Biochemistry

A divergent one-pot domino strategy for the synthesis of nickel(II) and copper(II) β-thiophene-fused 5,10,15,20-tetraarylporphyrins was developed through a thiol-Michael addition of thioglycolic/thiolactic acid to the corresponding 2-iminoporphyrins, formed in situ after the reaction of nickel(II) and copper(II) 2-formyl-5,10,15,20-tetraarylporphyrins with sterically hindered tert -butylamine in 1,2-dichloroethane at 80 °C. Interestingly, the reaction of 2-formylporphyrins with comparatively less sterically hindered primary amines and thioglycolic acid afforded a mixture of β-substituted porphyrinic thiazolidinones and β-thiophene-fused porphyrins...

Higher fungi of the genus Armillaria belonging to the phylum Basidiomycota produce bioactive sesquiterpenoid aryl esters called melleolides. A bioactivity-guided discovery process led to the identification of the new melleolide 5'‑methoxyarmillane (1) in organic extracts from the mycelium of Armillaria ostoyae. Remarkably, supplementation of rapeseed oil to the culture medium potato dextrose broth increased the production of 1 by a factor of six during the course of the 35 days fermentation. Compound 1 was isolated and its structure elucidated by UHPLC-QTOF-HR-MS/MS and NMR spectroscopy...

Protein kinase B (AKT1) is a serine/threonine kinase that regulates fundamental cellular processes, including cell survival, proliferation, and metabolism. AKT1 activity is controlled by two regulatory phosphorylation sites (Thr308, Ser473) that stimulate a downstream signaling cascade through phosphorylation of many target proteins. At either or both regulatory sites, hyperphosphorylation is associated with poor survival outcomes in many human cancers. Our previous biochemical and chemoproteomic studies showed that the phosphorylated forms of AKT1 have differential selectivity toward peptide substrates...

Radiation therapy is one of the most common treatments for cancer. However, enhancing tumors' radiation sensitivity and overcoming tolerance remain a challenge. Previous studies have shown that the Ras signaling pathway directly influences tumor radiation sensitivity. Herein, we designed a series of Ras-targeting stabilized peptides, with satisfactory binding affinity ( K D = 0.13 μM with HRas) and good cellular uptake. Peptide H5 inhibited downstream phosphorylation of ERK and increased radio-sensitivity in HeLa cells, resulting in significantly reduced clonogenic survival...

As a medicinal and edible food, Hippophae rhamnoides Linn. subsp. sinensis Rousi is plenty of bioactive secondary metabolites including flavonoids and their derivatives, which have a certain protective effect on oxidative damage. The present study isolated three new kaempferol derivatives (compound 1-3), named Hippophandine A-C, from H. rhamnoides seed residue. The structures of Hippophandine A-C were explicated by HR-ESI-MS, NMR, and chemical analyses. Hippophandine A-C (1, 5, and 10 µM) were used to attenuate H2O2-induced cell death in SH-SY5Y and explore the mechanism in oxidative damage...

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis...

This present review delineates the repertoire of vinyl cyclopropanes and their stuctural analogues to accomplish a wide array of oxa-cycles, aza-cycles, and thia-cycles under transition metal catalysis and metal-free approaches from early 2019 to the present date. The generation of electrophilic π-allyl intermediates and 1-3/1-5-dipolarophile chemistry originating from VCPs are always green, step- and atom-economical and sustainable strategies in comparsion with prefunctionalized and/or C-H activation protocols...

(171/200)ADCs represent a transformative class of medicine that combines the specificity of monoclonal antibodies with the potency of highly cytotoxic agents through linkers, aiming to enhance the therapeutic index of cytotoxic drugs. Given the complex molecular structures of ADCs, combining the molecular characteristics of small-molecule drugs and those of large-molecule biotherapeutics, there are several unique considerations when designing nonclinical-to-clinical PK/PD translation strategies.This complexity also demands a thorough understanding of the ADC's components-antibody, linker, and payload-to the overall toxicological, PK/PD, and efficacy profile...

This manuscript describes the synthesis of γ-lactam from the nitrogen insertion reaction of cyclobutanones using an oxime as an aminating reagent with a catalytic amount of Brønsted acid. This method was employed with a more stable oxime reagent, which is a precursor analog of hydroxylamine derivatives with explosive properties. The reaction was tolerated by various substituted cyclobutanones and less strained five- or six-membered ketones. The obtained γ-lactam products could be transformed into γ-aminobutyric acid derivatives via ring-opening hydrolysis...

