Discovery of Novel SIRT3 Inhibitors for the Cancer Differentiation Therapy by Structural Modification.

Inhibition of SIRT3 triggered differentiation of multiple myeloma (MM) cells. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound S27. A total of 49 compounds divided into two series were designed and synthesized.

Structural modification of 2-phenylquinoline-4-carboxylic acid containing SIRT3 inhibitors for the cancer differentiation therapy.

Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound P6. A total of 33 compounds were designed and synthesized.

DLK1 regulates periodontal inflammation by inhibiting NF-κB p65 and JNK signaling pathways.

The roles and molecular mechanisms of Delta-like 1 (DLK1) in periodontitis remain largely unknown. Here, we investigated the expression of DLK1 and NF-κB p65 in Porphyromonas gingivalis (Pg.)-induced periodontitis in vivo.

Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation.

Respiratory diseases like pulmonary arterial hypertension (PAH) frequently exhibit sexual dimorphism. Female PAH patients are more susceptible to the disease but have increased survival rates. This phenomenon is known as the estrogen paradox, and the underlying mechanisms are not fully understood.

4-Octyl itaconate promotes alveolar ridge preservation following tooth extraction.

The search for medications that can effectively reduce alveolar bone loss following tooth extraction is of great interest. This study aimed to observe the roles of 4-octyl itaconate (4-OI) in RANKL-induced osteoclastogenesis of bone marrow macrophages (BMMs) in vitro. Mandibular second molars were extracted to evaluate whether 4-OI could alleviate alveolar bone loss.

Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation.

Respiratory diseases like pulmonary arterial hypertension (PAH) frequently exhibit sexual dimorphism. Female PAH patients are more susceptible to the disease but have increased survival rates. This phenomenon is known as the estrogen paradox, and the underlying mechanisms are not fully understood.

TIPE2 regulates periodontal inflammation by inhibiting NF-κB p65 phosphorylation.

Background: The roles and molecular mechanisms of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) in periodontitis remain largely unknown.

Objective: This study aimed to determine the expression of TIPE2 and NF-κB p65 in rat Porphyromonas gingivalis-induced periodontics in vivo.

Methodology: Periodontal inflammation and alveolar bone resorption were analyzed using western blotting, micro-computed tomography, TRAP staining, immunohistochemistry, and immunofluorescence.

A sensitive LC-MS method for the determination of Sinomenine derivative SWX and its application to pharmacokinetic research in rats.

The goal of this work was to develop a sensitive and accurate method based on high performance liquid chromatography with tandem mass spectrometry (LC-MS) detection for determining the concentration of the Sinomenine derivative SWX in plasma and tissue of rat. Chromatographic separation was achieved on an Agilent SB-C18 (2.1*50 mm, 2.

Targeting feedback activation of signaling transduction pathways to overcome drug resistance in cancer.

Dysregulation or aberrant signaling transduction contributes to tumorigenesis. Targeting these abnormal signaling pathways becomes an effective anticancer strategy. However, feedback activation or crosstalk between signaling pathways drives adaptive drug resistance which causes failure of cancer therapy.

Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart.

Background: Abnormalities in Ca homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca homeostasis in cardiomyocytes. Alternative splicing of a single gene produces multiple triadin isoforms.

Characteristics of Online Health Care Services From China's Largest Online Medical Platform: Cross-sectional Survey Study.

Background: Internet hospitals in China are in great demand due to limited and unevenly distributed health care resources, lack of family doctors, increased burdens of chronic diseases, and rapid growth of the aged population. The COVID-19 epidemic catalyzed the expansion of online health care services. In recent years, internet hospitals have been rapidly developed.

Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the aim of utilizing mature hiPSC-CMs to model human cardiovascular disease.

Association of high HIF-1α levels in serous periodontitis with external root resorption by the NFATc1 pathway.

Whether external root resorption is associated with hypoxia in the periodontal ligaments of teeth with severe periodontitis remains unclear. Hypoxia inducible factor-1α (HIF-1α) expression and external resorption sites in the periodontal ligaments of these teeth were observed to elaborate upon the relationship between hypoxia and external root resorption in severe periodontitis. Histological analysis was performed to observe external root resorption.

Isoform-specific regulation of HCN4 channels by a family of endoplasmic reticulum proteins.

Ion channels in excitable cells function in macromolecular complexes in which auxiliary proteins modulate the biophysical properties of the pore-forming subunits. Hyperpolarization-activated, cyclic nucleotide-sensitive HCN4 channels are critical determinants of membrane excitability in cells throughout the body, including thalamocortical neurons and cardiac pacemaker cells. We previously showed that the properties of HCN4 channels differ dramatically in different cell types, possibly due to the endogenous expression of auxiliary proteins.

Isorhamnetin 3-O-neohesperidoside promotes the resorption of crown-covered bone during tooth eruption by osteoclastogenesis.

