ST3GAL1 and βII-spectrin pathways control CAR T cell migration to target tumors.

Adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells is becoming a promising treatment option for hematological malignancies. However, T cell immunotherapies have mostly failed in individuals with solid tumors. Here, with a CRISPR-Cas9 pooled library, we performed an in vivo targeted loss-of-function screen and identified ST3 β-galactoside α-2,3-sialyltransferase 1 (ST3GAL1) as a negative regulator of the cancer-specific migration of CAR T cells.

Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality.

Sepsis is a life-threatening systemic inflammatory condition causing approximately 11 million annual deaths worldwide. Although key hyperinflammation-based organ dysfunctions that drive disease pathology have been recognized, our understanding of the factors that predispose patients to septic mortality is limited. Due to the lack of reliable prognostic measures, the development of appropriate clinical management that improves patient survival remains challenging.

Identifying the Novel Inhibitors Against the Mycolic Acid Biosynthesis Pathway Target "mtFabH" of .

Mycolic acids are the key constituents of mycobacterial cell wall, which protect the bacteria from antibiotic susceptibility, helping to subvert and escape from the host immune system. Thus, the enzymes involved in regulating and biosynthesis of mycolic acids can be explored as potential drug targets to kill (Mtb). Herein, Kyoto Encyclopedia of Genes and Genomes is used to understand the fatty acid metabolism signaling pathway and integrative computational approach to identify the novel lead molecules against the mtFabH (β-ketoacyl-acyl carrier protein synthase III), the key regulatory enzyme of the mycolic acid pathway.

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

GLOBOCAN 2020 estimated more than 19.3 million new cases, and about 10 million patients were deceased from cancer in 2020. Clinical manifestations showed that several growth factor receptors consisting of transmembrane and cytoplasmic tyrosine kinase (TK) domains play a vital role in cancer progression.

Anti-breast cancer action of carbonic anhydrase IX inhibitor 4-[4-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-benzylidene-hydrazinocarbonyl]-benzenesulfonamide (BSM-0004): and studies.

Anti-breast cancer action of novel human carbonic anhydrase IX (hCA IX) inhibitor BSM-0004 has been investigated using and models of breast cancer. BSM-0004 was found to be a potent and selective hCA IX inhibitor with a Ki value of 96 nM. anticancer effect of BSM-0004 was analysed against MCF 7 and MDA-MA-231 cells, BSM-0004 exerted an effective cytotoxic effect under normoxic and hypoxic conditions, inducing apoptosis in MCF 7 cells.

Anti-inflammatory Effects of Seed Extract on Gelatinase-B (MMP-9) Regulation against Hyperglycemic Cardiomyocyte Stress.

Black berry () fruit is useful in curing diabetic complications; however, its role in diabetes-induced cardiomyopathy is not yet known. In this study, we investigated the regulation of gelatinase-B (MMP-9) by methanol seed extract (MSE) in diabetic cardiomyopathy using real-time PCR, RT-PCR, immunocytochemistry, gel diffusion assay, and substrate zymography. The regulatory effects of MSE on NF-B, TNF-, and IL-6 were also examined.

Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and In Vitro and In Vivo Investigations.

Two sets of benzenesulfonamide-based effective human carbonic anhydrase (hCA) inhibitors have been developed using the tail approach. The inhibitory action of these novel molecules was examined against four isoforms: hCA I, hCA II, hCA VII, and hCA XII. Most of the molecules disclosed low to medium nanomolar range inhibition against all tested isoforms.

Identifying the natural polyphenol catechin as a multi-targeted agent against SARS-CoV-2 for the plausible therapy of COVID-19: an integrated computational approach.

The global pandemic crisis, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines have not turned to be realistic within the timeframe needed to combat this pandemic. Here, we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, whichare crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection.

Exploring the Role of TRIP-Brs in Human Breast Cancer: An Investigation of Expression, Clinicopathological Significance, and Prognosis.

TRIP-Brs, a group of transcription factors (TFs) that modulate several mechanisms in higher organisms. However, the novel paradigm to target TRIP-Brs in specific cancer remains to be deciphered. In particular, comprehensive analysis of TRIP-Brs in clinicopathological and patients' prognosis, especially in breast cancer (BRCA), is being greatly ignored.

Production of a thermo-tolerant κ-carrageenase via a food-grade host and anti-oxidant activity of its enzymatic hydrolysate.

κ-Carrageenase cleaves the β-(1-4) linkages of κ-carrageenan into κ-carrageenan oligosaccharides (κ-COS), which exhibit various biological activities. In this study, a glycoside hydrolase (GH) family 16 κ-carrageenase gene, cgkA, was cloned from the marine bacterium Vibrio sp. SY01 and secretory expressed in a food-grade host, Yarrowia lipolytica.

Inhibitory Role of TRIP-Br1/XIAP in Necroptosis under Nutrient/Serum Starvation.

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy.

Novel Carbazole-Piperazine Hybrid Small Molecule Induces Apoptosis by Targeting BCL-2 and Inhibits Tumor Progression in Lung Adenocarcinoma in Vitro and Xenograft Mice Model.

Lung cancer is a type of deadly cancer and a leading cause of cancer associated death worldwide. BCL-2 protein is considered as an imperative target for the treatment of cancer due to their significant involvement in cell survival and death. A carbazole-piperazine hybrid molecule ECPU-0001 was designed and synthesized as a potent BCL-2 targeting agent with effective anticancer cancer activity.

IL-32γ suppresses lung cancer stem cell growth via inhibition of ITGAV-mediated STAT5 pathway.

