Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Hypoxia-inducible factor 1α activates the NLRP3 inflammasome to regulate epithelial differentiation in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is an upper airway inflammation disease associated with hypoxia-mediated inflammation. The effect of hypoxia-inducible factor 1α (HIF-1α) on NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in the pathogenesis of sinonasal mucosa is unclear. OBJECTIVE: We investigated the effect and mechanism of HIF-1α on NLRP3 inflammasome activation in the primary human nasal epithelial cells (hNECs). METHODS: We measured the expression levels of HIF-1α and the NLRP3 inflammasome in nasal biopsy samples and hNECs derived from negative controls (healthy) and patients with CRS with and without nasal polyps, then further analyzed the specific mechanism of HIF-1α regulation of the NLRP3 inflammasome and its effect on hNEC differentiation. RESULTS: Increased mRNA and protein expression levels of HIF-1α and the NLRP3 inflammasome were found in all CRS biopsy samples. HIF-1α enhanced expression of phosphorylated NLRP3 (S295) in both HEK293T cells and hNECs; it also promoted recruitment of caspase-1 and apoptotic speck-like protein containing caspase recruitment domain (aka ASC) by NLRP3. HIF-1α also improved NLRP3's stability by preventing NLRP3 degradation caused by hypoxia-mediated inflammation. In addition, HIF-1α could also increase expression of Mucin5AC and decrease expression of α-tubulin by promoting activation of the NLRP3 inflammasome in hNECs. In addition, HIF-1α could also directly promote P63 expression in hNECs. CONCLUSION: HIF-1α could potentially induce cilia loss and enhance the proliferation of goblet cells, possibly mediated by the regulation of NLRP3 phosphorylation in CRS inflammation.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

Asiatic acid re-sensitizes multidrug-resistant A549/DDP cells to cisplatin by down regulating long non-coding RNA metastasis associated lung adenocarcinoma transcript 1/ß-catenin signaling.

Drug resistance becomes a challenge in the therapeutic management of non-small cell lung cancer (NSCLC). According to our former research, asiatic acid (AA) re-sensitized A549/DDP cells to cisplatin (DDP) through decreasing multidrug resistance protein 1 (MDR1) expression level. However, the relevant underlying mechanisms are still unclear. Long non-coding RNA (lncRNA) MALAT1 shows close association with chemo-resistance. As reported in this research, AA increased apoptosis rate, down regulated the expression of MALAT1, p300, ß-catenin, and MDR1, up regulated the expression of miR-1297, and decreased ß-catenin nuclear translocation in A549/DDP cells. MALAT1 knockdown expression abolished the drug resistance of A549/DDP cells and increased cell apoptosis. MALAT1 could potentially produce interactions with miR-1297, which targeted to degradation of p300. In addition, p300 overexpression effectively rescued the effects of MALAT1 knockdown expression on A549/DDP cells and activate the expression of ß-catenin/MDR1 signaling, and these could be effectively blocked by AA treatment. Conclusively, AA could re-sensitize A549/DDP cells to DDP through down-regulating MALAT1/miR-1297/p300/ß-catenin signaling.

RP1-59D14.5 triggers autophagy and represses tumorigenesis and progression of prostate cancer via activation of the Hippo signaling pathway.

Prostate cancer (PCa) is one of the major malignant tumors among men worldwide. Long noncoding RNAs (lncRNAs) have been documented as important modulators in human cancers, including PCa. In our study, we investigated the role and potential mechanism of RP1-59D14.5 in PCa. RP1-59D14.5 expressed at a low level in PCa cells. Gain-of-function assays including colony formation and transwell assays displayed that RP1-59D14.5 overexpression repressed PCa cell proliferation, migration, and invasion. Besides, RP1-59D14.5 up-regulation induced autophagy in PCa cells. Mechanically, luciferase reporter assays and western blot verified that RP1-59D14.5 activated the Hippo pathway in PCa cells. Through RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we validated that RP1-59D14.5 functioned as a competing endogenous RNA (ceRNA) to regulate large tumor suppressor kinase 1/2 (LATS1/2) via targeting miR-147a. Moreover, RP1-59D14.5 recruited HUR to promote casein kinase 1 (CK1) expression. Collectively, RP1-59D14.5 promoted yes-associated protein (YAP) degradation to activate the Hippo pathway in PCa progression via targeting the miR-147a/LATS1/2 axis and recruiting HUR to promote the interaction of CK1 and ß-transducin repeat-containing protein (ßTrCP). These results implied that RP1-59D14.5 acted as a tumor suppressor in PCa, which might be a target for PCa treatment.

