Overexpression of synuclein-γ predicts lack of benefit from radiotherapy for breast cancer patients.

BACKGROUND: Although radiotherapy following mastectomy was demonstrated to reduce the recurring risk and improve the prognosis of patients with breast cancer, it is also notorious for comprehensive side effects, hence only a selected group of patients can benefit. Therefore, the screening of molecular markers capable of predicting the efficacy of radiotherapy is essential. METHODS: We have established a cohort of 454 breast cancer cases and selected 238 patients with indications for postoperative radiotherapy. Synuclein-γ (SNCG) protein levels were assessed by immunohistochemistry, and SNCG status was retrospectively correlated with clinical features and survival in patients treated or not treated with radiotherapy. Gene Set Enrichment Analysis (GSEA) and survival analysis for online datasets were also performed for further validation. RESULTS: Among patients that received radiotherapy (82/238), those demonstrating positive SNCG expression had a 55.0 month shorter median overall survival (OS) in comparison to those demonstrating negative SNCG expression (78.4 vs. 133.4 months, log rank χ (2) = 16.13; p < 0.001). Among the patients that received no radiotherapy (156/238), SNCG status was not correlated with OS (log rank χ (2) = 2.40; p = 0.121). A COX proportional hazard analysis confirmed SNCG as an independent predictor of OS, only for patients who have received radiotherapy. Similar results were also obtained for distant metastasis-free survival (DMFS). A GSEA analysis indicated that SNCG was strongly associated with genes related to a radiation stress response. A survival analysis was performed with online databases consisting of breast cancer, lung cancer, and glioblastoma and further confirmed SNCG's significance in predicting the survival of patients that have received radiotherapy. CONCLUSION: A positive SNCG may serve as a potential marker to identify breast cancer patients who are less likely to benefit from radiotherapy and may also be extended to other types of cancer. However, the role of SNCG in radiotherapy response still needs to be further validated in randomized controlled trials prior to being exploited in clinical practice.

Efficacy of palonosetron for preventing postoperative nausea and vomiting: a systematic review and meta-analysis.

PURPOSE: Palonosetron, a second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA), has unique characteristics relative to first-generation 5-HT3RAs such as ondansetron. Nevertheless, it remains unclear if palonosetron is better than ondansetron for the prevention of nausea and vomiting during the first 24 hr after surgery and is thus the focus of this systematic review. METHODS: We conducted a systematic search of the MEDLINE®, EMBASE™, Cochrane Central Register of Controlled Trials and Web of Science® databases to identify randomized controlled trials (RCTs) that addressed a comparison of the prophylactic antiemetic efficacy between palonosetron and ondansetron within 24 hr after surgery. The primary outcomes were the proportion of participants who experienced postoperative nausea (PON), postoperative vomiting (POV), or both, in the early (0-6 hr) or late (6-24 hr) period. The pooled relative risks (RRs) were calculated along with their corresponding 95% confidence intervals (CIs). RESULTS: We identified nine RCTs that comprised 741 participants. Palonosetron was superior to ondansetron in the reduction of early PON [RR, 0.51; 95% CI, 0.37 to 0.71], late PON (RR, 0.53; 95% CI, 0.36 to 0.77), and late POV (RR, 0.41; 95% CI, 0.28 to 0.62), but not early POV (RR, 0.77; 95% CI, 0.45 to 1.34). CONCLUSION: Palonosetron provides more effective prophylaxis of early PON, late PON, and late POV compared with ondansetron. Future studies are required to investigate the role of palonosetron during 24-72 hr following surgery.

Study on the improvement of complexation efficiency and anti-digestibility of phenolic acids based on electrospun starch fibers.

Phenolic acids can be encapsulated by starch electrospun fibers, and the structural and functional properties of the electrospun fiber are affected by the chemical structure of phenolic acid. In this study, five phenolic acids (protocatechuic acid (PA), p-hydroxybenzoic acid (PHBA), p-coumaric acid (PCA), ferulic acid (FA), and caffeic acid (CA)) were chosen to prepare electrospun fibers with high amylose corn starch (HACS) at different voltages. Morphology and complexation efficiency results revealed that the electrospun fibers prepared at 21.0 kV were smooth and continuous with high encapsulation efficiency (EE) and loading efficiency (LE). The chemical structure of phenolic acid played an important role in the structure and properties of electrospun fibers by influencing the complexation of HACS with phenolic acids and the inhibitory effect of amylase. As a result, electrospun fibers containing HACS-CA inclusion complex had higher relative crystallinity (25.47 %), higher thermal degradation temperatures (356.17 °C), and the strongest resistance to digestion (starch digestive ratio = 22.98 %). It is evident that electrospun fibers containing HACS-phenolic acid inclusion complexes not only achieve high phenolic acid complexation efficiency, but also resist the effects of the gastric and small intestinal environment on phenolic acids, thereby improving the bioaccessibility of phenolic acids.

Effects of Processing on Starch Structure, Textural, and Digestive Property of "Horisenbada", a Traditional Mongolian Food.

Horisenbada, prepared by the soaking, steaming, and baking of millets, is a traditional Mongolian food and is characterized by its long shelf life, convenience, and nutrition. In this study, the effect of processing on the starch structure, textural, and digestive property of millets was investigated. Compared to the soaking treatment, steaming and baking significantly reduced the molecular size and crystallinity of the millet starch, while baking increased the proportion of long amylose chains, partially destroyed starch granules, and formed a closely packed granular structure. Soaking and steaming significantly reduced the hardness of the millets, while the hardness of baked millets is comparable to that of raw millet grains. By fitting digestive curves with a first-order model and logarithm of the slope (LOS) plot, it showed that the baking treatment significantly reduced the digestibility of millets, the steaming treatment increased the digestibility of millets, while the soaked millets displayed a similar digestive property with raw millets, in terms of both digestion rate and digestion degree. This study could improve the understanding of the effects of processing on the palatability and health benefits of Horisenbada.

Acid-Resistant Mesoporous Metal-Organic Frameworks as Carriers for Targeted Hypoglycemic Peptide Delivery: Peptide Encapsulation, Release, and Bioactivity.

Oral administration of bioactive peptides with α-glucosidase inhibitory activities is a promising strategy for diabetes mellitus. The wheat germ peptide Leu-Asp-Leu-Gln-Arg (LDLQR) has been previously proven to inhibit the activity of α-glucosidase efficiently. However, it is still difficult to transport the peptide to the intestine completely due to the harsh condition of the stomach. Herein, an acid-resistant zirconium-based metal-organic framework, NU-1000, was used to immobilize LDLQR with a high encapsulation capacity (92.72%) and encapsulation efficiency (44.08%) in only 10 min. The in vitro release results showed that the acid-stable NU-1000 not only effectively protected LDLQR from degradation in the presence of stomach acid and pepsin effectively but also ensured the release of encapsulated LDLQR under simulated intestinal conditions. Furthermore, LDLQR@NU-1000 could slow down the elevated blood sugar caused by maltose in mice and the area under blood sugar curve decreased by almost 20% when compared with the control group. The inflammatory factor (IL-1ß, IL-6) in vivo and cell growth in vitro were almost the same between NU-1000 treatment and normal control groups. This study indicates NU-1000 is a promising vehicle for targeted peptide-based bioactive delivery to the small intestine.

V6a-amylose helical cavity and benzoic acids with para-hydroxyl structure facilitate the formation of inclusion complex.

Benzoic acids are always unstable during thermal processing. Herein, effects of typical molecular structure of benzoic acids and V-amylose on the formation and thermostability of inclusion complexes were investigated. Interestingly, the helical structure of six V-amylose transformed to V6a-amylose after complexing with four benzoic acids. Encapsulation efficiency (EE) and loading efficiency (LE) results presented that gentisic acid (DA) complexed with V6a-amylose achieving the highest EE of 79.76 % and LE of 7.25 %. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results demonstrated that DA, protocatechuic acid (PA), and gallic acid (GA) formed VI inclusion complexes with V-amylose, especially V6a-amylose-DA inclusion complexes with the highest crystallinity, while p-hydroxybenzoic acid (PHBA) was difficult to complex with V-amylose. Moreover, V6a-amylose-DA inclusion complexes showed the highest capacity in protecting the antioxidant activity from thermal processing. This suggested both V6a-amylose helical cavity and benzoic acids with para-hydroxyl structure facilitated the formation of thermostable inclusion complexes.

Ozonated autohemotherapy modulates the serum levels of inflammatory cytokines in gouty patients.

