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This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment. [ABSTRACT FROM AUTHOR]

Oxidative stress‐related DNA damage is a significant pathology for male subfertility and unexplained infertility (UI). Antioxidant supplement by food or nutrition may benefit sperm function of UI couples. However, the role of antioxidant status on fertilization outcome and embryo development for UI couples is not clear. A total of 63 semen samples from UI couples undergoing in vitro fertilization (IVF) treatment (26 pregnant cycles and 37 nonpregnant cycles) were recruited for this prospective observational study. The reactive oxygen species (ROS) levels of sperm cells are detected by a chemiluminescence assay. Total antioxidant capacity (TAC) of seminal plasma is evaluated according to an antioxidant assay kit. The skin carotenoid status in the male partners of UI couples is measured by resonance Raman spectroscopy to determine the antioxidant potential from dietary supplement. The skin carotenoid status (23,115 ± 6,831 vs. 19,432 ± 5,242 Raman intensity, p =.0329 by Mann–Whitney U test) and day 3 good embryo rates (49.6 ± 27.1% vs. 26.8 ± 23.1%, p =.002 by Mann–Whitney U test) are higher in pregnant cycles compared to those in nonpregnant cycles. The local antioxidant capacity (seminal TAC) is closely correlated with fertilization rates (r =.35, p =.005). In contrast, skin carotenoid status is intimately associated with good embryo rates in IVF cycles (r =.34, p =.007). In conclusion, the skin carotenoid status of male partners of UI couples may benefit embryo development and the subsequent pregnancy outcome of IVF treatment. Further investigation about the effect and mechanism of nutritional supplement on embryo development in IVF cycles for UI couples is deserved. [ABSTRACT FROM AUTHOR]

The use of corifollitropin alfa (CA) in assisted reproductive technology (ART) cycles is dependent on the antral follicle count and body weight of patients. The present study investigated the safety and efficacy of using 100μg of CA in predicted excessive responders based on serum anti-Mullerian hormone (AMH) level. The results of 381 ART cycles stimulated by CA versus daily recombinant follicle-stimulation hormone (rFSH) in patients with low (<1.0 ng/mL; n = 38 vs. n = 90), moderate (1.0–3.36 ng/mL; n = 38 vs. n = 95), and high (> 3.36 ng/mL; n = 48 vs. n = 72) serum AMH levels, were analyzed. Pregnancy and live birth rates did not significantly differ between CA and daily rFSH groups. In the patients with high AMH levels, serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) injection were significantly lower in the CA group than in the rFSH group (0.93 ± 0.55 vs. 1.16 ± 0.64 ng/mL). Furthermore, serum P4 levels on the day of hCG injection were negatively correlated with baseline AMH levels in the CA group, but not in the rFSH group, in the patients with high AMH levels. In conclusion, the use of 100 μg of CA in patients with high AMH levels is safe and effective and is associated with a lower P4 level on the day of hCG injection compared with the use of daily rFSH. [ABSTRACT FROM AUTHOR]

This retrospective analysis compared the efficiency of the gonadotropin- releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the GnRH agonist long (GnRH-a) protocol for patients with diminished ovarian reserve (DOR). A total of 1,233 patients with DOR (anti-Mullerian hormone <1.1 ng/mL) were recruited for this retrospective case-control study. They were divided into two groups according to female age. Younger patients were assigned to POSEIDON group3 (PG3: age ≤35 years); older patients were assigned to POSEIDON group 4 (PG4: age >35 years). All patients with DOR underwent controlled ovarian stimulation and fresh embryo transfer (ET) on day 3. We recruited 283 GnRH-a and 54 GnRH-ant cycles for PG3, and 663 GnRH-a and 233 GnRH-ant cycles for PG4. In PG3, the GnRH-a protocol was associated with a lower ET cancellation rate (30/283 = 10.2% vs. 12/54 = 22.2%, p = 0.018) and a higher live birth rate (7/54 = 13.0% vs. 78/283 = 27.6%, p = 0.024) than the GnRH-ant protocol for the initiated cycles. Furthermore, the GnRH-a protocol was correlated with a higher implantation rate than the GnRH-ant protocol for ET cycles (146/577 = 25.3% vs. 11/103 = 10.7%, P = 0.027). No differences in the ET cancellation rate, live birth rate and implantation rate between GnRH-a and GnRH-ant groups were observed among PG4 patients. In conclusion, the GnRH-a protocol was more effective than the GnRH-ant protocol for young patients with DOR. The low ET cancellation rate and high implantation rate may be related to embryo quality or endometrial receptivity, which warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people.Subjects and Methods: One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index.Results: Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05).Conclusion: This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications. [ABSTRACT FROM AUTHOR]

