[Huangpu Tongqiao Capsule improves cognitive impairment in rats with Wilson disease by inhibiting endoplasmic reticulum stress-mediated apoptosis pathway].

OBJECTIVE: To investigate the neuroprotective effect of Huangpu Tongqiao Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms. METHODS: SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting. RESULTS: Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (P<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all P<0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (P<0.01 or 0.05). CONCLUSION: HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.

[Correlation analysis of smell and taste loss with COVID-19 outbreak trend based on big data of internet].

Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.

Predicting cyanobacteria bloom occurrence in lakes and reservoirs before blooms occur.

With increased global warming, cyanobacteria are blooming more frequently in lakes and reservoirs, severely damaging the health and stability of aquatic ecosystems and threatening drinking water safety and human health. There is an urgent demand for the effective prediction and prevention of cyanobacterial blooms. However, it is difficult to effectively reduce the risks and loss caused by cyanobacterial blooms because most methods are unable to successfully predict cyanobacteria blooms. Therefore, in this study, we proposed a new cyanobacterial bloom occurrence prediction method to analyze the probability and driving factors of the blooms for effective prevention and control. Dominant cyanobacterial species with bloom capabilities were initially determined using a dominant species identification model, and the principal driving factors of the dominant species were then analyzed using canonical correspondence analysis (CCA). Cyanobacterial bloom probability was calculated using a newly-developed model, after which, the probable mutation points were identified and thresholds for the principal driving factors of cyanobacterial blooms were predicted. A total of 141 phytoplankton data sets from 90 stations were collected from six large-scale hydrology, water-quality ecology, integrated field surveys in Jinan City, China in 2014-2015 and used for model application and verification. The results showed that there were six dominant cyanobacterial species in the study area, and that the principal driving factors were water temperature, pH, total phosphorus, ammonia nitrogen, chemical oxygen demand, and dissolved oxygen. The cyanobacterial blooms corresponded to a threshold water temperature range, pH, total phosphorus (TP), ammonium nitrogen level, chemical oxygen demand, and dissolved oxygen levels of 19.5-32.5 °C, 7.0-9.38, 0.13-0.22 mg L-1, 0.38-0.63 mg L-1, 10.5-17.5 mg L-1, and 4.97-8.28 mg L-1, respectively. Comparison with research results from other global regions further supported the use of these thresholds, indicating that this method could be used in habitats beyond China. We found that the probability of cyanobacterial bloom was 0.75, a critical point for prevention and control. When this critical point was exceeded, cyanobacteria could proliferate rapidly, increasing the risk of cyanobacterial blooms. Changes in driving factors need to be rapidly controlled, based on these thresholds, to prevent cyanobacterial blooms. Temporal and spatial scales were critical factors potentially affecting the selection of driving factors. This method is versatile and can help determine the risk of cyanobacterial blooms and the thresholds of the principal driving factors. It can effectively predict and help prevent cyanobacterial blooms to reduce the global probability of occurrence, protect the health and stability of water ecosystems, ensure drinking water safety, and protect human health.

Quantitative assessment of the effects of human activities on phytoplankton communities in lakes and reservoirs.

Global algal blooms have been severely threatening safety of drinking water and development of socio-economy. Effective prevention and accurate control of algal blooms require a quantitative assessment of the influence of human activities and identification of priority areas. However, previous studies on the quantitative assessment of the effects of human activities on algal communities are lacking, severely hindering the effective and precise control of algal blooms. This paper proposes a quantitative assessment model to evaluate the impact intensity of human activities on phytoplankton. Applications showed that the proliferation of phytoplankton were more limited by nutrients such as total phosphorus and ammonia where waters are less influenced by human activities, yet were less limited by these nutrients where there are highly intensive human activities. The density of phytoplankton in waters increased with an increase in human activity intensity, particularly in concentrated agricultural areas, which are priority areas for the prevention and control of algal blooms. The methodologies can clearly identify key areas for algal bloom prevention and control and can provide scientific evidence for water and nutrient management throughout the world, reducing the risk of algal blooms and ensuring aquatic ecosystem health and potable water safety.

