Emerging insights into ethnic-specific TP53 germline variants.

The recent expansion of human genomics repositories has facilitated the discovery of novel TP53 variants in populations of different ethnic origins. Interpreting TP53 variants is a major clinical challenge because they are functionally diverse, confer highly variable predisposition to cancer (including elusive low-penetrance alleles), and interact with genetic modifiers that alter tumor susceptibility. Here, we discuss how a cancer risk continuum may relate to germline TP53 mutations on the basis of our current review of genotype-phenotype studies and an integrative analysis combining functional and sequencing datasets.

Agonistic nanobodies and antibodies to human VISTA.

The V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of murine anti-human VISTA (anti-hVISTA) monoclonal antibodies (mAbs), anti-hVISTA nanobodies (Nbs), and cross-reactive rat anti-murine/human VISTA (anti-hmVISTA) mAbs.

Microfluidic platform for studying osteocyte mechanoregulation of breast cancer bone metastasis.

Bone metastasis is a common, yet serious, complication of breast cancer. Breast cancer cells that extravasate from blood vessels to the bone devastate bone quality by interacting with bone cells and disrupting the bone remodeling balance. Although exercise is often suggested as a cancer intervention strategy and mechanical loading during exercise is known to regulate bone remodeling, its role in preventing bone metastasis remains unknown.

OCY454 Osteocytes as an in Vitro Cell Model for Bone Remodeling Under Mechanical Loading.

Osteocytes' mechano-regulation of bone formation and resorption is key to maintaining appropriate bone health. Although extensive in vitro studies have explored osteocyte mechanobiology using the well-established MLO-Y4 cell model, the low amount of sclerostin secreted by this cell line renders it inadequate for studying cross-talk between osteocytes and osteoblasts under mechanical loading. Here, we investigated the potential of the sclerostin-expressing OCY454 osteocyte cell model in fulfilling this role.

Piezo1 mediates neuron oxygen-glucose deprivation/reoxygenation injury via Ca/calpain signaling.

Objective: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca/calpain signaling.

Methods: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca/calpain signaling were investigated.

Mechanically stimulated osteocytes reduce the bone-metastatic potential of breast cancer cells in vitro by signaling through endothelial cells.

Bone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels.

Mechanical regulation of breast cancer migration and apoptosis via direct and indirect osteocyte signaling.

Bone metastases, the migration of cancers to bone, occur in 65-80% of patients with advanced breast cancer. Metastasized cancer cells interact with cells such as the bone-resorbing osteoclasts to alter bone remodeling. Exercise, often suggested as an intervention for cancer patients, regulates bone remodeling via osteocytes.

Highly efficient electrochemiluminescence based on pyrazolecarboxylic metal organic framework.

A series of transition metal complexes with the ligands 3-pyrazoledicarboxylic acid (H2L(1)) and ethyl 1-(2-ethoxy-2-oxoethyl)-1H-pyrazole-3-carboxylate (epzc) have been synthesized. The epzc generated 1-(carboxymethyl)-1H-pyrazole-3-carboxylic acid (H2L(2)) by an in situ hydrothermal hydrolysis reaction, using a one-pot method. Simple mononuclear [Co(HL(1))2(H2O)2] (1) and [Ni(L(2))(H2O)4] (4), dinuclear [Ni2(L(1))2(H2O)6]·H2O (2) and [Cu2(L(2))2(H2O)4] (5) and 2D frameworks [Cu2(L(1))2]n (3), [Co2(L(2))2(H2O)4]n (6) have been isolated.

Anesthesia for stem cell transplantation in autistic children: A prospective, randomized, double-blind comparison of propofol and etomidate following sevoflurane inhalation.

The objective of the present study was to comparatively investigate the feasibility and safety of etomidate and propofol use following sevoflurane inhalation in autistic children during the intrathecal transplantation of stem cells. The patients selected were 60 autistic children with American Society of Anesthesiologists physical status I, who were aged between two and 12 years and scheduled for stem cell transplantation. The children received an inhalation induction of 8% sevoflurane, followed by intravenous injection of etomidate (0.

Circulating sclerostin associated with vertebral bone marrow fat in older men but not women.

Context: Osteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF.

[Design, synthesis, and PPARgamma agonistic activity of novel indenone derivatives].

Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are of interest as a treatment of type II diabetes, and indenone derivatives are a new class of non-TZD PPARgamma agonists. Based on existing indenone derivatives, a series of novel ones have been designed and synthesized. Meanwhile the structures have been comfirmed with 1H NMR and MS.

Evaluation of effects of Fc domain high-mannose glycan on antibody stability.

Elevated levels of CH2 domain N-linked high-mannose (HM) glycans are commonly observed in therapeutic monoclonal antibodies at various stages of the development. The effect of HM glycans on antibody stability was evaluated by using two approaches. In the first approach, immunoglobulin G (IgG) 1 material containing 21% HM was incubated at 29°C for 6 weeks and fractionated into monomeric and aggregate species by using size-exclusion chromatography (SEC).

[Design, synthesis and biological assay of novel tripeptidic tetrazoles as inhibitors of 20S proteasome].

Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place. Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with 1H NMR, MS and elemental analysis. Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome.