Objective— Vascular calcification is a characteristic feature of atherosclerosis, diabetes mellitus, and end-stage renal disease. We have demonstrated that activation protein kinase B (AKT) upregulates runt-related transcription factor 2 (Runx2), key osteogenic crucial for vascular smooth muscle cells (VSMC). Using mice with SMC-specific deletion phosphatase tensin homolog (PTEN), major negative regulator AKT, the present studies uncovered novel molecular mechanism underlying PTEN/AKT/FOXO...

As a central event during liver fibrosis, hepatic stellate cells (HSC) have been thought to be potential therapeutic target for fibrosis. Previous studies shown that runt-related transcription factor 2 (Runx2) is associated with the development of non-alcoholic fatty disease, while its specific role in HSC activation and fibrosis remains elusive.In this study, we found Runx2 expression was significantly upregulated human different aetiologies. also gradually elevated mouse mainly expressed...

The N6-methyladenosine (m6A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but mechanism m6A for regulation in hepatocellular carcinoma cells (HCC) remains unclear. In study, knockdown Wilms' tumor 1-associating protein (WTAP) was made HCC study correlation between autophagy. A fluorescent confocal microscopy analysis showed that WTAP could facilitate HCC. Western blot level p-AMPK decreased WTAP-knockdown cells. Additionally, LKB1, upstream kinase...

Background: Digital transformation in the sports industry has become increasingly crucial for sustainable development, yet comprehensive empirical evidence on policy effectiveness and risk management remains limited. Purpose: This study investigates impact of support factors digital companies, examining heterogeneous effects across different firm characteristics regional contexts. Methods: Using panel data from 168 companies listed China’s A-shares markets New Third Board 2019 to 2023, this...

Abstract Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an essential enzyme involved in de novo purine biosynthesis, is connected with formation of various tumors. However, the specific biological roles and related mechanisms PAICS gastric cancer (GC) remain unclear. In present study, we identified for first time that was significantly upregulated GC high expression correlated poor prognosis patients GC. addition, knockdown...

Death receptor 4 (DR4) is a cell surface for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling well known the best-studied effector pathway downstream of Ras Raf. This study focuses on determining impact pharmacological MEK inhibition DR4 expression elucidating underlying mechanism. We found that several inhibitors including MEK162, AZD6244, PD0325901 effectively decreased protein levels in...

Abstract b-AP15 and its derivatives block proteasome deubiquitinase (DUB) activity have been developed tested in the clinic as potential cancer therapeutic agents. induces apoptosis cells, but underlying mechanisms are largely undefined. The current study focuses on studying modulatory effects of death receptor 5 (DR5) levels DR5 activation-induced well understanding mechanisms. Treatment with potently increased including cell surface different lines limited or no other related proteins DR4,...

Phosphorylated cAMP-responsive element binding protein-1 (p-CREB-1) is an important transcription factor which has been reported to be implicated in fibrogenesis. However, the association between p-CREB-1 and transforming growth factor-β1 (TGF-β1)-mediated liver fibrogenesis remains poorly understood. In present study, exogenous TGF-β1 recombinant protein was used activate hepatic stellate cells (HSCs), we established a rat model of tetrachloromethane (CCl4)‑induced fibrosis. Loss-...

We have demonstrated runt-related transcription factor 2 (Runx2) plays important role in atherosclerosis. It has been indicated that atherosclerosis shares the similar histopathology with nonalcoholic steatohepatitis (NASH), a progressive stage of fatty liver disease (NAFLD), on macrophages infiltration. However, function Runx2 NAFLD is completely unknown. Here, we investigated underlying mechanism triggering infiltration development NAFLD.Mice were fed high-fat diet (HFD) for long time....

The productivity of stably transfected cell lines is critical importance for the manufacturing therapeutic proteins. Various methods have been successfully implemented to increase production output mammalian cultures. Increasing evidence suggests that optimization gene coding sequences an expression vector can improve specific line yield recombinant protein. Here we demonstrate substantially enhances antibody in Chinese hamster ovary cells. When was applied heavy and light chain genes a...