Long-term follow-up of hepatic adenoma and adenomatosis: analysis of size change on imaging with histopathological correlation.

AIM: To analyse the change in size on follow-up of hepatic adenomas (HAs) and adenomatosis, and to investigate the relationship of imaging features with size change. MATERIALS AND METHODS: The study included 44 patients (142 lesions) who underwent magnetic resonance imaging (MRI) or computed tomography (CT) for diagnosis and follow-up of HA. The imaging features and percentage change in maximum tumour dimension were observed over a follow-up duration of up to 139 months. RESULTS: With an average follow-up of 43 months, 37% lesions decreased in size, 58% were stable, 4% increased; one lesion regressed completely. Adenomas were stratified into size groups (<3, 3-5, and ≥5 cm). Size change among the three groups was similar (p>0.05). Percent size change was different for lesions followed for ≤12 months (-7.2%) compared with lesions followed for 13-60 months (-20.5%), and those followed for ≥60 months (-23.5%; p<0.05); there was no difference between lesions followed for 13-60 months and ≥60 months (p=0.523). Baseline size and percent size change was similar between the hepatocyte nuclear factor 1α-inactivated HA (HA-H) and inflammatory HA (HA-I) subtype (p>0.05). CONCLUSION: Most adenomas were either stable or regressed on follow-up. Size change was independent of baseline size. After an initial size decrease within 5 years, no further size reduction was noted on extended follow-up. The percent size change in the HA-H and HA-I subtype was similar.

Tacrolimus alleviates Ox-LDL damage through inducing vascular endothelial autophagy.

OBJECTIVE: To study the protective effect of tacrolimus on vascular endothelium injured by oxidized low-density lipoprotein (ox-LDL) and its mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells were used as objects of study, and divided into control group, tacrolimus group and autophagy inhibition group. Control group received no ox-LDL, while tacrolimus group and autophagy inhibition group were treated with ox-LDL (100 µg/mL) for 3 h. Tacrolimus group was pre-treated with tacrolimus (100 nM) for 0.5 h, and the autophagy inhibition group was pre-treated with 3-methyladenine (3-MA) (10 mM) and tacrolimus (100 nM) for 0.5 h. The cell viability was detected via cell counting kit 8 (CCK8) assay, the cell apoptosis ratio was detected via flow cytometry and Hoechst staining, and the releases of superoxide dismutase (SOD), reactive oxygen species (ROS) and other cytokines were detected using the kit. Moreover, the autophagy level was detected via LC3 fluorescence staining, and the autophagy- and apoptosis-related molecules were detected via polymerase chain reaction (PCR) and Western blotting. RESULTS: In the absence of ox-LDL, neither tacrolimus nor 3-MA had an effect on the cell viability. After the addition of ox-LDL, the cell viability was significantly decreased, whereas tacrolimus could alleviate such damage to cells. Flow cytometry and Hoechst staining proved that tacrolimus could reduce the proportion of apoptotic cells induced by ox-LDL, while PCR and Western blotting confirmed the decreased expression of apoptosis-related proteins in tacrolimus group. 3-MA could up-regulate the ratio of apoptosis and the expressions of apoptosis-related proteins. The detection of SOD and ROS showed that ox-LDL could induce the cell oxidative stress injury, whereas tacrolimus could inhibit such an effect. The addition of 3-MA inhibited the effect of tacrolimus. Besides, LC3 fluorescence staining, PCR and Western blotting revealed that ox-LDL could induce the autophagy, while tacrolimus could enhance the autophagy. After the addition of 3-MA, the intracellular autophagy level was significantly inhibited. CONCLUSIONS: Tacrolimus protects vascular endothelial cells from ox-LDL damage through inducing the autophagy.

Short-term combined treatment with exenatide and metformin is superior to glimepiride combined metformin in improvement of serum testosterone levels in type 2 diabetic patients with obesity.

