Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection: A nationwide cohort study.

This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service-National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person-years of follow-up (median follow-up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20-1.35), HCV infection (HR: 1.31, 95% CI: 1.16-1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31-1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92-3.15)], gallbladder [1.55 (1.05-2.29)], pancreas [1.52 (1.07-2.15)], stomach [1.39 (1.22-1.58)], lung [1.27 (1.04-1.55)], colorectum [1.21 (1.03-1.42)] and thyroid cancer [1.20 (1.05-1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35-79.78)], gallbladder [2.90 (1.62-5.18)], prostate [2.51 (1.65-3.82)] and thyroid cancer [1.46 (1.10-1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.

Association between IL12B polymorphisms and inflammatory bowel disease in Caucasian population: A meta-analysis.

BACKGROUND: Published studies on association between IL12B (G/A) rs10045431, (T/C)rs6887695 polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian population have yielded conflicting results. The aim of this study was to potentially provide more reliable conclusions by conducting a meta-analysis. METHODS: Published studies concerned association between IL12B rs10045431, rs6887695 polymorphisms and IBD were searched from the Wiley Online Library, PubMed, Web of Science and the CNKI database. The odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of the relationship. The false positive report probabilities (FPRPs) test and trial sequential analysis (TSA) was performed to investigated the reliability of results. RESULTS: A total of 20 studies comprising 10761 Crohn's disease (CD), 10921 ulcerative colitis (UC) and 18381 controls were included in this meta-analysis. Overall, the pooled results showed that IL12B rs6887695 polymorphism significantly increased both CD and UC risk under all model, while IL12B rs10045431 polymorphism dramatically decreased both CD and UC risk under all model. FPRP and TSA demonstrated that above associations was confirmed in the present study. CONCLUSION: The results of meta-analysis indicate IL12B rs10045431 and rs6887695 polymorphisms significantly associate with IBD in Caucasian population.

Site-Selective Tyrosine Reaction for Antibody-Cell Conjugation and Targeted Immunotherapy.

Targeted immunotherapies capitalize on the exceptional binding capabilities of antibodies to stimulate a host response that effectuates long-lived tumor destruction. One example is the conjugation of immunoglobulins (IgGs) to immune effector cells, which equips the cells with the ability to recognize and accurately kill malignant cells through a process called antibody-dependent cellular cytotoxicity (ADCC). In this study, a chemoenzymatic reaction is developed that specifically functionalizes a single tyrosine (Tyr, Y) residue, Y296, in the Fc domain of therapeutic IgGs. A one-pot reaction that combines the tyrosinase-catalyzed oxidation of tyrosine to o-quinone with a subsequent [3+2] photoaddition with vinyl ether is employed. This reaction installs fluorescent molecules or bioorthogonal groups at Y296 of IgGs or the C-terminal Y-tag of an engineered nanobody. The Tyr-specific reaction is utilized in constructing monofunctionalized antibody-drug conjugates (ADCs) and antibody/nanobody-conjugated effector cells, such as natural killer cells or macrophages. These results demonstrate the potential of site-selective antibody reactions for enhancing targeted cancer immunotherapy.

Trialkylphosphonium oxoborates as C(sp3)-H oxyanion holes and their application in catalytic chemoselective acetalization.

The use of trialkylphosphonium oxoborates (TOB) as catalysts is reported. The site-isolated borate counter anion in a TOB catalyst increases the availability of C(sp3)-H to interact with electron donor substrates. The catalytic protocol is applicable to a wide range of substrates in the acetalization reaction and provides excellent chemoselectivity in the acetalization over thioacetalization in the presence of alcohols and thiols, which is otherwise hard to achieve using typical acid catalysts. Experimental and computational studies revealed that the TOB catalysts have multiple preorganized C(sp3)-Hs that serve as a mimic of oxyanion holes, which can stabilize the oxyanion intermediates via multiple C(sp3)-H non-classical hydrogen bond interactions.

Science diplomacy in medical physics - an international perspective.

Purpose: Science diplomacy in medical physics is a relatively young research field and translational practice that focuses on establishing international collaborations to address some of the questions biomedical professionals face globally. This paper aims to present an overview of science diplomacy in medical physics, from an international perspective, illustrating the ways collaborations within and across continents can lead to scientific and professional achievements that advance scientific growth and improve patients care. Methods: Science diplomacy actions were sought that promote collaborations in medical physics across the continents, related to professional and scientific aspects alike. Results: Several science diplomacy actions have been identified to promote education and training, to facilitate research and development, to effectively communicate science to the public, to enable equitable access of patients to healthcare and to focus on gender equity within the profession as well as healthcare provision. Scientific and professional organizations in the field of medical physics across all continents have adopted a number of efforts in their aims, many of them with great success, to promote science diplomacy and to foster international collaborations. Conclusions: Professionals in medical physics can advance through international cooperation, by building strong communication across scientific communities, addressing rising demands, exchange scientific information and knowledge.

Association between PTGER4 polymorphisms and inflammatory bowel disease risk in Caucasian: A meta-analysis.

BACKGROUND: The results from previous studies on association between prostaglandin E receptor 4 (PTGER4) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian were conflict. The present study aimed to investigate the genetic association by conducting a meta-analysis. METHODS: Systematic literature search was conducted through Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to investigate the associations between rs4613763 T/C, 17234657T/G polymorphisms, and IBD risk in Caucasian. RESULTS: Twenty case-control studies consisting of 18,495 Crohn disease (CD) patients and 4203 ulcerative colitis (UC) patients, as well as 26,063 controls were included in this meta-analysis. The rs4613763T/C polymorphism had obvious influence on CD, UC risk in Caucasian. However, rs17234657T/G polymorphism had obvious influence on CD but not UC in Caucasian. CONCLUSION: This meta-analysis suggested that both the rs4613763 T/C, rs17234657T/G polymorphisms had obvious influence on risk of CD in Caucasian. In addition, rs4613763 T/C, polymorphism had obvious influence on risk of UC in Caucasian.

Effects of Gegen (Puerariae lobatae Radix) water extract on improving detrusor overactivity in spontaneously hypertensive rats.

AIM: Ex vivo experiments showed that the water extract of Puerariae lobatae Radix (named Gegen in Chinese) induced detrusor relaxation. The aim of this study was to prove the in vivo efficacy of Gegen on improving detrusor overactivity and its possible synergism with darifenacin (a first-line muscarinic receptor-3 inhibitor) in spontaneously hypertensive rats (SHR), a rat model exhibiting symptoms of detrusor overactivity. METHOD: After daily oral administration of Gegen 30 (Gegen, 30mg/kg); Gegen 300 (Gegen, 300mg/kg); Low_Dar (darifenacin, 3mg/kg); High_Dar (darifenacin, 30mg/kg) Low_Dar+Gegen 30 or High_Dar+Gegen 30 for 3 weeks, bladder detrusor strips of the rats were isolated and assessed with different stimulators for the measurement of tonic and phasic contractile activities (including phasic amplitude and frequency). Modes of stimulation included the use of carbachol, isoprenaline and electrical field stimulation (EFS). RESULTS: All drug treatments significantly reduced carbachol-stimulated tonic contractile activities, but did not change the phasic amplitude. Meanwhile, the treatments with Gegen 300; Low_Dar; Low_Dar+Gegen 30; and High_Dar+Gegen 30 decreased carbachol-stimulated phasic frequency. Gegen 300 and Low_Dar+Gegen 30 showed stronger potency on lowering EFS-induced responses. Under isoprenaline-induced relaxation, only Gegen 300 significantly enhanced this relaxation by decreasing tonic contraction; Gegen 300; Low_Dar; Low_Dar+Gegen 30; and High_Dar+Gegen 30 increased the reduction of phasic frequency, but all treatment did not alter their phasic amplitude. Combination Index (CI) showed that the combination with Low_Dar and Gegen 30 had very strong synergism (CI <0.1) on inhibiting EFS-induced contractile response. CONCLUSION: Gegen improved detrusor overactivity through neurogenic and anti-muscarinic mechanisms. Gegen and darifenacin together attained synergism for detrusor overactivity treatment via the neurogenic pathway.

