Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells.

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.

Treatment-prognostication-adjustment a new therapeutic idea by analyzing T cell immune checkpoint in tumor microenvironment by algorithm: A bibliometric analysis.

To evaluate the temporal and spatial distribution of the knowledge network about tumor microenvironment and prognoses and explore new research hot spots and trends. Articles and reviews on tumor microenvironment and prognoses in the Web of Science journal from January 1999 to April 2022 were included. We used the CiteSpace and VOSviewer software to analyze the knowledge network composed of journals, institutions, countries, authors, and keywords. Frontiers in Immunology, Cancers, and Frontiers in Oncology have published more than 10% of articles in this field. China and the United States have contributed the most articles. Fudan University and Sun Yat-Sen University are the most active institutions. The authors in this field work closely; Zhang Wei and Douglas have made outstanding contributions. The three main research areas of tumor microenvironment and prognoses are microenvironment, prognosis, and immunotherapy. Until 2020, the main keywords were endothelial growth factor and adhesion. In the past three years, survival analysis, immune cell infiltration, and prediction model have been used. It can be seen that the focus in this field has shifted from tumor cell behavior and directly related molecules to prognosis prediction and non-tumor cells in the microenvironment. The future research trend may be to study the changes in the tumor microenvironment to predict the prognosis and guide the treatment. VOSviewer, CiteSpace, and Microsoft Excel 2019 were used to conduct a comprehensive visual analysis of the research on tumor environment and prognoses and provide valuable reference materials for researchers.

Global scientific trends on matrix metalloproteinase and osteosarcoma: A bibliometric and visualized analysis.

Objective: This study aimed to identify author, country, institutional, and journal collaborations and their impacts, assess the knowledge base, identify existing trends, and uncover emerging topics related to the role of Metalloproteinase in osteosarcoma. Methods: 945 Articles and reviews associated with the role of Metalloproteinase in osteosarcoma were obtained from the WoSCC and analyzed by Citespace and Vosviewer. Results: The main aspects of research on the role of MMP in OS are invasion and metastasis. The latest hotspots were found to be the mechanism of MMP promoting invasion and metastasis, lung metastasis, and antitumor activity. Notably, invasion, metastasis, and antitumor activity were potentially turning points in the MMP-OS field. In the future, the primary research hotspot in the field of MMP-OS may be to study the mechanism, explore their role in the OS lung metastasis, and determine their role in the cancer therapy process. Conclusion: This study thus offers a comprehensive overview of the MMP-OS-related field using bibliometrics and visual methods, which will provide a valuable reference for researchers interested in the field of MMP-OS.

Adenovirus vector-mediated single chain variable fragments target the nucleocapsid protein of porcine epidemic diarrhea virus and protect against viral infection in piglets.

Porcine epidemic diarrhea virus (PEDV) mainly infects the intestinal epithelial cells of pigs, causing porcine epidemic diarrhea (PED). In particular, the virus causes severe diarrhea, dehydration, and death in neonatal piglets. Maternal immunity effectively protects neonatal piglets from PEDV infection; however, maternal antibodies can only prevent PEDV attachment and entry into target cells, but have no effects on intracellular viruses. Intracellular antibodies targeting virus-encoded proteins are effective in preventing viral infection. We previously identified four single chain variable fragments (scFvs), ZW1-16, ZW3-21, ZW1-41, and ZW4-16, which specifically targeted the PEDV N protein and significantly inhibited PEDV replication and up-regulated interferon-λ1 (IFN-λ1) expression in host cells. In our current study, the four scFvs were subcloned into replication-defective adenovirus vectors to generate recombinant adenoviruses rAdV-ZW1-16, rAdV-ZW3-21, rAdV-ZW1-41, and rAdV-ZW4-16. ScFvs were successfully expressed in Human Embryonic Kidney 293 (HEK293) cells and intestinal porcine epithelial cell line J2 (IPEC-J2) and were biosafe for piglets as indicated by body temperature and weight, scFv excretion in feces, IFN-γ and interleukin-4 (IL-4) expression in jejunum, and pathological changes in porcine tissue after oral administration. Western blotting, immunofluorescence, and immunohistochemical analyses showed that scFvs were expressed in porcine jejunum. The prophylactic effects of rAdV-ZW, a cocktail of the four rAdV-scFvs, on piglet diarrhea caused by PEDV was investigated. Clinical symptoms in piglets orally challenged with PEDV, following a two-time treatment with rAdV-ZW, were significantly reduced when compared with PEDV-infected piglets treated with phosphate buffered saline (PBS) or rAdV-wild-type. Also, no death and jejunal lesions were observed. ScFv co-localization with the PEDV N protein in vivo was also observed. Next, the expression of pro-inflammatory serum cytokines such as tumor necrosis factor-α (TNF-α), IL-6, IL-8, IL-12, and IFN-λ was assessed by enzyme-linked immunosorbent assay (ELISA), which showed that scFvs significantly suppressed PEDV-induced pro-inflammatory cytokine expression and restored PEDV-inhibited IFN-λ expression. Therefore, our study supported a promising role for intracellular scFvs targeting the PEDV N protein to prevent and treat diarrhea in PEDV-infected piglets.

