LncARSR promotes glioma tumor growth by mediating glycolysis through the STAT3/HK2 axis.

BACKGROUND: Glioma represents the predominant malignant brain tumor. This investigation endeavors to elucidate the impact and prospective mechanisms of glycolysis-related lncARSR on glioma. METHODS: LncARSR level was assessed in normal glial cells and glioma cells. Cell proliferation, migration, and invasion measurements were conducted through CCK-8, wound healing, and transwell assay. Flow cytometry was utilized to measure cell apoptosis and cell cycle. Biochemical assay kits and immunoblotting were employed to measure the content of glycolysis-related indicators and protein expression, respectively. We analyzed the impact of both lncARSR knockdown and overexpression of the Signal Transducer and Activator of Transcription 3 (STAT3) on Hexokinase 2 (HK2) using dual luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) experiments. Further assessment of the impact of lncARSR on glioma progression was conducted through animal experiments. RESULTS: LncARSR was expressed at elevated levels in glioma cells compared to normal glial cells. Overexpressing lncARSR enhanced proliferation, migration, invasion, and G2/M phase arrest in glioma cells and also increased glucose, lactate, ATP production, as well as the expression of HK2, PFK1, PKM2, GLUT1, and LDHA. STAT3 binding to the HK2 gene promoter was weakened following the knockdown of lncARSR. Upregulation of STAT3 reversed the suppressed functions of knocking down lncARSR on cell proliferation, migration, invasion, G2/M phase arrest, and glycolysis and counteracted its promotional effect on cell apoptosis. In vivo, knocking down lncARSR inhibits glioma growth and ki67 and PCNA expression. CONCLUSION: LncARSR promotes the development of glioma by enhancing glycolysis through the STAT3-HK2 axis.

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. METHODS: PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. RESULTS: BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. CONCLUSION: Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.

Bai-He-Gu-Jin-Tang formula suppresses lung cancer via AKT/GSK3ß/ß-catenin and induces autophagy via the AMPK/mTORC1/ULK1 signaling pathway.

Aims: Bai-He-Gu-Jin-Tang (BHGJT) is a classic Chinese formula used to treat lung cancer, while the underlying molecular mechanism remains obscure. The aim of the study was to investigate the molecular mechanism of BHGJT on lung cancer and demonstrate the potential for synergistic treatment combining BHGJT with conventional therapy. Methods: Cell viability assay, colony formation assay and EdU assay were used to determine the in vitro effects of BHGJT, and a subcutaneous xenograft model was used to evaluate the in vivo effect. Cell cycle analysis, apoptosis rate analysis, immunohistochemical and immunofluorescent staining, Western blot assays and network pharmacology-based analysis were used to explore the underlying mechanisms. Results: We found that BHGJT inhibited cell proliferation via a dose-dependent pathway and obviously hindered tumor growth in vivo in lung cancer. Cell cycle arrest and apoptosis were pronouncedly induced by BHGJT via dysregulation of the cell cycle regulators CDK4 and Cyclin D1 and dysregulation of apoptosis-associated proteins, such as cleaved caspase 3/9 and the BCL-2 family. Based on a network pharmacology-based analysis and experimental evidence, we demonstrated that the AKT/GSK3ß/ß-catenin signaling pathways were responsible for BHGJT-induced apoptosis in lung cancer cells. Additionally, autophagy was induced by BHGJT via the AMPK/mTORC1/ULK1 signaling pathway, and blocking autophagy with either chloroquine or a ULK1 inhibitor increased the killing efficiency of BHGJT in lung cancer cells. Conclusion: Our findings indicate that the BHGJT formula efficiently inhibits lung cancer growth and represents a potential complementary and alternative treatment for lung cancer.

Nanoscale Formulations: Incorporating Curcumin into Combination Strategies for the Treatment of Lung Cancer.

