Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer.

OBJECTIVE: Gastric cancer (GC) is one of the malignant tumors with the highest mortality worldwide. Our previous studies have revealed that LINC00691 is up-regulated in serum of GC patients as a novel potential biomarker for GC diagnosis and prognosis. However, the roles of serum exosomal LINC00691 in GC has not been clarified. This study aimed to find the expression pattern of serum exosomal LINC00691 in GC patients and the correlation between the level of serum exosomal LINC00691 and the pathology of gastric cancer patients. METHODS: We collected the serum of 94 GC patients before surgery and extracted exosomes to detect the expression level of exosomal LINC00691, with 21 healthy volunteers and 17 patients with benign gastric diseases as controls. Surgical GC tissues and paired healthy tissues were collected to culture primary cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). We then treated NFs with LINC00691-rich GC cell culture supernatant or exosomes and detected the activation markers and biological functions of the fibroblasts. RESULTS: The results of real-time qPCR indicated that the serum exosomal LINC00691 of GC patients was significantly higher than that of healthy subjects and patients with benign gastric diseases, and was associated with the clinicopathology of GC patients. More interestingly, when the NFs were treated with GC exosomes, the level of LINC00691 was significantly increased, the cell proliferation and migration were noticeably enhanced, and the ability to accelerate GC cell proliferation and invasion was promoted, which means that the induced fibroblasts gained the properties of CAFs. In addition, we found that knockdown of LINC00691 and the use of the JAK2/STAT3 signaling pathway inhibitor ruxolitinib effectively deprived exosome-containing GC cell supernatants of the effects on NFs. CONCLUSION: Our study suggested that exosomal LINC00691 promoted NFs to gained the properties of CAFs depending on JAK2/STAT3 signaling pathway as a potential diagnostic biomarker for GC.

The Effect of Artificial Liver Support System on Prognosis of HBV-Derived Hepatorenal Syndrome: A Retrospective Cohort Study.

Hepatorenal syndrome (HRS) could occur when patients get decompensated liver cirrhosis. Meanwhile, hepatitis B virus (HBV) infection raises the risk of mortality of the end-stage liver diseases. As the artificial liver support system (ALSS) has been applied in liver failure, whether ALSS could benefit HBV-derived HRS remains uncertain. We retrospectively enlisted eligible HRS patients and compared the baseline characteristics and prognosis between HBV-derived HRS and non-HBV-derived HRS. Furthermore, propensity score matching (PSM) and Cox regression analyses were used to assess the beneficial effect of ALSS on HBV-derived HRS. In addition, a stratified analysis was carried out according to the degree of acute kidney injury (AKI) and the number of organ failures to observe in which populations ALSS can obtain the most excellent therapeutic effect. 669 patients were diagnosed as HRS, including 298 HBV negative and 371 HBV positive. Baseline characteristics were different between patients with HBV positive and HBV negative. HBV-derived HRS has higher 28-day mortality, though without a statistical difference. After PSM, 50 patients treated with ALSS and 150 patients treated with standard medical treatment (SMT) constituted a new cohort for the following analysis. We found that ALSS could significantly benefit HRS patients (P = 0.025). Moreover, the median survival time of patients treated with ALSS was longer than those treated with SMT. INR, neutrophil percentage, and treatment with ALSS were independent predictive factors for short-term mortality in HBV-derived HRS. The stratified analysis showed that ALSS could reduce the 28-day mortality of patients with HBV-derived HRS, especially those in AKI stage 3 and with organ failure ≥ 2. Additionally, serum bilirubin was significantly lower after ALSS, and the alteration of INR and creatinine were independent predictive elements for the mortality of HBV-derived HRS. HBV-derived HRS is more severe than non-HBV-derived HRS and has a worse prognosis. ALSS could reduce the short-term mortality of patients with HBV-derived HRS, especially those in AKI stage 3 and with organ failure ≥ 2. INR and the change of creatinine and INR could predict the prognosis of HBV-derived HRS. ChiCTR2200060123.

Antinuclear antibodies in healthy population: Positive association with abnormal tissue metabolism, inflammation and immune dysfunction.

Antinuclear antibodies (ANAs) are a spectrum of autoantibodies that react with cell nucleus structures. ANA assay is a screening test for the diagnosis of autoimmune disease. Although many patients with positive ANA did not develop autoimmune diseases, it is unclear whether high concentrations of ANA have potential damage to the body. In this study, we conducted an epidemiological survey of ANAs in healthy population, and further examined the associations of ANA with clinical laboratory indicators, inflammation indicators and immune function indicators in a large health checkup population-based cohort. We found the positive rate of ANA was 7.09%, of which the positive rate of female (10.2%) was higher than that of male (4.6%). Moreover, our data showed that ANA positive population present a higher rate of metabolic abnormalities than control group. We further detected the inflammatory and immune-related indicators of ANA positive population, and found that high ANA was correlated with inflammatory and immune dysfunction. In conclusion, our results indicated that the positive rate of ANA was high in healthy population. Moreover, high levels of ANAmight be involved in the metabolic abnormalities, inflammation and immune dysfunction. Thus, ANA testing should be routine for healthy people, and to avoid misdiagnosis, those who had clinical symptoms should be further examined for the subtype of ANA present in the serum.

ATF3 and PRAP1 play important roles in cisplatin-induced damages in microvascular endothelial cells.

BACKGROUND: The early intervention is a rational approach to reduce the cardiovascular disease mortality in cancer patients. Here, we tried to identify potential biomarkers for the endothelial damage caused by cisplatin, a typical chemotherapy compound, and explore its underlying mechanisms. METHODS: Microarray dataset GSE62523 were utilized to assess the gene differential expression from human micro-vascular endothelial cells (HMEC-1) treated with cisplatin. Then, the potential key genes were further validated by qRT-PCR and the γH2AX level was evaluated to monitor the DNA damages caused by cisplatin. RESULT: For the 'acute-exposure' settings that HMEC-1 were treated with 12.9 µM cisplatin for 6, 24 and 48 h, ATF3, LRRTM2, VCAM1 and PAPPA were identified as potential key genes in endothelial damage, while for the 'chronic-exposure' settings that cells were exposed to 0.52 µM cisplatin twice a week, SULF2, ACTA2 and PRAP1 were identified. In addition, further in vitro validation showed that knockdown of ATF3 attenuated the γH2AX level in cells exposed to cisplatin for 6 or 24 h and knockdown of PRAP1 increased the γH2AX level in cells exposed to cisplatin for 2 days. Notably, ATF3 has the ability to regulate the expression of HIST1H1D, FBXO6, APP, MDM2, STAT1 and TRAF1, while PRAP1 regulates YWHAB, MDM2, ISG15, LYN and CUL1 during cisplatin-induced DNA damage repair process. CONCLUSION: ATF3 and PRAP1 play important roles in cisplatin-induced DNA damage repair process. They may serve as potential early surrogate biomarkers of microvascular endothelial damage for cancer patients receiving chemotherapies.