Boosting the surface oxygen activity for high performance Iron-based perovskite oxide.

Surface oxygen activities always play an important role in various heterogeneous reaction processes. In this study, the surface oxygen activity of studied perovskite oxides is greatly enhanced after the composition and morphology are tuned. It is worth noting that the surface oxygen activity is enhanced correspondingly, accompanied by higher surface area, better reducibility, and superior low-temperature reactivity of studied catalysts. The sample introduced with nickel atom and nanorods structure possesses higher surface oxygen activity and vacancies with superior performance including T10 at 221 °C and T90 at 243 °C, nearly 90 °C elevations. Double perovskite oxides, especially with nanorods structure are verified to be composed of more surface active oxygen, which could be related to low-temperature redox ability and superior oxygen vacancies. Based on the DFT calculation, introducing nickel element is confirmed to be able to efficiently boost the generation of oxygen vacancies and adsorption of oxygen molecular, in accord with the analysis of characterization. To sum up, the strategy of introducing the nickel atom and nanorods structure could effectively tune the surface oxygen activity and generate more oxygen vacancies, which would be beneficial to the catalytic performance of toluene catalytic oxidation correspondingly.

Investigation of synergistic effects and high performance of La-Co composite oxides for toluene catalytic oxidation at low temperature.

Cobalt oxides have been considered as a kind of highly efficient catalyst for the oxidation of volatile organic compounds (VOCs). In this work, lanthanum-cobalt composite oxides were prepared by using the co-precipitation method, and toluene was used as the model compound. Diversified techniques including XRD, SEM, Raman spectra, XPS, H2-TPR, and N2 adsorption-desorption were applied to investigate the physicochemical properties of as-prepared materials. The composite catalysts showed different morphology including larger specific surface area and higher pore volume which would accelerate the adsorption of toluene and improve the amount of active sites on surface. Moreover, the addition of lanthanum could enhance the low-temperature reducibility, and it could be also beneficial to expose more Co3+ and adsorbed oxygen species on the surface of catalysts which could accelerate the oxidation of toluene and lower onset oxidation temperature. 0.05La-Co (with a molar ratio of lanthanum against cobalt is 0.05) showed the best catalytic performance. The complete conversion of toluene was achieved at 225 °C under the condition of toluene concentration = 1000 ppm and SV = 20,000 ml·g-1·h-1. Stability test over 0.05La-Co was conducted at 225 °C and it could maintain the 100% conversion of toluene for 720 min, indicating the excellent stability of as-prepared catalysts. Undoubtedly, lanthanum-cobalt composite oxide is a kind of promising material for the catalytic oxidation of VOCs.

Efficacy of Corticosteroid Injection for Treatment of Trigger Finger: A Meta-Analysis of Randomized Controlled Trials.

Purpose: To determine the efficacy and safety of corticosteroid injection for trigger finger by performing a meta-analysis of all relevant studies. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing corticosteroid injection with other treatments for trigger finger. Pooled summary estimates for outcomes, including success rate, relapse rate, visual analogue score (VAS) and complications, were calculated as standardized mean difference (SMD) or relative risk (RR) either on a fixed- or random-effect model via Stata 12.0 software. Results: Ten literatures involving 806 patients (387 in corticosteroid injection group and 419 in control group) were included. Pooled analysis showed there were no differences in the success rate, VAS and complications between patients undergoing corticosteroid injection and others. However, the relapse rate was significantly higher in patients treated with corticosteroid injection than that of other treatments (RR = 19.53, 95% CI = 6.23-61.19). Subgroup analysis indicated the efficacy of corticosteroid injection was superior to other non-surgical treatments (success rate: RR = 1.54, 95% CI = 1.01-2.35), but inferior to surgery (success rate: RR = 0.55, 95% CI = 0.48-0.63; relapse rate: RR = 21.15, 95% CI = 6.06-73.85; VAS: SMD = 3.49, 95% CI = 2.84-4.14). Conclusions: Corticosteroid injection may be an effective strategy for management of trigger finger, although surgery may be needed for some patients due to recurrence.