The cancer stem cells (CSCs) are thought to be responsible for cancer initiation, recurrence, and metastasis via a multifactorial process. IL-32γ has been known to inhibit several tumor developments. However, the role of IL-32γ in CSCs is unknown.

Prognostic and Clinicopathological Significance of SERTAD1 in Various Types of Cancer Risk: A Systematic Review and Retrospective Analysis.

SERTAD/TRIP-Br genes are considered as a key nuclear transcriptional player in diverse mechanisms of cell including carcinogenesis. The Oncomine-Online Platform was used for differential expression and biological insights. Kaplan-Meier survival estimated by KM-plotter/cBioPortal/PrognoScan with 95% CI.

Anti-tumor activity of wogonin, an extract from Scutellaria baicalensis, through regulating different signaling pathways.

Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis (Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anti-cancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt (also known as protein kinase B) and AMP-activated protein kinase (AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity.

Growth-inducing effects of argon plasma on soybean sprouts via the regulation of demethylation levels of energy metabolism-related genes.

This study was conducted to determine the effects of argon plasma on the growth of soybean [Glycine max (L.) Merr.] sprouts and investigate the regulation mechanism of energy metabolism.

Novel phyto-derivative BRM270 inhibits hepatocellular carcinoma cells proliferation by inducing G2/M phase cell cycle arrest and apoptosis in xenograft mice model.

Hepatocellular carcinoma (HCC) is a major threat to human health worldwide and development of novel antineoplastic drug is demanding task. BRM270 is a proprietary combination of traditional medicinal herbs, has been shown to be effective against a wide range of stem-like cancer initiating cells (SLCICs). However, the underlying mechanism and antitumor efficacy of BRM270 in human hepatocellular carcinoma (HCC) cells have not been well elucidated till date.

Novel Triazole-Piperazine Hybrid Molecules Induce Apoptosis via Activation of the Mitochondrial Pathway and Exhibit Antitumor Efficacy in Osteosarcoma Xenograft Nude Mice Model.

Mitochondria impart a crucial role in the regulation of programmed cell death and reactive oxygen species (ROS) generation, besides serving as a primary energy source. Mitochondria appeared as an important target for the therapy of cancer due to their significant contribution to cell survival and death. Here, we report the design and synthesis of a novel series of triazole-piperazine hybrids as potent anticancer agents.

Comparative Transcriptomic Analyses by RNA-seq to Elucidate Differentially Expressed Genes in the Muscle of Korean Thoroughbred Horses.

The athletic abilities of the horse serve as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. We analyzed differentially expressed genes in triceps brachii muscle tissues collected from Eonjena Taeyang and Jigusang Seryeok Thoroughbred horses and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. High-quality horse transcriptome data were generated, with over 22 million 90-bp pair-end reads.

An integrated in silico approach for functional and structural impact of non- synonymous SNPs in the MYH1 gene in Jeju Native Pigs.

Background: This study was performed to identify the non- synonymous polymorphisms in the myosin heavy chain 1 gene (MYH1) association with skeletal muscle development in economically important Jeju Native Pig (JNP) and Berkshire breeds. Herein, we present an in silico analysis, with a focus on (a) in silico approaches to predict the functional effect of non-synonymous SNP (nsSNP) in MYH1 on growth, and (b) molecular docking and dynamic simulation of MYH1 to predict the effects of those nsSNP on protein-protein association.

Results: The NextGENe (V 2.

Epigenetic induction of epithelial to mesenchymal transition by LCN2 mediates metastasis and tumorigenesis, which is abrogated by NF-κB inhibitor BRM270 in a xenograft model of lung adenocarcinoma.

Tumor initiating cancer stem-like cells (TICSCs) have recently become the object of intensive study. Human-Lipocalin-2 (hLCN2) acts as a biomarker for cancers. The aim of the present study was to explore new insights regarding the potential role of LCN2 in inducing epithelial to mesenchymal transition (EMT) by transfecting LCN2 into CD133+-A549-TICSCs and its cross-talk with the NF-κB signaling pathway in adenocarcinoma of the lung.

A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-κB Signaling Cascade.

Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-κB appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and childevrepen.

An Integrated In Silico Approach for the Structural and Functional Exploration of Lipocalin 2 and its Functional Insights with Metalloproteinase 9 and Lipoprotein Receptor-Related Protein 2.

Recent evidence demonstrated that Lipocalin 2 (LCN2) is garnering interest from a wide spectrum as biomarker. Here, we present an in silico characterization of LCN2 belonging to prominent organisms focusing for their physicochemical and structural differences. We found significant variations in physicochemical properties between organisms and low sequence similarity based on their amino acid properties alone.

The novel inhibitor BRM270 downregulates tumorigenesis by suppression of NF-κB signaling cascade in MDR-induced stem like cancer-initiating cells.

The nuclear factor κB (NF-κB) and interleukin-6 (IL-6) contribute to multidrug resistance (MDR) in tumor chemotherapy. The essential phenomenon of oncogenic activation of NF-κB in cancer-initiating cells showing MDR resulting from increased IL-6 expression is still unclear. Cancer stem cells (CSCs) have been the objective of intensive study.

Comparative transcriptomic analysis by RNA-seq to discern differential expression of genes in liver and muscle tissues of adult Berkshire and Jeju Native Pig.

RNA-seq is being rapidly adopted for the profiling of the transcriptomes in different areas of biology, especially in the studies related to gene regulation. The discovery of differentially expressed genes (DEGs) between adult animals of Jeju Native Pig (JNP) and Berkshire breeds of Sus scrofa, is of particular interest for the current study. For the better understanding of the gene expression profiles of the liver and longissimus dorsi muscle, DEGs were identified via RNA-seq.