CTNNB1-related disorder is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment, microcephaly, truncal hypotonia, peripheral spasticity, visual ...defects, and dysmorphic features. In this case series, we report the clinical and molecular findings of nine Chinese patients affected by CTNNB1-related disorders. The facial features of these affected individuals appear to resemble what had been previously described, with thin upper lip (77.8%) and hypoplastic alae nasi (77.8%) being the most common. Frequently reported clinical characteristics in our cohort include developmental delay (100%), peripheral spasticity (88.9%), truncal hypotonia (66.7%), microcephaly (66.7%), and dystonia (44.4%). While various eye manifestations were reported, two affected individuals (22.2%) in our cohort had familial exudative vitreoretinopathy. One of the affected individuals had craniosynostosis, a feature not reported in the literature before. To our knowledge, this is the first reported Chinese case series of CTNNB1-related neurodevelopmental disorders. Further studies are required to look into whether ethnic differences play a role in phenotypic variations.
Human papillomavirus (HPV) infections are a leading cause of viral‐induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV ...oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV‐induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/β‐catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV‐positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV‐associated diseases.
Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. ...One of the major aetiologies contributing to cervical cancer is the persistent infection by the cancer-causing types of the human papillomavirus. The disease is preventable if the premalignant lesion is detected early and managed effectively. In this review, we outlined the standard guidelines that have been introduced and implemented worldwide for decades, including the cytology, the HPV detection and genotyping, and the immunostaining of surrogate markers. In addition, the staging system used to classify the premalignancy and malignancy of the uterine cervix, as well as the safety and efficacy of the various treatment modalities in clinical trials for cervical cancers, are also discussed. In this millennial world, the advancements in computer-aided technology, including robotic modules and artificial intelligence (AI), are also incorporated into the screening, diagnostic, and treatment platforms. These innovations reduce the dependence on specialists and technologists, as well as the work burden and time incurred for sample processing. However, concerns over the practicality of these advancements remain, due to the high cost, lack of flexibility, and the judgment of a trained professional that is currently not replaceable by a machine.
IntroductionHealth information about COVID-19 has been circulating in social networking sites, including unproven claims that smoking and alcohol drinking could protect against COVID-19. We examined ...if exposure to such claims was associated with changes in tobacco and alcohol consumption.MethodsWe conducted a population-based, landline and mobile phone survey of 1501 randomly sampled adults aged 18 years or older (47.5% male) in Hong Kong in April 2020. Respondents reported if they had ever seen claims that ‘smoking/alcohol drinking can protect against COVID-19’ from popular social networking platforms. Current tobacco and alcohol users reported if they had increased or reduced their consumption since the outbreak. Prevalence data were weighted by sex, age and education of the general adult population.Results19.0% (95% CI 16.8% to 21.4%) of all respondents reported having seen claims that ‘smoking/alcohol drinking can protect against COVID-19’ from social networking sites. Multinomial logistic regression showed that exposure to the claims was significantly associated with increased tobacco use (OR 2.37, 95% CI 1.08 to 5.20) in current tobacco users (N=280) and increased alcohol use (OR 4.16, 95% CI 2.00 to 8.67) in current drinkers (N=722), adjusting for sex, age, education level, alcohol/tobacco use status, home isolation, anxiety and depressive symptoms, and survey method.ConclusionOur results first showed that exposure to health misinformation that smoking/alcohol drinking can protect against COVID-19 was associated with self-reported increases in tobacco and alcohol consumption in Chinese during the pandemic.
The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we ...identified, for the first time, that Aurora kinase B (AurB) is a
interacting partner of E6. We systematically characterized the AurB-E6 complex formation and its consequences in carcinogenesis using a series of
and cell-based assays. We also assessed the efficacy of Aurora kinase inhibitors in halting HPV-mediated carcinogenesis using
and
models. We showed that AurB activity was elevated in HPV-positive cells, and this correlated positively with the E6 protein level. E6 interacted directly with AurB in the nucleus or mitotic cells. A previously unidentified region of E6, located upstream of C-terminal E6-PBM, was important for AurB-E6 complex formation. AurB-E6 complex led to reduced AurB kinase activity. However, the AurB-E6 complex increased the hTERT protein level and its telomerase activity. On the other hand, AurB inhibition led to the inhibition of telomerase activity, cell proliferation, and tumor formation, even though this may occur in an HPV-independent manner. In summary, this study dissected the molecular mechanism of how E6 recruits AurB to induce cell immortalization and proliferation, leading to the eventual cancer development. Our findings revealed that the treatment of AZD1152 exerted a non-specific anti-tumor effect. Hence, a continuous effort to seek a specific and selective inhibitor that can halt HPV-mediated carcinogenesis should be warranted.
This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and ...2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.
An unstable expansion of the polyglutamine repeat within exon 1 of the protein Htt (huntingtin) causes HD (Huntington's disease). Mounting evidence shows that accumulation of N-terminal mutant Htt ...fragments is the source of disruption of normal cellular processes which ultimately leads to neuronal cell death. Understanding the degradation mechanism of mutant Htt and improving its clearance has emerged as a new direction in developing therapeutic approaches to treat HD. In the present study we show that the brain-enriched adaptor protein FE65 is a novel interacting partner of Htt. The binding is mediated through WW-polyproline interaction and is dependent on the length of the polyglutamine tract. Interestingly, a reduction in mutant Htt protein level was observed in FE65-knockdown cells, and the process requires the UPS (ubiquitin/proteasome system). Moreover, the ubiquitination level of mutant Htt was found to be enhanced when FE65 is knocked down. Immunofluroescence staining revealed that FE65 associates with mutant Htt aggregates. Additionally, we demonstrated that overexpression of FE65 increases mutant Htt-induced cell death both in vitro and in vivo. These results suggest that FE65 facilitates the accumulation of mutant Htt in cells by preventing its degradation via the UPS, and thereby enhances the toxicity of mutant Htt.
SARS-CoV-2 is a positive-sense single-stranded RNA virus with emerging mutations, especially on the Spike glycoprotein (S protein). To delineate the genomic diversity in association with geographic ...dispersion of SARS-CoV-2 variant lineages, we collected 939,591 complete S protein sequences deposited in the Global Initiative on Sharing All Influenza Data (GISAID) from December 2019 to April 2021. An exponential emergence of S protein variants was observed since October 2020 when the four major variants of concern (VOCs), namely, alpha (α) (B.1.1.7), beta (β) (B.1.351), gamma (γ) (P.1), and delta (δ) (B.1.617), started to circulate in various communities. We found that residues 452, 477, 484, and 501, the 4 key amino acids located in the hACE2 binding domain of S protein, were under positive selection. Through in silico protein structure prediction and immunoinformatics tools, we discovered D614G is the key determinant to S protein conformational change, while variations of N439K, T478I, E484K, and N501Y in S1-RBD also had an impact on S protein binding affinity to hACE2 and antigenicity. Finally, we predicted that the yet-to-be-identified hypothetical N439S, T478S, and N501K mutations could confer an even greater binding affinity to hACE2 and evade host immune surveillance more efficiently than the respective native variants. This study documented the evolution of SARS-CoV-2 S protein over the first 16 months of the pandemic and identified several key amino acid changes that are predicted to confer a substantial impact on transmission and immunological recognition. These findings convey crucial information to sequence-based surveillance programs and the design of next-generation vaccines. IMPORTANCE Our study showed the global distribution of SARS-CoV-2 S protein variants from January 2020 to the end of April 2021. We highlighted the key amino acids of S protein subjected to positive selection. Using computer-aided approaches, we predicted the impact of the amino acid variations in S protein on viral infectivity and antigenicity. We also predicted the potential amino acid mutations that could arise in favor of SARS-CoV-2 virulence. These findings are vital for vaccine designing and anti-SARS-CoV-2 drug discovery in an effort to combat COVID-19.
Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis with a low survival rate of ...15–25%. Depending upon the cell type, oesophageal carcinoma is categorised into oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC). ESCC is predominantly reported in developing countries, while EAC is more common in developed countries. Aside from the presence of exogenous co-factors, such as cigarette smoking, alcohol consumption, obesity, gastroesophageal reflux disease (GERD); infection with oncogenic viruses is suspected to be one of the major factors contributing to EC development. Oncogenic viruses, including human papillomavirus (HPV), Epstein Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) have been detected in various proportions of EC samples. Nonetheless, their aetiological roles in EC remain debatable. In this review, we garnered previous studies that focus on the association between oncogenic viruses and EC. Among these oncogenic viruses, HPV appears to have a stronger association with EC than the others. In addition, we also discuss the pros and cons of the treatment regimens to treat EC patients, including immunotherapy, chemo- and chemoradiotherapy, and their efficacy.
Purpose
To evaluate the reliability and validity of the 7-item Chinese Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS) in Hong Kong Chinese.
Methods
Under “A Jockey Club Initiative for a ...Harmonious Society” project, a random telephone survey was conducted in 2017 on 1331 Hong Kong Chinese residents aged ≥ 18. A confirmatory factor analysis (CFA) was conducted to test the factorial validity. The Spearman correlations of the SWEMWBS with other scales including the 12-item short form health survey (SF-12), family well-being, self-rated health, the global happiness item (GHI), subjective happiness scale (SHS), and patient health questionnaire-4 (PHQ-4), were used to evaluate the convergent and divergent validity. Known-group validity was also assessed. We calculated congeneric reliability based on standardized factor loadings and error variances. Two-week test–retest reliability was assessed in 100 randomly selected respondents using intraclass correlation coefficient (ICC).
Results
Among the weighted sample, 55.9% were female and 72.9% were 25 to 64 years old. The CFA indicated good validity of the SWEMWBS. The SWEMWBS had moderate correlations with SHS, SF-12 mental component, PHQ-4 and GHI, but a weak correlation with SF-12 physical component. Older respondents, those with higher education level, married, working, with higher household income reported higher level of well-being. The congeneric reliability of the SWEMWBS was 0.85. Moderate to good test–retest reliability was observed (ICC 0.70, 95% CI 0.55 to 0.80).
Conclusion
The Chinese SWEMWBS showed good validity and reliability for measuring well-being in the general population of Hong Kong.
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