Podocan promoting skeletal muscle post-injury regeneration by inhibiting TGF-ß signaling pathway.

Podocan, the fifth member of Small Leucine-Rich Proteoglycan (SLRP) family of extracellular matrix components, is poorly known in muscle development. Previous studies have shown that Podocan promotes C2C12 differentiation in mice. In this study, we elucidated the effect of Podocan on skeletal muscle post-injury regeneration and its underlying mechanism. Injection of Podocan protein promoted the process of mice skeletal muscle post-injury regeneration. This effect seemed to be from the acceleration of muscle satellite cell differentiation in vivo. Meanwhile, Podocan promoted myogenic differentiation in vitro by binding with TGF-ß1 to inhibit the activity of the TGF-ß signaling pathway. These results indicated that Podocan had the potential roles to enhance skeletal muscle post-injury regeneration. Its mechanism is likely the regulation of the expression of p-Smad2 and p-Smad4 related to the TGF-ß signaling pathway by interacting with TGF-ß1.

IL-6, TNF-α and IL-12p70 levels in patients with colorectal cancer and their predictive value in anti-vascular therapy.

We aimed to analyze the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12p70) in colorectal cancer and evaluate the predictive significance of clinical efficacy of patients with colorectal cancer treated with anti-vascular therapy combined with chemotherapy. A retrospective study of 162 patients with colorectal cancer in Fujian Medical University Hospital was conducted from January 2019 to December 2020. A comparative analysis of the levels of IL-6, TNF-α and IL-12p70 between the two groups were studied. The relationship between the levels and the clinical characteristics of patients was observed; the factors affecting the levels of IL-6, TNF-α, and IL-12p70 in colorectal cancer patients were analyzed, and the predictive validity of the efficacy of anti-vascular therapy was evaluated. We observed that the individual expression levels of IL-6, TNF-α and IL-12p70 in the patients with colorectal cancer are related to lymph node metastasis, TNM staging, and degree of differentiation (P<0.05); however, they are irrelevant to the age, sex, and tumor location of patients with colorectal cancer (P>0.05). The multiple stepwise regression analysis indicates that lymph node metastasis and TNM staging are independent risk factors that correlate with IL-6 and IL-12p70 levels in colorectal cancer patients (P<0.01). The degree of differentiation was found to be an independent risk factor connected to TNF- α levels of patients with colorectal cancer. The change of IL-12p70 level could predict the validity of anti-vascular treatment for advanced colorectal cancer. When evaluated for combined expression, IL-6 and IL-12p70 in patients with colorectal cancer closely related to lymph node metastasis and TNM staging. IL-12p70 can be used as a predictor of anti-vascular therapy with colorectal cancer.

Elevated Serum Alpha-Fetoprotein Is a Significant Prognostic Factor for Patients with Gastric Cancer: Results Based on a Large-Scale Retrospective Study.

Objectives: The aim of this work is to study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP)-positive gastric cancer (GC). Methods: A cohort study including 2,318 patients with GC who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP > 20 ng/ml, 8.24%) and 2,127 patients with AFP-negative GC (AFP ≤ 20 ng/ml, 91.76%). The clinicopathological features and prognostic factors were explored. Results: Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P < 0.05). The 5-year OS, DFS, and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P < 0.001; 39.79% vs. 34.03%, P < 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found that serum AFP levels (positive vs. negative), pT stage, pN stage, nerve invasion (yes or no), and venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20-300 ng/ml vs. 300-1,000 ng/ml vs. >1,000 ng/ml), pT stage, pN stage, and venous invasion (yes or no) were independent prognostic factors in AFP-positive GC. Conclusion: Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in patients with GC. As the level of AFP increases, the prognosis becomes worse.

Intraperitoneal infusion of recombinant human endostatin improves prognosis in gastric cancer ascites.

Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human endostatin in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human endostatin improved efficacy and survival for gastric cancer with ascites.

Ascites (a buildup of fluid in the abdomen) resulting from the spread of gastric cancer (GC) results in extremely poor clinical outcomes, and current treatments have shown little effectiveness. Previous results showed that abdominal injection with chemotherapeutic agents enabled an increase in the dose of chemotherapeutic agents and reduced side effects or undesirable effects in the abdominal cavity. This study aimed to investigate the effectiveness and safety of abdominal injection with the anticancer drug recombinant human endostatin in GC with ascites. Clinical data of 90 patients were inspected and analyzed in this study. Thirty-seven patients who received abdominal infusion with both cisplatin (CDDP) and recombinant human endostatin were included in an Endostar^® combined with CDDP group, and 53 patients who received abdominal infusion with CDDP alone were included in a CDDP group. The results showed that median survival time was longer in the combination group than in the CDDP group (9.7 months vs 8.1 months). Besides, therapeutic outcomes, including objective response rate and disease control rate, were better in the combination group. Side effects or undesirable effects were similar in the two groups. To conclude, abdominal injection with recombinant human endostatin improved survival time and therapeutic outcomes for GC patients with ascites.

Prenatal exposure and transplacental transfer of perfluoroalkyl substance isomers in participants from the upper and lower reaches of the Yangtze River.