Men with type 2 diabetes (T2D) and obesity are often characterised by low testosterone (T). We aimed to determine whether exenatide (EXE) combined metformin (MET) treatment has a better effect on serum total testosterone (TT) levels than glimepiride (GLI) combined MET treatment in men with T2D and obesity. In a multicentre, 12-week observational study, 176 obese T2D men with failed glycaemic control were included in the study: ninety men (mean age, 43.00 ± 8.50 years) in EXE + MET group and 86 men (mean age, 44.00 ± 7.00 years) in GLI + MET group. Serum TT levels were more significantly increased in EXE + MET group than GLI + MET group (121.72 ± 56.73 ng/dl versus 34.67 ± 16.30 ng/dl). The increasement of TT levels in those patients who lost body weight ≥5% was significantly greater than those who lost weight <5% in the two groups. The changes in TT levels are closely related to the changes in waist circumference (r = -.443, p < .001). Sexual function assessment of EXE + MET group was more significantly improved than GLI + MET group (p < .001). No serious adverse events were observed. In conclusion, short-term combined treatment with EXE and MET is superior to GLI combined MET treatment in the improvement of serum TT levels, which could lead to an improvement of sexual hypofunction in patients with obesity and T2D.

ClariVein™ - One year results of mechano-chemical ablation for varicose veins in a multi-ethnic Asian population from Singapore.

OBJECTIVES: This study assessed the effectiveness and patient experience of ClariVein for varicose veins and chronic venous insufficiency (CVI) in a multi-ethnic Asian population from Singapore. METHODS: A total of 121 patients underwent mechano-chemical ablation. Patients were reviewed at an interval of one week, and at 3, 6 and 12 months post procedure and underwent Duplex ultrasound with patient satisfaction assessment. RESULTS: At three months of follow-up, the great saphenous vein and short saphenous vein occlusion rates were 90.8% and 96.0%, respectively. At six months of follow-up, the GSV and short saphenous vein occlusion rates were 86.9% and 90.9%, respectively. At one year, great saphenous vein and short saphenous vein occlusion rates were 84.8% and 94.3%, respectively. CONCLUSIONS: Early results are similar to what is described so far in the mechano-chemical ablation literature but recurrences are more than expected at one year. This is disappointing but is tempered by the fact that the majority of patients were asymptomatic and required no reintervention.

LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway.

OBJECTIVE: The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that plays a key role in the malignant phenotype of tumors. Although abnormal regulation of lncRNA MALAT1 impacts clinical prognostic and tumor metastasis, its function remains unclear in ovarian cancer. PATIENTS AND METHODS: We collected 64 samples of surgical EOC tissues and 30 samples of normal ovarian tissues at the Department of Gynecology of Harbin Medical University (Harbin, China). The 30 control samples of ovarian surface epithelial tissues were obtained from patients diagnosed with uterine fibroids and scheduled hysterectomy with oophorectomy. RESULTS: The present study discovered that MALAT1 was upregulated in tumor tissues and ovarian cancer cell lines. Further, the 5-year overall survival was higher in the lower expression of the MALAT1 group. MALAT1 inhibition impeded cell proliferation, invasion and metastasis, and promoted cell apoptosis in both in vivo and in vitro. Furthermore, silencing of MALAT1 hindered the expression of epithelial-to-mesenchymal transition (EMT)-related genes and MMPS. The evidence showed that MALAT1 induce EMT via PI3K/AKT pathway. CONCLUSIONS: Our research suggests that MALAT1 transforms metastasis in EOC and may be a prospective therapeutic target.

High pretreatment neutrophil–lymphocyte ratio predicts recurrence and poor prognosis for combined small cell lung cancer

Backgrounds. Compared to pure small cell lung cancer (SCLC), combined small cell lung cancer (C-SCLC) has its own characteristics. High neutrophil to lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have been shown to be related to poor prognosis in several types of tumors. The aim of this study was to explore the prognosis value of NLR and PLR in patients with C-SCLC. Methods. A total of 112 patients diagnosed with C-SCLC between January 2000 and March 2009 were enrolled in the study. The clinicopathological parameters, laboratory analyses, and survival time were collected and analyzed. The correlation between NLR, PLR, and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. Results. The pretreatment NLR was elevated in 37.5 % patients (NLR ≥ 4.15; n = 42; H-NLR). NLR was significantly related to disease stage (p = 0.033) and tumor recurrence (p = 0.014). The median overall survival (OS) and progression-free survival (PFS) were significantly worse in the H-NLR group (OS: 22.0 months vs 11.7 months, p = 0.001; PFS: 11.1 vs 6.0 months, p < 0.001). However, PLR at diagnosis was not associated with OS or PFS. Multivariate analyses indicated elevated NLR (HR = 1.6; p = 0.001), disease stage (HR = 1.6; p = 0.001), and performance status (HR = 1.8; p = 0.015) as independent prognostic factors. Conclusions. High pretreatment NLR (≥4.15) is a potential useful indicator for C-SCLC recurrence and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients (AU)

No disponible

High pretreatment neutrophil-lymphocyte ratio predicts recurrence and poor prognosis for combined small cell lung cancer.

BACKGROUNDS: Compared to pure small cell lung cancer (SCLC), combined small cell lung cancer (C-SCLC) has its own characteristics. High neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be related to poor prognosis in several types of tumors. The aim of this study was to explore the prognosis value of NLR and PLR in patients with C-SCLC. METHODS: A total of 112 patients diagnosed with C-SCLC between January 2000 and March 2009 were enrolled in the study. The clinicopathological parameters, laboratory analyses, and survival time were collected and analyzed. The correlation between NLR, PLR, and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. RESULTS: The pretreatment NLR was elevated in 37.5 % patients (NLR ≥ 4.15; n = 42; H-NLR). NLR was significantly related to disease stage (p = 0.033) and tumor recurrence (p = 0.014). The median overall survival (OS) and progression-free survival (PFS) were significantly worse in the H-NLR group (OS: 22.0 months vs 11.7 months, p = 0.001; PFS: 11.1 vs 6.0 months, p < 0.001). However, PLR at diagnosis was not associated with OS or PFS. Multivariate analyses indicated elevated NLR (HR = 1.6; p = 0.001), disease stage (HR = 1.6; p = 0.001), and performance status (HR = 1.8; p = 0.015) as independent prognostic factors. CONCLUSIONS: High pretreatment NLR (≥4.15) is a potential useful indicator for C-SCLC recurrence and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients.

The efficacy and safety of zibotentan in the treatment of castration-resistant prostate cancer: a meta-analysis.

OBJECTIVE: Recently, novel endothelins like zibotentan and atrasentan and other novel taxanes have been introduced to treat prostate cancer. This study reviews zibotentan in the treatment of castration-resistant prostate cancer (CRPC) and derives a more precise estimate of their effect of treatment. MATERIALS AND METHODS: Two reviewers searched and extracted data of the published trials and review articles on zibotentan for prostate cancer using the Medline, Embase and Cochrane Controlled Trials Register database. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression-free survival (PFS), or time to PSA progression (TTP), and relative risk (RR) for the different types of toxicity. Four randomized controlled trials were identified. RESULTS: The pooled HR showed that zibotentan did not improve OS and PFS (HR = 0.92, 95%CI = 0.82-1.03, p = 0.161, HR = 0.98, 95% CI = 0.89-1.08, p = 0.714). Zibotentan had modest benefits on TTP (HR = 0.94, 95% CI = 0.91-0.97, p = 0.001). In addition, zibotentan led to more peripheral edema, anemia, cardiac failure and pneumonia. CONCLUSIONS: Our study concludes that zibotentan is not an attractive option for CRPC patients. However, additional studies on other novel therapies are needed to improve patient outcomes.

BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos.

Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader implicated in the pathogenesis of a number of different cancers and other diseases. Brd4-null mouse embryos die shortly after implantation and are compromised in their ability to maintain the inner cell mass, which gives rise to embryonic stem cells (ESCs). Here we report that BRD4 regulates expression of the pluripotency factor Nanog in mouse ESCs and preimplantation embryos, as well as in human ESCs and embryonic cancer stem cells. Inhibition of BRD4 function using a chemical inhibitor, small interfering RNAs, or a dominant-negative approach suppresses Nanog expression, and abolishes the self-renewal ability of ESCs. We also find that BRD4 associates with BRG1 (brahma-related gene 1, aka Smarca4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4)), a key regulator of ESC self-renewal and pluripotency, in the Nanog regulatory regions to regulate Nanog expression. Our study identifies Nanog as a novel BRD4 target gene, providing new insights for the biological function of BRD4 in stem cells and mouse embryos. Knowledge gained from these non-cancerous systems will facilitate future investigations of how Brd4 dysfunction leads to cancers.

Targeting microRNAs to modulate TRAIL-induced apoptosis of cancer cells.

MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs, which are evolutionarily conserved and function as regulators of gene expression. These molecules are involved in numerous biological processes including differentiation, development, proliferation and apoptosis. Further investigation identifies that miRNAs may act as either potent oncogenes or tumor-suppressor genes, linking to cancer initiation and progression. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), as a member of the TNF family, is an attractive therapeutic target in cancer because it directly induces tumor cell apoptosis and has no cytotoxicity to normal cell types in vitro or in vivo. However, the resistance to TRAIL-induced apoptosis limits its clinical effectiveness. Interestingly, several studies convincingly demonstrate a role of miRNAs in modulating sensitive/resistant phenotypes to TRAIL. Here, we review the current findings about miRNAs involved in TRAIL-induced apoptosis in different cancers.

Family history and prior allergies of cancers and the risk of adult leukemia in shandong province, china.

BACKGROUND: A case-control study was carried out to investigate the roles of prior allergies and family history of cancers and their interaction in the etiology of adult leukemia. METHODS: Prior allergies status and family history of cancers in first-degree relatives were compared between 131 incident leukemia cases and 206 hospital-based controls. Odds ratios (OR) were estimated using an unconditional regression model taking into account potential confounding factors. RESULTS: Significant association between adult leukemia and prior allergies and family history of cancer (OR=2.09, 95% CI: 1.22-3.58 for prior allergies; and OR=2.35, 95% CI: 1.09-5.03 for family history of cancer, OR=15.88, 95% CI: 1.77-142.55 for both the two factors (+), respectively) was found after adjusting for potential confounding factors. CONCLUSION: Prior allergies and family history of cancers may be risk factors for adult leukemia; their interaction was likely to be synergistic rather than additive for the risk of leukemia.

Additional diffusion-weighted imaging in the detection of new, very small hepatocellular carcinoma lesions after interventional therapy compared with conventional 3 T MRI alone.

AIM: To evaluate the added value of diffusion-weighted imaging (DWI) combined with conventional magnetic resonance imaging (MRI) in the detection of new, very small hepatocellular carcinoma lesions (≤1 cm) in patients with hepatocellular carcinoma following interventional therapy compared to conventional MRI alone. MATERIALS AND METHODS: After interventional therapy, 45 patients with hepatocellular carcinoma underwent conventional MRI and DWI with a b-value of 0 and 700 s/mm(2). Twenty-one new, small hepatocellular carcinoma lesions were confirmed in 16 patients at follow-up MRI. Two observers independently retrospectively analysed the two imaging sets in random order. The diagnostic performance using each imaging set was evaluated by received operating characteristic curve analysis. RESULTS: Twenty-one new, very small hepatocellular carcinoma lesions found in 16 patients was confirmed as the final result. The area under the receiver operating characteristic curve of the DWI/conventional MRI combination (observer 1, 0.952; observer 2, 0.976) and conventional MRI images alone (observer 1, 0.905; observer 2, 0.905) were statistically significant. The kappa value of the DWI/conventional MRI combination was 0.884, and that of conventional MRI was 0.722. Among the 21 lesions, 100% (21/21) of the lesions were both recognized by two independent reviewers on DWI, while only 76% (16/21) and 71% (15/21) of the lesions were regarded as very small hepatocellular carcinomas on conventional MRI. CONCLUSION: Due to the higher detection rate of new subcentimetre lesions in hepatocellular carcinoma patients following interventional therapy, DWI could be considered complementary to conventional MRI in the diagnosis of hepatocellular carcinoma.

