The gut microbiota has been implicated in a number of normal and disease biological processes. Recent studies have identified a subset of gut bacterial genes as potentially involved in inflammatory processes. In this work, we explore the sequence variability for some of these bacterial genes using a combination of deep sequencing and oligotyping, a data analysis application that identifies mutational hotspots in short stretches of DNA. The genes for pks island, tcpC and usp, all harbored by certain strains of E. coli and all implicated in inflammation, were amplified by PCR directly from stool samples and subjected to deep amplicon sequencing. For comparison, the same genes were amplified from individual bacterial clones. The amplicons for pks island and tcpC from stool samples showed minimal levels of heterogeneity comparable with the individual clones. The amplicons for usp from stool samples, by contrast, revealed the presence of five distinct oligotypes in two different regions. Of these, the oligotype GT was found to be present in the control uropathogenic clinical isolate and also detected in stool samples from individuals with colorectal cancer (CRC). Mutational hotspots were mapped onto the USP protein, revealing possible substitutions around Leu110, Glu114, and Arg115 in the middle of the pyocin domain (Gln110, Gln114, and Thr115 in most healthy samples), and also Arg218 in the middle of the nuclease domain (His218 in the uropathogenic strain). All of these results suggest that a level of variability within bacterial pro-inflammatory genes could explain differences in bacterial virulence and phenotype.

Despite advances in pharmacogenetics, the majority of heritability for treatment response cannot be explained by common variation, suggesting that factors such as epigenetics may play a key role. Regulatory genes, such as those involved in DNA methylation and transcriptional repression, are therefore excellent candidates for investigating antipsychotic treatment response. This study explored the differential expression of regulatory genes between patients with schizophrenia (chronic and antipsychotic-naïve first-episode patients) and healthy controls in order to identify candidate genes for association with antipsychotic treatment response. Seven candidate differentially expressed genes were identified, and four variants within these genes were found to be significantly associated with treatment response (DNMT3A rs2304429, HDAC5 rs11079983, and HDAC9 rs1178119 and rs11764843). Further analyses revealed that two of these variants (rs2304429 and rs11079983) are predicted to alter the expression of specific genes (DNMT3A, ASB16, and ASB16-AS1) in brain regions previously implicated in schizophrenia and treatment response. These results may aid in the development of biomarkers for antipsychotic treatment response, as well as novel drug targets.

Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the PPAR family and plays a critical role in inhibiting cell proliferation and tumorigenesis in various tumors. However, the role of PPAR-α in colorectal tumorigenesis is unclear. In the present study, we found that fenofibrate, a PPAR-α agonist, significantly inhibited cell proliferation and induced apoptosis in colorectal carcinoma cells. In addition, PPAR-α was expressed in the nucleus of colorectal carcinoma cells, and the expression of nuclear PPAR-α increased in colorectal carcinoma tissue compared with that of normal epithelium tissue (P<0.01). The correlation between the expression of nuclear PPAR-α and clinicopathological factors was evaluated in human colorectal carcinoma tissues, and the nuclear expression of PPAR-α was significantly higher in well-to-moderately differentiated adenocarcinoma than in mucinous adenocarcinoma (P<0.05). These findings indicate that activation of PPAR-α may be involved in anticancer effects in colorectal carcinomas, and nuclear expression of PPAR-α may be a therapeutic target for colorectal adenocarcinoma treatment.

This paper reports the synthesis and detailed characterisation of copper(II) and nickel(II) complexes with tridentate thiosemicarbazone ligands H 2 L1 and H 2 L2 derived from 2-acetylpyrazine. The ligands and their metal complexes were characterised by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR, and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The crystal structure of the H 2 L1 ligand was determined by single crystal X-ray diffraction studies. The spectral data showed that the thiosemicarbazone behaves as an NNS tridentate ligand through the nitrogen atoms of the azomethine group and pyrazine ring and the sulphur atom of the thioamide group. Elemental and thermal analyses indicated that the obtained metal complexes had a 1 : 1 stoichiometry (metal-ligand). The interactions between these complexes and calf thymus DNA (CT-DNA) were studied by electronic absorption and viscosity measurements. The activities of these compounds against oxidative DNA cleavage were examined by agarose gel electrophoresis. Cu(II) and Ni(II) complexes can wind DNA strands through groove interactions and promote strand breakage of the plasmid pmCherry under oxidative stress conditions. Moreover, all the complexes could interact more strongly with DNA than could with the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains (S. aureus ATCC 25923, L. monocytogenes ATCC 19115, and B. cereus ATCC 10876) and Gram-negative bacterial strains (E. coli ATCC 25922, S. typhimurium ATCC 14028, and K. pneumoniae ATCC BAA-2146) using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

In today's society, image resources are everywhere, and the number of available images can be overwhelming. Determining how to rapidly and effectively query, retrieve, and organize image information has become a popular research topic, and automatic image annotation is the key to text-based image retrieval. If the semantic images with annotations are not balanced among the training samples, the low-frequency labeling accuracy can be poor. In this study, a dual-channel convolution neural network (DCCNN) was designed to improve the accuracy of automatic labeling. The model integrates two convolutional neural network (CNN) channels with different structures. One channel is used for training based on the low-frequency samples and increases the proportion of low-frequency samples in the model, and the other is used for training based on all training sets. In the labeling process, the outputs of the two channels are fused to obtain a labeling decision. We verified the proposed model on the Caltech-256, Pascal VOC 2007, and Pascal VOC 2012 standard datasets. On the Pascal VOC 2012 dataset, the proposed DCCNN model achieves an overall labeling accuracy of up to 93.4% after 100 training iterations: 8.9% higher than the CNN and 15% higher than the traditional method. A similar accuracy can be achieved by the CNN only after 2,500 training iterations. On the 50,000-image dataset from Caltech-256 and Pascal VOC 2012, the performance of the DCCNN is relatively stable; it achieves an average labeling accuracy above 93%. In contrast, the CNN reaches an accuracy of only 91% even after extended training. Furthermore, the proposed DCCNN achieves a labeling accuracy for low-frequency words approximately 10% higher than that of the CNN, which further verifies the reliability of the proposed model in this study.

A series of complexing adsorbents is prepared by coating silica particles with linear polyhexamethylene guanidinium (PHMG) chloride followed by saturation with a number of sulphonated nitrosonaphthols reagents electrostatically retained by positively charged polymer layer. PHMG coated silica is hydrolytically stable even during treatment with 6 M HCl heated up to 50 °C. The adsorption of 1-nitroso-2-naphthol-3,6-disulfonic acid (nitroso-R-salt), 2-nitroso-1-naphthol-4-sulfonic acid (nitroso-N-salt), and 2-nitroso-1-naphthol-3,6-disulfonic acid (nitroso-K-salt) on PHMG modified silica was studied. The effective immobilisation of sulphonated nitrosonaphthols was achieved in the range of pH of 3 - 8, while the adsorption of the monosulphonated reagent (nitroso-N-salt) is twice as high as the disulphonated analogues (nitroso-R-salt and nitroso-K-salt). The adsorption of Cu(II), Fe(III), Co(II), Ni(II), Al(III), Zn(II), Pb(II), Mn(II), and Cr(III) on prepared complexing adsorbents under static and dynamic conditions was studied as a function of time, pH, sample volume, and presence of interfering ions. Metal ions can be desorbed by using 1 M HCl or 1 M HNO3. The preconcentration factors of metals under optimized conditions are varied from 20 to 80. The developed method was used for the preconcentration of trace metals from natural waters followed by ICP-OES determination. The sub-ppb limits of detection of metals are achieved.

Enterococci, once considered as a harmless commensal of intestine, have now emerged as medically important pathogens and are associated with both community-acquired and nosocomial infections. They bear the potential to exhibit resistance against all commonly used antibiotics either by inherent or acquired mechanism, posing a therapeutic challenge.

