared to 2020. Interpretation & conclusions: The cancer incidence is continuing to increase in India. The new estimates will be helpful in planning cancer prevention and control activities through the intervention of early detection, risk reduction and management.
Subject(s)
Breast Neoplasms , Neoplasms , Humans , Male , Female , Child , Incidence , Neoplasms/epidemiology , Neoplasms/diagnosis , Registries , India/epidemiologyABSTRACT
Background & objectives: Lung cancer is a significant public health concern in low- and middle-income countries such as India. The present article describes the epidemiology, and clinical profile of lung cancer in India, based on recent data from the National Cancer Registry Programme (NCRP). Methods: The latest data on lung cancer from the NCRP were collated from 28 population-based cancer registries and 58 hospital-based cancer registries across a five-year (2012-2016) reporting period. Results: The highest age-adjusted incidence rate and mortality (AAMR) was found amongst males and females in the Aizawl district of Mizoram. A significant increase in the annual per cent change of lung cancer incidence was observed in metropolitan cities from 1982 to 2016. About one-third of the cases (36.5%) in males and females (31.7%) were recorded in the age group of 55-64 yr. Adenocarcinoma accounted for about a third (34.3%) of the morphological type in males and half (52.7% ) amongst females. Out of 22,645 recorded lung cancer cases, close to half (44.8%) of the patients presented with distant spread, while over one-third (35.3%) had loco-regional spread of disease at the time of diagnosis. Interpretation & conclusions: Our estimates suggest that the number of cases is expected to rise sharply to 81,219 cases amongst males and 30,109 in females in 2025. The rising incidence and delayed diagnosis of lung cancer in India are grave concerns. The findings of the present study call for scaling up and intensification of lung cancer-specific preventive, early diagnosis and control measures.
Subject(s)
Adenocarcinoma , Lung Neoplasms , Neoplasms , Female , Humans , Incidence , India/epidemiology , Lung Neoplasms/epidemiology , Male , Middle Aged , Neoplasms/epidemiology , RegistriesABSTRACT
AIM: An immunoproteomic approach was followed to identify immunoreactive antigens of fish ectoparasite, Argulus siamensis with rohu (Labeo rohita) immune sera for screening of potential vaccine candidates. MATERIALS AND RESULTS: The whole adult Argulus antigen was run in 2D electrophoresis with IEF in 7 cm IPG strips of pH 4-7 and SDS-PAGE with 12% acrylamide concentration. Two parallel gels were run; one was stained with silver stain, and the other was Western blotted to nitrocellulose paper (NCP) and reacted with rohu anti-A siamensis sera. Fourteen protein spots corresponding to the spots developed in NCP were picked from the silver-stained gel and subjected to mass spectrometry in MALDI-TOF/TOF. The MS/MS spectra were analysed in MASCOT software with taxonomy 'other metazoa' and the proteins identified based on similarity with the proteins from heterologous species. The gene ontology analysis revealed a majority of proteins being involved in binding activity in 'molecular function' and belonging to metabolic processes in 'biologic process' categories. The possibility of these proteins as vaccine candidates against A siamensis is discussed in the paper. CONCLUSION: Three of the identified proteins namely, bromodomain-containing protein, anaphase-promoting complex subunit 5 and elongation factor-2 could possibly serve as vaccine candidates against argulosis in carps.
Subject(s)
Arguloida , Carps , Cyprinidae , Fish Diseases , Animals , Fish Diseases/prevention & control , Tandem Mass SpectrometryABSTRACT
Polymer nanocomposites (PNC) have attracted enormous scientific and technological interest due to their applications in energy storage, electronics, biosensing, drug delivery, cosmetics and packaging industry. Nanomaterials (platelet, fibers, spheroids, whiskers, rods) dispersed in different types of polymer matrices constitute such PNC. The degree of dispersion of the inorganic nanomaterials in the polymer matrix, as well as the structured arrangement of the nanomaterials, are some of the key factors influencing the overall performance of the nanocomposite. To this end, the surface functionalization of the nanomaterials determines its state of dispersion within the polymer matrix. For energy storage and electronics, these nanomaterials are usually chosen for their dielectric properties for enhancing the performance of device applications. Although several reviews on surface modification of nanomaterials have been reported, a review on the surface functionalization of nanomaterials as it pertains to polymer dielectrics is currently lacking. This review summarizes the recent developments in the surface modification of important metal oxide dielectric nanomaterials including Silicon dioxide (SiO2), titanium dioxide (TiO2), barium titanate (BaTiO3), and aluminum oxide (Al2O3) by chemical agents such as silanes, phosphonic acids, and dopamine. We report the impact of chemical modification of the nanomaterial on the dielectric performance (dielectric constant, breakdown strength, and energy density) of the nanocomposite. Aside from bringing novice and experts up to speed in the area of polymer dielectric nanocomposites, this review will serve as an intellectual resource in the selection of appropriate chemical agents for functionalizing nanomaterials for use in specific polymer matrix so as to potentially tune the final performance of nanocomposite.