Data on gestational exposure characteristics and transplacental transfer are quite limited for perfluoroalkyl substance (PFAS) isomers, especially those from large-scale comparative studies. To fill this gap, we examined isomers of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) in matched maternal and cord serum from Mianyang and Hangzhou, which are located in the upper and lower reaches of the Yangtze River, China, respectively. These data were compared with those from our previous study on Wuhan in the middle reach. The average ΣPFAS concentration increased from upstream to downstream (Mianyang (4.44 ng/mL) < Wuhan (9.88 ng/mL) < Hangzhou (19.72 ng/mL)) and may be related to the per capita consumption expenditure of each city. The ln-transformed PFAS concentrations showed significant differences between Mianyang and Hangzhou after adjusting confounding factors (p < 0.05). The percentages of linear PFOS and PFOA in maternal and cord serum from these cities all exceeded those in electrochemical fluorination products. The isomer profiles of PFASs in maternal and cord serum might be greatly influenced by local production processes of PFASs and residents' dietary habits. The transplacental transfer efficiencies decreased significantly with increasing concentrations in maternal serum for ΣPFAS, ΣPFOS, ΣPFOA, ΣPFHxS, n-PFOS, iso-PFOS, 4m-PFOS, 1m-PFOS, n-PFOA, n-PFHxS, and br-PFHxS (Spearman rank correlation coefficients (r) = 0.373-0.687, p < 0.01). These findings support an understanding of the regional characteristics in maternal exposure to PFASs along the Yangtze River, isomeric profiles of PFASs in these regions, and the transplacental transfer processes of PFAS isomers.

Sequence-dependent antiproliferative effects of gefitinib and docetaxel on non-small cell lung cancer (NSCLC) cells and the possible mechanism.

PURPOSE: Recent clinical trials showed that the sequential combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy could prolong the PFS and/or OS of advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation. The aim of present study was to assess the optimal combination sequence and to explore its possible mechanism. METHODS: PC-9 cells and A549 cells, the lung adenocarcinoma cells with mutant and wide-type EGFR respectively, were treated with docetaxel/gefitinib alone or in different combination schedules. The EGFR and K-ras gene status was determined by qPCR-HRM technique. Cell proliferation was detected by MTT assay. The expression and phosphorylation of EGFR, ERK, Akt and IGF-1R were detected by western blot. Cell cycle distribution was observed by flow cytometry. RESULTS: Only sequential administration of docetaxel followed by gefitinib (D → G) induced significant synergistic effect in both cell lines (Combination Index<0.9). The reverse sequence (G → D) resulted in an antagonistic interaction in both cell lines (CI>1.1), whereas the concurrent administration (D+G) showed additive (0.9

Size discrepancy: not a formidable problem in a mouse heterotopic aortic transplant.

OBJECTIVES: We sought to develop a better approach in establishing a heterotopic aortic transplant model. MATERIALS AND METHODS: We used "sleeve " operation and set up 2 heterotopic aortic transplant experimental groups (groups 1 and 2). In group 1, donors (BALB/c (H-2d) mice; weight, 25-30 g) had the same weight as the recipients (C57BL/6 (H-2d) mice; weight, 25-30 g); in group 2, donors had lower weights (BALB/c (H-2d) mice, weight, 15-20 g). Grafts were examined macroscopically and histologically 60 days after the transplant. RESULTS: The thrombosis incidence was 10% in group 1 (5 of 50) and 2% in group 2 (1 of 50) (P < .05). Intestinal obstructions led to a high mortality rate in both groups: 8% in group 1 and 10% in group 2 (P < .05). CONCLUSIONS: The issue of size discrepancy between donor and recipient aortas is not a problem in a heterotopic aortic transplant model with the use of a sleeve technique, while the high incidence of intestinal obstructions must be considered.

[Sequence-dependent effect of docetaxel with gefitinib on the proliferation and signal protein expression of human lung adenocarcinoma cell SPC-A1].

BACKGROUND AND OBJECTIVE: It has been proven that chemotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could not increase response for advanced non-small cell lung cancer (NSCLC), but its cellular mechanism was not well known. The aim of this study is to assess the effects of sequential administration of docetaxel and gefitinib on the cell proliferation and signal pathway of lung adenocarcinoma cell SPC-A1 and its cellular mechanism. METHODS: The mutation of EGFR and K-ras gene were examined by qPCR-HRM. MTT assay was used to measure the cell proliferation. The expression and phosphorylation of EGFR, ERK, AKT and IGF-1R were determined by Western blot. RESULTS: No EGFR or K-ras gene mutation was found in SPC-A1 cells. Compared with docetaxel or gefitinib alone, no synergistic effects on the cell proliferation were observed in cells treated with docetaxel and gefitinib concomitantly or gefitinib followed by docetaxel. However, sequential administration of gefitinib following docetaxel could remarkably increase the inhibition of docetaxel on cell proliferation. Docetaxel increased, and gefitinib decreased, the phosphorylation of EGFR and ERK respectively. The suppression of pEGFR and pERK induced by gefitinib could not be activated by docetaxel, whether simultaneously or subsequently. No significant effects on the expression of AKT and p-AKT were found when docetaxel and gefitinib were administered simultaneously or sequentially. Docetaxel decreased the expression of IGF-1R. CONCLUSION: The phosphorylation of both EGFR and ERK, not the phosphorylation of AKT or the expression of IGFR, may contribute to the synergistic effects of EFGR-TKI following chemotherapy on the cell proliferation of NSCLC.