Transcriptome-derived stromal and immune scores infer clinical outcomes of patients with cancer.

The stromal and immune cells that form the tumor microenvironment serve a key role in the aggressiveness of tumors. Current tumor-centric interpretations of cancer transcriptome data ignore the roles of stromal and immune cells. The aim of the present study was to investigate the clinical utility of stromal and immune cells in tissue-based transcriptome data. The 'Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data' (ESTIMATE) algorithm was used to probe diverse cancer datasets and the fraction of stromal and immune cells in tumor tissues was scored. The association between the ESTIMATE scores and patient survival data was asessed; it was indicated that the two scores have implications for patient survival, metastasis and recurrence. Analysis of a colorectal cancer progression dataset revealed that decreased levels immune cells could serve an important role in cancer progression. The results of the present study indicated that trasncriptome-derived stromal and immune scores may be a useful indicator of cancer prognosis.

Identification of low Ca(2+) stress-induced embryo apoptosis response genes in Arachis hypogaea by SSH-associated library lift (SSHaLL).

Calcium is a universal signal in the regulation of wide aspects in biology, but few are known about the function of calcium in the control of early embryo development. Ca(2+) deficiency in soil induces early embryo abortion in peanut, producing empty pods, which is a general problem; however, the underlying mechanism remains unclear. In this study, embryo abortion was characterized to be caused by apoptosis marked with cell wall degradation. Using a method of SSH cDNA libraries associated with library lift (SSHaLL), 62 differentially expressed genes were isolated from young peanut embryos. These genes were classified to be stress responses, catabolic process, carbohydrate and lipid metabolism, embryo morphogenesis, regulation, etc. The cell retardation with cell wall degradation was caused by up-regulated cell wall hydrolases and down-regulated cellular synthases genes. HsfA4a, which was characterized to be important to embryo development, was significantly down-regulated under Ca(2+) -deficient conditions from 15 days after pegging (DAP) to 30 DAP. Two AhCYP707A4 genes, encoding abscisic acid (ABA) 8'-hydroxylases, key enzymes for ABA catabolism, were up-regulated by 21-fold under Ca(2+) -deficient conditions upstream of HsfA4a, reducing the ABA level in early embryos. Over-expression of AhCYP707A4 in Nicotiana benthamiana showed a phenotype of low ABA content with high numbers of aborted embryos, small pods and less seeds, which confirms that AhCYP707A4 is a key player in regulation of Ca(2+) deficiency-induced embryo abortion via ABA-mediated apoptosis. The results elucidated the mechanism of low Ca(2+) -induced embryo abortion and described the method for other fields of study.

Proteomic analysis of the rat ovary following chronic low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (20, 50, or 125 ng/kg once weekly) TCDD for 29 wk. A proteomic analysis of the ovaries by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry showed distinct changes in the levels of several proteins that are relevant markers of TCDD toxicity. Serum estradiol (E2) levels of TCDD-treated animals were markedly lower than control. There were no significant differences in bone mineral density (BMD) of femurs. The body weight of the 125-ng/kg TCDD group was significantly decreased relative to control and there was also a significant reduction in absolute and relative ovarian weights. Expressions of selenium binding protein 2, glutathione S-transferase mu type 3, Lrpap1 protein, NADPH, and peptidylprolyl isomerase D were upregulated, while prohibitin and N-ethylmaleimide-sensitive factor expression levels were downregulated. Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure.

[Role of mitogen-activated protein kinase pathway in chloracne].

OBJECTIVE: To investigate the role of mitogen-activated protein kinase (MAPK) signal transduction pathway in chloracne. METHODS: Immunohistochemical technique was used to detect the expression of phosphorylated epidermal growth factor receptor (p-EGFR) and p-MAPK proteins in the epithelium of chloracne group and control group. RESULTS: p-EGFR and p-MAPK was found in all chloracne tissues, whereas no expression of p-EGFR and p-MAPK protein was found in control group. In the skin of chloracne patients, p-EGFR was mainly distributed in the membrane and the cytoplasm, especially in the vicinity of membrane; major positive signal of p-MAPK was in core and serosity. CONCLUSION: EGFR and MAPK phosphorylation is found in chloracne tissues. MAPK signal transduction pathway is one important molecular mechanism of chloracne.

Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin-exposed humans with chloracne.

Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue of chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne.