Integrative analysis of transcriptome and proteome in primary Sjögren syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immune-mediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. METHOD: Transcriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjögren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. RESULTS: As a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. CONCLUSION: Herein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

Engineered bacterial orthogonal DNA replication system for continuous evolution.

Continuous evolution can generate biomolecules for synthetic biology and enable evolutionary investigation. The orthogonal DNA replication system (OrthoRep) in yeast can efficiently mutate long DNA fragments in an easy-to-operate manner. However, such a system is lacking in bacteria. Therefore, we developed a bacterial orthogonal DNA replication system (BacORep) for continuous evolution. We achieved this by harnessing the temperate phage GIL16 DNA replication machinery in Bacillus thuringiensis with an engineered error-prone orthogonal DNA polymerase. BacORep introduces all 12 types of nucleotide substitution in 15-kilobase genes on orthogonally replicating linear plasmids with a 6,700-fold higher mutation rate than that of the host genome, the mutation rate of which is unchanged. Here we demonstrate the utility of BacORep-based continuous evolution by generating strong promoters applicable to model bacteria, Bacillus subtilis and Escherichia coli, and achieving a 7.4-fold methanol assimilation increase in B. thuringiensis. BacORep is a powerful tool for continuous evolution in prokaryotic cells.

Immune infiltration analysis reveals immune cell signatures in salivary gland tissue of primary Sjögren's syndrome.

Introduction: Mouse models are the basis for primary Sjögren's syndrome (pSS) research. However, the depth of comparisons between mice and humans in salivary gland (SG) immune cells remains limited. Methods: The gene expression profiles of SGs from normal subjects and pSS patients were downloaded from the Gene Expression Comprehensive Database. The proportion of infiltrating immune cell subsets was then assessed by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT). An experimental Sjögren's syndrome (ESS) mouse model was successfully constructed using SG protein. Based on mouse SG tissue RNA-Seq data, the seq-ImmuCC model was used to quantitatively analyze the compositional ratios of 10 immune cells in pSS patients and mouse model SG tissues. Results: Computed and obtained 31 human data samples using the CIBERSORT deconvolution method. The immune cell infiltration results showed that, compared to normal human SG tissue, the content of gamma delta T cells was significantly different from naive CD4+ T cells and significantly increased, while the plasma cell content decreased. Principal component analysis indicated differences in immune cell infiltration between pSS patients and normal subjects. Meanwhile, for ESS model mouse data analysis, we found that the proportion of macrophages increased, while the proportion of CD4+ T cells, B cells, and monocytes decreased. Furthermore, we found that the proportion of monocytes was decreased, while the proportion of macrophages was increased in the SG tissues of pSS patients and model mice. The infiltration of CD4+ T, CD8+ T, and B cells also showed some differences. Discussion: We comprehensively analyzed SG immune infiltration in pSS patients and model mice. We demonstrated conserved and nonconserved aspects of the immune system in mice and humans at the level of immune cells to help explain the primary regulation of immune mechanisms during the development of Sjögren's syndrome.

Sleep disturbances and sleep patterns in children with tic disorder: A case-control study.

Study objectives: To characterize sleep disturbances and sleep patterns in children with Tic disorder (TD), and explore their association with TD severity and types. Methods: A case-control study was conducted in 271 children with TD recruited from a clinical setting and 271 non-TD children recruited from a primary school, matched by age (mean = 8.47 years, SD = 1.53 years) and gender (15.1% female). The Children's Sleep Habits Questionnaire (CSHQ) was used to assess sleep patterns and sleep disturbances. The TD types and severity were assessed with the Yale Global Tic Severity Scale (YGTSS). Results: The TD children scored higher on CSHQ total score than non-TD group (t = 29.50, p < 0.001) and demonstrated severer global sleep disturbance. Compared to non-TD children, TD children presented with increased risks for global sleep disturbance (aOR: 1.95; 95% CI = 1.20-3.06), and most specific sleep disturbances, including bedtime resistance (aOR: 3.15; 95% CI = 1.96-5.06), sleep onset delay (aOR: 3.43; 95% CI = 1.58-7.46), sleep anxiety (aOR: 2.83; 95%CI = 1.83-4.38), parasomnias (aOR: 3.68; 95% CI = 2.02-6.62), night waking (aOR: 9.29; 95% CI = 2.64-32.65), sleep disordered breathing (aOR: 1.72; 95% CI = 1.03-2.90) and daytime sleepiness (aOR: 1.72; 95% CI = 1.09-2.74). Children with mild and moderate tics, Provisional Tic Disorder (PTD), Chronic Tic Disorder (CTD) and Tourette Syndrome (TS) presented with more global and more specific sleep disturbances. In addition, combined ADHD, etc. Conclusion: Children with TD are major risks for increased sleep disturbances, especially for those with severe and chronic symptoms. Furthermore, comorbid ADHD increases risk in certain areas of sleep. These findings highlight the importance to consider sleep outcomes in the assessment and treatment for children with TD.

Effect of surgical starting time and season on prognosis in octogenarians with colorectal cancer: a retrospective study.

Aim: To investigate the effect of surgical starting time and season on the prognosis of octogenarians with colorectal cancer. Patients & methods: A total of 291 patients aged 80 years or above who received elective colectomy for colorectal cancer between January 2007 and December 2018 in the National Cancer Center in China were included. Results: No significant time- or season-dependent difference in overall survival for all clinical stages was found in the study. Comparing perioperative outcomes, the morning group had a longer operative time than the afternoon group (p = 0.03), but no significant difference was found based on the season of colectomy. Conclusion: These findings provide insights into clinical outcomes for colorectal cancer patients aged more than 80 years.

Recurrent studies have demonstrated that in heart surgery, different surgical starting times can affect the patients' outcomes, mainly due to the 24-h cyclic variations in heart function. This variability also exists in bowel function. The surgical outcomes of elderly patients aged over 80 years are more susceptible to external factors due to their frailty, so we wanted to compare the differences in prognosis of elderly patients who underwent surgery at different times and seasons.

Long-term effect of anesthesia choice on patients with hepatocellular carcinoma undergoing open liver resection.

Clinical and experimental evidence suggested that anesthesia choice can influence cancer progression and patients' outcomes by modulating tumor microenvironment and tumorigenic pathways. Curative resection is the mainstay of therapy for hepatocellular carcinoma (HCC), which is an intractable disease due to high recurrence and poor prognosis. However, different anesthetics may play different roles in alleviating surgery-induced stress response and inflammatory cytokines release that are considered to be closely associated with proliferation, invasion and metastasis of tumor cells. Propofol, sevoflurane, non-steroidal anti-inflammatory drugs and local anesthetics have shown to exert anti-tumor effect on HCC mainly through regulating microRNAs or signaling pathways, while other inhalational agents, dexmedetomidine and opioids have the potential to promote tumor growth. In terms of anesthetic methods and analgesia strategies, propofol based total intravenous anesthesia and thoracic epidural analgesia could be preferred for HCC patients undergoing open liver resection rather than inhalational anesthesia. Local anesthesia techniques have great potential to attenuate perioperative stress response, hence they may contribute to more favorable outcomes. This review summarized the relations between different anesthesia choices and HCC patients' long-term outcomes as well as their underlying mechanisms. Due to the complexity of molecules interactions and signaling pathways, further studies are warranted to confirm these results so as to optimize anesthesia strategy for HCC patients.