Delayed resorption of crown-covered bone is a critical cause of delayed tooth eruption. Traditional herbal medicines may be good auxiliary treatments to promote the resorption of crown-covered bone. This study was carried out to analyse the effect of isorhamnetin 3-O-neohesperidoside on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro and resorption of the crown-covered bone of the lower first molars in mice in vivo.

Importin 8 is involved in human periodontitis by the NF-κB pathway.

This study was undertaken to investigate the roles of importin 8 (IPO8) and infiltrating macrophages in human periodontitis. Gingival tissues were collected from 18 male patients with mild and severe periodontitis. IPO8 expression was observed by immunohistochemistry and western blotting.

SNHG6 modulates oxidized low-density lipoprotein-induced endothelial cells injury through miR-135a-5p/ROCK in atherosclerosis.

Background: Plenty of long non-coding RNAs (lncRNAs) play vital roles in the progression of atherosclerosis. Small nucleolar RNA host gene 6 (SNHG6) is a well known lncRNA that is aberrantly high expressed in atherosclerosis patients. However, its function and basic mechanism in atherosclerosis events have not been well clarified.

Increased myocyte calcium sensitivity in end-stage pediatric dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure (HF) in children, resulting in high mortality and need for heart transplantation. The pathophysiology underlying pediatric DCM is largely unclear; however, there is emerging evidence that molecular adaptations and response to conventional HF medications differ between children and adults. To gain insight into alterations leading to systolic dysfunction in pediatric DCM, we measured cardiomyocyte contractile properties and sarcomeric protein phosphorylation in explanted pediatric DCM myocardium ( = 8 subjects) compared with nonfailing (NF) pediatric hearts ( = 8 subjects).

Vps15 is critical to mediate autophagy in AngII treated HUVECs probably by PDK1/PKC signaling pathway.

Aims: Vps15 is an important regulator on the activity of class III PI3K in autophagy induction. AngII plays a positive role of autophagy in the early protection of endothelial cells. In this study, the expression of Vps15 was knocked down using the specific shRNA to investigate the effects of Vps15 on cell autophagy, senescence and apoptosis in HUVECs stimulated by AngII.

Calcitonin gene related peptide gene-modified rat bone mesenchymal stem cells are effective seed cells in tissue engineering to repair skull defects.

The study is to verify whether Calcitonin gene related peptide (CGRP) gene-modified rat bone mesenchymal stem cells (BMSCs) are promising seed cells with great potential to repair bone defect. A recombinant lentiviral vector overexpressing CGRP peptide, pLenO-DCE-CGRP, was constructed and transfected into rBMSCs to obtain stable CGRP expression. Differently transfected rBMSCs: CGRP- modified rBMSCs (CGRP group), empty vector- modified rBMSCs (Vector group) and normal rBMSCs (Control group) were transferred to collagen scaffold to repair rat skull defects (n=6).

Periodontal ligament-associated protein-1 gets involved in the development of osseous eruption canal.

Osseous eruption is an important stage of tooth eruption process. The role of periodontal ligament-associated protein-1 (PLAP-1/asporin) in the development of osseous eruption canal remain undefined and were the focus of this study. C57BL/6 mice at postnatal days P11-13 and P 15-16 were chosen.

EMMPRIN-CypA contributes to the inflammatory processes in human periodontitis through infiltrating CD68 inflammatory cells.

Extracellular matrix metalloproteinase inducer (EMMPRIN) and its ligand cyclophilin A (CypA) levels increase in human inflammatory diseases, but EMMPRIN-CypA interactions and cell types expressing EMMPRIN and CypA in the pathogenesis of periodontitis are uncertain. Immunohistochemistry, immunofluorescence and western blotting revealed the level of EMMPRIN, CypA, and CD68 in human periodontitis. Double labelled immunofluorescence colocalized the expression of CD68 and CypA, and CD68 and EMMPRIN.

Protective effect of propofol on ischemia-reperfusion injury detected by HPLC-MS/MS targeted metabolic profiling.

Ischemia-reperfusion injury(IRI), described as tissue damage caused by reversible ischemic injury or hypoxia prior to the blood supply restoration, is a common pathological phenomenon. In recent study, a hypoxia-reoxygenation (H/R) in the presence or absence of propofol posthypoxia treatment (P-PostH) cell model was built to simulate the condition of IRI, and researchers found propofol may protect cells by suppressing autophagic cell death. To investigate the mechanism underling the protective effect of propofol.

Effect of hypoxia on the expression of RANKL/OPG in human periodontal ligament cells in vitro.

To investigate the impact of hypoxia on the expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in human periodontal ligament cells (hPDLCs) in vitro. hPDLCs were incubated in a hypoxic atmosphere of 2% O2, 5% CO2, 94% N2 at 37°C for 6, 12, 24 and 48 h. After that, cell proliferation assay was determined using CCK-8 technique.