Testosterone (T), the principal androgen, and its metabolite, dihydrotestosterone (DHT), are known to mediate their effects through binding to intracellular androgen receptors (iARs). In addition to their well-known genomic effects, androgens rapidly alter neuronal excitability through a non-genomic pathway mediated by membrane androgen receptors (mARs). The existence and specificity of mARs in the hippocampus were investigated in SAMP8 mice. Using T-BSA-FITC, we detected plasma membrane labeling by flow cytometry analysis for the presence of mARs. The specificity of binding was examined with iAR antagonist or anti-iAR antibody. Flow cytometry analysis showed that pretreatment with iAR antagonist, flutamide (F), failed to completely prevent the coupling action of the T-BSA-FITC membrane binding. In addition, we found classical iARs did not localize to the membrane of hippocampal neurons. These data indicate that these mARs might be not identical to classical iARs. Modulation of hippocampal synaptic plasticity by androgen has been attracting much attention. To identify the functional consequences induced by mARs, we analyzed the rapid effects of T on the density of dendritic spines using Golgi staining. The application of 50 μg/5 μl T and 30 μg/5 μl DHT induced a rapid increase in the dendritic spines within 2 h. Almost no difference was observed between T and T-BSA in the effect on thorn density. Next, we explored the protective mechanism and found that T and DHT altered the expression of synaptophysin (SYN) and postsynaptic dense material 95 (PSD95), which play crucial roles in cognitive function and synaptic plasticity.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model.

Activation of the cholinergic anti-inflammatory pathway (CAP), which relies on the alpha-7 nicotinic acetylcholine receptor, has been reported to reduce proinflammatory cytokine levels in experimental arthritis. To gain more insight regarding the role of the CAP in the pathogenesis of arthritis, the present study focused on the modulation of macrophage infiltration. In a mouse model of collagen‑induced arthritis (CIA), nicotine and vagotomy were used to stimulate and inhibit the CAP, respectively. Subsequently, arthritic scores were measured and histopathological assessment of joint sections was conducted. Cluster of differentiation (CD)11b‑positive macrophages in the synovium were studied by immunofluorescence histochemistry. The serum levels of chemokines, including macrophage inflammatory protein (MIP)‑1α, monocyte chemoattractant protein (MCP)‑1 and MIP‑2 were evaluated by ELISA. Furthermore, the expression levels of C‑C chemokine receptor (CCR)2 and intercellular adhesion molecule (ICAM)‑1 in the synovium were evaluated by immunohistochemical staining. The results indicated that treatment with nicotine significantly attenuated the clinical and histopathological changes associated with arthritis, reduced CD11b‑positive macrophages in the synovium, and downregulated the serum expression levels of MIP‑1α and MCP‑1. Conversely, vagotomy aggravated arthritis and upregulated the expression levels of MCP‑1. However, MIP‑2 expression did not differ among the control, CIA, vagotomy and nicotine groups. In addition, the expression levels of CCR2 were reduced in the nicotine group; however, they were increased in the vagotomy group compared with in the untreated CIA group. The expression levels of ICAM‑1 in the synovium were also influenced by activation of the CAP. Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.

Recently zwitterionic materials have been widely applied in the biomedical and bioengineering fields due to their excellent biocompatibility. Inspired by these, this study presents a graft-to strategy via covalent bond formation to fabricate safe and durable antibacterial textile surfaces. A novel zwitterionic sulfobetaine containing triazine reactive group was specifically designed and synthesized. MTT assay showed that it had no obvious cytotoxicity to human skin HaCaT cells as verified by ca. 89.9% relative viability at a rather high concentration of 0.8 mg·mL-1. In the evaluation for its skin sensitization, the maximum score for symptoms of erythema and edema in all tests were 0 in all observation periods. The sulfobetaine had a hydrophilic nature and the hydrophilicity of the textiles was enhanced by 43.9% when it was covalently grafted onto the textiles. Moreover, the textiles grafted with the reactive sulfobetaine exhibited durable antibacterial activities, which was verified by the fact that they showed antibacterial rates of 97.4% against gram-positive S. aureus and 93.2% against gram-negative E. coli even after they were laundered for 30 times. Therefore, the titled zwitterionic sulfobetaine is safe to human for healthcare and wound dressing and shows a promising prospect on antibacterial textile application.

The astonishing spectrum of scarabaeine lifestyles makes them an attractive group for studies in entomology and evolutionary biology. As a result of adaptions to specific food substrates and textures, the mouthparts of dung beetles, particularly the mandible, have undergone considerable evolutionary changes and differ distinctly from the presumptive ancestral conditions of the Coleoptera and Polyphaga. The possible functions of dung beetle mouthparts and the evolution of dung feeding have been controversial for decades.

Poly(L-diaminopropionic acid) (PDAP) is one of the four homopoly(amino acid)s that have been discovered in nature. However, the molecular mechanism of PDAP biosynthesis has yet to be described. In this work, the general layout of the PDAP biosynthetic pathway is characterised in Streptomyces albulus PD-1 by genome mining, gene disruption, heterologous expression and in vitro feeding experiments. As a result, L-diaminopropionic acid (L-DAP), which is the monomer of PDAP, is shown to be jointly synthesised by two protein homologues of cysteine synthetase and ornithine cyclodeaminase. Then, L-DAP is assembled into PDAP by a novel nonribosomal peptide synthetase (NRPS) with classical adenylation and peptidyl carrier protein domains. However, instead of the traditional condensation or thioesterase domain of NRPSs, this NRPS has seven transmembrane domains surrounding three tandem soluble domains at the C-terminus. As far as we know, this novel single-module NRPS structure has only been reported in poly(ε-L-lysine) synthetase. The similar NRPS structure of PDAP synthetase and poly(ε-L-lysine) synthetase may be a common characteristic of homopoly(amino acid)s synthetases. In this case, we may discover and/or design more homopoly(amino acid)s by mining this kind of novel NRPS structure in the future.

A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol (2:1, v/v). Chromatographic separation was achieved on a Diamonsil ODS chromatography column using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. The determination was performed by positive ion electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear over the concentration range of 5-1000 ng/mL (r = 0.9996). The intra- and inter-day precision (RSD%) was less than 6.1%, and the accuracy (RE%) was from -3.0%-2.5%. This method was successfully applied to the pharmacokinetic research of scopoletin in rats after intravenous (5 mg/kg) or oral (5, 10 and 20 mg/kg) administration. The result showed that oral bioavailability with a dose of 5 mg/kg was 6.62% ± 1.72%, 10 mg/kg, 5.59% ± 1.16%, and 20 mg/kg, 5.65% ± 0.75%.

Secondary pneumonia due to Staphylococcus aureus (S. aureus) causes significant morbidity and mortality. The aim of the research was designed a novel DNA vaccine encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV) HA2 protein to provide protection against both influenza and secondary infection with S. aureus. The DNA vaccine vector efficiently expressed the encoded antigen in mammalian cells, as determined by RT-PCR, Western blotting and immunofluorescence analysis. Mice were immunized with the vaccine by intramuscular injection before challenge with IAV and S. aureus. The pulmonary and the splenocyte culture IFN-γ levels were significant higher in immunized mice than their respective controls. Although the antibody titer in the HI test was low, the sera of mice immunized with the novel vaccine vector were effective in neutralisation assay in vitro. The vaccine could reduce the loss of body weight in mice during IAV challenge. Both Western blotting and RT-PCR showed that the vaccine markedly enhanced toll like receptor 2 (TLR2) expression in splenocytes after the secondary infection with S. aureus. The survival rate of mice with high TLR2 expression (pEGFP/Ag85A-HA2 or iPR) was significantly increased compared with mice immunized with pEGFP/HA2 after challenge with S. aureus. However, the pulmonary IL-10 concentration and S. aureus titer were significantly decreased in immunized mice, and expression of TLR2 was increased after challenge with S. aureus. These results demonstrated that Ag85A could strengthen the immune response to IAV and S. aureus, and TLR2 was involved in the host response to S. aureus.

To elucidate the veritable relationship between three hMLH1 polymorphisms (rs1800734, rs1799977, rs63750447) and cancer risk, we performed this meta-analysis based on overall published data up to May 2017, from PubMed, Web of knowledge, VIP, WanFang and CNKI database, and the references of the original studies or review articles. 57 publications including 31,484 cancer cases and 45,494 cancer-free controls were obtained. The quality assessment of six articles obtained a summarized score less than 6 in terms of the Newcastle-Ottawa Scale (NOS). All statistical analyses were calculated with the software STATA (Version 14.0; Stata Corp, College Station, TX). We found all the three polymorphisms can enhance overall cancer risk, especially in Asians, under different genetic comparisons. In the subgroup analysis by cancer type, we found a moderate association between rs1800734 and the risk of gastric cancer (allele model: OR = 1.14, P = 0.017; homozygote model: OR = 1.33, P = 0.019; dominant model: OR = 1.27, P = 0.024) and lung cancer in recessive model (OR = 1.27, P = 0.024). The G allele of rs1799977 polymorphism was proved to connect with susceptibility of colorectal cancer (allele model: OR = 1.21, P = 0.023; dominate model: OR = 1.32, P <0.0001) and prostate cancer (dominate model: OR = 1.36, P <0.0001). Rs63750447 showed an increased risk of colorectal cancer, endometrial cancer and gastric cancer under all genetic models. These findings provide evidence that hMLH1 polymorphisms may associate with cancer risk, especially in Asians.

Cytoplasmic male sterility (CMS) plays a crucial role in the utilization of hybrid vigor. Pollen development is often accompanied by oxidative metabolism responses and tapetal programmed cell death (PCD), and deficiency in these processes could lead to male sterility. Aegilops uniaristata cytoplasmic male sterility (Mu-CMS) wheat is a novel male-sterile line in wheat, which possess important potential in hybrid wheat breeding. However, its CMS mechanisms remain poorly understood. In our study, U87B1-706A, with the Aegilops uniaristata cytoplasm, and the maintainer line 706B were used to explore the abortive reason. Compared with 706B, histological analysis and PCD detection of the anther demonstrated that U87B1-706A appeared as delayed tapetal PCD as well as a disorganized organelle phenotype in the early uninucleate stage. Subsequently, a shrunken microspore and disordered exine structure were exhibited in the late uninucleate stage. While the activities of antioxidase increased markedly, the nonenzymatic antioxidant contents declined obviously following overacummulation of reactive oxygen species (ROS) during pollen development in U87B1-706A. Real-time quantitative PCR testified that the transcript levels of the superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) genes, encoding pivotal antioxidant enzymes, were up-regulated in early pollen development. Therefore, we deduce excess ROS as a signal may be related to the increased expression levels of enzyme genes, thereby breaking the antioxidative system balance, resulting in delayed tapetal PCD initiation, which finally led to pollen abortion and male sterility in U87B1-706A. These results provide evidence to further explore the mechanisms of abortive pollen in CMS wheat.

Thermo-sensitive male-sterility based on Aegilops kotschyi cytoplasm (K-TCMS) plays an important role in hybrid wheat breeding. This has important possible applications in two-line hybrid wheat breeding but the genetic basis and molecular regulation mechanism related to fertility restoration are poorly understood. In this study, comparative transcriptome profiling based on RNA sequencing was conducted for two near-isogenic lines comprising KTM3315R and its sterile counterpart KTM3315A, a total of six samples (3 repetitions per group), in order to identify fertility restoration genes and their metabolic pathways.

Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3' untranslated region (3'UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.

