Toll-Like Receptor Polymorphisms and the Risk of Cancer: Meta-analysis Study.

A systematic review and meta-analysis is a useful method to summarize the different results from primary data, which can then provide an evidence-based outcome. Meta-analysis generates quantitative data by calculating effect sizes, which include odd ratios, relative risks, proportions, correlation coefficients, and so forth. The study of single-nucleotide polymorphisms (SNPs) and the association with the interested outcome is one discipline that has resulted in inconsistent relations. Therefore, the meta-analysis aimed to summarize the relevant data on SNPs associated with the outcome of interest. Herein, we describe a comprehensive meta-analysis on Toll-like receptor-9 polymorphism and the risk of cervical cancer.

Prevalence and associated factors for self-reported symptoms of dry eye among Thai school children during the COVID-19 outbreak.

PURPOSE: COVID-19 pandemic caused an increase in digital screen time, which seemed to increase the prevalence of dry eye symptoms among the population with abnormally high digital screen usage hours. However, there are no reports of dry eye symptoms in school children with high digital usage hours. Therefore, the present study aimed to assess the prevalence of dry eye symptoms and evaluate the associated factors among school children aged 12 to 18 years during the COVID-19 outbreak. METHODS: Multistage cluster sampling was applied, and six sections of online questionnaires were distributed to selected respondents in November 2021. The odds ratio (OR) with confidence intervals (CIs) for the factors was calculated using binary logistic regression. All statistical significance was determined at p < 0.05. RESULTS: The findings revealed that 62.5% of 603 students showed symptoms of dry eye (DEQ-5 score ≥ 6). Significant associated factors included being female (adjusted OR (aOR) 1.54; 95% CIs 1.05-2.25), higher-grade student (aOR 1.77; 95% CIs 1.23-2.57), digital screen time use (6 to < 12 hours: aOR 2.00; 95% CIs 1.12-3.57, ≥12 hours: aOR 2.54; 95% CIs 1.39-4.76), and perceived stress (aOR 1.12; 95% CIs 1.08-1.16). The Thai-Perceived Stress Scale-10 scores were positively correlated with the scores on the 5-item dry eye questionnaire (Spearman's r = 0.38, p-value < 0.01). CONCLUSION: A high prevalence of dry eye symptoms might be common among school children during the COVID-19 outbreak. Significant risk factors include being female, being a higher-grade level student, prolonged use of digital screens, and perceived stress. However, contact lens use, smoking, and the most common digital device usage patterns were not found to be contributing factors.

Outbreak of COVID-19-Related Myopia Progression in Adults: A Preliminary Study.

Purpose: The COVID-19 pandemic has necessitated specific public health measures, resulting in the alteration of lifestyles, such as increased digital screen time and fewer outdoor activities. Such conditions have increased the progression of myopia in children. However, no investigation of myopia progression in early adulthood has been conducted during this period. Consequently, this study aimed to evaluate the outbreak of COVID-19-related myopia progression among adults at an optometry clinic during the COVID-19 pandemic. Materials and Methods: This was a retrospective cohort study in which participants aged 18-25 years who first visited (baseline) the optometry clinic between June 2019 and March 2020 were recruited for follow-up from November 2021 to March 2022. Spherical equivalent refraction (SER), uncorrected distance visual acuity (UCDVA), and binocular cross cylinder (BCC) were recorded at baseline and a follow-up visit. Using questionnaires, a survey was conducted to assess the lifestyle changes that transpired during the COVID-19 pandemic. Results: In total, 37 participants with a mean age of 22.5±1.4 years were enrolled, of which 89.2% were female. Following the outbreak of the COVID-19 pandemic, most participants self-reported increased daily use of digital devices (89.2%), online education (86.5%), and spending more time at home (94.6%), which increased by approximately 7.6±3.2 hours, 5.9±1.7 hours, and 13.2±7.5 hours, respectively. There were statistically significant differences between SER and BCC at baseline and after approximately 2 years of the COVID-19 pandemic (p < 0.05). The mean two-year myopia progression was -0.59±0.67 D (Maximum = 0.00 D, Minimum = -3.38 D). Conclusion: This study revealed that myopia could progress during adulthood among those who have lived under public health measures intended to address the COVID-19 pandemic.

Coronavirus disease 2019 outbreak and associated public health measures increase the progression of myopia among children and adolescents: Evidence synthesis.