IL-10 polymorphisms and prostate cancer risk: a meta-analysis.

Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). Three common polymorphisms in the promoter of interleukin-10 (IL-10) gene, -1082 A>G, -819 C>T and -592 C>A, have been implicated to alter the risk of PCa, but the results of relative studies are inconclusive or controversial. To derive a more precise estimation of the relationship, we performed an updated meta-analysis on the basis of 10 studies. A comprehensive search was conducted to examine all the eligible studies of IL-10 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Overall, there were no significant associations between increased risk of PCa and IL-10 -1082 A>G, -819 C>T and -592 C>A polymorphisms. However, meta-analysis suggested that IL-10 -819 C>T and -592 C>A polymorphisms might be modestly associated with PCa aggressiveness (T versus C, OR=1.162, 95% CI: 1.035-1.305, P=0.011; A versus C, OR=1.131, 95% CI: 1.012-1.264, P=0.030; respectively). IL-10 -819 C>T and -592 C>A polymorphisms might impact PCa progression. Variant alleles at both -819 and -592 were modestly associated with advanced stages of PCa. Additional well-designed studies are warranted to validate these findings.

Structures and relative stability of medium- and large-sized silicon clusters. VI. Fullerene cage motifs for low-lying clusters Si(39), Si(40), Si(50), Si(60), Si(70), and Si(80).

We performed a constrained search, combined with density-functional theory optimization, of low-energy geometric structures of silicon clusters Si(39), Si(40), Si(50), Si(60), Si(70), and Si(80). We used fullerene cages as structural motifs to construct initial configurations of endohedral fullerene structures. For Si(39), we examined six endohedral fullerene structures using all six homolog C(34) fullerene isomers as cage motifs. We found that the Si(39) constructed based on the C(34)(C(s):2) cage motif results in a new leading candidate for the lowest-energy structure whose energy is appreciably lower than that of the previously reported leading candidate obtained based on unbiased searches (combined with tight-binding optimization). The C(34)(C(s):2) cage motif also leads to a new candidate for the lowest-energy structure of Si(40) whose energy is notably lower than that of the previously reported leading candidate with outer cage homolog to the C(34)(C(1):1). Low-lying structures of larger silicon clusters Si(50) and Si(60) are also obtained on the basis of preconstructed endohedral fullerene structures. For Si(50), Si(60), and Si(80), the obtained low-energy structures are all notably lower in energy than the lowest-energy silicon structures obtained based on an unbiased search with the empirical Stillinger-Weber potential of silicon. Additionally, we found that the binding energy per atom (or cohesive energy) increases typically >10 meV with addition of every ten Si atoms. This result may be used as an empirical criterion (or the minimal requirement) to identify low-lying silicon clusters with size larger than Si(50).

BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers.

Breast cancer gene 1 (BRCA1) mutations predispose women to breast and ovarian cancers and men to increased risks for prostate cancer. We have previously showed BRCA1 splice variant BRCA1a/p110 to induce apoptosis of human breast cancer cells. In the current study, stable expression of BRCA1a/p110 resulted in inhibition of growth of estrogen receptor (ER)-positive and triple-negative (TN) human breast, ovarian, prostate and colon cancer cells and mouse fibroblast cells. Similar to wild-type BRCA1, only those cells with wild-type Rb were sensitive to BRCA1a-induced growth suppression and the status of p53 did not affect the ability of BRCA1a to suppress growth of tumor cells. BRCA1a also significantly inhibited tumor mass in nude mice bearing human CAL-51 TN breast cancer, ES-2 ovarian cancer and PC-3 prostate cancer xenografts. These results suggest that the majority of exon 11 sequences (residues 263-1365) are not required for the tumor suppressor function of BRCA1 proteins. This is the first report demonstrating antitumor activity of BRCA1a in human ER-positive and TN breast, hormone-independent ovarian and prostate cancer cells. Currently, there are no effective treatments against TN breast cancers and results from these studies will provide new treatments for one of the biggest needs in breast cancer research.