Influence of formaldehyde exposure on the molecules of the NO/cGMP-cAMP signaling pathway in different brain regions of Balb/c mice.

This toxicology study was conducted to assess the impact of formaldehyde, a common air pollutant found in Chinese gymnasiums, on the brain function of athletes. In this research, a total of 24 Balb/c male mice of SPF-grade were divided into four groups, each consisting of six mice. The mice were exposed to formaldehyde at different concentrations, including 0 mg/m3, 0.5 mg/m3, 3.0 mg/m3, and 3.0 mg/m3 in combination with an injection of L-NMMA (NG-monomethyl-L-arginine), which is a nitric oxide synthase antagonist. Following a one-week test period (8 h per day, over 7 days), measurements of biomarkers related to the nitric oxide (NO)/cGMP-cAMP signaling pathway were carried out on the experimental animals post-treatment. The study found that: (1) Exposure to formaldehyde can lead to brain cell apoptosis and neurotoxicity; (2) Additionally, formaldehyde exposure was found to alter the biomarkers of the NO/cGMP-cAMP signaling pathway, with some changes being statistically significant (p < 0.05 or p < 0.01); (3) The use of L-NMMA, an antagonist of the NO/cGMP-cAMP signaling pathway, was found to prevent these biomarker changes and had a protective effect on brain cells. The study suggests that the negative impact of formaldehyde on the brain function of mice is linked to the regulation of the NO/cGMP-cAMP signaling pathway.

Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog Pathway.

We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin's anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial-mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient's survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer.

The emerging role of triggering receptor expressed on myeloid cell-2 in malignant tumor.

Triggering receptor expressed on myeloid cell-2 (TREM2) is a transmembrane receptor which is specifically expressed on myeloid cells. To date, TREM2 has been confirmed as a key factor in many pathologies, such as Alzheimer's disease, obesity-related metabolic syndrome, fatty liver and atherosclerosis. However, the role of TREM2 in tumors remains poorly understood. TREM2 is highly expressed in more than 200 primary and metastatic tumors, a feature that makes TREM2 a potential clinical target for tumor immunotherapy. The tumor microenvironment (TME) is the "soil" which tumors survive on and exhibits immunosuppressive characteristics. During the development of a tumor, TME will secrete various chemotactic factors to recruit myeloid cells. It is clear now that cancer progression and metastasis depend on the interactions between cancer cells and myeloid cell infiltration in TME. As an important receptor involved in inflammatory suppression signaling pathways, TREM2 may play an important role in immune escape by the tumor. Recently, several studies have illustrated that TREM2 expressed on tumor infiltrated myeloid cells acts as a crucial regulator of the antitumor immune response. In this review, we systematically summarize recent publications about the latest advances in knowledge of TREM2 in cancer, especially focusing on its role in tumor associated myeloid cells and tumor immunotherapy.

Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) participate in tumor-elicited immunosuppression by dramatically blocking T-cell-induced antitumor responses, thereby influencing the effectiveness of cancer immunotherapies. Treatments that alter the differentiation and function of MDSCs can partially restore antitumor immune responses. The long noncoding RNA plasmacytoma variant translocation 1 (lncRNA Pvt1) is a potential oncogene in a variety of cancer types. However, whether lncRNA Pvt1 is involved in the regulation of MDSCs has not been thoroughly elucidated to date. METHODS: MDSCs or granulocytic MDSCs (G-MDSCs) were isolated by microbeads and flow cytometry. Bone marrow derived G-MDSCs were induced by IL-6 and GM-CSF. The expression of lncRNA Pvt1 was measured by qRT-PCR. Specific siRNA was used to knockdown the expression of lncRNA Pvt1 in G-MDSCs. RESULTS: In this study, we found that knockdown of lncRNA Pvt1 significantly inhibited the immunosuppressive function of G-MDSCs in vitro. Additionally, lncRNA Pvt1 knockdown reduced the ability of G-MDSCs to delay tumor progression in tumor-bearing mice in vivo. Notably, lncRNA Pvt1 was upregulated by HIF-1α under hypoxia in G-MDSCs. CONCLUSIONS: Taken together, our results demonstrate a critical role for lncRNA Pvt1 in regulating the immunosuppression activity of G-MDSCs, and lncRNA Pvt1 might thus be a potential antitumor immunotherapy target.

[Toxic effect of formaldehyde on mouse different brain regions].

The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.

Extraction of polysaccharides from Maca enhances the treatment effect of 5-FU by regulating CD4+T cells.

In our previous studies, we used a graded alcohol precipitation method to extract four maca polysaccharide components (MCP1, MCP2, MCP3, and MCP4) from maca with various molecular weights. Compared to other three components, MCP2 had stronger immunoregulatory abilities on CD4+T cells. To avoid the immunosuppressive effect of 5-fluorouracil (5-FU), maca polysaccharides in combination with 5-FU treatment were investigated in this study. The results show that 500 mg/kg and 1000 mg/kg MCP2 could significantly delay the growth of tumor and enhance the anti-tumor effect of 5-FU in vivo. Furthermore, MCP2 can partly recover the proliferation of CD4+T cells after being suppressed by 5-FU in vitro. Additionally, in order to explore the mechanism in which MCP2 acts on CD4+T cells, the MCP2 is marked with FITC fluorescence and synthesis MCP2-Tyr-FITC for the first time. Confocal microscope results show that MCP2-Tyr-FITC can directly bind to the surface of CD4+T cells. Together, our work demonstrates that maca polysaccharides could enhance the anti-tumor effect when combined with 5-FU by regulating CD4+T cells, suggesting a novel potential immunomodulator in tumor therapy.