Lung cancer remains the most common cancer worldwide. Although significant advances in screening have been made and early diagnosis strategies and therapeutic regimens have been developed, the overall survival rate remains bleak. Curcumin is extracted from the rhizomes of turmeric and exhibits a wide range of biological activities. In lung cancer, evidence has shown that curcumin can markedly inhibit tumor growth, invasion and metastasis, overcome resistance to therapy, and even eliminate cancer stem cells (CSCs). Herein, the underlying molecular mechanisms of curcumin were summarized by distinct biological processes. To solve the limiting factors that curtail the clinical applications of curcumin, nanoformulations encapsulating curcumin were surveyed in detail. Nanoparticles, including liposomes, micelles, carbon nanotubes (CNTs), solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions, were explored as proper carriers of curcumin. Moreover, it was firmly verified that curcumin has the ability to sensitize lung cancer cells to chemotherapeutic drugs, such as cisplatin and docetaxel, and to various targeted therapies. Regarding the advantages and drawbacks of curcumin, we concluded that combination therapy based on nanoparticles would be the optimal approach to broaden the application of curcumin in the clinic in the near future.

Comprehensive transcriptome analysis reveals genes in response to water deficit in the leaves of Saccharum narenga (Nees ex Steud.) hack.

BACKGROUND: Sugarcane is an important sugar and energy crop that is widely planted in the world. Among the environmental stresses, the water-deficit stress is the most limiting to plant productivity. Some groups have used PCR-based and microarray technologies to investigate the gene expression changes of multiple sugarcane cultivars under water stress. Our knowledge about sugarcane genes in response to water deficit is still poor. RESULTS: A wild sugarcane type, Saccharum narenga, was selected and treated with drought stress for 22 days. Leaves from drought treated (DTS) and control (CK) plants were obtained for deep sequencing. Paired-end sequencing enabled us to assemble 104,644 genes (N50 = 1605 bp), of which 38,721 were aligned to other databases, such as UniProt, NR, GO, KEGG and Pfam. Single-end and paired-end sequencing identified 30,297 genes (> 5 TPM) in all samples. Compared to CK, 3389 differentially expressed genes (DEGs) were identified in DTS samples, comprising 1772 up-regulated and 1617 down-regulated genes. Functional analysis showed that the DEGs were involved in biological pathways like response to blue light, metabolic pathways and plant hormone signal transduction. We further observed the expression patterns of several important gene families, including aquaporins, late embryogenesis abundant proteins, auxin related proteins, transcription factors (TFs), heat shock proteins, light harvesting chlorophyll a-b binding proteins, disease resistance proteins, and ribosomal proteins. Interestingly, the regulation of genes varied among different subfamilies of aquaporin and ribosomal proteins. In addition, DIVARICATA and heat stress TFs were first reported in sugarcane leaves in response to water deficit. Further, we showed potential miRNAs that might be involved in the regulation of gene changes in sugarcane leaves under the water-deficit stress. CONCLUSIONS: This is the first transcriptome study of Saccharum narenga and the assembled genes are a valuable resource for future research. Our findings will improve the understanding of the mechanism of gene regulation in sugarcane leaves under the water-deficit stress. The output of this study will also contribute to the sugarcane breeding program.

[Characteristics of N forms and N-transforming bacteria in paddy soil under different tillage patterns].

Paddy soil samples were collected in layers (0-5, 5-12, and 12-20 cm) during rice growth period to investigate the characteristics of the N forms and N-transforming bacteria in the soil profile under different tillage patterns (no-tillage with straw returning, NTS; conventional tillage with straw returning, CTS; no-tillage, NT; and conventional tillage, CT). In the whole rice growth period, ammonifying bacteria in 0-5 cm soil layer had the highest number under NTS, and nitrosobacteria in 0-5 cm and 5-12 cm soil layers were more abundant but in 12-20 cm soil layer were lesser under CT than under NT. Nitrosobacteria and denitrobacteria in 0-20 cm soil layer were lesser under NTS than under CTS. At elongating and ripening stages, anaerobic N-fixing bacteria in 0-5 cm soil layer were more abundant under NT than under CT. In the whole rice growth period, the alkali-hydrolyzable N and total N contents in 0-5 cm soil layer were significantly higher but in 5-12 cm and 12-20 cm soil layers were lower under NT than under CT, and the NH4(+)-N and NO3(-)-N contents in 0-20 cm soil layer were higher under NTS but in 12-20 cm soil layer had no significant differences between NT and CT. Correlation analysis and multiple polynomial regression analysis further revealed that there were significant relationships between soil NH4(+)-N and soil ammonifying bacteria, nitrosobacteria and denitrobacteria, and between soil alkali-hydrolyzable N and soil anaerobic N-fixing bacteria. Among the test tillage patterns, NTS could be the more desirable one for the N supply and fertility maintenance of paddy soil.