Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.Experimental Design: The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues.Results: MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer.Conclusions: Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets.

Head and neck carcinomas (HNCs) collectively are the sixth most common cancer with an annual incidence of about 400,000 cases in the US. The most well-established risk factors for HNCs are tobacco and alcohol abuse. With the increasing public awareness, the incidence of HNCs is decreasing. But there is an increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been observed during the last decade. This phenomena is associated with persistent infection with high-risk HPV. HPV associated OPSCC patients tend to be younger males of high socioeconomic status. The increasing incidence causes a significant loss to social resources, given that it’s reported that HPV associated OPSCC represents about 60% of OPSCC cases. There is a growing amount of data supporting the hypothesis that HPV-associated OPSCC has a better survival rate due to a higher sensitivity to chemotherapy and radiotherapy as compared to HPV-unrelated OPSCC. Although the HPV positivity is associated with increased radio-sensitivity, the underlying mechanisms are not yet fully understood. This review summarizes the current knowledge on the effects of HPV infection and its carcinogenesis on the radiosensitivity of OPSCC, from the molecular to histologic level, providing a comprehensive insight of this special tumor entity.

No abstract

trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the cardiovascular system in a number of studies. It is, however, unclear whether this naturally occurring compound can protect against cardiac hypertrophy. The aim of the present study was to investigate the effects of resveratrol on cardiac hypertrophy in vivo and the potential underlying mechanisms involving endothelin (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague-Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation controls were simultaneously established in the present study. The systolic blood pressure (SBP) of rats was measured at baseline and, along with heart weight, after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined. In the present study, it was shown that, compared with rats in the sham-operated group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg), heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7 +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/- 26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO concentration had increased to 40.1 +/- 14.6 micromol/L. These values were significantly different from those obtained for the PNX group. In conclusion, trans-resveratrol appears to be able to protect against the increase in SBP and subsequent cardiac hypertrophy in vivo and the mechanisms responsible may involve, at least in part, modulation of NO, AngII and ET-1 production.

No abstract

Sclerotinia sclerotiorum and Botrytis cinerea are typical necrotrophic pathogens that can attack more than 700 and 3000 plant species, respectively, and cause huge economic losses across numerous crops. In particular, the absence of resistant cultivars makes the stem rot because of S. sclerotiorum the major threat of rapeseed (Brassica napus) worldwide along with Botrytis. Previously, we identified an effector‐like protein (SsSSVP1) from S. sclerotiorum and a homologue of SsSSVP1 on B. cinerea genome and found that SsSSVP1 could interact with BnQCR8 of rapeseed, a subunit of the cytochrome b‐c1 complex. In this study, we found that BnQCR8 has eight homologous copies in rapeseed cultivar Westar and reduced the copy number of BnQCR8 using CRISPR/Cas9 to improve rapeseed resistance against S. sclerotiorum. Mutants with one or more copies of BnQCR8 edited showed strong resistance against S. sclerotiorum and B. cinerea. BnQCR8‐edited mutants did not show significant difference from Westar in terms of respiration and agronomic traits tested, including the plant shape, flowering time, silique size, seed number, thousand seed weight and seed oil content. These traits make it possible to use these mutants directly for commercial production. Our study highlights a common gene for breeding of rapeseed to unravel the key hindrance of rapeseed production caused by S. sclerotiorum and B. cinerea. In contrast to previously established methodologies, our findings provide a novel strategy to develop crops with high resistance against multiple pathogens by editing only a single gene that encodes the common target of pathogen effectors.

Here we will summarize the most appropriate and widely used reconstructive options for parotid and lateral skull base defects of various sizes, discussing the most recent evidence pertaining to each technique along with advantages and limitations of each reconstructive strategy.

Objective: Prediction and early intervention for hypocalcemia following parathyroidectomy and total thyroidectomy can decrease hospital cost and prevent severe hypocalcemia-related complications. This study aims to predict the severity of hypocalcemia after parathyroidectomy or thyroidectomy and to stratify patients into groups with different levels of risk for developing severe hypocalcemia, so that higher risk patients may be monitored more closely and receive earlier interventions. Methods: This was a retrospective cohort study of 100 patients with primary hyperparathyroidism who underwent parathyroidectomy as the primary treatment modality at a tertiary care hospital. Clinical information, including demographic information, perioperative PTH and calcium levels, vitamin D levels, weight of the pathologic glands removed, gland pathology, and re-admission rates, were retrieved. Statistical analysis was performed to analyze the association between collected variables and percentage of calcium drop following parathyroidectomy with statistical significant set at P-values <0.05. Results: Age, sex, and vitamin D level provided very minimal information to quantify risks of postoperative hypocalcemia. The percentage of decrease from preoperative PTH level to the lowest PTH level after the removal of the abnormal gland(s) is the most significant predicting factor for the severity of postoperative hypocalcemia. There is a mathematic regressional correlation between them. A formula was generated to quantify this linear relationship between them, and the nadir calcium can be calculated as [Formula: see text], where Canadir = the lowest postoperative calcium level, and PTHintraop = PTH level 15 minutes after removal of the abnormal gland, with the value of R2 > 0.7. The formula has been tested primarily in our patient population with good reliability. Conclusions: The highest preoperative, lowest postoperative, and change in PTH level can help us reliably calculate the trend of postoperative calcium level. Decision to pursue early interventions can be made based on the calculated result from the formula we obtained.