Severe obesity caused by prolactinoma related to the abnormal insulin metabolism-A case report.

The relationship between prolactinoma and obesity has not been well explained yet. This report introduced the diagnosis and treatment course of a severely obese male patient. After a series of examinations, the patient was finally diagnosed as prolactinoma after excluding other endocrine-related diseases, like diabetes. His plasma prolactin level (PRL) dropped after treatment with bromocriptine, and so did his weight. It is indicated that prolactinoma may lead to the occurrence of obesity, especially in male patients. The abnormal insulin metabolism caused by the elevation of PRL may be the main reason for this phenomenon. The case provides a fresh idea to control the weight of obese teenagers.

Homocysteine induced a calcium-mediated disruption of mitochondrial function and dynamics in endothelial cells.

Homocysteine (Hcy) is a sulfur-containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy-induced endothelial dysfunction is still unclear. Here, in Hcy-treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin-related protein 1 (Drp1) and phosphate-Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria-associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5-triphosphate receptor (IP3R)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy-treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co-treatment. In conclusion, Hcy-induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R-Grp75-VDAC complex in MAMs.

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

[Protective effect of ginsenoside Rg1 again PC-12 cells in OGD injury through mTOR/Akt/FoxO3 signaling pathway].

OBJECTIVE: To investigate the protective effect of ginsenoside Rg1 on oxygen-glucose deprivation (OGD) in PC-12 cells, and preliminarily discuss the potential molecular mechanism of mTOR/Akt/FoxO3 signaling pathway. METHOD: The OGD PC-12 cell model was established. The cell viability was measured by MTT assay. After the pretreatment with Rg1 with the concentration of 10, 20, 40 micromol x L(-1) for 24 h, the cell viability was observed. Lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) ac- tivity and malondialdehyde (MDA) level were detected by colorimetry assay. mTOR, p-Akt(ser473), p-Akt(tjr308), Akt, p-FoxO3, FoxO3 in cytoplasm and nucleus, and total FoxO3 protein expression were detected by Western blot assay. RESULT: OGD could significantly in- hibit cell proliferation in 4-24 h in a time-dependent manner. After pretreatment for 24 h, Rg1 (20, 40 micromol x L(-1)) could notably elevate the cell viability and SOD viability and reduce the LDH release and MDA content. Besides, Rg1 also inhibited OGD-induced mTOR and p-Akt(ser473) decreases. After treatment for 6 h, OGD could reduce FoxO3 phosphorylation and promote FoxO3 in cytoplasm. This data suggested that Rg1 could protect PC-12 cell injury through mTOR/p-Akt/FoxO3 signaling pathway. CONCLUSION: Ginsenoside Rg1 could attenuate OGD-induced PC-12 cell injury. Its action mechanism may be closely related to activation of mTOR/p-Akt/FoxO3 signaling pathway.

PPAR-beta facilitating maturation of hepatic-like tissue derived from mouse embryonic stem cells accompanied by mitochondriogenesis and membrane potential retention.

Relatively little is known about mitochondria metabolism in differentiating embryonic stem (ES) cells. Present research focused on several elements of cellular energy metabolism in hepatic-like tissue derived from mouse ES cells. We demonstrated that mitochondrial location patterns and mitochondrial membrane potential (DeltaPsi(m)) existed in subsequent differentiation of the tissue. Mitochondriogenesis appeared at the early stage and kept a normal DeltaPsi(m) in differentiated mature hepatocytes. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) expression was transitorily increased at the beginning, and kept a relatively low level later, which accompanied by expression of PPAR-gamma coactivator (PGC)-1alpha, a master regulator of mitochondrial biogenesis. PPAR-beta expression showed robust up-regulation in the late differentiation course. Enhanced co-expressions of PPAR-beta and albumin with catalysis of UDP-glucuronosyltransferases (UGTs) were observed at mature stage. While PPAR-gamma expression changed little before and after differentiation. Mitochondriogenesis could be accelerated by PPAR-alpha specific agonist WY14643 and abolished by its antagonist GW6471 at the early stage. Neither of them affected mitochondrial DeltaPsi(m) and albumin generation in the differentiated hepatocytes. Furthermore, maturation of hepatic-like tissue and mitochondriogenesis in hepatocyte could be efficiently stimulated by PPAR-beta specific agonist L165041 and abolished by PPAR-beta specific antagonist GSK0660, but not affected by PPAR-gamma specific agonist GW1929. In conclusion, the derived hepatic tissue morphologically possessed cellular energy metabolism features. PPAR-alpha seemed only necessary for early mitochondriogenesis, while less important for DeltaPsi(m) retention in the mature tissue derived. The stimulation of PPAR-beta but not -gamma enhanced hepatogenesis, hepatocytes maturation, and mitochondriogenesis. PPAR-beta took an important role in cellular energy metabolism of hepatogenesis.