Abstract Recurrent miscarriage (RM) seriously affects the physical and mental health of women of childbearing age, and 50% of the causes are unknown. Thus, it is valuable to investigate the causes of unexplained recurrent miscarriage (uRM). Similarities between tumor development and embryo implantation make us realize that tumor studies are informative for uRM. The non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1) is highly expressed in some tumors, and can promote tumor growth, invasion and migration. In this present paper, we firstly explore the role of NCK1 in uRM. We find that the NCK1 and PD-L1 are greatly reduced in peripheral blood mononuclear cells (PBMC) and decidua from patients with uRM. Next, we construct NCK1-knockdown HTR-8/SVneo cells, and find that NCK1-knockdown HTR-8/SVneo cells exhibit reduced proliferation and migration ability. Then we demonstrate that the expression of PD-L1 protein is decreased when the NCK1 is knocked down. In co-culture experiments with THP-1 and differently treated HTR-8/SVneo cells, we observe significantly increased proliferation of THP-1 in NCK1-knockdown group. In conclusion, NCK1 may be involved in RM by regulating trophoblast proliferation, migration, and regulating PD-L1-mediated macrophage proliferation at the maternal-fetal interface. Moreover, NCK1 has the potential to be a new predictor and therapeutic target.

Abstract Chronic inflammation plays a key role in the development and progression of several chronic diseases. Inhibiting the inflammatory cascade, thereby minimising the damage caused by the inflammatory mediators, can be one of the strategies in chronic disease management. In addition, inflammation is closely related to apoptosis, and inflammation can cause apoptosis. Lemon peel has been reported to have antioxidant and anti-inflammatory biological activities. This study aimed to investigate the antioxidant activity of fermented lemon peel (FLP) by Lactobacillus plantarum PNU and the effect of its extract (FLPE) on LPS-induced inflammatory response in RAW 264.7 cells. The results show that FLP has better antioxidant activity than unfermented lemon peel (UFLP). Compared with UFLP extract, FLPE more effectively inhibited the release of NO and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) and down-regulated pro-inflammatory genes (IL-1β, IL-6, NF-κB p65, COX-2, IFN-γ, iNOS, IL-5), and pro-apoptotic genes (caspase-3, caspase-9, p53, p21 and Bax), meanwhile, promoted the release of anti-inflammatory cytokine (IL-10) and up-regulated anti-inflammatory genes(IL-10 and IL-4), and anti-apoptotic gene (Bcl2) in LPS-induced RAW 264.7 cells. Therefore, this study elucidates the anti-inflammatory activity mechanism of fermented lemon peel by studying the balance of inflammatory response and the inhibition of apoptosis. It provides an important reference for the future research and treatment of chronic inflammation and related diseases, as well as the development of fermented foods with anti-inflammatory effects.

Abstract The Clerodendranthus spicatus (Thunb.) C. Y. Wu extract (CSTCYWE) was administered to D-galactose-induced aging mice to investigate the effect and mechanism of CSTCYWE on exercise endurance in aging mice. The effect of CSTCYWE on the improvement of exercise capacity in aging mice was evaluated by detecting serum biochemical indicators, pathological changes in tissues, and expression by qPCR. The composition of CSTCYWE was analyzed by HPLC. The experiment showed that CSTCYWE increased the running time and the exhaustive swimming time of aging mice to improve their exercise endurance. CSTCYWE also reduced the levels of BUN, BLA, and MDA and increased the levels of HG, MG, SOD, and GSH-Px in the serum of aging mice. Pathological observation found that CSTCYWE alleviated the liver and kidney tissue lesions and damage caused by aging. Meanwhile, CSTCYWE could down-regulate the relative mRNA expressions of nNOS, iNOS, TNF-α, and syncytin-1 and up-regulate the relative mRNA expressions of Cu/Zn-SOD, Mn-SOD, and CAT in the mouse liver tissue and skeletal muscle tissue. The results of component analysis showed that CSTCYWE contained caffeic acid, hypericin, isoquercetin, dihydroquercetin, rosmarinic acid, baicalin, luteolin, and baicalein. These active ingredients enable CSTCYWE to act on aging mice and improve their exercise capacity.

Abstract The percentage of obese individuals continues to grow worldwide, and the main factor leading to obesity is the imbalance of energy intake and consumption. The intestinal flora has important regulatory roles in metabolic disorders and obesity. Compared with normal-weight individuals, those that are obese showed remarkable changes in the composition of the intestinal flora. Several studies have reported that probiotics can reverse high-fat diet-induced obesity. Thus, altering the intestinal flora may be an effective approach to control or even prevent obesity, and some probiotics have been demonstrated to have effects on obesity. The purpose of this review is to summarize the experimental means used to study probiotics and obesity and to summarize the weight-loss effects and mechanisms of action of experimental and clinical probiotics, so as to help investigators understand the latest benefits of weight-loss probiotics and to provide a reference for follow-up research in this field.

