Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring.

Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ +CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.

Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome.

Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.

Integration of quantitative diffusion kurtosis imaging and prostate specific antigen in differential diagnostic of prostate cancer.

ABSTRACT: This study aimed to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and prostate-specific antigen (PSA) biomarkers in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH).A total of 43 cases of prostate diseases verified by pathology were enrolled in the present study. These cases were assigned to the BPH group (n = 20, 68.85±10.81 years old) and PCa group (n = 23, 74.13 ±â€Š7.37 years old). All patients underwent routine prostate magnetic resonance imaging and DKI examinations, and the mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA) values were calculated. Three serum indicators (PSA, free PSA [fPSA], and f/t PSA) were collected. We used univariate logistic regression to analyze the above quantitative parameters between the 2 groups, and the independent factors were further incorporated into the multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacy of the single indicator and combined model.The difference in PSA, f/t PSA, MK, and FA between PCa and BPH was statistically significant (P < .05). The AUC for the combined model (f/t PSA, MK, and FA) of 0.972 (95% confidence interval [CI]: 0.928, 1.000) was higher than the AUC of 0.902 (95% CI: 0.801, 1.000) for f/t PSA, 0.833 (95% CI: 0.707, 0.958) for MK, and 0.807 (95% CI: 0.679, 0.934) for FA.The MK and FA values for DKI and f/t PSA effectively identify PCa and BPH, compared to the PSA indicators. Combining DKI and PSA derivatives can further improve the diagnosis efficiency and might help in the clinical setting.

Long noncoding RNA GIHCG functions as an oncogene and serves as a serum diagnostic biomarker for cervical cancer.

Cervical cancer is the most common and lethal gynaecological tumor. Long noncoding RNAs (lncRNAs) have critical roles in various cancers, including cervical cancer. However, few studies investigated the diagnostic value of lncRNAs for cervical cancer. In this study, we investigated the expression pattern of a recently identified lncRNA GIHCG in cervical cancer tissues, cell lines, and serums by qRT-PCR. Furthermore, we explored the roles of GIHCG in cervical cancer using gain-of-function and loss-of-function assays. Our results revealed that GIHCG is up-regulated in cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cell line, respectively. Furthermore, serum GIHCG is significantly up-regulated in cervical cancer patients compared with healthy controls. ROC curve analysis revealed that serum GIHCG could accurately discriminate cervical cancer patients from healthy controls. Functionally, we found that overexpression of GIHCG promotes cell proliferation, inhibits cell apoptosis, and promotes cell migration of cervical cancer cells. Conversely, depletion of GIHCG inhibits cell proliferation, induces cell apoptosis, and inhibits cell migration of cervical cancer cells. Mechanistically, we found that GIHCG represses the expression of miR-200b. The expression of miR-200b is inversely correlated with the expression of GIHCG in cervical cancer tissues. Moreover, overexpression of miR-200b attenuates the roles of GIHCG in promoting cervical cancer tumor growth in vivo. In summary, this study demonstrated that GIHCG functions as an oncogene in cervical cancer via repressing miR-200b. This study also suggested that GIHCG may be a non-invasive diagnostic biomarker and a potential therapeutic target for cervical cancer.

Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography.

OBJECTIVE: This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). METHODS: A total of 558 consecutive participants (402 males and 156 females) aged 36-91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. RESULTS: In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. CONCLUSIONS: The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.

Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression.

Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein-Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor-κB (NF-κB) activation, manifested by increased phosphorylation of p65, a subunit of NF-κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.

[Effect of danzhi xiaoyao pill on ovulation induction of polycystic ovarian syndrome patients of pathogenic fire derived from stagnation of gan-qi].

OBJECTIVE: To observe the efficacy of Danzhi Xiaoyao Pill (DXP) in anovulation infertility patients with polycystic ovary syndrome (PCOS) of pathogenic fire derived from stagnation of Gan-qi (PFDSG) complicated insulin resistance (IR). METHODS: Sixty PCOS patients were randomly assigned to two group, the integrative medical treatment group (Group A) and the Western medical treatment group (Group B), 30 cases in each group. All patients took Metformin and Diane-35. Those in Group A took DXP additionally. The therapeutic course for all was 3 menstrual cycles. After treatment the ovulation was induced by oral administration of letrozole or injection of menotropins (HMG). The therapeutic efficacy was compared between the two groups. RESULTS: The levels of insulin, luteinizing hormone, and testosterone were obviously lower after treatment than before treatment in the two groups (P < 0.05). There was no statistical difference between the two groups after treatment. There was no statistical difference in body mass index (BMI) between the two groups before and after treatment (P > 0.05). Better effects were obtained in Group A in improving symptoms such as agitation and irritability, fullness in the chest and hypochondrium, swollen pain in the breast before menstruation, bitter and dry mouth, oligomenorrhea, abnormal color and amount of menstruation, and pulse and tongue (P < 0.05, P < 0.01). The ovulation rate was 86.1% (93/108 cases) in Group A, obviously higher than that in Group B (65.5%, 74/113 cases). The clinical pregnancy rate was 60.0% (18/30 cases) in Group A, obviously higher than that in Group B (36.7%, 11/30 cases), showing statistical difference (P < 0.05). CONCLUSIONS: DXP could improve the ovulation rate and the pregnancy rate in anovulation infertility patients with PCOS complicated IR. It also could significantly improve Chinese medical syndromes, showing obvious advantages over using Western medicine alone.

Uncoupling protein 2 expression affects androgen synthesis in polycystic ovary syndrome.

The roles of uncoupling protein-2 (UCP2) on the androgen synthesis of granulosa cells derived from patients with polycystic ovary syndrome (PCOS) and normal subjects were explored. Primary human granulosa cells from 18 patients who received in vitro fertilization (IVF) were examined; nine patients had PCOS with hyperandrogenism. Primary cultures were treated with genipin, a proton leak inhibitor, guanosine diphosphate (GDP), an UCP inhibitor, and triiodothyronine (T3), an inducer of UCP gene expression. Mitochondrial membrane potential was determined using the JC-1 assay. T3 induced P450scc and UCP2 expressions and testosterone synthesis in both normal and PCOS granulosa cells. Their expressions in response to T3 treatments were correlated in the PCOS group. Differences in testosterone synthesis were observed between normal and PCOS cells in response to genipin. Increased mitochondrial membrane potential was observed in response to genipin and GDP; while T3 decreased it. Increased ovarian UCP2 expression in response to T3 treatment in PCOS may alter pregnenolone synthesis by influencing P450scc expression, thus altering testosterone production. Further in vivo studies are necessary to fully elucidate the role of UCP2 in the hyperandrogenism commonly observed in PCOS.

2-Iodo-3-nitro-pyridine.

In the crystal structure of the title compound, C(5)H(3)IN(2)O(2), inter-molecular C-H⋯N hydrogen-bonding inter-actions link the mol-ecules into one-dimensional chains along the b axis.