MAPLE-based method to obtain biodegradable hybrid polymeric thin films with embedded antitumoral agents

In this work, antitumor compounds, lactoferrin [recombinant iron-free (Apo-rLf)], cisplatin (Cis) or their combination were embedded within a biodegradable polycaprolactone (PCL) polymer thin film, by a modified approach of a laser-based technique, matrix-assisted pulsed laser evaporation (MAPLE). The structural and morphological properties of the deposited hybrid films were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The in vitro effect on the cells’ morphology and proliferation of murine melanoma B16-F10 cells was investigated and correlated with the films’ surface chemistry and topography. Biological assays revealed decreased viability and proliferation, lower adherence, and morphological modifications in the case of melanoma cells cultured on both Apo-rLf and Cis thin films. The antitumor effect was enhanced by deposition of Apo-rLf with Cis within the same film. The unique capability of the new approach, based on MAPLE, to embed antitumor active factors within a biodegradable matrix for obtaining novel biodegradable hybrid platform with increased antitumor efficiency has been demonstrated.     

EGCG Prevents the Onset of an Inflammatory and Cancer-Associated Adipocyte-like Phenotype in Adipose-Derived Mesenchymal Stem/Stromal Cells in Response to the Triple-Negative Breast Cancer Secretome

Background: Triple-negative breast cancer (TNBC) cells secretome induces a pro-inflammatory microenvironment within the adipose tissue, which hosts both mature adipocytes and adipose-derived mesenchymal stem/stromal cells (ADMSC). The subsequent acquisition of a cancer-associated adipocyte (CAA)-like phenotype is, however, unknown in ADMSC. While epidemiological studies suggest that consuming a polyphenol-rich diet reduces the incidence of some obesity-related cancers, the chemopreventive impact of green tea-derived epigallocatechin-3-gallate (EGCG) against the cues that trigger the CAA phenotype remain undocumented in ADMSC. Methods: Human ADMSC were exposed to human TNBC-derived MDA-MB-231 conditioned media (TNBC cells secretome) supplemented or not with EGCG. Differential gene expression was assessed through RNA-Seq analysis and confirmed by RT-qPCR. Protein expression levels and the activation status of signal transduction pathways mediators were determined by Western blotting. ADMSC chemotaxis was assessed by a real-time cell migration assay. Results: The TNBC cells secretome induced in ADMSC the expression of the CAA cytokines CCL2, CCL5, IL-1β, and IL-6, and of immunomodulators COX2, HIF-1α, VEGFα, and PD-L1. The epithelial-to-mesenchymal biomarker Snail was found to control the CAA phenotype. EGCG inhibited the induction of CAA genes and the activation status of Smad2 and NF-κB. The induced chemotactic response was also inhibited by EGCG. Conclusion: The induction of an inflammatory and CAA-like phenotype in ADMSC can be triggered by the TNBC cells secretome, while still efficiently prevented by diet-derived polyphenols.     

Maternal mortality in India: a 20-year study from a large referral medical college hospital, West Bengal

Aim:  The present study was carried out to analyze the maternal death rate and its changing trends over a 20-year period in a large referral/teaching institution in Eastern India.
Methods:  A retrospective analysis of maternal deaths was carried out from January 1986 to December 2005 at the Department of Obstetrics and Gynaecology, R. G. Kar Medical College and Hospital, Kolkata, India. Records were divided into four 5-yearly periods: 1986–1990; 1991–1995; 1996–2000; and 2001–2005, for comparison of the trends. The initial interval from 1986 to 1990 was chosen as the reference period.
Results:  The cumulative maternal mortality ratio (MMR) was 599.3 per 100 000 live births. Comparison between the first 5-year period (1986–1991) and the last (2001–2005) showed a statistical significant downward trend in MMR (683.6 vs 474.3; P  < 0.001). Deaths due to direct causes are still the leading cause, accounting for 82.09% of total deaths. Hypertensive disorders (36.14%), hemorrhage (21.91%) and sepsis (19.54%) were still the major causes of direct obstetric deaths throughout the study period. Hypertensive disorders alone showed a substantial decline after the introduction of magnesium sulphate.
Conclusion:  The fall in maternal mortality has been very slow.     

Relationship between female sexual difficulties and mental health in patients referred to two public and private settings in Tehran, Iran

IntroductionSexual difficulty has various effects on patients suffering from this condition that can impact on interpersonal and marital relationships. Sexual function may be adversely affected by stress of any kind and emotional disorders. There have been limited studies focusing on the mental health of those suffering from this problem.AimTo determine the relationship between sexual difficulties and mental health in female patients seeking help in psychiatric clinics.MethodsThe study was based on the case–control design methodology in which the case group consisted of 165 outpatients of two psychiatric clinics, who were diagnosed with different mental disorders such as depression, anxiety, phobia, aggression, and somatic complaints (33 subjects for each type of disorder). The 33 subjects in the control group were chosen among the patients’ relatives and visitors who had no history of either seeking psychiatric help or taking psychiatric drugs. The subjects of both case and control groups were selected based on a convenience sampling method. Moreover, the data were collected based on two techniques of “interview” and “questionnaire;” the latter was of three different subcategories, each dealt with demographic characteristics, sexual difficulties, and a Symptom Check-List-90-Revised.Main Outcome MeasureAssessing female sexual difficulties associated with mental health and differences between women with and without psychiatric problems.ResultsThe obtained results indicated that there was a significant difference between the prevalence of sexual difficulties (e.g., sexual desire and orgasm disorders) in the case group and that of the control group. It was also revealed that there was a significant difference between the depressed, aggressive, as well as those with somatic complaints, and their control group counterparts.ConclusionsIn Iran, sexual difficulties seem to be more frequent in those seeking psychiatric help in clinics than in those within the normal population. Azar M, Noohi S, and Shafiee Kandjani AR. Relationship between female sexual difficulties and mental health in patients referred to two public and private settings in Tehran, Iran.     

利用反义技术抑制人乳头瘤病毒18 E6/E7的表达及其对宫颈癌HeLa细胞增殖凋亡的影响

目的 构建人乳头瘤病毒（HPV）18型E6／E7反义荧光真核表达载体,研究其对宫颈癌HeLa细胞增殖凋亡的影响。方法 以PCR法扩增HPV18型E6／E7区716bp片段并反向克隆到荧光真核表达载体pEGFP-C1,构建重组体pEGFP-HPV18E6E7as（EGFP-18AS）并转染人宫颈癌HeLa细胞。利用逆转录聚合酶链反应（RT—PCR）和Western印迹技术检测转染后E6、E7基因在mRNA和蛋白水平的变化;用四甲基偶氮唑盐微量酶反应比色法检测转染后细胞的的增殖活性;用流式细胞仪检测转染后细胞的凋亡率;荧光显微镜下观察凋亡细胞的形态学改变。结果 转染EGFP-18AS重组体后,HeLa细胞中E6、E7基因的mRNA表达和蛋白合成均明显下调;细胞增殖受到抑制;流式显示细胞G1期明显阻滞;同时在荧光显微镜下经Hoechst染色凋亡细胞出现染色质凝集、边集、碎裂等形态学改变。结论 重组质粒pEGFP—HPV18E6E7as能有效地抑制人宫颈癌HeLa细胞的生长和增殖,诱导其凋亡,证明了反义RNA技术的有效性,为宫颈癌的基因治疗提供了一种新的可能的途径。     

Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Background

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.

Methods

Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models.

Results

Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4–4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30–1.98), disease-free survival (HR = 1.26; 95 % CI 1.10–1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07–1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1–5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7–327,560.0 ng/mL) and Ishak stage 6 cirrhosis.

Conclusions

Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.     

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double‐blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m², 55% were women, and 222 completed the 12‐month follow‐up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low‐dose arm, and 36 ng/mL in the high‐dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C‐terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high‐dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high‐dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high‐dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.     

白细胞介素1α mRNA在神经胶质瘤中的表达及意义

目的定量检测白细胞介素1α（IL-1α）mRNA在神经胶质瘤组织和正常脑组织中的表达,并探讨其与临床特征的关系。方法运用实时荧光定量PCR检测31例神经胶质瘤组织和22例正常脑组织中IL-1α mRNA的表达,分析其与临床特征的相关性。结果IL-1α mRNA在神经胶质瘤组织中的相对表达量为0．10,在正常组脑组织中为0．01,两者差异具有统计学意义（U=207．0,P=0．016）。IL-1α mRNA在WHO Ⅲ-Ⅳ级神经胶质瘤中的相对表达量为0．72,在Ⅰ-Ⅱ级中为0．02,两者差异具有统计学意义（U=36．0,P=0．001）;而IL-1α RNA相对表达量在性别和年龄之间差异无统计学意义（P〉0．05）。结论IL-1α mRNA在神经胶质瘤组织中呈显著高表达,其可能在神经胶质瘤的恶变过程中发挥重要作用。