The fast-growing biopharmaceutical industry demands speedy development of highly efficient and reliable production systems to meet the increasing requirement for drug supplies. generation cell lines has traditionally involved manual operations that are labor-intensive, low-throughput vulnerable human errors. We report here an integrated high-throughput automated platform manufacturing protein therapeutics. combination BD FACS Aria Cell Sorter, CloneSelect Imager TECAN Freedom EVO liquid...

Observational studies report some association between circulating bilirubin levels and osteoporosis, but it is unknown if this causal or confounded. In two-sample Mendelian randomization (MR) study, we included a large genome-wide study (GWAS) associated with total among 317,639 people, meta-analysis to identify genetic variants bone mineral density (BMD) estimated by heel quantitative ultrasound (eBMD) 426,824 individuals fracture 1.2 million individuals. The results revealed that had no...

Abstract Hybridoma cultures are routinely used as a source for monoclonal antibody (mAb) production necessary preclinical evaluation. However, these typically have low volumetric and specific productivities. In this article, we examined the use timing of addition dimethyl sulfoxide (DMSO) medium additive to improve mAb in our hybridoma clone 19 (c19) cultures. From shake flask studies, defined optimal DMSO concentration time improved productivity. This coordinated with high cell viability...

Transforming growth factor (TGF)‑β3 has previously been reported to antagonize hepatic fibrosis in vivo and vitro. The present study aimed investigate the mechanism underlying involvement of TGF‑β3 fibrosis. Short hairpin (sh)RNA‑cAMP-responsive element binding protein (CREB) 1 small interfering (si)RNA‑Smad3 were utilized silence expression CREB1 Smad3 stellate cells (HSCs), whereas vector pRSV‑CREB1 was used induce overexpression HSCs. Cells treated with or without exogenous TGF‑β1, mRNA...

Receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) is significant in the activation inflammation. Runt-related transcription factor 2 (Runx2) promotes hepatic infiltration macrophages nonalcoholic fatty liver disease (NAFLD). We studied how RANKL affects Runx2-triggered macrophage NAFLD.30 male C57BL/6J mice at 4 weeks age were utilized this study, 20 received a high-fat diet (HFD), and 10 standard rodent chow over 8 months. The histopathologic features identified by H&E, Oil red...

To observe the chitooligosaccharides (COS) effect on proliferation inhibition and radiosensitivity of three types human gastric cancer cell line.CCK-8 assay was employed to obtain ratio COS BGC823 cells, MKN45 cells SGC7901 at 48 h after treatment proliferation-inhibition curve drawn with cells. The clonogenic used detect viability 0, 1, 2, 4, 6 8 Gy (6 dose grades) in RAY group + X-ray, survival analyze sensitization enhancement COS. Flow cytometry cycle apoptosis rate control group,...

Liver fibrosis is a reversible wound‑healing response to liver damage. Following injury, activated hepatic stellate cells (HSCs) cause excessive deposition of collagen and other components the extracellular matrix, which may eventually impair function. Transforming growth factor‑β1 (TGF‑β1) critical for development fibrosis, acts by activating HSCs, stimulating matrix inducing profibrotic responses. Certain studies have demonstrated that transcription factor, cyclic adenosine monophosphate...

Abstract Previous studies have demonstrated that transforming growth factor‐β3 (TGF‐β3) protected liver against fibrosis in vivo and vitro, but its regulation is poorly understood. In addition, the cAMP‐responsive element (CRE) TGF‐β3 promoter recognized as an important regulatory site for auto‐regulation. Thus, we hypothesize transcription factor CRE‐binding protein‐1 (CREB‐1) regulates auto‐induction of hepatic stellate cells (HSCs). We used exogenous to activate signal pathway...

Death receptor 4 (DR4) is a cell surface protein that generally thought to mediate apoptosis upon binding its ligand named TRAIL. However, contribution resistance has also been reported. MET (or c-MET) gene amplification represents an important mechanism for acquired EGFR tyrosine kinase inhibitors (EGFR-TKIs) against mutant non-small lung cancer (NSCLC). This study focuses on demonstrating the impact of inhibition DR4 modulation in MET-amplified NSCLC lines and underlying mechanisms....