Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Luteolin affects keloid fibroblast proliferation and apoptosis by regulating FRAT1 gene expression.

The current experiment was performed to investigate whether luteolin affects the proliferation and apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene. Keloid fibroblasts were treated with luteolin at different concentrations. MTT method, western blot, flow cytometry, and real-time quantitative PCR (qPCR) were used to detect cell proliferation, cyclin D1 (CyclinD1), p21, B-cell lymphoma / leukemia-2 (Bcl-2), Bcl-2 related X protein (Bax), FRAT1 protein expression, apoptosis and ARHI mRNA expression. Keloid fibroblasts were transfected with si-FRAT1, or pcDNA-FRAT1 and treated with luteolin to observe their roles in cell proliferation and apoptosis. Compared with the control group, luteolin significantly reduced the keloid fibroblast activity, CyclinD1, Bcl-2, and FRAT1 protein levels, and obviously improved the cell apoptosis rate, p21 and Bax protein expression (P<0.05). The expression of FRAT1 mRNA and protein in keloid fibroblasts was greatly increased (P<0.05). Inhibition of FRAT1 expression evidently decreased cell viability at 24 h, 48 h, and 72 h, CyclinD1, and Bcl-2 protein expression of keloid fibroblasts, while-dramatically enhanced cell apoptosis, p21, and Bax protein levels (P<0.05). FRAT1 overexpression reversed the inhibitory effect of luteolin on keloid fibroblast activity, FRAT1, CyclinD1, and Bcl-2 protein expression, and promotion of apoptosis, p21 and Bax protein expression. Luteolin can inhibit the proliferation and induce apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene.

Phenylethanol glycosides from the seeds of Aesculus chinensis var. chekiangensis.

Three new phenylethanol glycosides (1-3) and one known analogue (4) were isolated from the seeds of Aesculus chinensis Bge. var. chekiangensis. To the best of our knowledge, this represents the first isolation of phenylethanol glycosides from the genus of Aesculus, which enriched its chemical composition. Structure elucidations were performed via extensive NMR and HRESIMS data together with comparison with literature data. Thereafter, the isolated compounds were assayed for their neuroprotective activities against CoCl2-induced cytotoxicity in PC12 cells and compound 3 exhibited moderate activity.

Bioactive Triterpenoid Saponins From the Seeds of Aesculus chinensis Bge. var. chekiangensis.

Phytochemical investigation of Aesculus chinensis Bge. var. chekiangensis (Hu et Fang) Fang obtained 33 triterpenoid saponins, including 14 new ones, aesculiside C-P (1-14). The structure elucidations were performed through comprehensive MS, 1D and 2D-NMR analysis, and their absolute configuration was unambiguously determined by X-ray diffraction analysis as well as Mo2(OAc)4-induced ECD method for the first time. All the substances were examined for their cytotoxic activities against three tumor cell lines, Hep G2, HCT-116, and MGC-803. Of these, compounds 8, 9, 14-16, 18, and 22 exhibited potent cytotoxicities against all cell lines with IC50 of 2-21 µM, while compounds 3, 6, 7, 17-19, 20, 24, and 28 depicted moderate activity (IC50 13 to >40 µM). On these bases, the preliminary structure-activity correlations were also discussed. Meanwhile the neuroprotective properties of triterpenoid saponins from Aesculus genus were evaluated for the first time. Among them, compounds 1, 4, 12, 20, 22, 25, 29, and 31 exhibited moderate activities against COCl2-induced PC12 cell injury.

The expressions of NGF and VEGF in the fracture tissues are closely associated with accelerated clavicle fracture healing in patients with traumatic brain injury.

BACKGROUND: Angiogenesis and bone formation are vital for fracture healing. Nerve growth factor (NGF) not only promotes neuronal survival but also enhances the proliferation and differentiation of osteoblasts. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. However, the potential correlation of NGF and VEGF levels with fracture healing in patients with traumatic brain injury (TBI) remains unclear. METHODS: This study enrolled 22 patients with clavicle fracture and concomitant TBI (CFT group) and 25 patients with clavicle fracture alone (CF group). Serum NGF levels were measured with ELISA. The expressions of NGF, VEGF, and CD31 in callus tissues were measured with immunohistochemistry. RESULTS: The fracture healing time in CFT group (82.22±13.61 days) was significantly shorter than that in CF group (127±25.05 days; P<0.001). The expression of CD31, marker of blood vessels, in callus tissues of CFT group was higher compared with that of CF group. Serum NGF levels and the expression of NGF in callus tissues of CFT group were higher than those in CF group (P<0.01). The expressions of CD31, NGF, and VEGF are correlated with shorter fracture healing time. CONCLUSION: The formation of blood vessels was increased in CFT group compared with CF group. NGF and VEGF levels were higher in CFT group than in CF group and correlated with shorter fracture healing time. Accelerated fracture healing in patients with TBI may be due to NGF- and VEGF-mediated angiogenesis at the fracture site.

M2 macrophages are closely associated with accelerated clavicle fracture healing in patients with traumatic brain injury: a retrospective cohort study.

BACKGROUND: Mounting evidence indicate patients with traumatic brain injury (TBI) have an accelerated fracture healing. The healing process of bone fractures is greatly dependent on infiltrated macrophages. The macrophages are categorized into M1 or M2 phenotypes with different functions. This study is aimed to address the potential role of subtypes of macrophages in the process of fracture healing in patients with TBI. METHODS: Twenty-five cases of clavicle fracture alone (CF group) and 22 cases of clavicle fracture concomitant with TBI (CFT group) were retrospectively analyzed in this study. Callus tissues were harvested during operations. The expressions of COX-2, CD206, and CD68 were measured with immunohistochemistry. RESULTS: The percentages of M2 macrophages in total macrophages increased after bone fracture in both groups, while the percentages of M1-type macrophages are decreased. Interestingly, the increased percentages of M2 macrophages are significantly higher in CFT group than in CF group. Compared to CF group, the fracture callus volume was much larger (21.9 vs 8.5 cm3) and the fracture healing time was much shorter (82.2 vs 127.0 days) in CFT group. The percentage of M2 macrophages was negatively correlated with fracture healing time in patients (r = - 0.575, p < 0.01). CONCLUSIONS: The findings suggest that the percentages of M2 macrophages in callus tissues increased dramatically during the repairing stage in both CF and CFT group. Percentages of M2 macrophages are associated with accelerated fracture healing in patients with TBI. M2 macrophage polarization during the stage of bone regeneration may play a vital role in promoting bone fracture healing.

Impact of diabetes mellitus on the risk and survival of nasopharyngeal carcinoma: a meta-analysis.

BACKGROUND: Diabetes mellitus (DM) has been identified to be both a risk factor and a prognostic factor in a variety of malignancies, but its association with the risk and outcome of nasopharyngeal carcinoma (NPC) is still unclear. To elucidate this issue, we systematically reviewed the evidence concerning the association between DM status and NPC. MATERIALS AND METHODS: We identified studies by a literature search of PubMed, Embase, and ISI Web of Knowledge through May 31, 2017, and by searching the reference lists of pertinent articles. Odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were used to estimate the effect size. Heterogeneity across studies was evaluated by the Cochran's Q and I2 statistics. RESULTS: A total of nine studies were included. Four studies with a total sample size of 221,611 reported the effect of DM on NPC risk, and the other five studies with a sample size of 9,442 reported the impact of DM on survival in NPC patients. All included studies were retrospective, and mostly conducted in Asian populations. Meanwhile, condition of metformin usage was not considered in all studies. A pooled OR of 0.65 (95% CI: 0.43-0.98, P=0.04) revealed an inverse association between DM and NPC. Additionally, pooled analyses of studies investigating the prognosis value of DM revealed that preexisting DM had no effect on overall survival (HR =1.17, 95% CI: 0.94-1.46, P=0.16), local recurrence-free survival (HR =1.16, 95% CI: 0.80-1.67, P=0.44), and distant metastasis-free survival (HR =1.14, 95% CI: 0.92-1.40, P=0.22). CONCLUSION: Our results suggested that DM patients might have decreased NPC risk, and have little impact on prognosis of NPC patients. This conclusion should be limited to Asian population. Our results also suggest that more attention should be paid to metformin medication in further studies in order to clarify whether the effects of DM on NPC risk and prognosis are influenced by the anticancer effect of metformin.

Identification of rat faecal, urinary and biliary metabolites of thionorphine, a novel mixed agonist-antagonist analgesic, using liquid chromatography/electrospray ionization tandem mass spectrometry.

The biotransformation of thionorphine (N-cyclopropylmethyl-7alpha-[(s)-1-hydroxy-1-methyl-3-(2thiophene)-propyl]-6,14-endo-ethano tetrahydrooripavine), a new analgesic, was in-vestigated in rats. The results of metabolite analysis by liquid chromatography/electrospray ionization tandem mass spectrometry with positive ion mode, in which a mobile phase of 10 mM ammonium acetate (pH 3.0)/acetonitrile (25/75) was used, suggested that thionorphine is biotransformed to two potentially active metabolites, the N-dealkylated thionorphine (M-I) and the oxidized thionorphine (M-II), and subsequently form conjugates with glucuronic acid of both thionorphine and the metabolites.