A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart.

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy.

Membrane-bound IL-7 immobilized by the CD8 transmembrane region improves efficacy of CD19 CAR-T cell therapy.

Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains.

USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation.

Determination of platinum-resistance of women with ovarian cancer by FTIR spectroscopy combined with multivariate analyses and machine learning methods.

Patients with high-grade ovarian cancer have a poor prognosis, thus effective treatment remains an unmet medical issue of high importance. Moreover, finding the reason for resistance to cisplatin is a crucial task for the improvement of anti-cancer drugs. In this study, we showed for the first time a chemical difference in a serum collected from platinum-resistance and platinum-sensitive women suffering from ovarian cancer using Fourier Transform InfraRed (FTIR) spectroscopy followed by a data analysis by Principal Component Analysis (PCA), Hierarchical Component Analysis (HCA) and 4 different machine learning algorithms.

FTIR monitoring of the 13-valent pneumococcal conjugate vaccine for lung cancer patients: Changes in amides vibrations correlated with biochemical assays.

Lung cancer is one of the most lethal cancers. Unfortunately, respiratory tract infections are very common in lung cancer patients, delaying appropriate anticancer therapy. To increase therapy efficiency, in this study we examined the effect of 13-Valent Pneumococcal Conjugate Vaccine on the immune response in lung cancer patients, which indirectly affects the success of anticancer therapy.

Synthesis, Characterization, and Biological Activity of New 4'-Functionalized Bis-Terpyridine Ruthenium(II) Complexes: Anti-Inflammatory Activity Advances.

Ruthenium complexes incorporating 2,2' : 6',2''-terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA-binding, anti-inflammatory, antimicrobial, and anticancer properties. In this study, three new 4'-functionalized bis(terpyridine) Ru(II) complexes were synthesized. These complexes feature one ligand as 4-(2,2' : 6',2''-terpyridine-4'-yl) benzoic acid and the second ligand as either 4'-(2-thienyl)-2,2' : 6',2''-terpyridine, 4'-(3,4-dimethoxyphenyl)-2,2' : 6',2''-terpyridine, or 4'-(4-dimethylaminophenyl)-2,2' : 6',2''-terpyridine.

Effect of a Novel Food Rich in Miraculin on the Oral Microbiome of Malnourished Oncologic Patients with Dysgeusia.

Background/objectives: Dysgeusia contributes to the derangement of nutritional status in patients with cancer as well as worsening the quality of life. There has been a lack of effective treatments for taste disorders provided by the pharmaceutical industry.

Methods: This was a pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months.

The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition.

Acyl-coenzyme A: cholesterol acyltransferases are enzymes which are involved in the homeostasis of cholesterol. Impaired enzyme activity is associated with the occurrence of various diseases like Alzheimer's disease, atherosclerosis, and cancers. At present, mitotane is the only inhibitor of this class of enzymes in clinical use for the treatment of adrenocortical carcinoma but associated with common and severe adverse effects.

Structural basis for synthase activation and cellulose modification in the E. coli Type II Bcs secretion system.

Bacterial cellulosic polymers constitute a prevalent class of biofilm matrix exopolysaccharides that are synthesized by several types of bacterial cellulose secretion (Bcs) systems, which include conserved cyclic diguanylate (c-di-GMP)-dependent cellulose synthase modules together with diverse accessory subunits. In E. coli, the biogenesis of phosphoethanolamine (pEtN)-modified cellulose relies on the BcsRQABEFG macrocomplex, encompassing inner-membrane and cytosolic subunits, and an outer membrane porin, BcsC.

Generation and application of CES1-knockout Tet-Off-regulated CYP3A4 and UGT1A1-expressing Caco-2 cells.

Caco-2 cells, a human colorectal adenocarcinoma cell line, are widely used to model small intestinal epithelial cells in the drug development process because they can predict drug absorption with high accuracy. However, Caco-2 cells have several issues. First, Caco-2 cells have little expression of cytochrome P450 3A4 (CYP3A4), which is a major drug-metabolizing enzyme in the human intestine.

Drug repositioning identifies potential autophagy inhibitors for the LIR motif p62/SQSTM1 protein.

Autophagy is a critical cellular process for degrading damaged organelles and proteins under stressful conditions and has casually been shown to contribute to tumor survival and drug resistance. Sequestosome-1 (SQSTM1/p62) is an autophagy receptor that interacts with its binding partners via the LC3-interacting region (LIR). The p62 protein has been a highly researched target for its critical role in selective autophagy.

Synthetic trimeric interleukin-6 receptor complexes with a STAT3 phosphorylation dominated activation profile.

In Interleukin (IL)-6 signalling, IL-6 site I binds to the IL-6 receptor (IL-6R) first, following by IL-6 site II interaction to domain 2/3 of gp130 to form premature trimeric IL-6:IL-6R:gp130 receptor complexes. Formation of the mature hexameric receptor complex is then facilitated by the inter-trimeric interaction of IL-6 site III with domain 1 of the opposing gp130. The two gp130-associated Janus kinases (JAKs) trans-phosphorylate when their spatiotemporal pairing is correct, which causes the activation of STAT, ERK, and AKT pathways in a balanced manner.

PDCD4 deficiency in hepatocytes exacerbates nonalcoholic steatohepatitis through enhanced MHC class II transactivator expression.

Nonalcoholic steatohepatitis (NASH) is a primary cause of liver cirrhosis and hepatocellular carcinoma, presenting a significant and unmet medical challenge. The necessity to investigate the molecular mechanisms underlying NASH is highlighted by the observed decrease in programmed cell death 4 (PDCD4) expression in NASH patients, suggesting that PDCD4 may play a protective role in maintaining liver health. In this study, we identify PDCD4 as a natural inhibitor of NASH development in mice.

Determination of spectroscopy marker of atherosclerotic carotid stenosis using FTIR-ATR combined with machine learning and chemometrics analyses.

Atherosclerotic carotid stenosis (ACS) is a recognized risk factor for ischemic stroke. Currently, the gold diagnostic standard is Doppler ultrasound, the results of which do not provide certainty whether a given person should be qualified for surgery or not, because in some patients, carotid artery stenosis, for example at the level of 70 %, does not cause ischemic stroke in others yes. Therefore, there is a need for new methods that will clearly indicate the marker qualifying the patient for surgery.

Raman spectroscopy combined with machine learning and chemometrics analyses as a tool for identification atherosclerotic carotid stenosis from serum.

Atherosclerosis carotid stenosis (ACS) is one of the main causes of stroke. Unfortunately, the highest number of people go to the doctor with an advanced disease or as a result of a stroke, because carotid atherosclerosis does not cause obvious symptoms. Therefore, it is important to find a diagnostic method to detect the disease during routine tests (using blood or serum).