PURPOSE: Although studies have suggested that the coronavirus disease 2019 (COVID-19) outbreak increased myopia progression, they had different settings and analysis methods. This study compared myopia progression before and during the COVID-19 outbreak using meta-analysis. METHODS: Relevant literature was searched on EMBASE, PubMed, ClinEpiDB and Web of Science and reviewed until 8 October 2021. The Newcastle-Ottawa Scale was used to evaluate the quality of the original studies. The mean difference of change in spherical equivalent refraction (SER) was used for evaluation before and during the COVID-19 pandemic. RESULTS: The meta-analysis included eight studies with 773, 797 individuals aged 5-18 years. Pooled analysis indicated that the mean difference of annual myopia progression during the pandemic was 0.41 D higher (95% confidence interval [CI]: 0.35-0.48, p < 0.01) than before the pandemic. Subgroup analysis using cycloplegic (mean difference, 0.30 D; 95% CI, 0.22-0.38; p < 0.01) or noncycloplegic refraction (mean difference, 0.60 D; 95% CI, 0.27-0.93; p < 0.01) indicated that the mean difference of annual myopia progression during COVID-19 significantly increased in both refractive measurements. CONCLUSION: Our findings demonstrated that the COVID-19 pandemic accelerated myopic progression compared to the past. Government policies are urgently required to prevent and control myopia progression.

Microbial dysbiosis and microbiota-gut-retina axis: The lesson from brain neurodegenerative diseases to primary open-angle glaucoma pathogenesis of autoimmunity.

In recent years, microbiota-associated neurodegenerative diseases have been exploited and provided new insight into disease pathogenesis. However, primary open-angle glaucoma (POAG), known as a complex neurodegenerative disease resulting from retinal ganglion cell death and optic nerve damage, can cause irreversible blindness and visual field loss. POAG, which shares several similarities with Parkinson's disease (PD) and Alzheimer's disease (AD), has limited studies and slow progression in the understanding of pathogenesis when compared to PD and AD. In this review, we summarized the current knowledge of POAG and commensal microbiota, combined with several lines of evidence in PD and AD to propose a possible hypothesis for POAG pathogenesis: microorganisms cause glaucoma via gut-retina axis, resulting in autoantibodies and autoreactive T cells that lead to autoimmunity. Furthermore, dual-hit hypothesis, an example of a commensal pathogen that causes PD, was partially exported in POAG. Finally, future perspectives are suggested to expand understanding of POAG.

The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis.

Primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) cause irreversible blindness while current medications cannot completely inhibit disease progression. An understanding of immunopathogenesis is thus a keystone to develop novel drug targets and genetic markers are still required for early diagnosis. Toll-like receptor 4 (TLR4) is an essential player in inflammation in various diseases. However, the TLR4 polymorphisms have not been completely elucidated in both types of glaucoma. The aim of the present study was to identify the association between TLR4 polymorphism and glaucoma (POAG and NTG) via the use of a comprehensive review and meta-analysis. The relevant studies were collected from PubMed, Excerpta Medica Database (EMBASE), and Web of Science to identify eight included articles, assessed for quality by a modified Newcastle-Ottawa Scale (NOS) for gene association study. A meta-analysis was applied to calculate the pooled odds-ratio and 95% confidence intervals (CIs) to evaluate the association between TLR4 polymorphism and glaucoma. The results revealed that TLR4 rs1927911 A/G, rs12377632 C/T, and rs2149356 G/T significantly decrease the risk of POAG and NTG in allele contrast models 0.71-, 0.71-, and 0.67-fold, respectively. Moreover, rs4986790 A/G and rs4986791 C/T showed a stringent association with POAG in allele contrast, heterozygous, recessive, and overdominant models. In conclusion, this meta-analysis represented a significant correlation between TLR4 polymorphisms and both types of glaucoma suggesting that TLR4 might be involved in the pathogenesis of glaucoma and may be applied as a genetic marker for disease screening.

The associations between Toll-like receptor 4 gene polymorphisms and hepatitis C virus infection: a systematic review and meta-analysis.

Background and objective: The hepatitis C virus (HCV) is able to cause a life-threatening disease relating to lethal hepatocellular carcinoma. Previous, Toll-like receptor polymorphisms were proposed as promising biomarker for HCV-related hepatocellular carcinoma and disease progression. This study aimed to summarize the association of TLR4 polymorphisms and HCV infection through meta-analysis.Methods: We applied a systematic review and meta-analysis performed by using PubMed, EMBASE and Web of Science searches. The Modified Newcastle-Ottawa scale was used for quality assessment. The odd-ratio (OR) and 95% confidence interval (CI) were calculated to assess the association. In silico analysis was applied for proposing the function as microRNA (miRNA) of non-coding polymorphism. Finally, the miRNA target was predicted and annotated to suggest the possible relationship between polymorphism and HCV infection.Results: Our meta-analysis incorporated seven studies involving rs4986791, rs4986790 and rs2149356. No association exists between rs4986791 and HCV infection. However, the heterozygous model (AG vs GG) of rs4986790 significantly associates with HCV infection (OR = 0.33, 95% CI = 0.21-0.49, P<0.0001). Moreover, the rs2149356 TG genotype also associates with HCV infection in the over-dominant model (TG vs TT+TG: OR = 0.54, 95% CI = 0.40-0.75). In silico analysis of rs2149356G allele showed that this mutation is siRNA, which targets the set of genes, especially in the autophagy pathway.Conclusion: We demonstrated that rs4986790 and rs2149356 are associated with HCV infection.