BACKGROUND: In a critically ill patient, when an arterial blood sample is processed on an arterial blood gas (ABG) analyzer, it also measures electrolytes apart from analyzing the blood gases. The turnaround time for ABG analysis is way too less compared to the conventional electrolyte analysis with a serum sample. OBJECTIVE: This study intends to investigate whether values of electrolytes estimated in arterial blood can substitute the routinely practiced method...

Late diagnosis is one of the main reasons for high mortality rates in cancer patients. Therefore, investigating the molecular mechanisms involved in tumor progression can improve the cancer diagnosis in the early stages of the tumor progression. MicroRNAs (miRNAs) have important roles in regulation of cell growth, proliferation, metabolism, and migration. Since, deregulation of miR-409 has been reported in a wide range of cancers, in the present review, we investigated the molecular mechanisms of miR-409 during tumor progression and invasion...

Glaucoma is a common cause of blindness worldwide. Genetic effects are believed to contribute to the onset and progress of glaucoma, but the underlying pathological mechanisms are not fully understood. Here, we set out to introduce mutations into the CDKN2B-AS1 gene, which is known as being the closely associated with glaucoma, in a human neuronal cell line in vitro . We introduced gene mutations with CRISPR/Cas9 into exons and introns into the CDKN2B-AS1 gene. Both mutations strongly promoted neuronal cell death in normal culture conditions...

AIM: The purpose of this study was to examine the effect of pemafibrate in a murine model of non-alcoholic steatohepatitis (NASH). METHODS: Forty-two, 19-week-old, male, C57BL/6J mice were divided into three groups: a Control group (n = 14), a dextran sulfate sodium (DSS) group (n = 14), and a DSS + PEM group (n = 14). All mice were given a standard rodent diet for the first week, followed by a choline-deficient, high-fat diet (CDHF) for the next 12 weeks...

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited...

OBJECTIVES: Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8+ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8+ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I)...

Allostery, the presence of functional interactions between distant parts of proteins, is a critical concept in the field of biochemistry and molecular biology, particularly in the context of protein function and regulation. Understanding the principles of allosteric regulation is essential for advancing our knowledge of biology and developing new therapeutic strategies. This paper presents AlloViz, an open-source Python package designed to quantitatively determine, analyse, and visually represent allosteric communication networks on the basis of molecular dynamics (MD) simulation data...

For the first time, an original synthetic approach has been developed that enables the introduce ten tetrazole fragments into the pillar[5]arene structure. A supramolecular electrochemical probe was assembled for the first time from the obtained macrocycles and an electrochemically active signal converter: methylene blue (MB) dye. The ability of pillar[5]arene containing tetrazole fragments to selectively bind MB was confirmed by UV-vis and 2D 1 H-1 H NOESY spectroscopy. The stoichiometry of the resulting pillar[5]arene/MB complex = 1 : 2...

The generation of insulin-producing cells (IPCs) is an attractive approach for replacing damaged β cells in diabetic patients. In the present work, we introduced a hybrid platform of decellularized amniotic membrane (dAM) and fibrin encapsulation for differentiating adipose tissue-derived stem cells (ASCs) into IPCs. ASCs were isolated from healthy donors and characterized. Human AM was decellularized, and its morphology, DNA, collagen, glycosaminoglycan (GAG) contents, and biocompatibility were evaluated...

Polymerase chain reaction (PCR) is an important tool for exogenous gene acquisition and recombinants identification. There exist two problems when using Serratia marcescens as a template for PCR amplification: amplified PCR products are rapidly degraded, and the results of PCR amplification are unstable. The aim of the present work was to elucidate the reasons for this. By mixing PCR products amplified from Escherichia coli DH5α with S. marcescens supernatant or pellet, we found that the DNA-degrading substance in S...

Diabetes mellitus is associated with secondary complications such as diabetic retinopathy (DR), nephropathy (DN), and cardiomyopathy (DCM), all of which significantly impact patient health. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory responses and endothelial dysfunction, both crucial in the pathogenesis of these complications. The goal of this review is to investigate at potential therapy methods that target ICAM-1 pathways and to better understand the multifaceted role of ICAM-1 in secondary diabetic problems...