Abstract Xinjiang is a multi-ethnic region in China, traditional fermented yogurt is the main food of local herdsmen. This study aimed to summarize the literature data in recent years and data on the constipation-inhibitory effect of probiotics isolated from naturally fermented yogurt in Xinjiang, China. Xinjiang naturally fermented yogurt is rich in microbial resources, of which many in the food industry have been or are being developed and utilized as probiotics. Lactobacillus, naturally fermented yogurt of Xinjiang, has been verified to have a good constipation-inhibitory effect. Lactic acid bacteria isolated from naturally fermented yogurt in Xinjiang, China, has a good effect in terms of improving the symptoms of constipated experimental animals and could be used as probiotics. Some in-depth studies found that these lactic acid bacteria had target effects in regulating the stem cell factor (SCF)/stem cell factor receptor (c-Kit) signaling pathway and nitric oxide synthase expression and thus played a role in inhibiting constipation. The constipation-inhibitory effect of Xinjiang naturally fermented yogurt probiotics is also better than that of general commercial probiotics and can be used as high-quality probiotics to improve constipation. This study summarized available findings, provided some research ideas, and gave some directions for future research.

Abstract This study looked at the inhibitory effects of Apocynum venetum tea flavonoids extract (AVTFE) on mouse glioma G422 cells. Through the use of high performance liquid chromatography, the flavonoids in AVTFE were examined (HPLC). Meanwhile, mice were injected with glioma G422 cells to create a mouse model of a transplanted tumor. AVTFE might significantly (P < 0.05) lower serum sIL-2R content and raise serum IFN-γ content in tumor-bearing mice, according to an analysis of mouse serum. In addition to reducing the rise in spleen weight and spleen index in mice brought on by transplanted tumors, AVTFE can limit the development of transplanted tumors in G422 cell mice. AVTFE can also boost immunity by encouraging T and B lymphocyte proliferation in tumor-bearing animals. AVTFE was therefore verified to have immunomodulatory properties and to limit the proliferation of glioma G422 cells.

Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection.

Immune-mediated inflammation plays a key role in the pathology of abdominal aortic aneurysm (AAA). We aimed to use a computational approach to profile the immune infiltration patterns and related core genes in AAA samples based on the overexpression of gene signatures. The microarray datasets of AAA and normal abdominal tissues were acquired from gene expression omnibus (GEO) database. We evaluated the composition of immune infiltrates through microenvironment cell populations (MCP)-counter. Weighted gene correlation network analysis (WGCNA) was employed to construct the co-expression network and extract gene information in the most relevant module. Functional and pathway enrichment analysis was performed and immune infiltration related core genes were screened. AAA tissues had a higher level of infiltration by cytotoxic lymphocytes, NK cells, T cells, fibroblasts, myeloid dendritic cells, and neutrophils than normal aorta. The red module was strongly correlated with the infiltrating levels of T cells and cytotoxic lymphocytes. Gene ontology (GO) and pathway analyses revealed that genes in the most relevant module were mainly enriched in T cell activation, regulation of lymphocyte activation, cytokine-cytokine receptor interaction, and chemokine signaling pathway, etc. The expression of GZMK, CCL5, GZMA, CD2, and EOMES showed significant correlations with cytotoxic lymphocytes, while CD247, CD2, CD6, RASGRP1, and CD48 expression were positively associated with T cell infiltration. In conclusion, we comprehensively analyzed profiles of infiltrated immune cells in AAA tissues and their associated marker genes. Our data may provide a novel clue to indicate the underlying molecular mechanisms of AAA formation in terms of immune infiltration.

This aim of this study was to assess the molecular mechanism of osteoporosis in schizophrenia patients with risperidone use. Here, we investigated the effects of risperidone on cellular proliferation and apoptosis of a preosteoblast cell line, MC3T3-E1. Cell viability and apoptotic rate of MC3T3-E1 were detected by cell counting kit-8 and flow cytometry at a serial dose of risperidone and at different time points, respectively. Bone transformation relevant gene serum osteocalcin (BGP), collagen 1, tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) mRNA levels were determined by real-time PCR (qPCR). Their protein expression patterns were evaluated using western blot. The results revealed that risperidone dramatically inhibited MC3T3-E1 cell proliferation in a dose-dependent manner. It also significantly induced MC3T3-E1 cell apoptosis. TNF-α gene and protein levels were greatly enhanced after risperidone treatment. In contrast, BGP, collagen 1, OPG, and RANKL gene and protein levels were markedly downregulated. Our study indicated that risperidone suppressed MC3T3-E1 cell proliferation and induced apoptosis. It also regulated BGP gene and protein expression.

