The prognostic implications of SIRTs expression in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Sirtuins (SIRTs) have key roles in cancer progression. However, the prognostic implications of SIRTs in breast cancer (BC) remains a subject of debate and controversy. Thus, we performed a meta-analysis to identify the precise prognostic value of SIRTs in BC patients. METHODS: Systematic literature searching was conducted in PubMed, Cochrane Library, Web of Science, and Embase databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association of SIRTs expression and survival outcomes in BC patients. RESULTS: A total of 22 original studies with 6317 patients were eligible for this meta-analysis. The results showed that in patients with BC, elevated SIRTs levels were associated with shorter overall survival (OS) and disease-free survival (DFS) both in univariate (HR = 1.56, 95% CI 1.21-2.00; HR = 1.67, 95% CI 1.32-2.12, respectively) and multivariate analysis models (HR = 2.11, 95% CI 1.48-3.00; HR = 1.70, 95% CI 1.20-2.39, respectively). Notably, further subgroup analysis revealed that overexpression of SIRT1 and SIRT6 predicted poor OS (HR = 2.65, 95% CI 1.54-4.56; HR = 2.53, 95% CI 1.64-3.90, respectively) and DFS (HR = 1.65, 95% CI 1.07-2.56; HR = 2.74; 95% CI 1.88-4.01, respectively) in BC. CONCLUSIONS: Our data has elucidated that SIRT1 and SIRT6 could serve as prognostic biomarkers for patients with BC and may contribute to refined patient management.

The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis.

EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.

Meta-analysis for psychological impact of breast reconstruction in patients with breast cancer.

AIMS: This meta-analysis aimed to evaluate the impact of breast reconstruction on the psychological aspects in patients with breast cancer. METHODS: A literature search on PubMed, Embase, ScienceDirect and Google scholar databases was conducted up to September 2017. The pooled risk radio (RR) or standard mean difference (SMD) and the corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software. RESULTS: A total of 5 studies were included in this meta-analysis. There were 551 breast cancer patients receiving mastectomy plus breast reconstruction and 574 breast cancer patients receiving mastectomy alone. The results showed that breast reconstruction can significantly decrease the incidence of anxiety (RR = 0.62, 95% CI 0.47-0.82, P = 0.0006)/depression (RR = 0.54, 95% CI 0.32-0.93, P = 0.02) and scale score for evaluating anxiety (SMD = - 0.20, 95% CI - 0.37 to - 0.03, P = 0.02)/depression (SMD = - 0.22, 95% CI - 0.39 to - 0.66, P = 0.007) compared with mastectomy alone. CONCLUSIONS: Breast reconstruction after mastectomy was benefit for improving the psychological damages in patients with breast cancer.

Exogenous BDNF Increases Mitochondrial pCREB and Alleviates Neuronal Metabolic Defects Following Mechanical Injury in a MPTP-Dependent Way.

Metabolic defects are common pathological phenomena following traumatic brain injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic factor (BDNF) is an important regulator of neuronal survival, development, function, and plasticity. This study was designed to investigate the potential effects of BDNF on TBI-induced metabolic defects and their underlying molecular mechanisms. BDNF was added into cultured neurons to a concentration of 25, 50, and 100 ng/ml, respectively, right after mechanical injury and metabolite levels were analyzed 4 h post injury. The mitochondrial phosphorylated cAMP response element-binding protein (pCREB) distribution and complex V synthesis, as well as their roles in metabolic defects, were evaluated. We found that exogenous BDNF improved metabolic defects, especially the uncoupling of oxidative phosphorylation. BDNF increased pCREB in mitochondrial inner membrane and matrix and promoted mitochondrial complex V synthesis. We also found that these results were negatively regulated by the mitochondrial permeability transition pore (MPTP) antagonist CsA and positively regulated by the MPTP agonist atractyloside. BDNF's protectional effects on metabolic defects were abolished by CREB knockout. When administrated in a dominant interfering CREB mutant (A-CREB) model, mitochondrial pCREB accumulation could still be observed, but the synthesis of complex V and alleviation of metabolic defects were repressed. Our data demonstrate that exogenous BDNF mitigates neuronal metabolic defects following mechanical injury by promoting the pCREB accumulation in mitochondrial inner membrane and matrix, which is regulated by MPTP opening, thus facilitating the synthesis of mitochondrial complex V.

Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it's role in metabolic defects and neuronal apoptosis after TBI.

Metabolic defects and neuronal apoptosis initiated by traumatic brain injury (TBI) contribute to subsequent neurodegeneration. They are all regulated by mechanisms centered around mitochondrion. Type-1 cannabinoid receptor (CB1) is a G-protein coupled receptor (GPCR) enriched on neuronal plasma membrane. Recent evidences point to the substantial presence of CB1 receptors on neuronal mitochondrial outer membranes (mtCB1) and the activation of mtCB1 influences aerobic respiration via inhibiting mitochondrial cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/complex I pathway. The expression and role of neuronal mtCB1 under TBI are unknown. Using TBI models of cultured neurons, wild type and CB1 knockout mice, we found mtCB1 quickly upregulated after TBI. Activation of mtCB1 promoted metabolic defects accompanied with ATP shortage but protected neurons from apoptosis. Selective activation of plasma membrane CB1 showed no effects on neuronal metabolism and apoptosis. Activation of mtCB1 receptors inhibited mitochondrial cAMP/PKA/complex I and resulted in exacerbated metabolic defects accompanied with a higher ratio of ATP reduction to oxygen consumption decrease as well as neuronal apoptosis. Further research found the remarkable accumulation of protein kinase B (AKT) on neuronal mitochondria following TBI and the activation of mtCB1 upregulated mitochondrial AKT/complex V activity. Upregulation of mitochondrial AKT/complex V activity showed anti-apoptosis effects and alleviated ATP shortage in metabolic defects. Taken together, we have identified mtCB1 quickly upregulate after TBI and a dual role the mtCB1 might play in metabolic defects and neuronal apoptosis initiated by TBI: the inhibition of mitochondrial cAMP/PKA/complex I aggravates metabolic defects, energy insufficiency as well as neuronal apoptosis, but the coactivation of mitochondrial AKT/complex V mitigates energy insufficiency and neuronal apoptosis.

MiR-181b promotes chemoresistance in breast cancer by regulating Bim expression.

MicroRNAs are emerging as critical regulators of the initiation and progression of multiple types of human cancers, including breast cancer. In the present study, the expression of miR-181b in breast cancer patient serum and breast cancer cell lines was evaluated. It was demonstrated that the miR-181b level was significantly upregulated in patient serum and breast cancer cell lines compared with that in normal controls. The results of in vitro 3H thymidine incorporation and Transwell migration assay indicated that miR-181b overexpression markedly promoted the proliferation and metastasis of breast cancer cells. These data suggest that miR-181b is a tumor promoter in breast cancer. Furthermore, miR-181b expression was found to be upregulated in doxorubicin (DOX)-resistant T-47D cells (T-47D-R) compared with that in the parental T-47D cells, and upregulation of miR-181b expression decreased the anticancer effect of DOX in the T-47D cells. Mechanistic studies demonstrated that the Bim gene, an essential initiator of apoptosis, was inhibited by miR-181b overexpression. We observed that knockdown of miR-181b by its specific inhibitors significantly re-sensitized the T-47D-R cells to the cytotoxicity of DOX. Importantly, we demonstrated that miR-181b inhibitors increased the level of Bim in the T-47D-R cells, resulting in the loss of mitochondrial membrane potential (MMP) and the activation of caspases caused by DOX. In summary, the results of the present study suggest that miR-181b functions as an oncogene during breast cancer development, and the miR-181b/Bim pathway may be a novel target used to overcome the chemoresistance in breast cancer.

