Different WDR36 Mutation Pattern in Chinese Patients with Primary Open-angle Glaucoma

Purpose: To determine the distribution of WD repeat domain 36 (WDR36) sequence variants in Chinese patients with primary open-angle glaucoma (POAG). Methods: One hundred and thirty-five unrelated POAG patients (82 high tension glaucoma [HTG], 42 normal tension glaucoma [NTG], and 11 juvenile-onset POAG [JOAG] patients) and 77 unrelated controls were recruited. All 23 coding exons and splicing junctions of WDR36 were sequenced using BigDye® Terminator v3.1 cycle sequencing kit. Single nucleotide polymorphism (SNP) and haplotype associations were analyzed using PLINK (version 1.04). Results: Nineteen sequence alterations were identified, and eight of them were novel including two novel nonsynonymous SNPs (L240V and I713V). Except the common I264V polymorphism, no other previously reported disease-causing or disease-susceptibility mutations were found. The novel I713V mutation was observed in three (3.7%) patients with HTG. One intronic SNP, IVS5+30C>T (rs10038177), showed significantly higher frequency of minor allele T in HTG patients (16.5%) than in controls (1.3%; Odds ratio [OR]=15.0, p=7.9×10−7, Bonferroni corrected p=1.5×10−5). Haplotype GTA, which is composed of rs13153937, rs10038177, and rs11241095, was significantly associated with HTG (OR=22.5, p=0.002, Bonferroni corrected p=0.013). Neither the individual SNPs nor haplotypes of WDR36 were associated with NTG or JOAG (Bonferroni corrected p>0.05). Conclusions: Findings in this study suggest WDR36 to be associated with sporadic HTG but not with NTG or JOAG. Our results also suggest a different mutation pattern of WDR36 in the Chinese population from other ethnic populations

New Perspectives on Chinese Herbal Medicine (Zhong-Yao) Research and Development

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery

Color-Octet-Electroweak-Doublet Scalars and the CDF Dijet Anomaly

We study the phenomenology of color-octet scalars in the (8, 2)1/2 representation in the context of the 3.2\sigma excess, in the dijet invariant mass spectrum of the W+jj final state, recently observed by the CDF collaboration. We consider the region of parameter space with a sizable mass splitting between the charged and neutral color-octet scalars and consistent with electroweak precision data. We implement the principle of Minimal Flavor Violation (MFV) in order to suppress FCNC currents and reduce the number of free parameters. The excess in the W+jj channel corresponds to the charged current decay of the heavier neutral octet scalar into its lighter charged partner which decays into the two jets. In the MFV scenario, the production of the neutral color-octet is dominated by gluon fusion due to the Yukawa suppression of production via initial state quarks. As a result, no visible excess is expected in the \gamma+jj channel due to Yukawa and CKM suppression. Contributions to the Z+jj final state are suppressed for a mass spectrum where the decay of the heavier color-octet to this final state is mediated by an off-shell neutral color-octet partner. MFV allows one to control fraction of bottom quarks in the final state jets by a single ratio of two free parameters.Comment: 14 pages, 6 figures, typos corrected, references added, text and figures modified in some places for better clarity, version to appear in Physics Letters

MicroRNAs-Based Imaging Techniques in Cancer Diagnosis and Therapy.

Cancer is one of the most serious global health concerns in different populations. Several studies indicated that there are many potentially promising cellular and molecular targets for cancer therapy within cancer cells and their microenvironment. Among different cellular and molecular targets involved in cancer pathogenesis, microRNAs (miRNAs) are well known as key targets for cancer therapy. miRNAs are one of main classes of non-coding RNAs. These molecules play important roles in different critical processes of cancer pathogenesis. Hence, this makes miRNAs as a suitable tool for cancer diagnosis and therapy. There are different approaches for monitoring miRNAs in cancer patients. Some conventional approaches including next-generation sequencing, real-time polymerase chain reaction (PCR), northern blotting, and microarrays could be used for assessment of miRNAs expression. Some studies revealed that the utilization of these approaches associated with various limitations. Recently, it has been revealed that molecular imaging techniques are powerful tools for monitoring of different cellular and molecular targets involved in various diseases such as cancer. These techniques help investigators to investigate and monitor miRNAs functions through assessing different targets by fluorescent proteins, bioluminescent enzymes, molecular beacons, as well as various nanoparticles. Therefore, utilization of molecular imaging techniques could assist investigators to better monitor and more effectively treat patients during different phases of malignancy. Here, we give a review on the current state of miRNAs-based imaging techniques in cancer diagnosis and therapy. J. Cell. Biochem. 9999: 1-8, 2017. © 2017 Wiley Periodicals, Inc

