Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats.

Xyloglucan is one of the major polysaccharides found in the plant cell wall and seeds. Owing to its complex branched structure, several different hydrolases are required to degrade it. Isoprimeverose-producing enzymes (IPase) are unique among the glycoside hydrolase 3 family in that they recognize and release a disaccharide from the nonreducing end of xyloglucan oligosaccharides. Only two IPases have been previously isolated and characterized. A novel IPase from Phaeoacremonium minimum (PmIPase) was expressed and characterized. The xylopyranosyl residue at the nonreducing end of xyloglucan oligosaccharides was essential for hydrolytic activity, and PmIPase was unable to hydrolyze cellobiose into d-glucose. PmIPase had a Km for xyloglucan oligosaccharide substrate that was much lower than that of the reported IPase isolated from Aspergillus oryzae. This indicates that PmIPase was able to produce isoprimeverose efficiently from low concentrations of xyloglucan oligosaccharides. PmIPase also exhibited transglycosylation activity and was able to transfer isoprimeverose units to its substrates.

Cells are neither flat nor smooth, which has serious implications for prevailing plasma membrane models and cellular processes like cell signalling, adhesion and molecular clustering. Using probability distributions from diffusion simulations, we demonstrate that 2D and 3D Euclidean distance measurements substantially underestimate diffusion on non-flat surfaces. Intuitively, the shortest within surface distance (SWSD), the geodesic distance, should reduce this problem. The SWSD is accurate for foldable surfaces but, although it outperforms 2D and 3D Euclidean measurements, it still underestimates movement on deformed surfaces. We demonstrate that the reason behind the underestimation is that topographical features themselves can produce both super- and subdiffusion, i.e. the appearance of anomalous diffusion. Differentiating between topography-induced and genuine anomalous diffusion requires characterising the surface by simulating Brownian motion on high-resolution cell surface images and a comparison with the experimental data.

Alzheimer's disease (AD) and diabetes are clinically positively correlated. However, the connection between them is not clarified. Here, using Drosophila as a model system, we show that reducing insulin signaling can effectively suppress the toxicity from Aβ (Amyloid beta 42) expression. On the other hand, Aβ accumulation led to the elevation of fly insulin-like peptides (ILPs) and activation of insulin signaling in the brain. Mechanistically, these observations are attributed to a reciprocal competition between Drosophila insulin-like peptides and Aβ for the activity of insulin-degrading enzyme (IDE). Intriguingly, peripheral insulin signaling is decreased despite its heightened activity in the brain. While many upstream factors may modify Aβ toxicity, our results suggest that insulin signaling is the main downstream executor of Aβ damage, and thus may serve as a promising target for Alzheimer's treatment in non-diabetes patients. This study explains why more Alzheimer's cases are found in diabetes patients.

Potassium ion (K+) homeostasis and dynamics play critical roles in biological activities. Here we describe three genetically encoded K+ indicators. KIRIN1 (potassium (K) ion ratiometric indicator) and KIRIN1-GR are Förster resonance energy transfer (FRET)-based indicators with a bacterial K+ binding protein (Kbp) inserting between the fluorescent protein FRET pairs mCerulean3/cp173Venus and Clover/mRuby2, respectively. GINKO1 (green indicator of K+ for optical imaging) is a single fluorescent protein-based K+ indicator constructed by insertion of Kbp into enhanced green fluorescent protein (EGFP). These indicators are suitable for detecting K+ at physiologically relevant concentrations in vitro and in cells. KIRIN1 enabled imaging of cytosolic K+ depletion in live cells and K+ efflux and reuptake in cultured neurons. GINKO1, in conjunction with red fluorescent Ca2+ indicator, enable dual-color imaging of K+ and Ca2+ dynamics in neurons and glial cells. These results demonstrate that KIRIN1 and GINKO1 are useful tools for imaging intracellular K+ dynamics.

Granulosa cell (GC) proliferation is essential for follicular development. FSH is a key factor in GC proliferation, and a continuous supply of high levels of ATP is necessary for cell proliferation. However, genes encoding proteins of the glycolytic pathways are poorly expressed in GCs. Therefore, we hypothesized that mitochondrial gene expression and protein synthesis play a primary role in ATP production during GC proliferation. To test this hypothesis, we performed an in vivo study of GCs collected from 23-day-old mice ovaries with or without equine chorionic gonadotropin (eCG) priming. It was observed that mitochondrial activity with membrane potential, expression of protein-coding genes (Nd1-6, Cytb, Atpase6,8) and transcription-related genes (Polrmt, Tfam, Tfb2m), copy number of mitochondrial (mt-)DNA, and protein synthesis were increased in GCs after 24 hours of eCG injection and mostly maintained elevated up to 48 hours. Therefore, we performed in vitro culture of GCs in DMEM medium supplemented with FSH, testosterone, and serum and containing different glucose concentrations with or without d-chloramphenicol (CRP) for 24 hours. GC proliferation and ATP production were observed to be independent of glucose concentration. Furthermore, FSH-induced mitochondrial activity with membrane potential, ATP content, BrdU-incorporated cell proliferation, intensity of mt-ND1 and mt-ND6 proteins, and expressions of marker genes for proliferation and differentiation were significantly decreased by CRP treatment. These results revealed the crucial role of mitochondria in the supply of ATP and the necessity of mitochondrial gene expression and protein synthesis in not only the proliferation but also the differentiation of GCs during follicular development.

This National Cancer Database (NCDB) analysis evaluates the clinical outcomes of postoperative chemotherapy followed by concurrent chemoradiation (C + CRT) compared to concurrent chemoradiation (CRT) alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer.

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA-associated shift in microbial community composition (P < 0.001), independent of sex, with no evidence of a UDCA effect on microbial richness (P > 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post-UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow-up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex-specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.

α-Amylases are starch-degrading enzymes and used widely, the study on thermostability of α-amylase is a central requirement for its application in life science and biotechnology.

To date, the relationship of Th17 and Treg cells to Henoch-Schonlein purpura (HSP) in children remains controversial. Therefore, a systematic review and meta-analysis was conducted to reveal the potential role of the Th17 and Treg cells in children in acute stage of HSP.

Several studies have reported the benefits of traditional Chinese exercises (TCEs) on hypertension; however, a consensus regarding the effectiveness and safety of TCEs for patients with hypertension has not been reached.

The relationship between asbestos and prostate cancer (PCa) is not well understood due to small number of cases. This study aimed to determine the incidence and mortality of PCa among workers or residents exposed to asbestos based on a systematic review and meta-analysis METHODS: All published studies citing the standardized mortality ratio (SMR) or standardized incidence ratio (SIR) of PCa in workers or residents exposed to asbestos were collected by conducting a search on PubMed, EMBASE, Cochrane Library, and Web of Science before April 2018. Standardized mortality rate for PCa with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA (Version14.0). This study is registered with PROSPERO, number CRD42018095195.

Dyslipidemia is one of the most popular metabolic diseases and an important risk factor for arteriosclerotic cardiovascular diseases. In China, Wendan decoction (WDD) has been widely used to treat hyperlipidemia. However, no systematic review has been found. In order to evaluate the efficacy and safety of WDD in the treatment of dyslipidemia, a meta-analysis and systematic evaluation are conducted.

Nicorandil, which is a mitochondrial ATP-sensitive potassium channel opener, is believed to improve perioperative myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI), but recent studies have shown that nicorandil treatment did not improve functional and clinical outcomes in patients with angina pectoris who underwent elective PCI. We performed a meta-analysis to investigate the protective effect of nicorandil on perioperative injury in patients with angina pectoris who underwent elective PCI.

