apoptosis-repressor-with-caspase-recruitment-domain-uncommon

Apoptosis Repressor with Caspase Recruitment Domain in Uncommon Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma: An Aging Hypothesis

Uncommon epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma comprises clinically and biologically heterogeneous subgroups with variable ...

Qujing First People's Hospital

HYPB is a human histone H3 lysine 36 (H3K36)-specific methyltransferase and acts as the ortholog of yeast Set2. This study explored the physiological function of mammalian HYPB using knockout mice. Homozygous disruption of Hypb impaired H3K36 trimethylation but not mono- or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb(-/-) embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant embryos and yolk sacs could not be remodeled into large blood vessels or intricate networks, and the aberrantly rounded mesodermal cells exhibited weakened interaction with endothelial cells. The embryonic vessels failed to invade the labyrinthine layer of placenta, which impaired the embryonic-maternal vascular connection. These defects could not be rescued by wild-type tetraploid blastocysts, excluding the possibility that they were caused by the extraembryonic tissues. Consistent with these phenotypes, gene expression profiling in wild-type and Hypb(-/-) yolk sacs revealed that the Hypb disruption altered the expression of some genes involved in vascular remodeling. At the cellular level, Hypb(-/-) embryonic stem cell-derived embryonic bodies, as well as in vitro-cultured human endothelial cells with siRNA-mediated suppression of HYPB, showed obvious defects in cell migration and invasion during vessel formation, suggesting an intrinsic role of Hypb in vascular development. Taken together, these results indicate that Hypb is required for embryonic vascular remodeling and provide a tool to study the function of H3K36 methylation in vasculogenesis/angiogenesis.

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.

Epithelial ovarian cancer (EOC) is the major cause of deaths from gynecologic malignancies, and metastasis is the main cause of cancer related death. Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that has the ability to inhibit collagen matrix synthesis. In this study, we found that high CTHRC1 expression was associated with poor prognosis of EOC. In vitro experiments showed that CTHRC1 promoted migration and invasion of ovarian cancer cells. CTHRC1 had no effect on ovarian cancer cells viability. Additionally, EGFR inhibitors reduced the promotion effects of CTHRC1 on EOC cell invasion. After silencing of CTHRC1, downregulated expression of phosphorylation of EGFR/ERK1/2/AKT was observed in ovarian cancer cells. Taken together, our results suggest a role for CTHRC1 in the progression of ovarian cancer and identified CTHRC1 as a potentially important predictor for human ovarian cancer prognosis.

Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling.

Ovarian cancer is one of the three most deadly gynecological cancers, with the highest mortality rate. As the main cause of death, metastasis is considered to be a crucial factor that reduces the survival time of ovarian carcinoma patients. YWHAZ (also known as 14‑3‑3ζ) influences diverse vital cellular processes such as metabolism, signal transduction, apoptosis and cell cycle regulation. In the present study, we determined that YWHAZ is upregulated in ovarian cancers in contrast to normal tissues by immunohistochemical staining. High YWHAZ expression was found to be associated with TNM stage and metastasis‑free prognosis of ovarian cancer patients. Silencing of YWHAZ inhibited the proliferation and facilitated serum starvation‑induced apoptosis of ovarian cancer cells. Cell migration was also suppressed by YWHAZ silencing. Furthermore, using an in vivo metastatic model, we found that YWHAZ silence also inhibited ovarian cancer metastasis in vivo. Notably, glycolysis was clearly inhibited in YWHAZ‑silenced ovarian cancer cells as determined by lactate production assay and Seahorse XF analysis. YWHAZ also regulated the PI3K/Akt1/vimentin signaling pathway in ovarian cancer cells as detected by western blot analysis. Taken together, our results demonstrated that YWHAZ plays an important role in the progression of ovarian cancer and can be used as a potential target for the diagnosis and treatment of epithelial ovarian cancer.

YWHAZ promotes ovarian cancer metastasis by modulating glycolysis.

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5-15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.

C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.

Kinesio Taping (KT) is proved useful to many musculoskeletal disorders. But the mechanism remains unclear. The kinesio tape works by sticking to the skin surface. So exploring the interaction between the tape and the skin and analyzing its biomechanical influence may be an effective way to explore the mechanism of the tape.

Effects of Kinesio taping on skin deformation during knee flexion and extension: a preliminary study.

This study aimed to improve Knee Osteoarthritis (KOA) therapy by evaluating the knowledge framework and investigating research trends in inflammatory mechanisms. Conducting a thorough search on July 31, 2023, using the Science Citation Index Expanded of the Web of Science Core Collection, we identified 1,083 articles authored by 6,159 individuals from 3,610 institutions across 299 countries. China led in productivity with 377 papers, followed by the United States (253) and Japan (60). The University of California System (20 publications), Guangzhou University of Science and Technology (19), Duke University (18), and Shanghai Jiao Tong University (18) were the top institutions. Notably, the USA and Southern Medical University China held significant centrality in countries and institutions, respectively. Among 1,084 co-occurring keywords, "expression", "rheumatoid arthritis", "articular cartilage", "F kappa b", and "Synovial fluid" emerged as highly correlated topics. Analyzing inflammatory mechanisms in KOA through visualization tools offers insights into the knowledge framework, aiding in identifying future trends for better pain control. The study employed CiteSpace, VOS Viewer, and Tableau to analyze research hotspots and frontiers in inflammation mechanisms in KOA. It focused on essential signaling pathways in articular cartilage, synovial membrane, subchondral bone, and synovial fluids of OA patients and animal models, along with potential therapeutic reagents. Future exploration of the interaction between mechanisms can elucidate key factors in different pathways and the efficacy of injection therapy on inflammation.

Article	Year
Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 20133625	2010
Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling. Oncology reports\| PubMed ID: 27779718	2016
YWHAZ promotes ovarian cancer metastasis by modulating glycolysis. Oncology reports\| PubMed ID: 30535456	2019
C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model. Human molecular genetics\| PubMed ID: 32592472	2020
Effects of Kinesio taping on skin deformation during knee flexion and extension: a preliminary study. BMC musculoskeletal disorders\| PubMed ID: 35227229	2022
Bibliometric analysis of the inflammatory mechanisms in knee osteoarthritis in recent 30 years. American journal of clinical and experimental immunology\| PubMed ID: 38187364	2023

Fei He

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