The effects of a family-centered psychosocial-based nutrition intervention in patients with advanced cancer: the PiCNIC2 pilot randomised controlled trial

BACKGROUND: Malnutrition in advanced cancer patients is common but limited and inconclusive data exists on the effectiveness of nutrition interventions. Feasibility and acceptability of a novel family-based nutritional psychosocial intervention were established recently. The aims of this present study were to assess the feasibility of undertaking a randomised controlled trial of the latter intervention, to pilot test outcome measures and to explore preliminary outcomes.METHODS: Pilot randomised controlled trial recruiting advanced cancer patients and family caregivers in Australia and Hong Kong. Participants were randomised and assigned to one of two groups, either a family-centered nutritional intervention or the control group receiving usual care only. The intervention provided 2-3 h of direct dietitian contact time with patients and family members over a 4-6-week period. During the intervention, issues with nutrition impact symptoms and food or eating-related psychosocial concerns were addressed through nutrition counselling, with a focus on improving nutrition-related communication between the dyads and setting nutritional goals. Feasibility assessment included recruitment, consent rate, retention rate, and acceptability of assessment tools. Validated nutritional and quality of life self-reported measures were used to collect patient and caregiver outcome data, including the 3-day food diary, the Patient-Generated Subjective Global Assessment Short Form, the Functional Assessment Anorexia/Cachexia scale, Eating-related Distress or Enjoyment, and measures of self-efficacy, carers' distress, anxiety and depression.RESULTS: Seventy-four patients and 54 family caregivers participated in the study. Recruitment was challenging, and for every patient agreeing to participate, 14-31 patients had to be screened. The consent rate was 44% in patients and 55% in caregivers. Only half the participants completed the trial's final assessment. The data showed promise for some patient outcomes in the intervention group, particularly with improvements in eating-related distress (p = 0.046 in the Australian data; p = 0.07 in the Hong Kong data), eating-related enjoyment (p = 0.024, Hong Kong data) and quality of life (p = 0.045, Australian data). Energy and protein intake also increased in a clinically meaningful way. Caregiver data on eating-related distress, anxiety, depression and caregiving burden, however, showed little or no change.CONCLUSIONS: Despite challenges with participant recruitment, the intervention demonstrates good potential to have positive effects on patients' nutritional status and eating-related distress. The results of this trial warrant a larger and fully-powered trial to ascertain the effectiveness of this intervention.TRIAL REGISTRATION: The trial was registered with the Australian &amp; New Zealand Clinical Trials Registry, registration number ACTRN12618001352291 .</p

Multivariate Neural Representations of Value during Reward Anticipation and Consummation in the Human Orbitofrontal Cortex

The role of the orbitofrontal cortex (OFC) in value processing is a focus of research. Conventional imaging analysis, where smoothing and averaging are employed, may not be sufficiently sensitive in studying the OFC, which has heterogeneous anatomical structures and functions. In this study, we employed representational similarity analysis (RSA) to reveal the multi-voxel fMRI patterns in the OFC associated with value processing during the anticipatory and the consummatory phases. We found that multi-voxel activation patterns in the OFC encoded magnitude and partial valence information (win vs. loss) but not outcome (favourable vs. unfavourable) during reward consummation. Furthermore, the lateral OFC rather than the medial OFC encoded loss information. Also, we found that OFC encoded values in a similar way to the ventral striatum (VS) or the anterior insula (AI) during reward anticipation regardless of motivated response and to the medial prefrontal cortex (MPFC) and the VS in reward consummation. In contrast, univariate analysis did not show changes of activation in the OFC. These findings suggest an important role of the OFC in value processing during reward anticipation and consummation.This study was supported by grants from the National Science Fund China (81088001, 31500894 and 91132701), the Strategic Priority Research Programme (B) of the Chinese Academy of Science (XDB02030002), the Beijing Training Project for the Leading Talents in S & T (Z151100000315020), the Beijing Municipal Science & Technology Commission Grant, and a grant from the initiation fund of the CAS/SAFEA International Partnership Programme for Creative Research Team (Y2CX131003). LS is funded by the NIHR Biomedical Research Centre and Biomedical Research Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge