Regulatory enzymes

AIMS: Vascular aging is characterized by vessel stiffening, with increased deposition of extracellular matrix (ECM) proteins including collagens. Oxidative DNA damage occurs in vascular aging, but how it regulates ECM proteins and vascular stiffening is unknown. We sought to determine the relationship between oxidative DNA damage and ECM regulatory proteins in vascular aging. METHODS AND RESULTS: We examined oxidative DNA damage, the major base excision repair (BER) enzyme 8-Oxoguanine DNA Glycosylase (Ogg1) and its regulators, multiple physiological markers of aging, and ECM proteomics in mice from 22-72w...

Cancer remains a significant global health challenge, necessitating innovative approaches to enhance the efficacy and specificity of therapeutic interventions while minimizing adverse effects on healthy tissues. Nanotechnology has emerged as a promising avenue in cancer treatment, offering novel strategies for targeted drug delivery. Nanoparticles, liposomes, and polymer-based systems have played pivotal roles in revolutionizing cancer therapy. Nanotechnology possesses unique physicochemical properties, enabling efficient encapsulation of therapeutic agents and controlled and prolonged release at tumour sites...

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h...

BACKGROUND: Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. METHODS: We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE-/- ) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis...

Ubiquitination and deubiquitination are important forms of posttranslational modification that govern protein homeostasis. Deubiquitinating enzymes (DUBs), a protein superfamily consisting of more than 100 members, deconjugate ubiquitin chains from client proteins to regulate cellular homeostasis. However, the dysregulation of DUBs is reportedly associated with several diseases, including cancer. The tumor microenvironment (TME) is a highly complex entity comprising diverse noncancerous cells (e.g., immune cells and stromal cells) and the extracellular matrix (ECM)...

BACKGROUND: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. METHODS: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior...

Neuroblastoma (NB) is the most common and deadliest extracranial solid tumor in children. Targeting tumor-associated macrophages (TAMs) is a strategy for attenuating tumor-promoting states. The crosstalk between cancer cells and TAMs plays a pivotal role in mediating tumor progression in NB. The overexpression of Hexokinase-3 (HK3), a pivotal enzyme in glucose metabolism, has been associated with poor prognosis in NB patients. Furthermore, it correlates with the infiltration of M2-like macrophages within NB tumors, indicating its significant involvement in tumor progression...

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars...

The combined transcriptome outcome provides an important clue to the regulatory cascade centering on lncRNA GARR2 and CPS2 gene in GA response. Long non-coding RNAs (lncRNAs) serve as regulatory components in transcriptional hierarchy governing multiple aspects of biological processes. Dissecting regulatory mechanisms underpinning tetracyclic diterpenoid gibberellin (GA) cascade holds both theoretical and applied significance. However, roles of lncRNAs in transcriptional modulation of GA pathway remain largely elusive...

UNLABELLED: Intracellular pools of deoxynucleoside triphosphates (dNTPs) are strictly maintained throughout the cell cycle to ensure accurate and efficient DNA replication. DNA synthesis requires an abundance of dNTPs, but elevated dNTP concentrations in nonreplicating cells delay entry into S phase. Enzymes known as deoxyguanosine triphosphate triphosphohydrolases (Dgts) hydrolyze dNTPs into deoxynucleosides and triphosphates, and we propose that Dgts restrict dNTP concentrations to promote the G1 to S phase transition...

Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules...

SAMHD1 regulates cellular nucleotide homeostasis, controlling dNTP levels by catalysing their hydrolysis into 2'-deoxynucleosides and triphosphate. In differentiated CD4+ macrophage and resting T-cells SAMHD1 activity results in the inhibition of HIV-1 infection through a dNTP blockade. In cancer, SAMHD1 desensitizes cells to nucleoside-analogue chemotherapies. Here we employ time-resolved cryogenic-EM imaging and single-particle analysis to visualise assembly, allostery and catalysis by this multi-subunit enzyme...

Taking inspiration from natural systems, in which molecular switches are ubiquitous in the biochemistry regulatory network, we aim to design and construct synthetic molecular switches driven by DNA-modifying enzymes, such as DNA polymerase and nicking endonuclease. The enzymatic treatments on our synthetic DNA constructs controllably switch ON or OFF the sticky end cohesion and in turn cascade to the structural association or disassociation. Here we showcase the concept in multiple DNA nanostructure systems with robust assembly/disassembly performance...

Constitutive Androstane Receptor (CAR, Nr1i3), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid and lipid metabolizing enzymes, stimulates liver hypertrophy and hyperplasia, and ultimately, hepatocellular carcinogenesis. The mechanisms linking early CAR responses to later disease development are poorly understood. Here we show that exposure of CD-1 mice to TCPOBOP, a halogenated xenochemical and selective CAR agonist ligand, induces pericentral steatosis marked by hepatic accumulation of cholesterol and neutral lipid, and elevated circulating alanine aminotransferase, indicating hepatocyte damage...

Cuticular wax is a protective layer on the aerial surfaces of land plants. In Arabidopsis (Arabidopsis thaliana), cuticular wax is mainly constituted of compounds derived from very-long-chain fatty acids (VLCFAs) with chain lengths longer than C28. CER2-LIKE (ECERIFERUM2-LIKE) proteins interact with CER6/KCS6 (ECERIFERUM6/β-Ketoacyl-CoA Synthase6), the key enzyme of the fatty acid elongase complex, to modify its substrate specificity for VLCFA elongation past C28. However, the molecular regulatory mechanism of CER2-LIKE proteins remains unclear...

The rapid industrial revolution significantly increased heavy metal pollution, becoming a major global environmental concern. This pollution is considered as one of the most harmful and toxic threats to all environmental components (air, soil, water, animals, and plants until reaching to human). Therefore, scientists try to find a promising and eco-friendly technique to solve this problem i.e., bacterial bioremediation. Various heavy metal resistance mechanisms were reported. Omics technologies can significantly improve our understanding of heavy metal resistant bacteria and their communities...

Silicon application mitigates phosphate deficiency in barley through an interplay with auxin and nitric oxide, enhancing growth, photosynthesis, and redox balance, highlighting the potential of silicon as a fertilizer for overcoming nutritional stresses. Silicon (Si) is reported to attenuate nutritional stresses in plants, but studies on the effect of Si application to plants grown under phosphate (Pi) deficiency are still very scarce, especially in barley. Therefore, the present work was undertaken to investigate the potential role of Si in mitigating the adverse impacts of Pi deficiency in barley Hordeum vulgare L...

Glutamine synthetase (GS) is a key enzyme involved in nitrogen assimilation and the maintenance of C/N balance, and it is strictly regulated in all bacteria. In cyanobacteria, glutamine synthetase expression is controlled by nitrogen control A (NtcA) transcription factor, which operates global nitrogen regulation in these photosynthetic organisms. Furthermore, post-translational regulation of GS is operated by protein-protein interaction with GS inactivating factors (IFs). Here, we describe an additional regulatory mechanism involving an antisense RNA...

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process...

OBJECTIVES: The caecum bridges the small and large intestine and plays a front-line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically. METHODS: To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues...