Prunella vulgaris L protects glucocorticoids-induced osteogenesis inhibition in bone marrow mesenchymal stem cells through activating the Smad pathway.

OBJECTIVE: To elucidate the role of Prunella vulgaris L (PVL) in protecting glucocorticoids (GC)-induced osteogenesis inhibition, thereafter, protecting the deterioration of osteoporosis (OP). MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was conducted to assess the influence of PVL treatment on MSCs viability. Osteogenesis in MSCs was induced by Dexamethasone (DEX) stimulation. Regulatory effects of PVL on osteogenesis-related gene expressions, ALP activity, and mineralization ability in DEX-induced MSCs were determined. At last, protein levels of p-Smad1/5/9 and total-Smad1/5/9 influenced by DEX and PVL were measured by Western blot. RESULTS: PVL treatment did not pose a time- or dose-dependent influence on MSCs viability. DEX induction in MSCs downregulated ALP, RUNX2, Bglap, and Osterix. ALP activity and mineralization in DEX-induced MSCs were suppressed. Downregulated osteogenesis-related genes decreased ALP activity and mineralization in MSCs undergoing DEX stimulation were partially reversed by PVL treatment. Moreover, the downregulated p-Smad1/5/9 level in DEX-induced MSCs was elevated by PVL treatment, while total-Smad1/5/9 was not affected. CONCLUSIONS: PVL alleviated GC-induced suppression in MSCs osteogenesis by activating the Smad pathway, thereafter, protecting the deterioration of OP.

MicroRNA-374b inhibits migration and invasion of glioma cells by targeting EGFR.

OBJECTIVE: To investigate the expression level of microRNA-374b in glioma tissues and its influence on the invasive ability of glioma cells. Meanwhile, the regulatory mechanism of microRNA-374b in glioma was also explored. PATIENTS AND METHODS: The expression level of microRNA-374b in 32 glioma tissues and para-cancerous tissues were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The relationship between microRNA-374b expression and clinical indicators of glioma was analyzed. Meanwhile, the expression of microRNA-374b in glioma cells was verified by qRT-PCR as well. Subsequently, microRNA-374b over-expression model was constructed in glioma cell lines, including U251 and U87. Next, the effect of microRNA-374b on cellular biological functions was analyzed using cell counting kit-8 (CCK-8) assay, Wound healing test and transwell invasion assay, respectively. Finally, the relationship between miRNA and epidermal growth factor receptor (EGFR) was explored. RESULTS: QRT-PCR results showed that the expression level of microRNA-374b in glioma was significantly lower than that of adjacent tissues, and the difference was statistically significant. Compared with patients with higher expression of microRNA-374b, the occurrence rate of lymph node or distant metastasis was significantly higher in those with lower microRNA-374b expression. In addition, compared with NC group, the proliferation, invasion and migration abilities of cells in microRNA-374b mimics group was significantly decreased. Subsequently, results demonstrated that the expression of EGFR was significantly increased in glioma cells and tissues, which was negatively correlated with microRNA-374b expression. Subsequent cell recovery experiment indicated that microRNA-374b and EGFR had a mutual regulation and could affect the malignant progression of glioma all together. CONCLUSIONS: MicroRNA-374b could inhibit the invasion and migration of glioma by regulating EGFR. Moreover, the expression of microRNA-374b was significantly associated with lymph node metastasis, distant metastasis and poor prognosis.

In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist.

Solid rationales are still present for the identification of synthetic ligands to simultaneously target multiple PPAR subtypes for the treatment of T2DM. The purpose of this study was to characterize the in vitro and in vivo differential effects of chiglitazar, a non-TZD type of PPAR pan-agonist currently in phase III clinic development in China, from PPARγ-selective agonist like rosiglitazone. Chiglitazar showed transactivating activity in each PPARα, γ, and δ subtype and upregulated the expression of PPARα and/or PPARδ downstream genes involved in the key processes of lipid metabolism and thermogenesis. Comparable blood glucose lowering effect was observed between chiglitazar and rosiglitazone, but chiglitazar did not significantly increase the body weight in KKAy and fat pad weight in db/db mice. Chiglitazar had high distribution in liver, pancreas, and skeleton muscles but was less present in kidney, heart, and adipose in rats. Heart weight increase was not observed in rats treated with chiglitazar for 6 months at a dose as high as 45 mg kg(-1). The in vitro and in vivo differential features of chiglitazar are informative and encouraging for the further development of this synthetic ligand for the potential use in T2DM.

Metal-metal interactions in weakly coupled mixed-valence E- and Z-diferrocenylethylene complexes.

