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Abstract Objective To analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury. Method A total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was

Abstract Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness.

Ampelopsis grossedentata is a flavonoid-rich healthy tea, traditionally used as a Chinese herbal medicine, that effectively treats T2DM. In the present study, we investigated the anti-diabetic effect of total flavonoids extracted from Ampelopsis grossedentata (AGT) and the underlying mechanisms using 16S rDNA sequencing and metabolomics. The results indicated that after AGT treatment for 6 weeks, the body weight, liver index, fasting blood glucose (FBG), OGTT-AUC, and serum lipid levels were reduced, and pathological injuries of the liver improved significantly in ZDF rats. Meanwhile, AGT increased the abundance and diversity of gut microbiota, especially BSH-active bacteria, which reduced T-β-MCA and T-α-MCA levels and further activate FXR and FGF15. The activation of FXR-FGF15 axis inhibited excessive bile acid accumulation and liver gluconeogenesis upon AGT treatment. Taken together, our results suggested that AGT ameliorated glycolipid metabolism disorder via the “microbiota-gut-liver” axis, indicating that AGT may be a potential therapeutic strategy for treating T2DM.

Abstract Background Recent studies have indicated that a ketogenic diet can be used as an adjuvant therapy to enhance sensitivity to chemotherapy and radiotherapy in cancer patients. However, there are no sufficient data and no consistent international treatment guidelines supporting a ketogenic diet as an adjuvant therapy for metastatic breast cancer. Therefore, this trial was designed to observe whether irinotecan with a ketogenic diet can promote sensitivity to chemotherapy and remit target lesions in locally recurrent or metastatic Her-2-negative breast cancer patients. Methods/design This trial aims to recruit 518 women with locally recurrent or metastatic breast cancer admitted to the Liaoning Cancer Hospital and Institute (Shenyang, China) in northeast China. All patients will be randomly assigned into the combined intervention group (n = 259) or the control group (n = 259), followed by treatment with irinotecan + ketogenic diet or irinotecan + normal diet, respectively. The primary endpoints are sensitivity to irinotecan and the objective response rate of target lesions; the secondary endpoints include quality of life scores (EORTC QLQ-C30), progression-free survival, overall survival time, incidence of adverse events, and cost-effectiveness. The endpoints will be evaluated at baseline (before drug administration), during treatment, 4 weeks after treatment completion, and every 3months (beginning 2 months after treatment completion). Discussion This trial attempts to investigate whether irinotecan treatment with a ketogenic diet for locally recurrent or metastatic breast cancer among women in northeast China can enhance the disease’s sensitivity to chemotherapy and reduce target lesions. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR1900024597 . Registered on 18 July 2019. Protocol Version: 1.1, 24 February 2017.

Session Initiation Protocol (SIP) is the most widely used signalling protocol for controlling communication, establishing, maintaining, and terminating sessions on the Internet. However, since sensitive information is often transmitted through open channels, a security authentication scheme is essential. Recently, Islam et al. proposed an authentication scheme for SIP, and argued that the scheme is immune to known attacks. However, we discover that their scheme fails to achieve user anonymity, and it cannot even resist impersonation attack. Therefore, this study proposes an enhanced mutual authentication scheme to eliminate the drawbacks of the scheme proposed by Islam et al. In addition, our proposed scheme is based on extended chaotic map, which avoids computationally expensive elliptic curve point multiplication. Then, we use Burrows-Abadi-Needham logic to prove that the proposed scheme achieves secure mutual authentication, and we use the Real-Or-Random model to analyze the formal security verification of the session key. Finally, we compare the performance and the security features of the proposed scheme with some existing schemes. Therefore, we provide better safety and efficiency than related schemes and the proposed scheme is suitable for SIP.

Abstract Background Gastric cancer is the second most common cause of cancer-related mortality; thus, the mechanisms underlying tumor metastasis and growth in gastric cancer need to be extensively explored. Methods Differentially expressed genes were examined in gastric cancer samples with lymph node metastasis (LNM) and without LNM using mRNA microarray and RT-qPCR. The effects of G antigen 7B (GAGE7B) on the metastasis, growth, and angiogenesis of gastric cancer were investigated in vitro and in vivo. GAGE7B protein expression was detected by immunohistochemical (IHC) analysis. Microarray, RT-qPCR, and western blot assays were performed to detect downstream target genes of GAGE7B. Dual-luciferase reporter and western blot assays were used to identify miRNAs that could negatively regulate GAGE7B. Results GAGE7B was significantly overexpressed in samples with LNM. High expression levels of GAGE7B were associated with advanced clinical stage and poor patient survival. GAGE7B dramatically enhanced the metastasis, growth, and angiogenesis ability of gastric cancer. GAGE7B was further demonstrated to promote the progression of gastric cancer by activating the p38δ/pMAPKAPK2/pHSP27 pathway. However, the GAGE7B-induced p38δ/pMAPKAPK2/pHSP27 pathway was inactivated by miR-30c, as the expression levels of both GAGE7B and p38δ were found to be directly suppressed by miR-30c. Intriguingly, GAGE7B was found to be a ceRNA for p38δ, as it activated the p38δ/pMAPKAPK2/pHSP27 pathway by competitively binding miR-30c. Conclusions GAGE7B may serve as a prognostic indicator in gastric cancer. GAGE7B significantly promotes gastric cancer progression by upregulating the p38δ/pMAPKAPK2/pHSP27 pathway, but it is negatively regulated by miR-30c. GAGE7B and miR-30c may be potential therapeutic targets in gastric cancer.

The objectives of this study were to estimate genetic parameters of lactation average somatic cell scores (LSCS) and examine genetic associations between LSCS and production traits in the first three lactations of Chinese Holstein cows using single-parity multi-trait animal model and multi-trait repeatability animal model. There were totally 273 605 lactation records of Chinese Holstein cows with first calving from 2001 to 2012. Heritability estimates for LSCS ranged from 0.144 to 0.187. Genetic correlations between LSCS and 305 days milk, protein percentage and fat percentage were −0.079, −0.082 and −0.135, respectively. Phenotypic correlation between LSCS and 305 days milk yield was negative (−0.103 to −0.190). Genetic correlation between 305 days milk and fat percentage or protein percentage was highly negative. Genetic correlation between milk fat percentage and milk protein percentage was highly favorable. Heritabilities of production traits decreased with increase of parity, whereas heritability of LSCS increased with increase of parity.

The protocadherin 7 is a member of the protocadherin family that expressed aberrantly in many types of human cancers. However, its expression, function, and underlying mechanisms are little known in gastric cancer. In this study, we detected protocadherin 7 expression in gastric cancer tissues and non-tumorous gastric mucosa tissues by real-time quantitative polymerase chain reaction and immunohistochemistry. The association of protocadherin 7 expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) and transwell assays were performed to assess the effect of protocadherin 7 on proliferation, migration, and invasion in gastric cancer cell lines. Moreover, real-time quantitative polymerase chain reaction and western blot were used to detect the expression of epithelial–mesenchymal transition markers. Protocadherin 7 expression was decreased gradiently from normal tissue to gastric cancer, especially in gastric cancer tissue with lymph node metastasis. Low expression of protocadherin 7 was significantly associated with Lauren’s classification ( p = 0.0005), lymph node metastases ( p = 0.0002), and tumor node metastasis stage ( p = 0.0221), as well as poor prognosis ( p 0.05). Additionally, our results demonstrated that E-cadherin expression was down-regulated in gastric cancer cells with protocadherin 7 depletion. Our data indicated that protocadherin 7 may play important roles in the invasion and metastasis of gastric cancer, and protocadherin 7 could suppress cell migration and invasion through E-cadherin inhibition. Protocadherin 7 can serve as a novel biomarker for diagnostic and prognosis in patients with gastric cancer.

Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Currently, there are no therapies available that can delay, stop, or reverse the pathological progression of NDs in clinical settings. As the population ages, NDs are imposing a huge burden on public health systems and affected families. Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments. While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms, the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap. Old World nonhuman primates (NHPs), such as rhesus, cynomolgus, and vervet monkeys, are phylogenetically, physiologically, biochemically, and behaviorally most relevant to humans. This is particularly evident in the similarity of the structure and function of their central nervous systems, rendering such species uniquely valuable for neuroscience research. Recently, the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms. This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained, as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis. [ABSTRACT FROM AUTHOR]

Objective To study the use of traditional Chinese medicine (TCM) or both TCM and guideline-recommended Western medicine (WM) in Chinese patients with coronary heart disease (CHD). Methods A cross-sectional nationwide survey of 2803 CHD outpatients was completed by collecting information, including general demographic data, disease history, and use of drugs (including TCM and WM). Results Of the 2712 CHD outpatients with complete drug treatment data, only 3.1% received TCM without any WM for CHD, 30.0% received both TCM and WM recommended by current CHD guidelines, and 66.9% received only WM. Patients with a longer history of CHD or with a history of stroke, were more likely to use TCM. However, 90.6% of CHD patients who used TCM also used certain WM. Furthermore, patients who used more types of TCM tended to use much less WM recommended by current guidelines. Conclusion A substantial proportion of Chinese CHD outpatients use both TCM and WM for secondary prevention of CHD. It is important to assess the effect of combined TCM and WM on major clinical outcomes in Chinese CHD patients. [ABSTRACT FROM AUTHOR]