Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

Background/Aims: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood. Methods: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting. Results: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. Conclusion: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells

Multiple organ infection and the pathogenesis of SARS

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features

Adaption of Seasonal H1N1 Influenza Virus in Mice

The experimental infection of a mouse lung with influenza A virus has proven to be an invaluable model for studying the mechanisms of viral adaptation and virulence. The mouse adaption of human influenza A virus can result in mutations in the HA and other proteins, which is associated with increased virulence in mouse lungs. In this study, a mouse-adapted seasonal H1N1 virus was obtained through serial lung-to-lung passages and had significantly increased virulence and pathogenicity in mice. Genetic analysis indicated that the increased virulence of the mouse-adapted virus was attributed to incremental acquisition of three mutations in the HA protein (T89I, N125T, and D221G). However, the mouse adaption of influenza A virus did not change the specificity and affinity of receptor binding and the pH-dependent membrane fusion of HA, as well as the in vitro replication in MDCK cells. Notably, infection with the mouse adapted virus induced severe lymphopenia and modulated cytokine and chemokine responses in mice. Apparently, mouse adaption of human influenza A virus may change the ability to replicate in mouse lungs, which induces strong immune responses and inflammation in mice. Therefore, our findings may provide new insights into understanding the mechanisms underlying the mouse adaption and pathogenicity of highly virulent influenza viruses

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus.

This study aims to investigate the fetal outcomes and associated factors of adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus erythematosus (SLE). Clinical data from 251 SLE patients with 263 pregnancies from 2001 to 2015 were analyzed retrospectively. APOs occurred in 70.0% of pregnancies, in which pregnancy loss occurred in 28.5%; preterm delivery occurred in 21.3%; intrauterine growth retardation occurred in 12.2%; and fetal distress occurred in 8.0%. Over time, the rate of APOs decreased from 82.8% during 2001~2005 to 59.6% during 2011~2015. In multivariate analysis, predictors of APOs included positive antiphospholipid antibodies (OR 8.4, 95% CI 1.7~40.8, P = 0.008), lower complement (OR 3.6, 95% CI 1.3~9.9, P = 0.01), hypoalbuminemia (OR 3.2, 95% CI 1.2~8.3, P = 0.02), and hypertension (OR 14.6, 95% CI 1.5~141.6, P = 0.02). The use of antimalarial medications was associated with lower risk for APOs (OR 0.3, 95% CI 0.1~0.7, P = 0.01). In total, 109 patients underwent fetal umbilical artery Doppler in the third trimester. The The adjusted systole/diastole (S/D) ratio, pulsatility index (PI) and resistance index (RI) of SLE patients with APOs were higher than that of patients without APOs (2.9±0.9 vs. 2.4±0.5, P = 0.001). Lupus pregnancy was still at high risk of APOs in terms of pregnancy loss and preterm delivery. Umbilical artery Doppler was a good monitor method for APOs in the third trimester

Fetal and Maternal Outcomes of Planned Pregnancy in Patients with Systemic Lupus Erythematosus: A Retrospective Multicenter Study

Objective. To investigate the fetal and maternal outcomes as well as predictors of APOs in women with SLE who conceived when the disease was stable, the so-called “planned pregnancy.” Methods. A retrospective multicenter study of 243 patients with SLE who underwent a planned pregnancy was performed. APOs in fetus and mothers were recorded. Results. The average age at conception was 28.9 ± 3.9 years. Duration of SLE prior to pregnancy was 4.4 ± 4.3 years. Fetal APOs occurred in 86 (86/243, 35.4%) patients. Preterm births, intrauterine growth retardation (IUGR), fetal distress, and fetal loss accounted for 22.2%, 14.8%, 11.1%, and 4.9%, respectively. Forty-two preterm infants (42/54, 77.8%) were delivered after the 34th week of gestation. All the preterm infants were viable. Fifty-two patients (52/243, 21.4%) had disease flares, among which 45 cases (45/52, 86.5%) were mild, 6 (6/52, 11.5%) were moderate, and 1 (1/52, 1.9%) was severe. Disease flares were mainly presented as active lupus nephritis (41/52, 78.8%), thrombocytopenia (10/52, 19.2%), and skin/mucosa lesions (9/52, 17.3%). Pregnancy-induced hypertension (PIH) occurred in 29 patients, among which 3 were gestational hypertension and 26 were preeclampsia. Multiple analysis showed that disease flares (OR, 8.1; CI, 3.8–17.2) and anticardiolipin antibody positivity (OR, 7.4; CI, 2.5–21.8) were associated with composite fetal APOs. Conclusion. Planned pregnancy improved fetal and maternal outcomes, presenting as a lower rate of fetal loss, more favorable outcomes for preterm infants, and less severe disease flares during pregnancy