[Clinical observation of depression after breast cancer operation treated with aurieular point sticking therapy].

OBJECTIVE: To compare the differences in the efficacy on depression after breast cancer operation treated with auricular point sticking therapy, the combined program of auricular point sticking therapy and TCM psychotherapy and medication with deanxit. METHODS: Ninety patients were randomized into 3 groups, 30 cases in each one. In the western medication group, the simple oral administration of deanxit was applied, one tablet a day. In the auricular point group, Xin (GO15), Shen (CO10), Gan(CO12), Shenmen(TF4), Pizhixia (AT), Neifenmi (CO18) were selected and stimulated with auricular point sticking on either side in each treatment, once a week. In the combined program group, on the basis of the treatment as the auricular point group, TCM psychotherapy was combined with. The treatment of 4 weeks made one session. One session and 4 weeks follow-up were required. The self-rating depression scale (SDS) was used to compare the score before and after treatment in the patients of each group and the efficacy was assessed. RESULTS: (1) Compared with those before treatment, in 4 weeks of treatment and 4 weeks of follow-up, SDS scores were all reduced apparently in the 3 groups (all P<0.001). After 4 weeks of follow-up in the auricular point group, after 2 and 4 weeks of treatment and 4 weeks of follow-up in the combined program group, SDS scores were all lower than those in the western medication group (all P<0.05). (2) After 4 weeks of treatment, the curative rate in the combined program group was higher than that in the auricular point group and the western medication group [60.0% (18/30) vs. 40.0% (12/30), 36.7% (11/30), both P<0.05)]. After 4 weeks of follow-up, the curative rate in either the combined program group or the auricular point group was higher than that in the western medication group [60.0% (18/30), 30.0% (19/30) vs. 23.3% (7/30), both P<0.05]. CONCLUSION: The auricular point sticking therapy, the combined program of auricular point sticking therapy and TCM psychotherapy, and medication with deanxit all relieve depression after breast cancer operation. The efficacy of the combined program with auricular point sticking therapy and TCM psychotherapy involved is the best, and the efficacy of the auricular point sticking therapy is better than the oral administration of deanxit.

Predictive value of early decreased plasma ghrelin level for three-month cognitive deterioration in patients with mild traumatic brain injury.

The orexigenic hormone, ghrelin, is tightly linked to cognition impairment in neurodegenerative disorders. No previous studies have investigated the early ghrelin concentration change in patients with mild traumatic brain injury (mTBI) and it's relationship to cognitive deterioration. This study was performed to investigate the early plasma ghrelin concentrations in patients with mTBI and to explore the relationship between ghrelin and cognitive deterioration. Plasma ghrelin concentrations of 118 adults after acute mTBI were determined by enzyme-linked immunosorbent assay. Forty patients (33.9%) had cognitive deterioration three months after mTBI. Plasma ghrelin levels were significantly lower in mTBI patients with cognitive deterioration than patients without cognitive deterioration (38.8±4.5 pg/mL vs 50.8±7.7 pg/mL, P<0.001). Decreased Plasma ghrelin level was identified as an independent predictor for three-month cognitive deterioration after mTBI (odds ratio, 0.746; 95% confidence interval, 0.651-0.856; P<0.001). Plasma ghrelin level was negatively associated with serum adrenocorticotrophin hormone level (t=-6.854, P<0.001) and age (t=-6.112, P<0.001). A plasma ghrelin level of 41.6 pg/mL predicted three-month cognitive deterioration after mTBI with the optimal sensitivity (85.9%) and specificity (80.0%) values (area under curve, 0.904; 95% confidence interval, 0.852-0.957; P<0.001). The predictive value of ghrelin was bigger than that of serum adrenocorticotrophin hormone level (area under curve, 0.638; 95% confidence interval, 0.536-0.741; P=0.014) and age (area under curve, 0.638; 95% confidence interval, 0.536-0.741; P=0.014) for three-month cognitive deterioration after mTBI.