Peptidyl‑prolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) is a member of a large superfamily of phosphorylation‑dependent peptidyl‑prolyl cis/trans isomerases, which not only regulates multiple targets at various stages of cellular processes, but is also involved in the pathogenesis of several diseases, including microbial infection, cancer, asthma and Alzheimer's disease. However, the role of Pin1 in cardiac fibrosis remains to be fully elucidated. The present study investigated the potential mechanism of Pin1 in isoprenaline (ISO)‑induced myocardial fibrosis in rats. The rats were randomly divided into three groups. Echocardiography was used to evaluate changes in the size, shape and function of the heart, and histological staining was performed to visualize inflammatory cell infiltration and fibrosis. Reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemistry and Picrosirius red staining were used to differentiate collagen subtypes. Additionally, cardiac‑specific phosphorylation of mitogen‑activated protein kinase kinase 1/2 (MEK1/2) and extracellular‑signal regulated protein kinase 1/2 (ERK1/2), and the activities of Pin1 and α‑smooth muscle actin (α‑SMA) and other oxidative stress parameters were estimated in the heart. The administration of ISO resulted in an increase in cardiac parameters and elevated the heart‑to‑body weight ratio. Histopathological examination of heart tissues revealed interstitial inflammatory cellular infiltrate and disorganized collagen fiber deposition. In addition, lipid peroxidation products and oxidative stress marker activity in plasma and tissues were significantly increased in the ISO‑treated rats. Western blot analysis showed significantly elevated protein levels of phosphorylated Pin1, MEK1/2, ERK1/2 and α‑SMA in remodeling hearts. Treatment with juglone following intraperitoneal injection of ISO significantly prevented inflammatory cell infiltration, improved cardiac function, and suppressed oxidative stresses and fibrotic alterations. In conclusion, the results of the present study suggested that the activation of Pin1 promoted cardiac extracellular matrix deposition and oxidative stress damage by regulating the phosphorylation of the MEK1/2‑ERK1/2 signaling pathway and the expression of α‑SMA. By contrast, the inhibition of Pin1 alleviated cardiac damage and fibrosis in the experimental models, suggesting that Pin1 contributed to the development of cardiac remodeling in ISO‑administered rats, and that the inactivation of Pin1 may be a novel therapeutic candidate for the treatment of cardiovascular disease and heart failure.

The present study investigated the association between Snail1 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) and to determine the possible mechanism underlying this interrelation. A total of 19 patients were included in the current study and were divided into two groups: A sinus rhythm (SR) group (n=9) and an AF group (n=10). All patients underwent heart valve replacement surgery, during which ~200 mg right atrium tissue was obtained. Hematoxylin and eosin and Masson's trichrome-stained sections were used to evaluate the morphological changes of cardiomyocytes and the level of fibrosis. Immunohistochemistry was applied to observe the location and expression of Snail1. Reverse transcription-quantitative polymerase chain reaction was used to measure Snail1 mRNA levels. Western blotting was used to determine changes in the expression of Snail1, as well as in the expression of proteins involved in the Wnt pathway, including Wnt1, Wnt 3a, Wnt8a, Wnt5a and Wnt11. Compared with the SR group, expanded cardiomyocytes and higher collagen deposition was detected in the atrial tissue of the AF group. The expression of Snail1 mRNA and protein was significantly higher in the AF group than in the SR group (P<0.05). Additionally, the expression of Wnt1, 3a and 8a in the canonical Wnt signaling pathway, and Wnt5a and 11 in the noncanonical Wnt signaling pathway were significantly increased in the AF group. Furthermore, the phosphorylation level of glycogen synthase kinase 3β (GSK3β) and the levels of β-catenin and GSK3β were significantly increased in the AF group compared with the SR group (P<0.05). Snail1 may be involved in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease and may be developed as a novel biomarker to evaluate myocardial fibrosis in the future. Additionally, the current study suggests that the Wnt signaling pathway may participate in the process of increased Snail1 expression and atrial fibrosis in patients with AF and RHD.

Recurrent tonsillitis (RT) is often treated with antibiotic therapy and surgery. Although these treatments have advantages, they are also controversial. The purpose of this study is to analyze the safety and effectiveness of traditional Chinese medicine (TCM) cauterization in the treatment of RT, so as to provide an alternative for the clinicians and to cover the shortage of therapeutic methods.