Cancer has been considered a serious global health problem and a leading cause of morbidity and mortality worldwide. Despite recent advances in cancer therapy, treatments of advance stage cancers are mostly ineffective resulting in poor survival of patients. Recent evidences suggest that multipotent human mesenchymal stem cells (hMSCs) play important roles in growth and metastasis of several cancers by enhancing their engraftment and inducing tumor neovascularization. However, the effect of hMSCs on cancer cells is still controversial because there are also evidences demonstrating that hMSCs inhibited growth and metastasis of some cancers.

Malaria and HIV/AIDS infections are among the major public health concerns in sub-Saharan Africa, where they are associated with high morbidity and mortality. Recent findings indicate that individual people living with HIV/AIDS (PLWHA) with lower levels of CD4 T-cell count below 200/mm3 tend to experience higher mean malaria parasite densities than their counterparts with higher CD4 T-cells counts.

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6'-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS's absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

Motherwort injection, a common traditional Chinese medicine, is widely used for the prevention of postpartum hemorrhage (PPH), which has been found to be potential benefit in clinical practice.

Diabetes mellitus is a complicated health condition with multiple causes and many treatment options. Various myths may influence diabetics' health-seeking behavior, and they may use traditional medicines, which include normal foods and herbs, for primary health care. The aim of this study was to determine patients' and herbalists' practices and perspectives regarding the use of traditional medicines and the role of traditional medicines in the management of diabetes.

Traditional Chinese medicine (TCM) has a longstanding history and has gained widespread clinical applications. San Cao Decoction (SCD) is an experience prescription first formulated by Prof. Duzhou Liu. We previously demonstrated its antihypertensive effects; however, to systematically explain the underlying mechanisms of action, we employed a systems pharmacology approach for pharmacokinetic screening and target prediction by constructing protein-protein interaction networks of hypertension-related and putative SCD-related targets, and Database for Annotation, Visualization, and Integrated Discovery enrichment analysis. We identified 123 active compounds in SCD and 116 hypertension-related targets. Furthermore, the enrichment analysis of the drug-target network showed that SCD acts in a multidimensional manner to regulate PI3K-Akt-endothelial nitric oxide synthase signaling to maintain blood pressure. Our results highlighted the molecular mechanisms of antihypertensive actions of medicinal herbs at a systematic level.

Lycopodium clavatum is a dry whole grass of Lycopodium japonicum Thunb.; it has been extensively used to anti-inflammatory, antioxidant, and antimicrobial actions and inhibits acetylcholinesterase activity. However, it lacks further compounds research of Lycopodium clavatum in vivo and in vitro. In this work, a rapid method was established using the ultra high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multiple data-processing approaches for compounds analysis of Lycopodium clavatum in vitro and in vivo. Finally, 30 peaks were characterized in 75% ethanol extract of Lycopodium clavatum and 17 peaks were characterized in rat plasma that including 12 prototype compounds and 5 metabolites. Methylation and demethylation are the main transformation reactions of Lycopodium clavatum in rat serum. This work could be helpful for understanding the complex compounds of Lycopodium clavatum and further analyzing the pharmacological studies of active compounds.

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

Bladder cancer is a common malignancy with uncontrolled and rapid growth. Although lots of the important regulatory networks in bladder cancer have been found, the cancer-relevant genes remain to be further identified.

