Development of a novel Fc fusion protein dual glucagon-like peptide-1 and gastric inhibitory polypeptide receptor agonists.

Aim: To develop and investigate an imbalanced dual gastric inhibitory polypeptide receptor (GIPR)/glucagon-like peptide-1 receptor (GLP-1 R) agonist with Fc fusion protein structure.

Methods: We designed and constructed an Fc fusion protein that is a dual agonist (HEC-CG115) with an empirically optimized potency ratio for GLP-1R and GIPR. The long-term effects of HEC-CG115 on body weight and glycaemic control were evaluated in diet-induced obese mice and diabetic db/db mice.

Peri-Implantitis Regenerative Therapy: A Review.

The surgical techniques available to clinicians to treat peri-implant diseases can be divided into resective and regenerative. Peri-implant diseases are inflammatory conditions affecting the soft and hard tissues around dental implants. Despite the large number of investigations aimed at identifying the best approach to treat these conditions, there is still no universally recognized protocol to solve these complications successfully and predictably.

Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis.

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3.

Osteocytes control myeloid cell proliferation and differentiation through Gsα-dependent and -independent mechanisms.

Osteocytes, the bone cells embedded in the mineralized matrix, control bone modeling, and remodeling through direct contact with adjacent cells and via paracrine and endocrine factors that affect cells in the bone marrow microenvironment or distant organs. Osteocytes express numerous G protein-coupled receptors (GPCRs) and thus mice lacking the stimulatory subunit of G-protein (Gsα) in osteocytes (Dmp1-Gsα mice) have abnormal myelopoiesis, osteopenia, and reduced adipose tissue. We previously reported that the severe osteopenia and the changes in adipose tissue present in these mice were mediated by increased sclerostin, which suppress osteoblast functions and promote browning of white adipocytes.

Restrains Reactive Oxygen Species-Associated Pulmonary Fibrosis via Targeting Nrf2-Nox4 Redox Balance.

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF.

Effects of histone deacetylase inhibitor Scriptaid and parathyroid hormone on osteocyte functions and metabolism.

Bone is a highly metabolic organ that undergoes continuous remodeling to maintain its structural integrity. During development, bones, in particular osteoblasts, rely on glucose uptake. However, the role of glucose metabolism in osteocytes is unknown.

Tanshinone IIA Activates Nuclear Factor-Erythroid 2-Related Factor 2 to Restrain Pulmonary Fibrosis via Regulation of Redox Homeostasis and Glutaminolysis.

Aims: Pulmonary fibrosis (PF) is characterized by myofibroblast activation through oxidative stress. However, the precise regulation of myofibroblast transdifferentiation remains largely uncharacterized.

Results: In this study, we found that tanshinone IIA (Tan-IIA), an active component in the root of Salvia miltiorrhiza Bunge, can suppress reactive oxygen species (ROS)-mediated activation of myofibroblast and reduce extracellular matrix deposition in bleomycin (BLM)-challenged mice through the regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2).

Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway.

NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root of Salvia miltiorrhiza Bge.

Carbonic anhydrase III protects osteocytes from oxidative stress.

Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly cell-to-cell communication and indirectly secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines-together with new genome editing tools-has allowed a closer look at the biology and molecular makeup of these cells.

Osteocyte Mechanobiology.

Purpose Of Review: Over the past decades, osteocytes have emerged as mechano-sensors of bone and master regulators of bone homeostasis. This article summarizes latest research and progress made in understanding osteocyte mechanobiology and critically reviews tools currently available to study these cells.

Recent Findings: Whereas increased mechanical forces promote bone formation, decrease loading is always associated with bone loss and skeletal fragility.

GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation.

Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior-posterior patterning disorder.

Estrogen Deficiency Leads to Further Bone Loss in the Mandible of CKD Mice.

Background: Chronic kidney disease (CKD) has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants.

Identification and Structure-Activity Relationships of Diarylhydrazides as Novel Potent and Selective Human Enterovirus Inhibitors.

Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 μM against EV71.

FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice.

Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants.

Evaluation of periodontitis and bone loss in patients undergoing hemodialysis.

Background: Chronic kidney disease has been a worldwide public health challenge and also a risk factor for oral health. The objectives of this study are to investigate the periodontal status in Chinese patients undergoing hemodialysis (HD) and assess periodontal bone loss (BL) using cone-beam computerized tomography (CBCT).

Methods: The patients in the HD and control groups received periodontal and CBCT examinations in the same period.

Vitamin D supplementation enhances the fixation of titanium implants in chronic kidney disease mice.

Vitamin D (Vit D) deficiency is a common condition in chronic kidney disease (CKD) patients that negatively affects bone regeneration and fracture healing. Previous study has shown that timely healing of titanium implants is impaired in CKD. This study aimed to investigate the effect of Vit D supplementation on implant osseointegration in CKD mice.

Effect of chronic kidney disease on the healing of titanium implants.

Chronic kidney disease (CKD) has become a worldwide public health problem. However, its effect on osseointegration of dental implants is largely unknown. The aim of this study is to investigate whether CKD impairs the quality of the osseointegration of titanium implants.

Inorganic polyphosphates stimulate FGF23 expression through the FGFR pathway.

Polyphosphate (polyP) is composed of linear polymers of orthophosphate residues linked by high-energy phosphoanhydride bonds. It has been reported to improve osteoblastic differentiation, stimulate periodontal tissue regeneration, and accelerate bone repair. The aim of this study was to evaluate the effect of polyP on the expression of FGF23, a hormone secreted mostly be mature osteoblasts and osteocytes.

[Zoledronic acid incorporated in chitosan/calcium phosphate ceramic: characterization and in vitro response of osteoblast cells].

Objective: To develop a new local delivery system, zoledronic-acid-loaded chitosan/calcium phosphate ceramic, and to determine its characterization and in vitro response of osteoblast cells.

Methods: Zoledronic-acid-loaded chitosan/calcium phosphate ceramic were prepared by solution casting method at a concentration of 10(-5), 10(-4), and 10(-3) mol/L, respectively. The physicochemical properties of the resulting materials were determined using SEM and FTIR.