Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-ß signaling responses in ovarian cancer.

In pathologies including cancer, aberrant Transforming Growth Factor-ß (TGF-ß) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pathway. Central to the success of these interventions is pinpointing factors that decisively modulate the TGF-ß responses. Betaglycan/type III TGF-ß receptor (TßRIII), is an established co-receptor for the TGF-ß superfamily known to bind directly to TGF-ßs 1-3 and inhibin A/B. Betaglycan can be membrane-bound and also undergo ectodomain cleavage to produce soluble-betaglycan that can sequester its ligands. Its extracellular domain undergoes heparan sulfate and chondroitin sulfate glycosaminoglycan modifications, transforming betaglycan into a proteoglycan. We report the unexpected discovery that the heparan sulfate glycosaminoglycan chains on betaglycan are critical for the ectodomain shedding. In the absence of such glycosaminoglycan chains betaglycan is not shed, a feature indispensable for the ability of betaglycan to suppress TGF-ß signaling and the cells' responses to exogenous TGF-ß ligands. Using unbiased transcriptomics, we identified TIMP3 as a key inhibitor of betaglycan shedding thereby influencing TGF-ß signaling. Our results bear significant clinical relevance as modified betaglycan is present in the ascites of patients with ovarian cancer and can serve as a marker for predicting patient outcomes and TGF-ß signaling responses. These studies are the first to demonstrate a unique reliance on the glycosaminoglycan chains of betaglycan for shedding and influence on TGF-ß signaling responses. Dysregulated shedding of TGF-ß receptors plays a vital role in determining the response and availability of TGF-ßs', which is crucial for prognostic predictions and understanding of TGF-ß signaling dynamics.

The Role of Microglia in Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are a leading cause of irreversible visual loss in the developed world. The primary driver of pathology in IRDs is pathogenic genetic variant. However, there is increasing evidence, from recent studies, for a role of the immune system in disease mechanism, particularly retinal microglia. Microglia are the primary immune cells in the retina and actively contribute to disease pathogenesis when activated locally by phagocytosing photoreceptors, inducing inflammation and signaling infiltration of circulating monocytes. In this article, we discuss the evidence for the contribution of retinal microglia to IRD pathogenesis reported so far using mice model.

Liquid crystal droplet design by using pseudopeptidic bottlebrush polymer additives.

Liquid crystal (LC) droplets are promising candidates for sensing applications due to their high sensitivity to surface anchoring changes, resulting in readily detectable optical effects. Herein, we have designed and synthesized amino acid-based bottlebrush polymers and investigated their impact on LC director configurations in the droplets. The pseudopeptidic bottlebrush polymers with an aromatic (phenyl) and aliphatic appendages are synthesized using ring-opening metathesis polymerization (ROMP). Polymer dispersed liquid crystal (PDLC) samples are prepared by employing pseudopeptidic bottlebrush polymers and 4-cyano-4'-pentylbiphenyl (5CB) LC via solvent-induced phase separation (SIPS) technique. Due to π-π stacking, the phenyl group favours radial configuration, whereas the repulsion between 5CB and aliphatic groups induces molecular alignment leading to bipolar droplet arrangement. The impact of various pendant groups attached to the polymer on the prepared PDLC sample's surface characteristics and free energy components is illustrated. The sensing capability of 5CB dispersed in pseudopeptidic bottlebrush polymers for various pH solutions is investigated using polarizing optical microscopy (POM). The PDLC samples are moderately permeable to water and sensitive to different pH solutions. The results demonstrate a simplified and straightforward approach for preparing LC-based biosensors and chemical sensors.

Intranasal curcumin protects against LPS-induced airway remodeling by modulating toll-like receptor-4 (TLR-4) and matrixmetalloproteinase-9 (MMP-9) expression via affecting MAP kinases in mouse model.