The role of hypoxia in the pathophysiology of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal cavity characterized by excessive nasal mucus secretion and nasal congestion. The development of CRS is related to pathological mechanisms induced by hypoxia. Under hypoxic conditions, the stable expression of both Hypoxia inducible factor-1 (HIF-1) α and HIF-2α are involved in the immune response and inflammatory pathways of CRS. The imbalance in the composition of nasal microbiota may affect the hypoxic state of CRS and perpetuate existing inflammation. Hypoxia affects the differentiation of nasal epithelial cells such as ciliated cells and goblet cells, induces fibroblast proliferation, and leads to epithelial-mesenchymal transition (EMT) and tissue remodeling. Hypoxia also affects the proliferation and differentiation of macrophages, eosinophils, basophils, and mast cells in sinonasal mucosa, and thus influences the inflammatory state of CRS by regulating T cells and B cells. Given the multifactorial nature in which HIF is linked to CRS, this study aims to elucidate the effect of hypoxia on the pathogenic mechanisms of CRS.

Chinese Medicine Formula Siwu-Yin Inhibits Esophageal Precancerous Lesions by Improving Intestinal Flora and Macrophage Polarization.

Siwu-Yin (SWY), a traditional Chinese medicinal formula, can replenish blood and nourish Yin. It was recorded in ancient Chinese medicine books in treating esophageal dysphagia, which has similar symptoms and prognosis with esophageal precancerous lesions and esophageal cancer. However, its effect has not been established in vivo. This study explores the antiesophageal cancer effect of SWY on rats with esophageal precancerous lesions. By performing 16S rRNA gene sequencing and metabolomics, it was suggested that SWY may improve the composition of intestinal flora of rats by regulating the synthesis and secretion of bile acids. In addition, flow cytometry results showed that SWY treatment modified tumor microenvironment by improving macrophage polarization and therefore inhibiting the occurrence of esophageal precancerous lesions.

Molecular classification of patients with NMIBC predicts the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine-immunohistochemistry-based classification.

OBJECTIVE: To investigate the relationships between non-muscle invasive bladder cancer molecular subtypes and predict the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine. METHODS: A total of 160 patients with T1 stage non-muscle invasive bladder cancer were enrolled in this study. Fifty-three patients underwent anthracycline (Pirarubicin and Pharmorubicin) therapy and 107 patients accepted gemcitabine therapy. Uroplakin II and CK20 were categorized as immunohistochemistry (IHC) markers for luminal subtype, whereas CK5/6 and CD44 were categorized as immunohistochemistry markers for basal subtype. The cluster results with immunohistochemical score indicated that non-muscle invasive bladder cancer can be subgrouped into three major classes. RESULTS: Class 2 showed the luminal-like characteristics, whereas class 3 showed the basal-like characteristics. Class 1 showed no high expression of luminal or basal-associated immunohistochemistry markers. The molecular subtype is an independent risk factor for recurrence-free survival (P = 0.030) and progression-free survival (P = 0.006) in patients with T1 stage non-muscle invasive bladder cancer. In class 1 and class 2 (luminal-like) subtypes, gemcitabine and anthracycline show no difference in recurrence-free survival and progression-free survival. Gemcitabine was associated with reduced recurrence compared with anthracycline (P = 0.039) in class 3 (basal-like) subtypes and show no difference in decreasing progression. CONCLUSIONS: The molecular classification based on immunohistochemical results is an independent risk factor for the prognosis of non-muscle invasive bladder cancer with T1 stage. Different therapeutic methods should be selected according to different molecular subtypes.

LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression.

Breast cancer (BC) is a malignant disease and the most commonly diagnosed cancer in women. Numerous studies have previously verified the important role of long non-coding RNAs in a number of biological processes in BC. In the present study, analysis of The Cancer Genome Atlas database and reverse transcription-quantitative PCR demonstrated that LOC102724163 expression levels were significantly upregulated in BC tissues compared to matched adjacent normal tissues and were associated with an unfavorable prognosis in patients with BC. Gain or loss of function assays indicated that overexpression of LOC102724163 significantly increased tumorgenicity in vivo and cell migration, proliferation and invasion in vitro. In the mechanistical aspect, LOC102724163 sponged microRNA (miR)-508-5p to elevate MUC19 expression. Additionally, rescue assays ascertained the function of the LOC102724163/miR-508-5p/MUC19 axis in the proliferation and invasion of BC cells. To the best of our knowledge, this is the first study to have demonstrated that LOC102724163 may act as a competing endogenous RNA to control MUC19 expression levels by competitively sponging miR-508-5p to modulate BC progression. Therefore, the present study has provided new insights into BC diagnosis and treatment.