ABSTRACT In order to deepen understanding the interactions between ionic liquid and chitin/chitosan/cellulose at the molecular level, we have performed a study on the electronic structures, topological properties, nonconvalent interactions between 1-ethyl-3-methyl imidazolium chloride and chitin/chitosan/cellulose by using density functional theory. The results indicate that interactions between chitin/chitosan/cellulose and 1-ethyl-3-methyl imidazolium chloride are stronger that the intra-interaction of chitin/chitosan/cellulose, implying that chitin/chitosan/cellulose can dissolve in 1-ethyl-3-methyl imidazolium chloride.

Abstract This paper presents a series of uniaxial compressive experiments on natural lake ice under moderate strain-rate in the range of 10−1 to 102 s−1 at −0.1 °C. Natural lake ice samples of 8 cm by 8 cm in cross section and 20 cm high were used to investigate strain-rate dependence of uniaxial compressive strength and flaw effects on ice strength under moderate strain rates. The fracture modes of ice at moderate strain rates were also systematically investigated by using high-speed camera. It is found uniaxial compressive strength of natural lake ice increases with increasing strain-rate in the employed moderate strain-rate range. And natural flaws such as air bubble have a significant effect on uniaxial compressive strength of ice under moderate strain-rate, higher air content ice possesses lower compressive strength. Ice fracture mode depends on strain-rate (or compressive velocity) of ice specimen, varying from splitting at strain rates lower than 10 s−1 to crushing at strain rates higher than 10 s−1. Ice specimen crushes into fine fragments may due to insufficient time for micro cracks to propagate, thus results in higher strength. In addition, dependence of compressive strength on strain-rate in a wide strain-rate range is also discussed.

ABSTRACT Aims: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p < 0.001, Hazard Ratio (HR) = 2.203), elevated alanine aminotransferase (ALT) levels (p < 0.001, HR = 2.049), and non-vertical transmission (p = 0.006, HR = 1.656) were predictors of HBeAg seroconversion. Conclusion: Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

ABSTRACT The genus Aconitum has strong toxicity, but the acute toxicity of baked Aconitum flavum Hand.-Mazz., Ranunculaceae, was reduced significantly on the premise of keeping anti-inflammatory and anti-nociceptive activities. However, the risk associated with long-term use is unknown. In a sub-chronic toxicity study, rats were orally administered A. flavum at doses of 0.76–3.03 g/kg for 90 days and further recovered for 14 days. Our results showed that oral treatment with A. flavum for 90 days caused significant changes in some hematological indicators at doses of 3.03 and 1.52 g/kg, such as red blood cell, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These results indicated that the A. flavum affects the structure and function of red blood cell. Furthermore, significant changes were observed in the white blood cell at dose of 3.03 g/kg in male rats, which confirmed tissue damage or toxicity. The liver function tests exhibited non-significant alterations in aspertate aminotransferase, alanine aminotransferase and avenin-like storage proteinsgene. But other parameters, such as total protein and albumin were obviously decreased at all doses. A. flavum also caused a significant decrease in glucose, cholesterol and triacylglyceride at all doses. For kidney function, there were significant elevations in urea and creatinine at doses of 3.03 and 1.52 g/kg. The levels of certain electrolytes (Na+, K+ and Cl-) were significantly different after 90 days of treatment with A. flavum (3.03 and 1.52 g/kg). Organs were observed by light microscopy after hematoxylin-eosin staining. Hemosiderin depositions in the spleen were observed in the A. flavum group. These data demonstrated that the subtoxicity of A. flavum was reduced considerably by baked, but the subchronic toxicity effects on the liver, kidney and spleen should not be ignored.

Abstract To study the hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed. Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01). The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene. This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced liver injury in mice.

Density functional theory has been employed to investigate the interactions between copper(I) bis(trifluoromethylsulfonyl)imide (Cu[Tf2N]) and C3H8/C3H6. The calculations were based on the model of Cu[Tf2N], and performed at X3LYP/6-31++G** level. The calculated interaction energies indicated that the adsorption ability of Cu[Tf2N] for C3H8/C3H6 followed the order of C3H8 < C3H6. The noncovalent interactions in real space, based on the electron density and its derivatives, reveal the nature of interactions between Cu[Tf2N] and C3H8AC3H6. The natural bond orbital (NBO) analysis of the second-order perturbation energy has been performed to investigate the interaction mechanism of C3H8/C3H6 on ionic liquid Cu[Tf2N].