The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution.

Although hippocampus-derived androgens play an important role in hippocampal synaptic plasticity, studies at the cellular level have received relatively less attention. Furthermore, the underlying signalling pathways associated with synaptic plasticity remain unclear. Results of the present study demonstrated that testosterone treatment of primary cultured rat hippocampal neurons resulted in a rapid increase in spine density, accompanied by the elevation of protein and messenger RNA levels of synaptophysin, developmentally regulated brain protein (Drebrin), and the N-methyl-D-aspartate receptor NR1 subunit. Testosterone treatment also increased the phosphorylation levels of extracellular-regulated protein kinase (ERK)1/2 and cAMP-responsive element binding protein (CREB), rather than p38 and Jun N-terminal kinase (JNK). U0126 significantly reversed the testosterone-mediated phosphorylation of CREB. Importantly, the increase in spine density was not induced by testosterone under U0126 treatment. These findings suggest that the ERK1/2-CREB signalling pathway plays an important role in testosterone-mediated rapid spinogenesis of cultured rat hippocampal neurons. Results of this study will be helpful in further clarifying the physiological function of testosterone and related signalling pathways in vitro.

The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them.

The dysregulation of hepatic lipid metabolism is one of the hallmarks in many liver diseases including alcoholic liver diseases (ALD) and non-alcoholic fatty liver diseases (NAFLD). Hepatic inflammation, lipoperoxidative stress as well as the imbalance between lipid availability and lipid disposal, are direct causes of liver steatosis. The application of herbal medicines with anti-oxidative stress and lipid-balancing properties has been extensively attempted as pharmaceutical intervention for liver disorders in experimental and clinical studies. Although the molecular mechanisms underlying their hepatoprotective effects warrant further exploration, increasing evidence demonstrated that many herbal medicines are involved in regulating lipid accumulation processes including hepatic lipolytic and lipogenic pathways, such as mitochondrial and peroxisomal β-oxidation, the secretion of very low density lipoprotein (VLDL), the non-esterified fatty acid (NEFA) uptake, and some vital hepatic lipogenic enzymes. Therefore, in this review, the pathways or crucial mediators participated in the dysregulation of hepatic lipid metabolism are systematically summarized, followed by the current evidences and advances in the positive impacts of herbal medicines and natural products on the lipid metabolism pathways are detailed. Furthermore, several herbal formulas, herbs or herbal derivatives, such as Erchen Dection, Danshen, resveratrol, and berberine, which have been extensively studied for their promising potential in mediating lipid metabolism, are particularly highlighted in this review.

This study aimed to investigate the correlation between CT features and liver function and p53 expression in hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Forty patients with HCC, 30 patients with cirrhosis and 30 patients with chronic hepatitis were enrolled between December, 2015 and December, 2016. At the same time, normal liver tissues collected from 30 patients with hepatic hemangioma were used as the normal control group. All the patients were scanned by CT. Average body surface area, left outer lobe and caudate lobe volume, and the proportions of left outer lobe and caudate lobe to the whole liver were calculated. Biochemical indexes of liver function were determined. The pathological tissues of all the subjects were analyzed. Compared with the control group, total liver volume of the HCC group was significantly reduced (P<0.05). Compared with the HCC group, the volume of the left outer lobe increased in the hepatitis group and the cirrhosis group. Compared with control group, caudate lobe volume increased significantly in the hepatitis group (P<0.05). Compared with the control group, the volume of the left outer lobe and the proportion of caudate lobe to the whole liver volume was significantly increased in all three groups (P<0.05). Liver function-related indicators in the HCC and cirrhosis groups were significantly different from those in the control group (P<0.05). The expression level of p53 in HCC was significantly higher than that in the control group (P<0.05). The accuracy of diagnosis by using both p53 and CT was higher than the use of p53 or CT alone. CT can accurately measure the volume of each lobe of the liver, and p53 has important clinical values in the diagnosis of liver diseases. Thus, the reasonable combination of the two can effectively improve the diagnostic accuracy.