We aimed to evaluate the safety and efficacy of combined airway and esophageal stents under fluoroscopy guidance and local anesthesia for patients with malignant tracheobronchial and esophageal disease. This retrospective analysis included 35 consecutive patients underwent combined stenting from March 2012 to August 2016. All patients underwent chest computed tomography scans before stenting and during follow-up. Thirty-nine airway stents and 43 esophageal covered stents were implanted. The indication of stenting, technical success and postinterventional complications were collected and analyzed. Thirty-nine airway stents and 43 esophageal covered stents were implanted. Stenting failed in 1 airway stent, and 2 esophageal stents, with technology success rates of 97.4% and 95.3%, respectively. No procedure-related death occurred, only 1 patient died from failure of respiration due to esophagotracheal fistula. The median interval between 2 stenting was 13.0 days. Both dyspnea and dysphasia were significantly relieved after stenting. Restenosis after stenting (7.7%) was the most common complication for airway stenting, all these cases required second stenting. Stent migration (7.0%) was the most common complication after esophageal stenting, 1 case had to receive airway stenting and 1 case received replacement of esophageal stent. During follow up, 23 patients were clinically cured, 2 patients were improved in symptoms, and 1 was invalid. Eight deaths were found in total. The 1-year, 3-year, and 5-year survival rates were 82.4%, 78.8%, and 78.8%, respectively. In conclusion, combined airway and esophageal stents implantation under fluoroscopy guidance and local anesthesia are safe and effective for malignant tracheobronchial and esophageal disease.

The IUCN (International Union for Conservation of Nature) Red List categories and criteria are the most widely used framework for assessing the relative extinction risk of species. The criteria are based on quantitative thresholds relating to the size, trends, and structure of species' distributions and populations. However, data on these parameters are sparse and uncertain for many species and unavailable for others, potentially leading to their misclassification or classification as data deficient. We devised an approach that combines data on land-cover change, species-specific habitat preferences, population abundance, and dispersal distance to estimate key parameters (extent of occurrence, maximum area of occupancy, population size and trend, and degree of fragmentation) and hence predict IUCN Red List categories for species. We applied our approach to nonpelagic birds and terrestrial mammals globally (∼15,000 species). The predicted categories were fairly consistent with published IUCN Red List assessments, but more optimistic overall. We predicted 4.2% of species (467 birds and 143 mammals) to be more threatened than currently assessed and 20.2% of data deficient species (10 birds and 114 mammals) to be at risk of extinction. Incorporating the habitat fragmentation subcriterion reduced these predictions 1.5-2.3% and 6.4-14.9% (depending on the quantitative definition of fragmentation) for threatened and data deficient species, respectively, highlighting the need for improved guidance for IUCN Red List assessors on the application of this aspect of the IUCN Red List criteria. Our approach complements traditional methods of estimating parameters for IUCN Red List assessments. Furthermore, it readily provides an early-warning system to identify species potentially warranting changes in their extinction-risk category based on periodic updates of land-cover information. Given our method relies on optimistic assumptions about species distribution and abundance, all species predicted to be more at risk than currently evaluated should be prioritized for reassessment.

In flies, the olfactory information is carried from the first relay in the brain, the antennal lobe, to the mushroom body (MB) and the lateral horn (LH). Olfactory associations are formed in the MB. The LH was ascribed a role in innate responses based on the stereotyped connectivity with the antennal lobe, stereotyped physiological responses to odors, and MB silencing experiments. Direct evidence for the functional role of the LH is still missing. Here, we investigate the behavioral role of the LH neurons (LHNs) directly, using the CO2 response as a paradigm. Our results show the involvement of the LH in innate responses. Specifically, we demonstrate that activity in two sets of neurons is required for the full behavioral response to CO2. Tests of the behavioral response to other odors indicate the neurons are selective to CO2 response. Using calcium imaging, we observe that the two sets of neurons respond to CO2 in a different manner. Using independent manipulation and recording of the two sets of neurons, we find that the one that projects to the superior intermediate protocerebrum (SIP) also outputs to the local neurons within the LH. The design of simultaneous output at the LH and the SIP, an output of the MB, allows for coordination between innate and learned responses.

Beiging of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of metabolic diseases through norepinephrine (NE)-mediated signaling pathways. Although previous studies report NE clearance mechanisms via SLC6A2 on sympathetic neurons or proinflammatory macrophages in adipose tissues (ATs), the low catecholamine clearance capacity of SLC6A2 may limit the cleaning efficiency. Here, we report that mouse organic cation transporter 3 (Oct3; Slc22a3) is highly expressed in WAT and displays the greatest uptake rate of NE as a selective non-neural route of NE clearance in white adipocytes, which differs from other known routes such as adjacent neurons or macrophages. We further show that adipocytes express high levels of NE degradation enzymes Maoa, Maob, and Comt, providing the molecular basis on NE clearance by adipocytes together with its reuptake transporter Oct3. Under NE administration, ablation of Oct3 induces higher body temperature, thermogenesis, and lipolysis compared with littermate controls. After prolonged cold challenge, inguinal WAT (ingWAT) in adipose-specific Oct3-deficient mice shows much stronger browning characteristics and significantly elevated expression of thermogenic and mitochondrial biogenesis genes than in littermate controls, and this response involves enhanced β-adrenergic receptor (β-AR)/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)-responsive element binding protein (Creb) pathway activation. Glycolytic genes are reprogrammed to significantly higher levels to compensate for the loss of ATP production in adipose-specific Oct3 knockout (KO) mice, indicating the fundamental role of glucose metabolism during beiging. Inhibition of β-AR largely abolishes the higher lipolytic and thermogenic activities in Oct3-deficient ingWAT, indicating the NE overload in the vicinity of adipocytes in Oct3 KO adipocytes. Of note, reduced functional alleles in human OCT3 are also identified to be associated with increased basal metabolic rate (BMR). Collectively, our results demonstrate that Oct3 governs β-AR activity as a NE recycling transporter in white adipocytes, offering potential therapeutic applications for metabolic disorders.

Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 (IGF1) receptor (IGF1R). Models were parameterized using published datasets reporting protein copy numbers and site-specific binding affinities. Simulations were facilitated by a novel application of model restructuration, to reduce redundancy in rule-derived equations. We compare predictions obtained via numerical simulation of the model to those obtained through simple prediction methods, such as through an analytical approximation, or ranking by copy number and/or KD value, and find that the simple methods are unable to recapitulate the predictions of numerical simulations. We created 45 cell line-specific models that demonstrate how early events in IGF1R signaling depend on the protein abundance profile of a cell. Simulations, facilitated by model restructuration, identified pairs of IGF1R binding partners that are recruited in anti-correlated and correlated fashions, despite no inclusion of cooperativity in our models. This work shows that the outcome of competition depends on the physicochemical parameters that characterize pairwise interactions, as well as network properties, including network connectivity and the relative abundances of competitors.

C-reactive proteins (CRPs) are among the faster acute-phase inflammation-responses proteins encoded by one gene (hcrp) in humans and seven genes (crp1-7) in zebrafish (Danio rerio) with importance in bacterial and viral infections. In this study, we described novel preferential bindings of 25-hydroxycholesterol (25HOCh) to CRP1-7 compared with other lipids and explored the antiviral effects of both 25HOCh and CRP1-7 against spring viremia carp virus (SVCV) infection in zebrafish. Both in silico and in vitro results confirmed the antiviral effect of 25HOCh and CRP1-7 interactions, thereby showing that the crosstalk between them differed among the zebrafish isoforms. The presence of oxidized cholesterols in human atherosclerotic plaques amplifies the importance that similar interactions may occur for vascular and/or neurodegenerative diseases during viral infections. In this context, the zebrafish model offers a genetic tool to further investigate these interactions.