Complete mitochondrial genome of Peronia verruculata (Gastropoda: Pulmonata: Systellommatophora: Onchidiidae).

The complete mitochondrial genome sequence of Peronia verruculata is firstly described in the article. The mitogenome (13,861 bp) contains 22 tRNA genes, 2 ribosomal RNA genes and 13 protein-coding genes. The characteristic is the typical bivalvia mitochondrial gene composition.

Suppressive effect of natural sesquiterpenoids on inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) activity in mouse macrophage cells.

Prostaglandins and nitric oxide produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the processes of inflammation and carcinogenesis. These potential COX-2 and iNOS inhibitors have been considered as antiinflammatory and cancer chemopreventive agents. In this study, we investigated the effect of natural sesquiterpenoids isolated from plants of the Zingiberaceae family on the activities of COX-2 and iNOS in cultured lipopolysaccharide (LPS)-activated mouse macrophage cell RAW 264.7 to discover new lead compounds as COX-2 or iNOS inhibitors. Xanthorrhizol, a sesquiterpenoid, isolated from the rhizome of Curcuma xanthorrhiza Roxb. (Zingiberaceae), exhibited a potent inhibition of COX-2 (IC50 = 0.2 microg/mL) and iNOS activity (IC50 = 1.0 microg/mL) in the assay system of prostaglandin E2 (PGE2) accumulation and nitric oxide production, respectively. Western blot analyses revealed that the inhibitory potential of xanthorrhizol on the COX-2 activity coincided well with the suppression of COX-2 protein expression in LPS-induced macrophages. In addition, sesquiterpenoids beta-turmerone and ar-turmerone isolated from the rhizome of Curcuma zedoaria Roscoe (Zingiberaceae) also showed a potent inhibitory activity of COX-2 (beta-turmerone, IC50 = 1.6 microg/mL; ar-turmerone, IC50 = 5.2 microg/mL) and iNOS (beta-turmerone, IC50 = 4.6 microg/mL; ar-turmerone, IC50 = 3.2 microg/mL). These results suggest that natural sesquiterpenoids from C. xanthorrhiza and C. zedoaria might be lead candidates for further developing COX-2 or iNOS inhibitors possessing cancer chemopreventive or anti-inflammatory properties.

Chronic ketamine treatment-induced changes in contractility characteristics of the mouse detrusor.

PURPOSE: To understand bladder contractility changes induced by chronic ketamine treatment, noting the prevalence of its abuse worldwide. METHODS: A mouse model of chronic ketamine treatment was used and detrusor strip contractility was measured. Rising and falling phases of contractile responses as well as maximal, average sustained and phasic contractions were measured. RESULTS: While maximal contractility of ketamine-treated strips was identical to the saline controls, the former displayed slower contraction rates under K(+)-Krebs, carbachol and electrical stimulation. The decay phase of electrically stimulated responses was also slower at most stimulation frequencies in the ketamine-treated strips. Greater sensitivity to varying the strengths of stimuli was observed in the ketamine-treated strips. CONCLUSIONS: Altered contractility characteristics of the bladder after chronic ketamine treatment were revealed, which could potentially be useful in the development of improved treatment regimens.

Low concentrations of niflumic acid enhance basal spontaneous and carbachol-induced contractions of the detrusor.

PURPOSE: The urinary bladder expresses Ca(2+)-activated Cl(-) channels (CACC), but its physiological role in governing contractility remains to be defined. The CACC modulator niflumic acid (NFA) is widely used despite the variable results arisen from different drug concentrations used. This study was designed to examine the effects of NFA at low concentrations on detrusor strip contractility. METHODS: Rat detrusor strips with mucosa-intact (+MU) and mucosa-denuded (-MU) were prepared in transverse (Tr) and longitudinal (Lg) with respect to the bladder orientation. Isometric force measurements were made at baseline (for spontaneous phasic contractile activity) and during drug stimulation (by carbachol, CCh) with and without NFA. RESULTS: NFA (1 and 10 µmol/L) pretreatment enhanced CCh-induced contractions more in +MU than -MU strips with no selectivity on contractile direction. For spontaneous phasic contractions, NFA-treated strips in the Tr direction showed increased phasic amplitude, while phasic frequency was unchanged. CONCLUSIONS: The findings suggest low concentrations of NFA having a potentiating effect on detrusor contractions that was sensitive to the MU and contractile direction.

Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade.

NMDA receptor (NMDA-R) is an important molecular entity governing a wide range of functions in the central nervous system. For example, the NMDA-R is involved in memory and cognition, and impairment of both (as in Alzheimer's Disease) is attributed to NMDA-mediated neurotoxicity. With greater understanding of the NMDA-R structure, antagonists with varying degrees of binding-site and subtype selectivity have been developed and put into clinical use. Discovery of target-specific Chinese herbs have also been made in parallel. This article provides an overview of the known active sites on the NMDA-R, followed by a discussion of the relevant herbs and their constituents. Experimental evidence supporting the inhibitory role of the herbal compounds on the NMDA-R is highlighted. For some of the compounds, potential research directions are also proposed to further elucidate the underlying mechanisms of the herbs. It is envisaged that future investigations based on the present data will allow more clinically relevant herbs to be identified.

Complete mitochondrial genome of the jackknife clam Solen grandis (Veneroida, Solenidae).

The complete mitochondrial genome sequence of Solen grandis that lives in sub-tidal waters and being buried in muddy to fine sand substrates, is described in this paper. The mitogenome (16,794 bp) consists of 12 protein-coding genes (loss of ATPase subunit 8), 22 tRNA genes, 2 rRNA genes and 1 putative control region. It is the typical bivalve mitochondrial gene composition.

Choroidal neovascularization secondary to sorsby fundus dystrophy treated with intravitreal bevacizumab.

PURPOSE: To report a case of extrafoveal choroidal neovascularization secondary to Sorsby fundus dystrophy that maintained 20/20 visual acuity over 14 months with intravitreal bevacizumab therapy. METHODS: Interventional case report of as-needed treatment with intravitreal bevacizumab of a 38-year-old lady with choroidal neovascularization from Sorsby fundus dystrophy. RESULTS: Three injections of intravitreal bevacizumab were given over 14.5 months, maintaining visual acuity at 20/20. CONCLUSION: Intravitreal bevacizumab therapy appears to maintain vision in patients with choroidal neovascularization from Sorsby fundus dystrophy.

Complete mitochondrial genome of Paraoncidium reevesii (Gastropoda, Pulmonata, Systellommatophora, Onchidiidae).

The complete mitochondrial genome of Paraoncidium reevesii was firstly determined in this paper. The mitogenome (13,842 bp) consists of 13 protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes, and 1 putative control region (CR). CR is not well characterized due to lack of discrete conserved sequence blocks. This characteristic is similar with CRs of other invertebrate mitochondrial genomes.

Protective effects and potential mechanisms of Pien Tze Huang on cerebral chronic ischemia and hypertensive stroke.

BACKGROUND: Stroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH), a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats. METHODS: The effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR) and stroke prone SHR (SHRsp) were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA) and immunostaining. RESULTS: Pien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCR2 in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS) damage and possibly subsequent cell death (caspase 3 assay) as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum. CONCLUSION: Pien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria.

Solid-phase artificial chaperone-assisted refolding using insoluble beta-cyclodextrin-acrylamide copolymer beads.

Solid-phase refolding methods are advantageous since they facilitate both separation of solid additives from the refolded protein and recycling of the additives. Beta-cyclodextrin-acrylamide copolymer hydrogel beads were used as a matrix for detergents in solid-phase artificial chaperone-assisted refolding and improved the yield of lysozyme (up to 65%) and carbonic anhydrase B (up to 80%), compared with conventional solid host matrices.