The presence of an activating mutation of the Wnt/β-catenin signaling pathway is found in ~90% of colorectal cancer (CRC) cases. Death domain-associated protein (DAXX), a nuclear protein, interacts with β-catenin in CRC cells. We investigated DAXX expression in 106 matched sample pairs of CRC and adjacent normal tissue by Western blotting. This study evaluated DAXX expression and its clinical implications in CRC. The results revealed that DAXX expression was significantly lower in the patients with the positive serum carcinoembryonic antigen (CEA) screening results compared to the patients with negative CEA screening levels (p < 0.001). It has been reported that CD24 is a Wnt target in CRC cells. Here, we further revealed that DAXX expression was significantly correlated with CD24 expression (rho = 0.360, p < 0.001) in 106 patients. Consistent with this, in the CEA-positive subgroup, of which the carcinomas expressed DAXX at low levels, they were significantly correlated with CD24 expression (rho = 0.461, p < 0.005). Therefore, reduced DAXX expression is associated with reduced CD24 expression in CRC. Notably, in the Hct116 cells, DAXX knockdown using short-hairpin RNA against DAXX (shDAXX) not only caused significant cell proliferation, but also promoted metastasis. The DAXX-knockdown cells also demonstrated significantly decreased CD24 expression, however the intracellular localization of CD24 did not change. Thus, DAXX might be considered as a potential regulator of CD24 or β-catenin expression, which might be correlated with proliferative and metastatic potential of CRC. [ABSTRACT FROM AUTHOR]

Studies have revealed that people with hyperglycemia have a high risk of colorectal cancer (CRC). Hyperglycemia may be responsible for supplying energy to CRC cells. However, the potential molecular mechanism for this association remains unclear. Furthermore, microRNA-9 (miR-9) has a tumor-suppressive function in CRC. Aberrant reduced expression of miR-9 is involved in the development and progression of malignancy caused by a high glucose (HG) concentration. In this study, we used an HG concentration to activate miR-9 downregulation in CRC cells. Our results indicated that miR-9 decreased the insulin-like growth factor-1 receptor (IGF1R)/Src signaling pathway and downstream cyclin B1 and N-cadherin but upregulated E-cadherin. The HG concentration not only promoted cell proliferation, increased the G1 population, and modulated epithelial-to-mesenchymal transition (EMT) protein expression and morphology but also promoted the cell migration and invasion ability of SW480 (low metastatic potential) and SW620 (high metastatic potential) cells. In addition, low glucose concentrations could reverse the effect of the HG concentration in SW480 and SW620 cells. In conclusion, our results provide new evidence for multiple signaling pathways being regulated through hyperglycemia in CRC. We propose that blood sugar control may serve as a potential strategy for the clinical management of CRC. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) immunity plays an important role in the proliferation and apoptosis of aberrant cells. Immune dysregulation has been studied in various prognostic subgroups. This study analyzed 60 patients with MDS via multidimensional flow cytometry to evaluate the expression of aberrant markers, such as CD7 and cytoplasmic CD3 on lymphocytes. The Revised International Prognostic Scoring System (IPSS-R) scores were used to classify the patients into risk groups. The results showed a significant downregulation of CyCD3- T cells in low-intermediate versus high-risk patients ( p = 0.013). This study is the first to show that a significant decrease in cyCD3- T cells in patients with a lower IPSS-R score may indicate microenvironmental changes conducive to transformation in MDS.

Background: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC., Methodology/principal Findings: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60)., Conclusions: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.

Background: A novel human nuclear receptor interaction protein (NRIP) has recently been discovered by Chen SL et al, which may play a role in enhancing the transcriptional activity of steroid nuclear receptors in prostate (LNCaP) and cervical (C33A) cancer cell lines. However, knowledge about the biological functions and clinical implications of NRIP, is still incomplete. Our aim was to determine the distribution of NRIP expression and to delineate the cell types that express NRIP in various malignant tumors and healthy non-pathological tissues. This information will significantly affect the exploration of its physiological roles in healthy and tumor cells., Methods: By using tissue microarray (TMA) technology and an anti-NRIP monoclonal antibody immunohistochemical (IHC) survey, NRIP expression was examined in 48 types of tumors and in a control group of 48 matched or unmatched healthy non-neoplastic tissues., Results: Our survey results showed that ten cases were revealed to express the NRIP in six malignancies (esophageal, colon, breast, ovarian, skin, and pancreatic cancers), but not all of these specific tumor types consistently showed positive NRIP expression. Moreover, malignant tumors of the stomach, prostate, liver, lung, kidney, uterine cervix, urinary bladder, lymph node, testis, and tongue revealed no NRIP expression. Among the control group of 48 matched and unmatched non-neoplastic tissues, all of them demonstrated IHC scores less than the cut-off threshold of 3. In addition, ten cores out of thirty-six carcinomatous tissues revealed positive NRIP expression, which indicated that NRIP expression increases significantly in carcinoma tissue cores, comparing to the matched controlled healthy tissues., Conclusion: This is the first study to use a human TMA and IHC to validate the nuclear localization for this newly identified NRIP expression. In considering the use of NRIP as a potential diagnostic tool for human malignancies survey, it is important to note that NRIP expression carries a sensitivity of only 23%, but has a specificity of 100%. There is also a significant difference in positive NRIP expression between primary carcinomatous tissues and matched controlled healthy tissues. Although further large-scale studies will merit to be conducted to evaluate its role as a potential adjunct for cancer diagnosis, data from this study provides valuable references for the future investigation of the biological functions of NRIP in humans.