Obesity and inflammation are reportedly associated with the pathogenesis of sarcopenia, which is characterized by age-related loss of skeletal muscle mass. Intramuscular fat deposits have been found to compromise muscle integrity; however, the relevant fat compounds and their roles as mediators of muscular inflammation are not known. The aim of this study was to identify potential correlations between inflammation markers and lipid compounds that accumulate in the quadriceps muscle of previously described Sprague-Dawley (SD) rat model for high-fat diet- (HFD-) induced muscle loss. Six-month-old SD rats were continuously fed a control (CD) or HFD until the age of 21 months. Magnetic resonance imaging (MRI) revealed a significant decline in muscle cross-sectional area in male SD rats as a result of HFD, but not in female rats. Here, we developed a new procedure to quantitatively identify and classify the fatty acid methyl esters (FAMEs) in rats' quadriceps muscles from our former study using gas chromatography-mass spectrometry (GC-MS). Fatty acid analysis revealed accumulation of octadecadienoic (linoleic acid), octadecanoic (stearic acid), and octadecenoic (vaccenic acid) acids exclusively in the quadriceps muscles of male rats. The designated fatty acids were mainly incorporated into triacylglycerols (TAGs) or free fatty acids (FFAs), and their proportions were significantly elevated by consumption of a HFD. Furthermore, the number of resident immune cells and the levels of the chemokines RANTES, MCP-1, and MIP-2 were significantly increased in quadriceps muscle tissue of HFD-fed male, but not female rats. Together, HFD-induced muscle loss in aged male SD rats is associated with greater deposits of long-chain fatty acid esters and increased levels of the inflammatory markers RANTES, MCP-1, and MIP-2 in skeletal muscle tissue. This trend is further reinforced by long-term consumption of a HFD, which may provoke synergistic crosstalk between long-chain fatty acids and inflammatory pathways in sarcopenic muscle.

It has been suggested that mesangial IgA deposits are dimeric or polymeric in IgA nephropathy (IgAN). However, evidence concerning the molecular form of serum IgA in IgAN is controversial. And there is no direct evidence that the serum levels of joining chain- (J chain-) containing IgA (J-IgA) are elevated in IgAN. In this study, we aimed to measure serum J-IgA and glomerular J chain deposition with anti-J chain monoclonal antibody in IgAN.

The most common neurological complication in patients receiving successful combination antiretroviral therapy (cART) is peripheral neuropathic pain. Data show that distal symmetric polyneuropathy (DSP) also develops along with murine acquired immunodeficiency syndrome (MAIDS) after infection with the LP-BM5 murine retrovirus mixture. Links between cannabinoid receptor 2 (CB2R) and peripheral neuropathy have been established in animal models using nerve transection, chemotherapy-induced pain, and various other stimuli. Diverse types of neuropathic pain respond differently to standard drug intervention, and little is currently known regarding the effects of modulation through CB2Rs. In this study, we evaluated whether treatment with the exogenous synthetic CB2R agonists JWH015, JWH133, Gp1a, and HU308 controls neuropathic pain and neuroinflammation in animals with chronic retroviral infection. Hind-paw mechanical hypersensitivity in CB2R agonist-treated versus untreated animals was assessed using the MouseMet electronic von Frey system. Multicolor flow cytometry was used to determine the effects of CB2R agonists on macrophage activation and T-lymphocyte infiltration into dorsal root ganglia (DRG) and lumbar spinal cord (LSC). Results demonstrated that, following weekly intraperitoneal injections starting at 5 wk p.i., JWH015, JWH133, and Gp1a, but not HU308 (5 mg/kg), significantly ameliorated allodynia when assessed 2 h after ligand injection. However, these same agonists (2x/wk) did not display antiallodynic effects when mechanical sensitivity was assessed 24 h after ligand injection. Infection-induced macrophage activation and T-cell infiltration into the DRG and LSC were observed at 12 wk p.i., but this neuroinflammation was not affected by treatment with any CB2R agonist. Activation of JAK/STAT3 has been shown to contribute to development of neuropathic pain in the LSC and pretreatment of primary murine microglia (2 h) with JWH015-, JWH133-, or Gp1a-blocked IFN-gamma-induced phosphorylation of STAT1 and STAT3. Taken together, these data show that CB2R agonists demonstrate acute, but not long-term, antiallodynic effects on retrovirus infection-induced neuropathic pain.

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n = 10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1β and caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.