To study metal-to-metal interactions in mixed-valence states of two weakly coupling ferrocenyl groups assembled in E or Z conformation on an ethylenic double bond, E-1,2-dimethyldiferrocenylethylene (1), Z-1,2-dimethyldi-ferrocenylethylene (2), and 1,2-diferrocenylcyclohexene (3) were synthesized and structurally characterized. Crystals of 1 are triclinic, P1, with a = 7.494(9) A, b = 10.801(3) A, c = 11.971(2) A, alpha = 102.17(2) degrees, beta = 106.12(9) degrees, gamma = 90.42(2) degrees, V = 907.8 A3, and Z = 2. Crystals of 2 are monoclinic, P2(1)/c, with a = 13.601(8) A, b = 11.104(4) A, c = 13.732(1) A, beta = 114.26(7) degrees, V = 1890.8(3) A3, and Z = 4. Crystals of 3 are orthorhombic, P2(1)2(1)2(1), with a = 5.766(2) A, b = 13.090(1) A, c = 26.695(2) A, V = 2014.9(3) A3, and Z = 4. Intervalence transition spectra (IT) and electrochemical data have been determined and compared with those of diferrocenyl-benzene (para, ortho, and meta). The comproportionation constants in nitrobenzene at 25 degrees C were found to be 490 and 813 for 1 and 3, respectively. That of 2 was not measured because of the fact that 2+ isomerizes rapidly in all solvents tested, yielding nearly a racemic mixture of E and Z conformers. This finding helps to clear the paradoxical phenomenon between experimental results of mixed-valence complexes of E- and Z-1,2-bis(1'-ethyl-1-ferrocenyl)-1,2-dimethylethylene and theories. The stability of the mixed-valence species was discussed in terms of resonance delocalization, Coulomb repulsion energy, inductive effect, magnetic interaction, structural factors, and statistical factor. According to our analysis based on the Hush formalism, the contribution due to Coulomb repulsion energy dominates the overall stability of the mixed-valence state in 1+, 2+, and 3+. Stabilization that arises from resonance delocalization is only minor and contributes less than 4% to the overall stability, even in 3+ where linked Cp rings and the ethylenic plane are coplanar. In calculating the resonance contribution, crystallographic Fe-Fe distances of 7.44 A (1) and 6.68 A (3) were used for 1+, and 3+, respectively.

[On the mechanisms of cardiac hypertrophy].

Here we reviewed the progress of researches on the mechanism of cardiac hypertrophy and discussed its putative mechanisms. With regard to the heredity and variability of familial hypertrophic cardiomyopathy and mitochondrial cardiomyopathy and other changes, we emphasize that the imbalance between the energy supply and demand of the overloaded pressure determines the occurrence of cardiac hypertrophy. Also we refer to the involving roles of the mechanical stress and some paracrine/autocrine factors in cardiac hypertrophy. Finally we hypothesize that there exists an unknown small molecule being involved in regulating the gene expression and phenotype in cardiac hypertrophy.

Comparison of Shams' test for rectal mucus to an immunological test for fecal occult blood in large intestinal carcinoma screening. Analysis of a check-up of 6480 asymptomatic subjects.

The sugar moiety detected from rectal mucus by the Galactose oxidase-schiff (Shams' test) is considered a substitutive test for immunological fecal occult blood test (FOBT) in screening colorectal carcinoma. Two strategies of screening were applied in 6480 subjects over 40 years of age, and 130 cm flexible colonoscope used for sigmoidoscopy or pancolonoscopy. Of them, 3820 were taken for immune FOBT (SPA test) and Shams' test. Only those who showed positive tests were chosen for 60 cm flexible sigmoidoscopy, while another 2660 subjects for both sigmoidoscopy and tests at the same time. Additionally, 130 cm flexible pancolonoscopy was carried out in 103 individuals with positive Shams' test for evaluating the false positive rate. Shams' test showed a sensitivity of 85.7% for colorectal cancer, 47.1% for adenomas in preselected patients, while the positive rate of SPA test were 90.5% and 41.2% respectively. In 3820 asymptomatic subjects undergoing sequential screening (aged 45 years and higher), Shams' test showed 9.1% positive, SPA showed 11.2% and 620 (16.2%) subjects were selected for sigmoidoscopy based on their positive galactose oxidase result or positive FOBT result. Two early stage carcinomas and 33 adenomas (0.32% and 4.2% respectively in sigmoidoscopy) were found. Another 2 660 subjects were taken for sigmoidoscopy screening. Four carcinomas and 78 adenomas were found. Of them, only two carcinoma (50%) and 17 (21.8%) or 22 (28.2%) adenomas were positive in Shams' or SPA test. But both tests combined in screening showed a rate of 61.3% in adenomas and 75.0% in cancers. 103 subjects with positive Shams' test were taken for pancolonoscopy. 82.5% showed no lesions.(ABSTRACT TRUNCATED AT 250 WORDS)