Weihua Dong

BACKGROUND: Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood. METHODS: In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression. RESULTS: COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor. CONCLUSION: COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.

The aim of this study was to investigate the effects of progesterone (PROG) on blood-brain barrier (BBB) permeability, cerebral edema and the expression of matrix metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore the mechanism of its neuroprotective effect. Sixty 7-day-old Wistar rats were divided into sham surgery, hypoxic ischemia (HI) and drug prophylaxis (PROG) groups. HIBD animal models were established. All the animals were sacrificed after 24 h. The BBB was assessed using Evans blue. Cerebral moisture capacity was determined using the dry-wet method. MMP-9 was detected in the brain tissues using enzyme-linked immunosorbent assay. The expression of AQP-4 and MMP-9 in the cerebral cortex was observed using immunohistochemistry and real-time polymerase chain reaction. The MMP-9 levels in the cortex, BBB permeability, cerebral moisture capacity and expression of AQP-4 and MMP-9 in the HI group were significantly higher compared with those in the sham surgery group (P<0.01), and they were significantly lower in the drug prophylaxis group compared with those in the HI group (P<0.05). In conclusion, PROG reduces BBB damage and cerebral edema and inhibits MMP-9 generation to protect rat brains against HIBD. The protective effect of PROG may be correlated with downregulated expression of AQP-4 and MMP-9 in the cerebral cortex.

BACKGROUND: Colon cancer is one of the most common malignant tumors, and B cell Translocation Gene (BTG)1 is involved in the occurrence and development of colon cancer, however, the underlying molecular mechanism remains unclear. OBJECTIVE: In this study, we investigated the expression of BTG1 protein in colon cancer, and its association with clinicopathology and prognosis. METHODS: The tumor specimens from 59 patients with colon cancer who had undergone radical colectomy were selected as the observation group. Para-carcinoma tissues from the same patients were selected as the control group. The expressions of BTG1 mRNA and protein in the specimen of two groups were analyzed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot. According to the immunohistochemical results, the patients were divided into BTG1-negative and BTG1-positive groups. The postoperative cumulative survival rate in the two groups was analyzed. The association of the expression of BTG1 protein with the clinicopathological features and postoperative survival was investigated. RESULTS: Compared with the control group, the expression levels of BTG1 mRNA and BTG1 protein were significantly decreased in the observation group (P < 0.05). Immunohistochemical analysis revealed that there were 12 positive tumor samples and 47 negative samples. The expression of BTG1 was negatively associated with the degree of differentiation and lymphatic metastasis. The cumulative survival rate of BTG1-positive patients was significantly increased compared with that of BTG1- negative patients (P < 0.05). Stepwise Cox regression analysis showed that lymphatic metastasis, tumor size and BTG1 expression level were independent prognostic factors for overall survival in patients with colon cancer. CONCLUSION: BTG1 protein in colon cancer tissues were expressed at low levels, which was associated with the clinicopathological features, postoperative recurrence and survival of patients.

Recent studies found that progesterone (PROG) has a noticeable preventive effect on brain injuries. However, the underlying mechanisms of these effects, particularly on hypoxic ischemic brain damage (HIBD), remain unclear. This study observed the influence of PROG on the expression of cycloxygenase-2 (COX-2) and interleukin-1β (IL-1β) in HIBD neonatal rats, and explored the corresponding molecular mechanisms underlying the neuroprotective effect of PROG. Sixty 7-day-old neonatal Wistar rats were divided into sham operation (control), hypoxic ischemia (HI), and drug prophylaxis (PROG) groups, and HIBD animal models were routinely established. The PROG group was intraperitoneally injected with 0.5 g/L PROG at a dosage of 8 mg/kg 30 min before establishment of the model. All the animals were sacrificed 24 h after modeling. Changes in the COX-2 and IL-1β contents in the brain tissues were determined using enzyme-linked immunosorbent assay. Protein expression was observed using immunohistochemistry, and mRNA expression was determined using reverse transcription polymerase chain reaction. The expression and contents of COX-2 and IL-1β in the HI group were significantly higher than those in the control group (P < 0.01). Compared with the HI group, the PROG group showed noticeably lower expression and contents of COX-2 and IL-1β (P < 0.05). In conclusion, PROG can inhibit the expression of COX-2 and IL-1β in brain tissue, further reducing the level of COX-2 and IL-1β, which may be one of the mechanisms for protection from HIBD.