Functionalized Cu-based metal oxide nanoparticles with enhanced Cd+2 adsorption capacity and their ecotoxicity assessment by molecular docking.

In the present study, synthesis of eco-friendly Cu-based metal oxides nanoparticles [CuO, Cu2O, and CuO&Cu2O nanoparticles (NPs)] without and with functionalization with Diethylene glycol (DEG) has been demonstrated. The synthesized NPs were screened for their ability to adsorb multiple heavy metal ions from an aqueous solution. Based on the maximum Cadmium (Cd+2) ion adsorption capacity, functionalized Cu2O (fCu2O) NPs were selected for the detailed characterization and batch studies. The average size of fCu2O NPs was found to be 57.4 ± 6.14 nm in comparison to NPs without capping (72.6 ± 5.19 nm). The experimental parameters viz. contact time, initial pH, and initial concentration were optimized, and the obtained results were interpreted using standard isotherms and kinetic models. The maximum Cd+2 adsorption on fCu2O NPs was observed at initial solution pH 7. The adsorption of Cd+2 was found to be decreased at acidic pH due to the protonation of functional groups present on the NPs surface. A maximum Cd+2 adsorption capacity of 204 ± 6.2 mg g-1 was obtained from the Langmuir adsorption isotherm. The crystal structure of NPs was prepared and docked with the protein targets of selected soil microbes in order to determine their ecotoxicity. The obtained results showed that NPs exhibited low affinity towards protein targets in comparison to the standard used. It suggests that NPs have less impact on the functionality of soil microbes and are thus safe for their disposal into the soil micro-environment.

A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer.

Despite substantial improvements in the treatment landscape of prostate cancer, the evolution of hormone therapy-resistant and metastatic prostate cancer remains a major cause of cancer-related death globally. The mainstay of treatment for advanced prostate cancer is targeting of androgen receptor signaling, including androgen deprivation therapy plus second-generation androgen receptor blockade (e.g., enzalutamide, apalutamide, darolutamide), and/or androgen synthesis inhibition (abiraterone). While these agents have significantly prolonged the lives of patients with advanced prostate cancer, is nearly universal. This therapy resistance is mediated by diverse mechanisms, including both androgen receptor-dependent mechanisms, such as androgen receptor mutations, amplifications, alternative splicing, and amplification, as well as non-androgen receptor-mediated mechanisms, such as lineage plasticity toward neuroendocrine-like or epithelial-mesenchymal transition (EMT)-like lineages. Our prior work identified the EMT transcriptional regulator Snail as critical to hormonal therapy resistance and is commonly detected in human metastatic prostate cancer. In the current study, we sought to interrogate the actionable landscape of EMT-mediated hormone therapy resistant prostate cancer to identify synthetic lethality and collateral sensitivity approaches to treating this aggressive, therapy-resistant disease state. Using a combination of high-throughput drug screens and multi-parameter phenotyping by confluence imaging, ATP production, and phenotypic plasticity reporters of EMT, we identified candidate synthetic lethalities to Snail-mediated EMT in prostate cancer. These analyses identified multiple actionable targets, such as XPO1, PI3K/mTOR, aurora kinases, c-MET, polo-like kinases, and JAK/STAT as synthetic lethalities in Snail+ prostate cancer. We validated these targets in a subsequent validation screen in an LNCaP-derived model of resistance to sequential androgen deprivation and enzalutamide. This follow-up screen provided validation of inhibitors of JAK/STAT and PI3K/mTOR as therapeutic vulnerabilities for both Snail+ and enzalutamide-resistant prostate cancer.

PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas.

Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis and frequently present significant challenges for cancer therapies. Recent studies have highlighted the dynamic interaction between immunosuppression and the dysregulation of energy metabolism in modulating the tumor microenvironment to promote cancer aggressiveness. However, a pan-cancer association among these two hallmarks, and a potent common driver for them-epithelial-mesenchymal transition (EMT)-remains to be done. This meta-analysis across 184 publicly available transcriptomic datasets as well as The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along with other immune checkpoint markers correlate positively with a partial EMT and an elevated glycolysis signature but a reduced OXPHOS signature in many carcinomas. These trends were also recapitulated in single-cell, RNA-seq, time-course EMT induction data across cell lines. Furthermore, across multiple cancer types, concurrent enrichment of glycolysis and PD-L1 results in worse outcomes in terms of overall survival as compared to enrichment for only PD-L1 activity or expression. These results highlight potential functional synergy among these interconnected axes of cellular plasticity in enabling metastasis and multi-drug resistance in cancer.

Conjunctival impression cytology for detection of early vitamin A deficiency in children.

Children presenting with recurrent infections have a high risk of developing vitamin A deficiency. Conjunctival impression cytology (CIC) was used in the present study in such children to detect subclinical deficiency and to monitor the outcome after therapy. Seventy children with history of recurrent infections, and 10 healthy children in the age group of six months to five years were included in the study. CIC was performed using millipore filter paper and stained with PAS stain. A three tier grading system was used consisting of normal, borderline abnormal and abnormal for interpretation. Vitamin A supplementation was given in children in the latter two categories. Repeat cytology showed reversal to normal in these children. Hence in children with high risk of developing vitamin A deficiency, it is suggested to do CIC for detection and monitoring it.