Search

Abstract: HOX transcript antisense intergenic RNA (HOTAIR) is one of the most studied long noncoding RNAs (lncRNAs) and is aberrantly expressed in colorectal cancer (CRC). We thus performed a comprehensive study based on meta-analysis and validation of the TCGA database to investigate clinicopathological and prognostic value of HOTAIR in CRC. Six studies enrolling 629 CRC patients were included in the analysis. The results indicated that high HOTAIR expression predicted worse OS (hazard ratio [HR] = 2.46, 95% confidence interval [CI]: 1.82-3.32, P < 0.01) and RFS (HR = 1.97, 95% CI: 1.27-3.05, P < 0.01) for CRC patients. High HOTAIR expression was also significantly associated with venous invasion (OR = 2.53, 95% CI: 1.12-5.68, P = 0.02), advanced tumor infiltration (OR = 3.35, 95% CI: 1.34-8.42, P = 0.01) and distant metastasis (OR = 5.52, 95% CI: 1.22-25.01, P = 0.03). Then, the results were validated by the TCGA database, showing that the up-regulated expression of HOTAIR was significantly related to poor OS (P = 0.01) and RFS (P = 0.04) in CRC. Our meta-analysis indicated that high HOTAIR expression was closely associated with poor clinical outcomes and could be a reliable prognostic biomarker for CRC patients.

Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019., Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software., Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030., Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Liu, He, Li, Li, Wu, Manyande, Feng and Xiang.)

Connectomics has developed from an initial observation under an electron microscope to the present well-known medical imaging research approach. The emergence of the most popular transneuronal tracers has further advanced connectomics research. Researchers use the virus trans-nerve tracing method to trace the whole brain, mark the brain nerve circuit and nerve connection structure, and construct a complete nerve conduction pathway. This review assesses current methods of studying cortical to muscle connections using viral neuronal tracers and demonstrates their application in disease diagnosis and prognosis., Competing Interests: None., (AJTR Copyright © 2022.)

The diversity and complexity of sympathetic function highlight the importance of fundamental research. Little is known about the interaction of superior cervical sympathetic ganglion (SCG) and gut microbiota. In this study, the engagement of the sympathetic ganglia with gut microbiota was investigated. Bilateral superior cervical ganglionectomy (SCGx) significantly altered the microbiota composition in rats 14 days post-surgery, and these microbiotas may participate in several biological pathways in the host, suggesting the vital role of the cervical sympathetic ganglion in regulating the microbiome-brain axis, and further confirming that the sympathetic nervous system (SNS) regulates the microbiome-brain axis., Competing Interests: None., (AJTR Copyright © 2022.)

As an emerging framework in neuroscience, brain connectomics is well suited for investigating key questions on brain complexity by combining viral transneuronal tracing and whole brain graphic methodologies using analytical tools of network science. Transsynaptic viral tract-tracing in the toolbox of neural labeling methods has been a significant development in the connectomics field to decipher the circuit-level architecture of the cerebral cortex. In the present work, we reviewed the current methods enabling structural connectivity from the viscera to the cerebral cortex mapping with viral transneuronal tracers and showed how such neuroanatomic connectomic data could be used to infer new structural and functional information in viscera-cerebral cortex circuits., Competing Interests: None., (AJTR Copyright © 2021.)

There is a growing concern about consciousness loss during epileptic seizures. Understanding neural mechanisms could lead to a better comprehension of cerebral circuit function in the control of consciousness loss in intractable epilepsy. We propose that ventrolateral preoptic area (VLPO)- PnO (nucleus pontis oralis) circuits may serve a major role in the loss of consciousness in drug-refractory epilepsy. Future behavioural and neuroimaging studies are clearly needed to understand the functional connectivity between the VLPO and PnO during loss of consciousness in drug-refractory epilepsy, to greatly prevent unconsciousness in this disorder and improve the quality of life in patients with intractable epilepsy.

PURPOSE Heat-shock protein 27 (Hsp27), encoded by HSPB1, plays crucial roles in tumorigenesis and cell survival and is reported to be an independent prognosis marker for cancer. We hypothesized that genetic variants of the HSPB1 gene may be associated with lung cancer susceptibility and survival. PATIENTS AND METHODS We first resequenced the full-length HSPB1 gene and then genotyped three selected tag single nucleotide polymorphisms (SNPs) in 1,152 paired Chinese lung cancer patient cases and controls. Another 500 paired patient cases and controls were used for replication. We also evaluated the roles of these tagSNPs in the overall survival of 248 patients with advanced non-small-cell lung cancer (NSCLC), and validated the results in another 335 patients with advanced NSCLC. The genotype-phenotype correlation was assessed in 309 workers with occupational exposure to polycyclic-aromatic hydrocarbons (PAHs) as well as by luciferase reporter assay and Western blotting analysis. RESULTS The -1271C allele was associated with a significantly increased lung cancer risk in the two independent patient case-control studies (P < .05 for both), but it conferred a favorable survival for patients with advanced NSCLC in two independent cohorts (adjusted hazard ratio, 0.66 and 0.75, respectively). The occupational PAH-exposed workers carrying the -1271C allele showed higher DNA damage levels than those with the -1271G allele (P = .027). Furthermore, the -1271C allele significantly decreased luciferase activity in four cell lines and resulted in lower Hsp27 expression levels in normal lung tissues when compared with -1271G allele (P < .05). CONCLUSION The functional HSPB1 promoter -1271G>C variant may affect lung cancer susceptibility and survival by modulating endogenous Hsp27 synthesis levels.