OBJECTIVE: Bacterial infections can exacerbate asthmatic inflammation depending on lipopolysaccharide (LPS) composition, the outermost component of cell wall, its exposure timings as well as host's immune status. In present study, Balb/c mice were exposed to antigen (ovalbumin) and LPS simultaneously to establish an asthmatic model. Curcumin (diferuloylmethane), well known for its anti-inflammatory potential, was administered through intranasal route 1 h before LPS and OVA (ovalbumin) exposure to evaluate its efficacy against airway structural changes. METHODS: Inflammatory cell infiltration in lungs was measured by flow cytometry and further eosinophils were especially measured by immunofluorescence detection of major basic protein (MBP) as marker of eosinophilc granule protein. We also measured reactive oxygen species (ROS) in BALF by spectrofluorometry. MMP-9 activity was evaluated by gelatin zymography and mRNA expressions of MMP-9, TIMP-1, TGF-ß1, IL-13, Collagen-1 and TLR-4 were measured in lungs. Protein expression of MAP kinases (P-ERK, P-JNK, P-p38), TLR-4, Cox-2, Lox-5 and Eotaxin was measured by western blotting. Hydroxyproline level and masson's trichrome staining were used to evaluate collagen deposition in lung. RESULTS: Exposure to LPS (0.1 µg) exacerbates airway inflammation and induces structural changes in lungs by enhanced ROS production, collagen deposition, expression of genes involved in airway remodeling and activation of MAP kinases pathway enzymes. Intranasal curcumin pretreatment had significantly suppressed inflammatory mediators and airway remodeling proteins. CONCLUSION: Our results strongly suggest that intranasal curcumin effectively protects LPS-induced airway inflammation and structural changes by modulating genes involved in airway remodeling in safer way; hence, it can be considered as supplementary alternative towards asthma treatments.

Curcumin inhibits lipopolysaccharide (LPS)-induced endotoxemia and airway inflammation through modulation of sequential release of inflammatory mediators (TNF-α and TGF-ß1) in murine model.

OBJECTIVE: Curcumin (diferuloylmethane), a major component of turmeric is well known for its anti-inflammatory potential. Present study investigates sequential release of inflammatory mediators post LPS challenge (10 mg/kg,i.p.) causing lung inflammation and its modulation by curcumin through different routes (20 mg/kg, i.p and 10 mg/kg, i.n.) in murine model. Dexamethasone (1 mg/kg, i.p) was used as standard drug. METHODS: Lung Inflammation was evaluated by histopathological analysis, myeloperoxidase (MPO) activity followed by inflammatory cell count and total protein content measurements in bronchoalveolar fluid (BALF). Reactive oxygen species (ROS), nitrite and TNF-α levels were measured as markers of endotoxin shock at different time points (1-72 h). The mRNA expression of transforming growth factors-ß1 (TGF-ß1), iNOS and Toll-like receptor-4 (TLR-4) were measured followed by Masson's trichrome staining and hydroxyproline levels as collagen deposition marker leading to fibrotic changes in lungs. RESULTS: We found that LPS-induced lung inflammation and injury was maximum 24-h post LPS challenge shown by MPO and histological analysis which was further supported by elevated nitrite and ROS levels whereas TNF-α level was highest after 1 h. Endotoxin-induced mortality was significantly reduced in curcumin (i.p) pretreatment groups up to 72-h post LPS challenge. Significant inhibition in mRNA expression of iNOS, TGF-ß1 and TNF-α level was noted after curcumin treatment along with lowered MPO activity, inflammatory cell count, ROS, nitrite levels and collagen deposition in lungs. CONCLUSION: Our results suggest that higher endotoxin dose causes inflammatory mediator release in chronological order which tend to increase with time and reached maximum after 24-h post-endotoxin (LPS) exposure. Intraperitoneal route of curcumin administration was better in modulating inflammatory mediator release in early phase as compared to intranasal route of administration. It can be used as supplementary therapeutic intervention at early stage of endotoxemia, having fewer side effects.

Lipopolysaccharide (LPS) exposure differently affects allergic asthma exacerbations and its amelioration by intranasal curcumin in mice.

AIM: Lipopolysaccharide (LPS) is ubiquitous in the environment and can therefore, exacerbate allergic responses. Studies have suggested immunoregulatory effects of LPS according to route, dose and stage of exposure. Present study has examined whether dose and stage of LPS exposure (during sensitization and challenge with OVA) exacerbates airway inflammations, antigen specific-IgE level, histamine release, Th1/Th2 cytokine response. Further, anti-asthmatic potential of curcumin, through intranasal route has been evaluated for the first time in LPS induced airway inflammation in an ovalbumin (OVA)-challenged mouse asthma model. METHODS: Balb/c mice were first sensitized with OVA on 1st and 8th day and exposed to two LPS doses (0.1/1.0 µg) separately on 2nd day and then further exposed to LPS with OVA-aerosol (from 9 to 14 day). Further, lower LPS dose (0.1 µg) was chosen for OVA exposed mouse model of asthma exacerbation study. Intranasal curcumin was administered from 9th to 14th day before every LPS exposure. RESULTS: Exposure to LPS (0.1 µg) exacerbates airway inflammations in terms of IgE level, Th2-cytokine response (IL-4 and IL-5), histamine release, EPO and MPO activities and oxidative stress. Intranasal curcumin has effectively ameliorated airway exacerbations whereas dexamethasone, a known glucocorticosteroid, was not promising as compared to intranasal curcumin. CONCLUSION: Schedule and dose of LPS exposure determines asthma exacerbations and intranasal curcumin could be better immunomodulatory agent in LPS exposed asthma exacerbations.

Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17.

Rab GTPases regulate various membrane trafficking pathways but the mechanisms by which GTPase-activating proteins recognise specific Rabs are not clear. Rab8 is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome. Here, we provide evidence to show that TBC1D17, a Rab GTPase-activating protein, through its catalytic activity, regulates Rab8-mediated endocytic trafficking of transferrin receptor. Optineurin, a Rab8-binding effector protein, mediates the interaction and colocalisation of TBC1D17 with Rab8. A non-catalytic region of TBC1D17 is required for direct interaction with optineurin. Co-expression of Rab8, but not other Rabs tested, rescues the inhibition of transferrin receptor trafficking by TBC1D17. The activated GTP-bound form of Rab8 is localised to the tubules emanating from the endocytic recycling compartment. Through its catalytic activity, TBC1D17 inhibits recruitment of Rab8 to the tubules and reduces colocalisation of transferrin receptor and Rab8. Knockdown of optineurin or TBC1D17 results in enhanced recruitment of Rab8 to the tubules. A glaucoma-associated mutant of optineurin, E50K, causes enhanced inhibition of Rab8 by TBC1D17, resulting in defective endocytic recycling of transferrin receptor. Our results show that TBC1D17, through its interaction with optineurin, regulates Rab8-mediated endocytic recycling of transferrin receptor and recruitment of Rab8 to the endocytic recycling tubules. We describe a mechanism of regulating a Rab GTPase by an effector protein (optineurin) that acts as an adaptor to bring together a Rab (Rab8) and its GTPase-activating protein (TBC1D17).

Safe and sustainable food packaging: Argemone albiflora mediated green synthesized silver-carrageenan nanocomposite films.

Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all over the world for the treatment of microbial infections, jaundice, skin diseases etc. GC-MS analysis was used to examine the phytochemical found in the Argemone albiflora leaf extract which reduces the metal ions to nanoscale. The biopolymer employed in the synthesis of nanocomposite film was carrageenan, a natural carbohydrate (polysaccharide) extracted from edible red seaweeds. We developed a food packing that is biodegradable, eco-friendly, economical and free from harmful chemicals. These films possess better UV barrier and mechanical and antimicrobial properties with 1 mM AgNO3 solution. The presence of silver nanoparticles in the carrageenan matrix was evident from FESEM. The mechanical properties were analysed by a Universal testing machine (UTM) and different properties like water vapour permeability (WVP), moisture content (MC) and total soluble matter (TSM) important for food packing applications were also analysed. The antimicrobial properties of the synthesized film samples were studied against E. coli and S. aureus pathogenic bacteria. These films were employed for the storage of cottage cheese (dairy product) and strawberries (fruit). This packing increased the shelf life of the packed food effectively. Ag/Carr films are biodegradable within four weeks.

Valorization of fish processing by-products for protein hydrolysate recovery: Opportunities, challenges and regulatory issues.

Protein-rich fish processing by-products, often called rest raw materials (RRM), account for approximately 60% of the total fish biomass. However, a considerable amount of these RRM is utilized for low-value products such as fish meal and silage. A promising and valuable approach for maximizing the utilization of RRM involves the extraction of bioactive fish protein hydrolysate (FPH). This review assesses and compares different hydrolyzation methods to produce FPH. Furthermore, the review highlights the purification strategy, nutritional compositions, and bioactive properties of FPH. Finally, it concludes by outlining the application of FPH in food products together with various safety and regulatory issues related to the commercialization of FPH as a protein ingredient in food. This review paves the way for future applications by highlighting efficient biotechnological methods for valorizing RRM into FPH and addressing safety concerns, enabling the widespread utilization of FPH as a valuable and sustainable source of protein.

Green synthesis of chitosan-encapsulated CuO nanocomposites for efficient degradation of cephalosporin antibiotics in contaminated water.

The synthesis and characterization of chitosan encapsulated copper oxide nanocomposites (CuNPs) using plant extracts for the photocatalytic degradation of second-generation antibiotics, cefixime and cefuroxime, were investigated. The study revealed that the presence of diverse chemical components in the plant extract significantly influenced the size of the CuNPs, with transmission electron microscopy (TEM) showing spherical shapes and sizes ranging from 11-35 nm. The encapsulation process was confirmed by an increase in size for certain samples, indicating successful encapsulation. X-ray photoelectron spectroscopy (XPS) analysis further elucidated the chemical makeup, confirming the valency state of Cu2+ and the presence of Cu-O bonding, with no contaminants detected. Photocatalytic activity assessments demonstrated that the copper oxide nanocomposites exhibited significant degradation capabilities against both antibiotics under UV light irradiation, with encapsulated nanocomposites (EnCu30) showing up to 96.18% degradation of cefuroxime within 60 min. The study highlighted the influence of chitosan encapsulation on enhancing photocatalytic performance, attributed to its high adsorption capability. Recycling studies confirmed the sustainability of the Cu nanocomposites, maintaining over 89% degradation rate after five consecutive cycles. This research underscores the potential of green-synthesized CuNPs as efficient, stable photocatalysts for the degradation of harmful antibiotics, contributing to environmental sustainability and public health protection.

Seroprevalence of Hepatitis C Virus Among Blood Donors in a Tribal-Preponderant Region of India.

INTRODUCTION: Hepatitis C is a global health burden with significant morbidity and mortality. It primarily affects the liver and causes acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Common modes of transmission of hepatitis C virus (HCV) infection are blood transfusion, needlestick injury, and mother-fetus transmission, among which transmission, blood transfusion is one of the most important causes. Blood transfusion is one of the pillars in the management of patients that saves lives and improves morbidity. Blood donation in India is done by voluntary and replacement blood donors of both sexes. The aim of this study is to determine the seroprevalence of HCV among blood donors in the Jharkhand state, a tribal-preponderant region of India, and to see the trend over the years. MATERIAL AND METHODS: This is a nine-year retrospective observational study from 2015 to 2023 that screened for anti-HCV antibodies (third-generation kit: Abbott Diagnostics) using the chemiluminescence technique. RESULTS: In this study, in total, 249,461 units of blood were collected, of which the majority of donations were by male and replacement donors (RDs) comprising 230,757 (92.50%) and 188,047 (75.38%), respectively. The mean number of blood donations by replacement and male donors (MDs) was more than for voluntary donors (VDs) and female donors (FDs) (20894.11 ± 3041.71 RDs vs. 6823.77 ± 2332.96 VDs, p < 0.0001 and 25639.66 ± 2810.08 MDs vs. 2078.22 ± 828.16 FD, p < 0.0001), respectively. The overall prevalence of HCV was 0.63%, and all seropositive donors were male. CONCLUSION: Replacement blood donation contributes to the major part of blood donation and is primarily done by males in this tribal population-dominant region of India. Seroprevalence of HCV is high in the population of this part of India, and there is a constant or slightly upward trend in hepatitis C infection among individuals.

An Analysis of Antibody Response to COVID-19 Vaccination Among Medicos in a Predominantly Tribal State in India: A Comparative Study.

Introduction Global health is still being impacted by the coronavirus disease 2019 (COVID-19) pandemic. Objectives We evaluated the antibody response in this study in individuals who received two doses of the COVID-19 vaccination, both with and without a history of SARS-CoV-2 infection. Methodology It was a hospital-based cross-sectional study conducted among healthcare personnel at a tertiary institution of a predominantly tribal state in India. Results A total of 187 medical students made up the vaccinee group; the majority (152; 81.3%) were between the ages of 18 and 23; 128 (68.4%) of the students were female; and 104 (55.6%) had received the Covishield (AstraZeneca plc, England, UK) vaccination. Of the subjects, 51 (27.3%) had a history of COVID-19 infection. For those who were infected, the antibody titer peaked after six months, whereas it took twice as long for those who were not. Up to a year later, the antibody titers for Covaxin (Bharat Biotech, Hyderabad, India) and Covishield remained equal; however, Covishield titers drastically decreased while Covaxin stayed constant when an infection history was present. Conclusion The study's findings show that immunization in individuals who have previously contracted COVID-19 induces a higher level of antibody response than immunization in individuals who have not previously contracted the virus.

A rare case of genital myiasis in a patient with genital prolapse.

Genital myiasis is an infestation of genital organs by fly larvae, where they feed and develop as parasites. They can cause severe infection, inflammatory reaction and can be linked to psychiatric disturbances. We report a rare case of genital myiasis in an elderly postmenopausal woman aged 82 years from Udaipur, Rajasthan. She presented with complaints of intense pain in the genital region and was diagnosed as a case of genital myiasis of a prolapsed uterus. Pelvic examination revealed 'Stage-IV' genitourinary prolapse according to Pelvic Organ Prolapse-Quantification (POP-Q classification), with a big excavatory ulcer indwelled with maggots of Musca domestica. About 100 such maggots were subsequently manually removed with forceps. With proper surgical and nonsurgical interventions, the patient healed completely and the prolapse was reduced completely.

Removal of organic and inorganic effluents from wastewater by using degradation and adsorption properties of transition metal-doped nickel ferrite.

Removal of water pollutants (methylene blue dye and heavy metals) was achieved by zinc/manganese-doped nickel ferrites (Ni1 - xMxFe2O4, where x = 0.00, 0.025, 0.10). Degradation of dye was achieved under natural solar light illumination. Degradation studies of dye were conducted under different parameters such as contact time-80 min, dye's concentration-5 mg/L, pH-7, and dosage of ferrites-15 mg. The adsorption of dye was studied using non-linear kinetics models (pseudo-first-order and pseudo-second-order) and isotherm models (Langmuir and Freundlich). The adsorption of dye followed pseudo-first-order kinetics (R2 = 0.99377) than second-order kinetics (R2 = 0.98063) and Langmuir isotherm model (R2 = 0.96095) than Freundlich model (R2 = 0.95962) with maximum adsorption efficiency of 29.62 mg/g. Doping of nickel ferrites caused an increase in the removal percentage of methylene blue dye (80 to 90%) and inorganic effluents (75 to 95% for lead and 47 to 82% for cadmium). In addition to this, band gap energy (2.43 to 3.26 eV) (UV-Vis spectroscopy), pore radius (65.2 to 74.8 A°), and specific surface area (16.45 to 27.95 m2/g) (BET analysis) were also increased. Generally, the results of the study revealed that synthesized nanoparticles can act as potential candidate for the removal of effluents from wastewater under optimum parameters along with recyclability, reusability, and separation under the influence of a magnetic field.