LncRNA Snhg6 regulates the differentiation of MDSCs by regulating the ubiquitination of EZH2.

Myeloid-derived suppressor cells (MDSCs) are derived from bone marrow progenitor cells commonly, which is a heterogeneous cell group composed of immature granulocytes, dendritic cells, macrophages and early undifferentiated bone marrow precursor cells. Its differentiation and immunosuppressive function are regulated by complex network signals, but the specific regulation mechanisms are not yet fully understood. In this study, we found that in mouse of Lewis lung cancer xenograft, long non-coding RNA Snhg6 (lncRNA Snhg6) was highly expressed in tumor-derived MDSCs compared with spleen-derived MDSCs. LncRNA Snhg6 facilitated the differentiation of CD11b+ Ly6G- Ly6Chigh monocytic MDSCs (Mo-MDSCs) rather than CD11b+ Ly6G+ Ly6Clow polymorphonuclear MDSCs (PMN-MDSCs), but did not affect the immunosuppressive function of MDSCs. Notably, lncRNA Snhg6 could inhibit the expression of EZH2 by ubiquitination pathway at protein level rather than mRNA level during the differentiation of mouse bone marrow cells into MDSCs in vitro. EZH2 may be an important factor in the regulation of lncRNA Snhg6 to promote the differentiation of Mo-MDSCs. So what we found may provide new ideas and targets for anti-tumor immunotherapy targeting MDSCs.

LncRNAs: The Regulator of Glucose and Lipid Metabolism in Tumor Cells.

Metabolism is a complex network of regulatory system. Cells often alter their metabolism in response to the changes in their environment. These adaptive changes are particularly pronounced in tumor cells, known as metabolic reprogramming. Metabolic reprogramming is considered to be one of the top 10 characteristics of tumor cells. Glucose and lipid metabolism are important components of metabolic reprogramming. A large number of experimental studies have shown that long non-coding RNAs (lncRNAs) play an important role in glucose and lipid metabolism. The current review briefly introduces the regulatory effect of lncRNAs on glucose and lipid metabolism of tumor cells, and the significance of lncRNA-mediated metabolism in tumor therapy, hoping to provide new strategies for clinical targeting tumor therapy.

Biodiesel production from high acid value waste frying oil catalyzed by superacid heteropolyacid.

Transesterification of waste cooking oil with high acid value and high water contents using heteropolyacid H3PW12O40 x 6H2O (PW12) as catalyst was investigated. The hexahydrate form of PW(12) was found to be the most promising catalyst which exhibited highest ester yield 87% for transesterification of waste cooking oil and ester yield 97% for esterification of long-chain palmitic acid, respectively. The PW12 acid catalyst shows higher activity under the optimized reaction conditions compared with conventional homogeneous catalyst sulfuric acid, and can easily be separated from the products by distillation of the excess methanol and can be reused more times. The most important feature of this catalyst is that the catalytic activity is not affected by the content of free fatty acids (FFAs) and the content of water in the waste cooking oil and the transesterification can occur at a lower temperature (65 degrees C), a lower methanol oil ratio (70:1) and be finished within a shorter time. The results illustrate that PW12 acid is an excellent water-tolerant and environmentally benign acid catalyst for production of biodiesel from waste cooking oil.

Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment.

Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m³) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations.

Zn(1.2)H(0.6)PW(12)O(40) Nanotubes with double acid sites as heterogeneous catalysts for the production of biodiesel from waste cooking oil.

Out of the frying pan: A ZnPW nanotube catalyst containing Brønsted and Lewis double acid sites promotes the conversion of waste cooking oil into biodiesel. The catalytic activity of the ZnPW nanotubes is stable to the presence of free fatty acids or water in the feedstock. The high catalytic activity of the ZnPW nanotubes is attributed to the synergistic effect of Lewis acid sites and Brønsted acid sites.Zinc dodecatungstophosphate (Zn(1.2)H(0.6)PW(12)O(40); ZnPW) nanotubes, which feature Lewis acid and Brønsted acid sites, were prepared using cellulose fibers as templates. The structure, acid properties, and catalytic activity of the nanotubes as heterogeneous catalysts for biodiesel production were then studied in detail. The ZnPW nanocatalyst exhibited higher catalytic activities for the simultaneous esterification and transesterification of palmitic acid than the parent acid catalyst 12-tungstophosphoric acid (H(3)PW(12)O(40)). Moreover, the doubly acidic nanotubes led to markedly enhanced yields of methyl esters in the conversion of waste cooking oil (containing 26.89 wt % free fatty acids and 1 % moisture) to biodiesel. The catalyst could be recycled and reused with negligible loss in activity over five cycles. The ZnPW nanocatalyst is acid- and water-tolerant and is an environmentally benign heterogeneous catalyst for the production of biodiesel from low-quality feedstocks.