Roles of complement system in psychiatric disorders. / è¡¥ä½“ç³»ç»Ÿåœ¨ç²¾ç¥žç±»ç–¾ç— ä¸­çš„ä½œç”¨.

The complement system is an important part of the innate immune system, including more than 50 secretory proteins and membrane-bound proteins, and it contributes to the clearance of apoptotic cells and invading pathogens to limit inflammatory immune responses and maintaining brain homeostasis. Complement activity is strictly regulated to protect cells from random attacks or to prevent the deposition of complement proteins in physiological cases. However, overactivation or abnormal regulation of the complement cascade in the brain can lead to neuronal damage and brain dysfunction. Recent studies have pointed out that changes in complement molecules exist in patients with psychiatric diseases and play an important role in the occurrence and development of diseases by regulating the function of neurons and glial cells. Therefore, summarizing the latest research progress of complement system in psychiatric diseases such as schizophrenia, autism spectrum disorder, major depression, bipolar disorder and anxiety disorder can provide new ideas for preventing and controlling psychiatric diseases caused by abnormal activation of complement system.

circRPS28 (hsa_circ_0049055) is a novel contributor for papillary thyroid carcinoma by regulating cell growth and motility via functioning as ceRNA for miR-345-5p to regulate frizzled family receptor 8 (FZD8).

Circular RNA 40S ribosomal protein S28 (circRPS28; hsa_circ_0049055) is upregulated in papillary thyroid carcinoma (PTC) patients. However, its role remained uncovered in the progression of PTC. Above all, expression of circRPS28 was determined in PTC samples by real-time quantitative PCR and circRPS28 was highly expressed in tumor tissues and cells. Besides, circRPS28 was predominantly distributed in the cytoplasm. Functional experiments were launched using colony formation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2-deoxyuridine (EdU) assay, transwell assays, scratch wound assay, and flow cytometry. As a result, blocking circRPS28 restrained PTC cell viability, EdU positive cell rate, colony formation number, wounding healing rate, and numbers of migration and invasion cells, accompanied with apoptosis rate promotion. These effects paralleled with low B-cell lymphoma (Bcl)-2 level and high Bcl-2-associated X protein (Bax), matrix metalloproteinase-2 (MMP2), and MMP9 levels, as analyzed by western blotting. Overexpressing microRNA (miR)-345-5p exerted similar roles to circRPS28 silencing. Notably, dual-luciferase reporter assay and RNA immunoprecipitation confirmed the target relationship between circRPS28 and miR-345-5p, miR-345-5p and frizzled family receptor 8 (FZD8). Downregulating miR-345-5p abrogated effects of circRPS28 blockage in PTC cells, and restoring FZD8 counteracted miR-345-5p roles, either. Furthermore, xenograft tumor model was established in mice, and exhausting circRPS28 delayed the growth of PTC cells in vivo by regulating miR-345-5p and FZD8. In conclusion, we demonstrated that blocking circRPS28 and/or promoting miR-345-5p suppressed PTC cell growth and motility via regulating FZD8. This study might suggest a novel circRPS28/miR-345-5p/FZD8 competing endogenous RNA pathway in PTC.

[GLIS family zinc finger protein 2 (GLIS2) negatively regulates the Wnt/ß-catenin pathway to inhibit the osteogenic differentiation of human bone marrow mesenchymal stem cells].

Objective To investigate how the human GLIS family zinc finger protein 2 (GLIS2) regulate the Wnt/ß-catenin pathway and its influence on the differentiation of human bone marrow mesenchymal stem cells (BMMSCs). Methods Human BMMSCs were randomly divided into blank group, osteogenic induction group, GLIS2 gene overexpression (ad-GLIS2) group, ad-GLIS2 negative control group, gene knockdown (si-GLIS2) group, and si-GLIS2 negative control (si-NC) group. The expression of GLIS2 mRNA in each group was detected by reverse transcription-PCR to determine the transfection status; alkaline phosphatase (ALP) activity was detected by phenyl-p-nitrophenyl phosphate (PNPP), and calcified nodule formation was tested by alizarin red staining to determine its osteogenic properties; the activation of intracellular Wnt/ß-catenin pathway was detected by T cell factor/lymphoid enhancer factor (TCF/LEF) reporter kit; the expression of GLIS2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osterix was detected by Western blot analysis. The interaction between GLIS2 and ß-catenin was verified by GST-pulldown. Results Compared with the blank group, the ALP activity and calcified nodule formation of BMMSCs in the osteogenic induction group increased, and the Wnt/ß-catenin pathway activity and the expression of osteogenic differentiation-related proteins increased, the osteogenic ability increased, while the expression of GLIS2 decreased. Up-regulating the expression of GLIS2 could inhibit the osteogenic differentiation of BMMSCs, while suppress the activity of the Wnt/ß-catenin pathway and the expression of osteogenic differentiation-related proteins on the contrary. Down-regulating the expression of GLIS2 could promote the osteogenic differentiation of BMMSCs, and improve the activity of the Wnt/ß-catenin pathway and the expression of osteogenic differentiation-related proteins. There was an interaction between ß-catenin and GLIS2. Conclusion GLIS2 may negatively regulate the activation of Wnt/ß-catenin pathway and affect the osteogenic differentiation of BMMSCs.

Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway.

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.

Added value of circulating miRNA expression profiling to sonographic TI-RADS classification in the diagnosis of thyroid nodules.

Potential use of sonographic TI-RADS classification combined with circulating miRNA expression profiling in the diagnosis of thyroid nodules was explored. Retrospective analysis was performed on clinical data of 121 patients with thyroid nodules. The biopsy specimens of patients obtained through ultrasound-guided aspiration and blood specimens were evaluated in Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 2018 to June 2019. In addition, the blood specimen test results of 121 healthy volunteers (control group) who underwent physical examination were retrospectively analyzed. Results of sonographic TI-RADS classification and circulating miRNA expression profiling were compared with the pathological results. Of the 212 nodules, 2 fell into TI-RADS category 2 and were diagnosed as benign. Malignant nodules accounted for 4.35, 37.14, 84.78, 93.33 and 96.77% of those nodules that fell into TI-RADS categories 3, 4a, 4b, 4c and 5, respectively. Of the 121 patients, 92.55% had with nodular goiter, 3.31% had inflammatory nodules, 2.48% toxic nodular goiter, 0.83% thyroid cysts and 0.83% thyroid tumors. A nodule that fell into a higher TI-RADS classification category had a higher risk of malignancy. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with either benign or malignant thyroid nodules compaed to those in the control group. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with malignant thyroid nodules than those in patients with benign thyroid nodule (P<0.05). The AUC of the combined diagnostic method was 0.973, which was significantly different from the AUCs of the individual diagnostic method (P<0.05). In conclusion, sonographic TI-RADS classification combined with circulating miRNA expression profiling can improve the diagnosis of thyroid nodules.