Effect of Pink Perch Gelatin on Physiochemical, Textural, Sensory, and Storage Characteristics of Ready-to-Cook Low-Fat Chicken Meatballs.

In recent years consumer demand for low-fat convenience food is increasing rapidly. This study was designed to develop low-fat ready-to-cook (RTC) chicken meatballs using pink perch gelatin. Meatballs were prepared using different concentrations of fish gelatin (3%, 4%, 5%, and 6%). The effect of fish gelatin content on the physico-chemical, textural, cooking, and sensory properties of meatballs was studied. Further, the shelf-life of meatballs was also studied at 4 °C for 15 days and -18 °C for 60 days. The addition of fish gelatin to meatballs decreased the fat content by 67.2% and 79.7% and increased the protein content by 20.1% and 66.4% in comparison to control and Branded Meatballs, respectively. As compared to the Control Meatballs, the addition of fish gelatin also reduced hardness by 26.4% and increased yield and moisture retention in the RTC meatballs by 15.4% and 20.9%, respectively. Sensory analysis suggested that a 5% fish gelatin addition in meatballs has the best acceptability among all tested treatments. Storage study indicated that the addition of fish gelatin to RTC meatballs delayed lipid oxidation during both refrigerated and frozen storage. The results suggested that pink perch gelatin can be used as a fat replacer in chicken meatballs and can potentially increase their shelf-life.

Optimization of single-step gelatin extraction from pink perch (Nemipterus japonicus) skin and bone obtained from surimi industry using a green solvent.

Surimi industry produces a large quantity of byproducts that are currently being utilized to produce low-value commodities. This study aims to extract gelatin from pink perch skin and bone obtained from the surimi industry using a green single-step extraction method. In addition to using a green solvent, that is, acetic acid, the new method combines the multiple steps of pre-treatment and hydrolysis into one single-step extraction process. Response surface methodology was used to optimize extraction parameters (pH, temperature, and time) to maximize yield and l-hydroxyproline (l-hyp) content. The optimum condition for gelatin extraction was obtained at pH 3, 75°C, and 30 min. At optimum conditions, gelatin yield and l-hyp content were observed to be 16.07% and 41.26 mg g-1 , respectively. The gelatin obtained at optimized condition was further compared with commercial bovine gelatin (BG) in terms of chemical composition and textural, functional, and rheological properties. The results suggested that the optimized pink perch gelatin had higher protein content (92.06%), better gel strength (251.08 g), higher imino acid (18.01%), and improved textural and functional properties than the commercially available BG. The optimized single-step gelatin extraction method from pink perch skin and bones is a promising, rapid, and efficient method for the production of good-quality gelatin, which can be further used for the development of high-value products such as food formulations. PRACTICAL APPLICATION: Fish gelatin is widely used in food product development. Most of the existing methods of the development of high-value product such as gelatin, use multi-step process and harsh mineral acid, therefore, are time-consuming and harmful to the environment. This study provides a green single-step gelatin extraction method that provides an efficient, rapid, and convenient method of gelatin extraction and a sustainable solution for fish industry byproduct utilization. The data obtained with this laboratory-scale study provides a strong basis for scale-up studies.

Enhancing wheat crop production with eco-friendly chitosan encapsulated nickel oxide nanocomposites: A safe and sustainable solution for higher yield.

In this work, we looked at using nickel oxide (NiO) nanocomposites with chitosan encapsulation as a nano-primer to improve wheat crop output. A straightforward green precipitation procedure was used to create the nanocomposites, and they were then characterized using several methods. According to the findings, the chitosan-encapsulated NiO nanocomposites possessed a large surface area and were resilient to changes in pH. Following this, wheat seeds were primed with the nanocomposites, and under greenhouse circumstances, the impact on crop growth was assessed. The findings demonstrated that, in comparison to the control group, nanocomposites priming considerably enhanced wheat growth and germination rate up to 99 %. In comparison to untreated plants, the wheat plants treated with the nanocomposites primer had greater plant height i.e. shoot length (11.4 cm) and root length (10.3 cm), leaf area, and biomass accumulation. Further research into the mechanism underlying the priming effect of nanocomposites on wheat growth revealed that the nanocomposites enhanced nutrient absorption, photosynthesis, and stress tolerance in wheat plants. In conclusion, our research shows that chitosan-encapsulated NiO nanocomposites have the potential to improve wheat crop productivity in an environmentally benign and long-term manner, offering a viable strategy for sustainable farming.

Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition.

Anoikis resistance or evasion of cell death triggered by cell detachment into suspension is a hallmark of cancer that is concurrent with cell survival and metastasis. The effects of frequent matrix detachment encounters on the development of anoikis resistance in cancer remains poorly defined. Here we show using a panel of ovarian cancer models, that repeated exposure to suspension stress in vitro followed by attached recovery growth leads to the development of anoikis resistance paralleling in vivo development of anoikis resistance in ovarian cancer ascites. This resistance is concurrent with enhanced invasion, chemoresistance and the ability of anoikis adapted cells to metastasize to distant sites. Adapted anoikis resistant cells show a heightened dependency on oxidative phosphorylation and can also evade immune surveillance. We find that such acquired anoikis resistance is not genetic, as acquired resistance persists for a finite duration in the absence of suspension stress. Transcriptional reprogramming is however essential to this process, as acquisition of adaptive anoikis resistance in vitro and in vivo is exquisitely sensitive to inhibition of CDK8/19 Mediator kinase, a pleiotropic regulator of transcriptional reprogramming. Our data demonstrate that growth after recovery from repeated exposure to suspension stress is a direct contributor to metastasis and that inhibition of CDK8/19 Mediator kinase during such adaptation provides a therapeutic opportunity to prevent both local and distant metastasis in cancer.

Impact of the COVID-19 Pandemic on Blood Donation Patterns: A Systematic Review and Meta-Analysis.

Blood centers, which are arguably the backbone of every hospital, depend on blood donors for a constant and regular supply of blood. Like many other fields, the COVID-19 pandemic severely affected blood donations. In this article, we aim to systematically search the studies done on blood donation during the COVID-19 pandemic period, analyze the pandemic's effect on blood donation, and examine the methodology used to overcome the problem. We performed a systematic review and meta-analysis to investigate the effect of the COVID-19 pandemic on blood donation. Two independent reviewers searched different databases, such as PubMed, ProQuest, Scopus, and Google Scholar. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Joanna Briggs Institute critical appraisal checklist for overall study characteristics. We included a total of 15 studies. There was an overall decrease in blood donation of 25%, with some regions showing a decrease of as much as 71%. However, some regions were able to experience a 2-10% increase in blood donation after taking stringent and early measures to prevent such decreases. The COVID-19 pandemic and consequent lockdown greatly affected blood transfusion services, resulting in a progressive decline in blood donations that threatened the lives of many patients who were fully dependent on blood transfusion. However, by making appropriate and early decisions and taking action, policymakers and the rest of society can prevent such shortages, potentially saving millions of lives.