Modeling human skeletal development using human pluripotent stem cells.

Chondrocytes and osteoblasts differentiated from induced pluripotent stem cells (iPSCs) will provide insights into skeletal development and genetic skeletal disorders and will generate cells for regenerative medicine applications. Here, we describe a method that directs iPSC-derived sclerotome to chondroprogenitors in 3D pellet culture then to articular chondrocytes or, alternatively, along the growth plate cartilage pathway to become hypertrophic chondrocytes that can transition to osteoblasts. Osteogenic organoids deposit and mineralize a collagen I extracellular matrix (ECM), mirroring in vivo endochondral bone formation. We have identified gene expression signatures at key developmental stages including chondrocyte maturation, hypertrophy, and transition to osteoblasts and show that this system can be used to model genetic cartilage and bone disorders.

Occupational skin dermatoses among health care workers: A review of adverse skin reactions to personal protective equipment.

Occupational skin-related problems include dermatoses caused by agents in the working environment. For health care workers, these occupational dermatoses could be due to usage of Personal Protective Equipment (PPE), such as gloves, masks, goggles, and other protective equipment. These PPE contribute to both allergic and irritant contact dermatitis. This review summarized the skin damage after PPE usage and hand hygiene protocol. Recommendations should be established to prevent these occupational dermatoses from PPE usage.

Generation of a heterozygous COL1A1 (c.3969_3970insT) osteogenesis imperfecta mutation human iPSC line, MCRIi001-A-1, using CRISPR/Cas9 editing.

To develop a disease model for the human 'brittle bone' disease, osteogenesis imperfecta, we have used gene editing to produce a facsimile of the patient heterozygous COL1A1 mutation in an established control iPSC line. The gene-edited line had a normal karyotype, expressed pluripotency markers and differentiated into cells representative of the three embryonic germ layers. This iPSC line and the isogenic parental iPSC line will be of use in exploring osteogenesis imperfecta disease mechanisms and therapeutic approaches in vitro.

Serum amyloid A1 in combination with integrin αVß3 increases glioblastoma cells mobility and progression.

Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM-associated marker proteins from human plasma and GBM cell cultures. Additional plasma and 52 brain tissues obtained from patients with gliomas were used to validate the association rate of serum amyloid A1 (SAA1) in different grades of gliomas and its distribution in tumors. Microarray database analysis further validated the coefficient of SAA1 levels in gliomas. The cellular mechanisms of SAA1 in GBM proliferation and infiltration were investigated in vitro. We analyzed the correlation between SAA1 and patients' medication requirement to demonstrate the clinical effects of SAA1 in GBM. SAA1 was identified from MS analysis, and its level was revealed to be correlated with the disease grade, clinical severity, and survival rate of patients with gliomas. In vitro cultures, including GBM cells and normal astrocytes, revealed that SAA1 promotes cell migration and invasion through integrin αVß3 to activate the Erk signaling pathway. Magnetic resonance imaging and tumor region-specific microarray analysis identified a correlation between SAA1 and GBM cell infiltration in patients. In summary, our results demonstrate that SAA1 in combination with integrin αV and ß3 can serve as an indicator of high glioblastoma risk. We also identified the cellular mechanisms of SAA1 contributing to GBM progression, which can serve as the basis for future GBM therapy.

Sex hormone-binding globulin (SHBG) is a potential early diagnostic biomarker for gastric cancer.

The use of blood plasma biomarkers in gastric cancer (GC) management is limited due to a lack of reliable biomarkers. An LC-MS/MS assay and a bioinformatic analysis were performed to identify blood plasma biomarkers in a GC discovery cohort. The data obtained were verified and validated by western blotting and an ELISA in an independent study cohort. A label-free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C-1, gelsolin, sex hormone-binding globulin (SHBG), and complement component C4-A were significantly overexpressed in GC patients. A western blot assay of these plasma proteins showed that only SHBG was consistently overexpressed in the patient group. ELISA measurement of SHBG blood plasma levels confirmed that the patient group had significantly higher SHBG levels than the control group. SHBG levels in the patient group remained significantly higher after being stratified by gender, age, and disease stage. These findings show that LC-MS/MS is powerful and highly sensitive for plasma biomarker discovery, and SHBG could be a potential plasma biomarker for GC management.