Roles of Toll-Like Receptor 4 for Cellular Pathogenesis in Primary Open-Angle Glaucoma: A potential therapeutic strategy.

In recent years, glaucoma has been proposed as an autoimmune disease and an understanding immune-regulation concept has been applied for novel glaucoma therapy. Current evidence suggests an innate immunity is a keystone step for primary open angle glaucoma (POAG) pathogenesis resulting from trabecular meshwork (TM) cell fibrosis and retinal ganglion cell (RGC) death. Toll-like receptor 4 (TLR4) is a common player in the innate immunity, which appears on the TM and RGC of POAG. The activation of TLR4 regulates several molecules involving both fibrosis and cell death. Inhibition of TLR4 decreases TGF-ß2-induced fibrosis in TM cells and enhances cell survival of RGC in both optic nerve crush and ischemia models. In this review, we will summarize the molecular mechanisms of TLR4 related to POAG pathogenesis. An understanding of this mechanism may provide novel development of therapeutic strategies for POAG.

Inhibition of protein kinase C promotes dengue virus replication.

BACKGROUND: Dengue virus (DENV) is a member of the Flaviviridae family, transmitted to human via mosquito. DENV infection is common in tropical areas and occasionally causes life-threatening symptoms. DENV contains a relatively short positive-stranded RNA genome, which encodes ten viral proteins. Thus, the viral life cycle is necessarily rely on or regulated by host factors. METHODS: In silico analyses in conjunction with in vitro kinase assay were used to study kinases that potentially phosphorylate DENV NS5. Potential kinase was inhibited or activated by a specific inhibitor (or siRNA), or an activator. Results of the inhibition and activation on viral entry/replication and host cell survival were examined. RESULTS: Our in silico analyses indicated that the non-structural protein 5 (NS5), especially the RNA-dependent RNA polymerase (RdRp) domain, contains conserved phosphorylation sites for protein kinase C (PKC). Phosphorylation of NS5 RdRp was further verified by PKC in vitro kinase assay. Inhibitions of PKC by a PKC-specific chemical inhibitor or siRNA suppressed NS5 phosphorylation in vivo, increased viral replication and reduced viability of the DENV-infected cells. In contrary, activation of PKC effectively suppressed intracellular viral number. CONCLUSIONS: These results indicated that PKC may act as a restricting mechanism that modulates the DENV replication and represses the viral outburst in the host cells.

Development of viable TAP-tagged dengue virus for investigation of host-virus interactions in viral replication.

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life-threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast two-hybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof-of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions.

Polymorphisms of the pfmdr1 but not the pfnhe-1 gene is associated with in vitro quinine sensitivity in Thai isolates of Plasmodium falciparum.

BACKGROUND: The emergence of Plasmodium falciparum resistance to most currently used anti-malarial drugs is a major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Quinine (QN) with tetracycline/doxycycline has been used as the second-line treatment for uncomplicated falciparum malaria. In addition, QN monotherapy has been the first-line treatment for falciparum malaria in pregnant women. However, reduced in vitro and in vivo responses to QN have been reported. To date, a few genetic markers for QN resistance have been proposed including Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum Na+/H+ exchanger (pfnhe-1). This study was to investigate the role of the pfmdr1 and pfnhe-1 gene on in vitro QN sensitivity in Thai isolates of P. falciparum. METHODS: Eighty-five Thai isolates of P. falciparum from the Thai-Myanmar and Thai-Cambodia borders from 2003-2008 were determined for in vitro QN sensitivity using radioisotopic assay. Polymorphisms of the pfmdr1 and pfnhe-1 gene were determined by PCR-RFLP and sequence analysis. Associations between the in vitro QN sensitivity and the polymorphisms of the pfmdr1 and pfnhe-1 gene were evaluated. RESULTS: The mean QN IC50 was 202.8 nM (range 25.7-654.4 nM). Only four isolates were QN resistant when the IC50 of >500 nM was used as the cut-off point. Significant associations were found between the pfmdr1 mutations at codons N86Y and N1042D and in vitro QN sensitivity. However, no associations with the number of DNNND, DDNNNDNHNDD, and NHNDNHNNDDD repeats in the microsatellite ms4760 of the pfnhe-1 gene were identified. CONCLUSION: Data from the present study put doubt regarding the pfnhe-1 gene as to whether it could be used as the suitable marker for QN resistance in Thailand. In contrast, it confirms the influence of the pfmdr1 gene on in vitro QN sensitivity.