Worldwide review with meta-analysis of women's awareness about breast cancer.

OBJECTIVE: To summarize the awareness levels of breast cancer (BC) worldwide and investigate factors associated with BC awareness to determine differences in awareness between China and other countries. METHODS: This systematic review followed the PRISMA guidelines and included 92 articles up to July, 2021. We calculated percentages for BC awareness levels and conducted subgroup analysis and cumulative meta-analysis. RESULTS: A total 84% (95% confidence interval [95%CI]: 78-90%) of women knew about BC; however, only 51% (95%CI: 37-66%) and 40% (95%CI: 24-56%) of women were aware of BC symptoms and BC risk factors, respectively. The most commonly known BC symptom was breast lump (71%, 95%CI: 62-80%), and BC family history was the most well-known BC risk factor (61%, 95%CI: 54-69%). Subgroup analysis showed lower awareness levels among Chinese and Asian women than women from other countries. Cumulative meta-analysis showed no obvious progress in BC awareness levels over time. We investigated 15 awareness-related factors, the most frequent of which were education level (61.8%), occupation (29.4%), and age (26.5%). CONCLUSION: BC awareness levels remain low. Improving BC awareness is critical, especially in developing countries. PRACTICE IMPLICATIONS: Effective education programs are urgently needed to improve women's BC awareness.

Machine Learning Model in Predicting Sarcopenia in Crohn's Disease Based on Simple Clinical and Anthropometric Measures.

Sarcopenia is associated with increased morbidity and mortality in Crohn's disease. The present study is aimed at investigating the different diagnostic performance of different machine learning models in identifying sarcopenia in Crohn's disease. Patients diagnosed with Crohn's disease at our center provided clinical, anthropometric, and radiological data. The cross-sectional CT slice at L3 was used for segmentation and the calculation of body composition. The prevalence of sarcopenia was calculated, and the clinical parameters were compared. A total of 167 patients were included in the present study, of which 127 (76.0%) were male and 40 (24.0%) were female, with an average age of 36.1 ± 14.3 years old. Based on the previously defined cut-off value of sarcopenia, 118 (70.7%) patients had sarcopenia. Seven machine learning models were trained with the randomly allocated training cohort (80%) then evaluated on the validation cohort (20%). A comprehensive comparison showed that LightGBM was the most ideal diagnostic model, with an AUC of 0.933, AUCPR of 0.970, sensitivity of 72.7%, and specificity of 87.0%. The LightGBM model may facilitate a population management strategy with early identification of sarcopenia in Crohn's disease, while providing guidance for nutritional support and an alternative surveillance modality for long-term patient follow-up.

Comparison between anterolateral thigh free flap and jejunal flap for tissue reconstruction in patients underwent resection of pharyngoesophageal squamous cell carcinoma after radiotherapy failure: a retrospective study.

BACKGROUND: Anterolateral thigh (ALT) free flap and jejunal flap (JF) were commonly used in tissue reconstruction for pharyngoesophageal squamous cell carcinoma (PESCC) with worsening tissue adhesion and necrosis after radiotherapy failure. However, the results of tissue reconstruction and postoperative complications of these two flaps are controversial. The purpose of this study was to compare outcomes between group ALT free flap and group JF in PESCC after radiotherapy failure. METHODS: Intraoperative information and postoperative outcomes of patients with PESCC after radiotherapy failure who underwent ALT and JF reconstruction from January 2005 to December 2019 were compared and analyzed. RESULTS: The defect size of ALT (Numbers, 34) and JF (Numbers, 31) was 36.19 ± 11.35 cm2 and 35.58 ± 14.32 cm2 (p = 0.884), respectively. ALT and JF showed no significant difference in operation time (p = 0.683) and blood loss (p = 0.198). For postoperative outcomes within 30 days both in recipient site and donor site including wound bleeding, wound dehiscence, wound infection, and pharyngocutaneous fistula, ALT free flap and JF showed similar results. Flap compromise (Numbers, 2 VS.3, p = 0.663), flap take backs (Numbers, 1 VS.1, p = 1.000), partial flap failures (Numbers, 4 VS.2, p = 0.674), and total flap failures (Numbers, 0 VS.0, p = 1.000) showed no difference between the two groups. In addition, no significance was found in hypoproteinemia between the two groups (Numbers, 4 VS.2, p = 0.674). ALT free flap was not statistically different from JF in the incidence of dysphagia at the postoperative 6 months (Numbers of liquid diet, 5VS.5; Numbers of partial tube feeding, 6VS.7; Numbers of total tube feeding, 3VS.1, p = 0.790) and 12 months (Numbers of liquid diet, 8VS.7; Numbers of partial tube feeding, 8VS.7; Numbers of total tube feeding, 5VS.5, p = 0.998). The cause of dysphagia not found to differ between the two groups both in postoperative 6 months (p = 0.814) and 12 months (p = 0.845). CONCLUSION: Compared with JF, ALT free flap for PESCC patients after radiotherapy failure showed similar results in postoperative outcomes. ALT free flap may serve as a safe and feasible alternative for PESCC patients after radiotherapy failure.

Up-Regulation of LINC00665 Facilitates the Malignant Progression of Prostate Cancer by Epigenetically Silencing KLF2 Through EZH2 and LSD1.

This study aimed to explore the function of LINC00665 on the proliferation and metastasis of prostate cancer (PCa), and the potential regulatory mechanisms were also investigated. The expression level of LINC00665 in 50 pairs of PCa tissues and adjacent ones was studied by qRT-PCR, and the associations between LINC00665 and clinicopathological characteristics of PCa patients were analyzed. Control group (sh-NC) and LINC00665 knock-down group (sh-LINC00665) were set in 22RV1 and DU145 cells, respectively. The biological functions of LINC00665 in PCa cell lines were assessed by CCK-8, EdU, Transwell assays, and the nude mouse xenograft model was used to evaluate the tumorigenicity in vivo. In addition, qRT-PCR, Western Blot, RIP and ChIP assays were also used to determine the regulation mechanism of LINC00665 in PCa cell lines. In this study, our results showed that LINC00665 expression level in PCa cancer tissues was significantly up-regulated, compared with that in adjacent ones. Besides, similar results were found in PCa cell lines. Knock-down of LINC00665 significantly attenuated the proliferation and migration ability in 22RV1 and DU145 cells, compared to sh-NC. Mechanically, LINC00665 could interact with EZH2 and LSD1, recruiting them to KLF2 promoter region to inhibit its transcription. Moreover, the tumor-suppressive effects mediated by sh-LINC00665 were significantly reversed through the down-regulation of KLF2. Also, the suppression of LINC00665 impaired tumor growth of PCa in vivo. In summary, LINC00665 exerted the oncogenic functions in PCa cell lines by epigenetically silencing KLF2 expression by binding to EZH2 and LSD1, illuminating a novel mechanism of LINC00665 in the malignant progression of PCa and furnishing a prospective therapeutic biomarker to combat PCa.

Elevated microRNA-21 Is a Brake of Inflammation Involved in the Development of Nasal Polyps.

Background: CRSwNP is an inflammatory disease but the mechanism is not yet fully understood. MiR-21, a member of miRNAs, has been reported to play roles in mediating inflammation. However, the expression of miR-21 and its role in patients with CRSwNP remain elusive. Methods: Turbinates from control subjects, uncinate processes from CRSsNP, polyp tissues from CRSwNP, and nasal epithelial cells brushed from nasal mucosa were collected. The expression of miR-21 and cytokines in nasal tissues and epithelial cells were detected by qPCR. The localization of miR-21 was detected by ISH, and its target was identified by bioinformation analysis, qPCR, IHC, WB, and luciferase reporter system. The protein and mRNA of PDCD4 and NF-κB P65 were determined by WB and qPCR after miR-21 transfection in HNEpC. The role of miR-21 on cytokines was analyzed in HNEpC and nasal polyp explants. Results: MiR-21 was upregulated in CRSwNP relative to control subjects by qPCR, which was determined mainly in nasal epithelial cells of CRSwNP by ISH. Both pro-inflammation cytokines (IL-1ß, IL-6, IL-8, IL-25, and TSLP) and a suppressive cytokine (IL-10) were overexpressed in the epithelial cells of CRSwNP. The expression of miR-21 was positively correlated with IL-10 and negatively correlated with IL-6, IL-8, IL-33, and TSLP in the epithelial cells of CRSwNP. As a potential target of miR-21, the expression of PDCD4 was negatively correlated with miR-21 in CRSwNP. In HNEpC, miR-21 could reduce the expression of PDCD4 at both mRNA and protein levels, and bioinformation analysis and luciferase reporter system confirmed PDCD4 as one target of miR-21. Furthermore, miR-21 could decrease the activation of NF-κB and increase IL-10 mRNA. Both SEB and LPS could elevate miR-21, with IL-25, IL-33, TSLP induced by SEB and IL-1ß, IL-6, IL-8 induced by LPS, while the miR-21 could regulate the expression of IL-33, TSLP, IL-1ß, IL- 6 and IL-8 in vitro and ex vivo. Clinically, miR-21 expression was inversely correlated with the Lund-Mackay CT scores and the Lund-Kennedy scores in CRSwNP. Conclusion: MiR-21 could be a prominent negative feedback factor in the inflammation process to attenuate the expression of pro-inflammatory cytokines, thereby playing an anti-inflammation role in CRSwNP.

Introducing frequency representation into convolution neural networks for medical image segmentation via twin-Kernel Fourier convolution.

BACKGROUND AND OBJECTIVE: For medical image segmentation, deep learning-based methods have achieved state-of-the-art performance. However, the powerful spectral representation in the field of image processing is rarely considered in these models. METHODS: In this work, we propose to introduce frequency representation into convolution neural networks (CNNs) and design a novel model, tKFC-Net, to combine powerful feature representation in both frequency and spatial domains. Through the Fast Fourier Transform (FFT) operation, frequency representation is employed on pooling, upsampling, and convolution without any adjustments to the network architecture. Furthermore, we replace original convolution with twin-Kernel Fourier Convolution (t-KFC), a new designed convolution layer, to specify the convolution kernels for particular functions and extract features from different frequency components. RESULTS: We experimentally show that our method has an edge over other models in the task of medical image segmentation. Evaluated on four datasets-skin lesion segmentation (ISIC 2018), retinal blood vessel segmentation (DRIVE), lung segmentation (COVID-19-CT-Seg), and brain tumor segmentation (BraTS 2019), the proposed model achieves outstanding results: the metric F1-Score is 0.878 for ISIC 2018, 0.8185 for DRIVE, 0.9830 for COVID-19-CT-Seg, and 0.8457 for BraTS 2019. CONCLUSION: The introduction of spectral representation retains spectral features which result in more accurate segmentation. The proposed method is orthogonal to other topology improvement methods and very convenient to be combined.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Purified anthocyanins from Zea mays L. cob ameliorates chronic liver injury in mice via modulating of oxidative stress and apoptosis.

BACKGROUND: Purple corn (Zea mays L.) is one of the main economic crops in China and has been used in the treatment of cystitis, urinary infections and obesity. However, purple corncobs, the by-product remaining after processing and having an intense purple-black color, are normally disposed of as waste or used as animal feed. Therefore, to further expand the medicinal value of purple corncob, its content was analyzed and, after purification, the effect and mechanism of purified purple corncob anthocyanins (PPCCA) on CCl4 -induced chronic liver injury in mice were investigated. RESULTS: It was observed that the total anthocyanin content (TAC) from PPCCA (317.51 ± 9.30 mg cyanidin 3-O-glucoside (C-3-G) g-1 dry weight) was significantly higher than that from the purified purple corn seed anthocyanin (266.73 ± 3.67 mg C-3-G g-1 dry weight), of which C-3-G accounted for 90.6% and 90.4% of the TAC, respectively. Furthermore, compared with the CCl4 group, PPCCA treatment significantly reduced liver index, serum total bilirubin, alanine transaminase, aspartate transaminase and liver malondialdehyde levels, but increased liver superoxide dismutase activity. The pathological changes were also improved, such as more regular arrangement of hepatocytes, less swelling, and fewer vacuoles and apoptotic cells. Additionally, mechanistic studies showed that PPCCA downregulated the expression of Caspase-3, Bax and cytochrome P450 2E1 proteins in the liver and upregulated the expression of Bcl-2. CONCLUSION: These results demonstrated that PPCCA could ameliorate CCl4 -induced chronic liver injury by regulating oxidative stress and hepatocyte apoptosis pathways. © 2021 Society of Chemical Industry.