OBJECTIVES: Ozonated autohemotherapy (O3-AHT) has been used to effectively treat gout, but the underlying therapeutic mechanisms remain unknown. In this study, as an initial effort to understand the therapeutic mechanisms of O3-AHT, we aim to examine the effect of O3-AHT on serum inflammatory cytokine levels in gouty patients. PATIENTS AND METHODS: Three groups of patients and healthy subjects were recruited, including the gouty (n=10), hyperuricemia (n=10), and healthy control (n=11) groups. Cytometric bead array was applied to examine 12 cytokines before (T0), during (T1), and after (T2) therapies. RESULTS: Three cytokines, IL-8, IL-12, and MCP-1, were detectable in all participants. Before O3-AHT, the average serum levels of IL-8 and MCP-1 were higher in the gout group than in the hyperuricemia and healthy control groups, confirming the inflammation status in gouty patients. After the 5th course of O3-AHT (T1), IL-8 level was significantly increased compared to that at T0. IL-12 level was also raised at T1, although the difference did not reach statistical significance. After completing the therapy, both IL-8 and IL-12 levels decreased to levels lower than those at T0. MCP-1 level remained essentially unchanged during and after treatment. CONCLUSION: Our results indicate that O3-AHT induces a significant change in serum cytokine levels, suggesting that modulating the inflammatory process is one of the therapeutic mechanisms underlying O3-AHT. In addition, the sensitive response of serum IL-8 and IL-12 levels to O3-AHT suggests that these cytokines may be developed as biomarkers to evaluate the therapeutic effect of O3-AHT in gouty patients.

Combined expression of metastasis related markers Naa10p, SNCG and PRL-3 and its prognostic value in breast cancer patients.

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3- subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+ subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients.

Coexpression of ANXA2, SOD2 and HOXA13 predicts poor prognosis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer, and is the sixth leading cause of cancer-related mortality among all types of cancers. Previously, we found that the homeobox A13 gene (HOXA13) plays a crucial role in the carcinogenesis of ESCC and both Annexin A2 (ANXA2) and superoxide dismutase 2 (SOD2) were its potential targets. Samples from 258 patients from two independent cohorts were collected. RT-qPCR and immunohistochemistry (IHC) were used to detect the expression levels of HOXA13, ANXA2 and SOD2. Kaplan­Meier survival curve analysis and Cox proportional hazards regression model were employed to determine their prognostic significance. Results showed that ESCC tissues had higher ANXA2 and SOD2 mRNA and protein levels than the non-cancerous tissues. ANXA2 and SOD2 were found to be positively correlated with HOXA13 expression not only at the mRNA level but also at the protein level. In both the study cohort and the validation cohort, the median overall survival time of patients with high expression of HOXA13, ANXA2 and SOD2 was shorter than the survival time of the patients with low expression. The Cox proportional hazards model revealed that both TNM stage and coexpression of HOXA13/ANXA2/SOD2 are independent predictors of overall survival of ESCC patients. In conclusion, the present study demonstrated that ANXA2 and SOD2 are potential target genes of HOXA13 and their coexpression predicts the poor prognosis of ESCC patients.

N-acetyltransferase 2 phenotype and risk of esophageal cancer: a meta analysis.

N-acetyltransferase 2 (NAT2) gene encodes a phase II enzyme taking part in detoxification of aromatic amines. Published studies have demonstrated that N-Acetyltransferase 2 (NAT2) phenotype is a risk factor of various cancers. Many studies have investigated the association between NAT2 phenotype and susceptibility to esophageal cancer but yielded controversial results. To derive a more precise estimation of this association, a meta-analysis was performed. Electronic databases (Pubmed/Medline, ISI Web of Science and China National Knowledge Infrastructure) in English and Chinese were searched. A total of 5 articles including 476 cases and 1,093 controls were included in this meta-analysis. Odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate intensity of associations. Pooling studies together, NAT2 slow acetylator phenotype was a significant risk factor of esophageal squamous cell cancer (OR=1.35, 95% CI=1.03-1.77, n=5 studies) but not esophageal adenocarcinoma (OR=0.97, 95% CI=0.47-2.04, n=2 studies). There was a significant association between NAT2 acetylator phenotypes and ESCC in South Asian populations (OR=1.51, 95% CI=1.03-2.20), but not in East Asian populations (OR=1.19, 95% CI=0.80-1.77). Significant association between NAT2 acetylator phenotypes and esophageal cancer was found in population-based control subgroup (OR=1.63, 95% CI=1.07-2.50) but not in hospital-based control subgroup (OR=1.19, 95% CI=0.84-1.69). There is a significant association between NAT2 acetylator phenotype and esophageal cancer in both smokers (OR=1.681, 95% CI=1.179-2.395) and non-smokers (OR=1.614, 95% CI=1.173-2.222). In conclusion, NAT2 slow acetylator phenotype was a significant risk factor of ESCC in Asian populations.