Distribution of intensity and M2 factor for a partially coherent flat-topped beam in bidirectional turbulent atmosphere and plasma connection.

This study investigates the bidirectional transmission of a partially coherent flat-topped beam in a turbulent atmosphere and plasma. Analytical formulas for the intensity distribution and M2 factor are derived based on the optical transmission matrix, Collins formula, and second moment theory with Wigner distribution function. Numerical results show that the beam order and transverse spatial coherence width can be selected appropriately to mitigate turbulence and plasma induced evolution properties. The partially coherent flat-topped beam propagation through a turbulent atmosphere and plasma of the forward transmission effect on the intensity distribution and M2 factor are smaller than that of the reverse transmission. Under the same conditions, the M2 factor of a partially coherent flat-topped beam is smaller than the Gaussian beam in bidirectional transmission. Our results can be used in long-distance free-space optical communications.

Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease.

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.

Hypothalamic FTO promotes high-fat diet-induced leptin resistance in mice through increasing CX3CL1 expression.

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity.

Expression and tissue distribution analysis of vimentin and transthyretin proteins associated with coat colors in sheep (Ovis aries).

OBJECTIVE: Pigment production and distribution are controlled through multiple proteins, resulting in different coat color phenotypes of sheep. METHODS: The expression distribution of vimentin (VIM) and transthyretin (TTR) in white and black sheep skins was detected by liquid chromatography-electrospray ionization tandem MS (LC-ESI-MS/MS), gene ontology (GO) statistics, immunohistochemistry, Western blot, and quantitative real time polymerase chain reaction (qRT-PCR) to evaluate their role in the coat color formation of sheep. RESULTS: LC-ESI-MS/MS results showed VIM and TTR proteins in white and black skin tissues of sheep. Meanwhile, GO functional annotation analysis suggested that VIM and TTR proteins were mainly concentrated in cellular components and biological process, respectively. Further research confirmed that VIM and TTR proteins were expressed at significantly higher levels in black sheep skins than in white sheep skins by Western blot, respectively. Immunohistochemistry notably detected VIM and TTR in hair follicle, dermal papilla, and outer root sheath of white and black sheep skins. qRT-PCR results also revealed that the expression of VIM and TTR mRNAs was higher in black sheep skins than in white sheep skins. CONCLUSION: The expression of VIM and TTR were higher in black sheep skins than in white sheep skins and the transcription and translation were unanimous in this study. VIM and TTR proteins were expressed in hair follicles of white and black sheep skins. These results suggested that VIM and TTR were involved in the coat color formation of sheep.

Proteogenomic characterization of ferroptosis regulators reveals therapeutic potential in glioblastoma.

BACKGROUND: Ferroptosis is iron-dependent non-apoptotic cell death, that is characterized by the excessive accumulation of lipid peroxides. Ferroptosis-inducing therapy also shows promise in the treatment of cancers. However, ferroptosis-inducing therapy for glioblastoma multiforme (GBM) is still in the exploratory stage. METHODS: We identified the differentially expressed ferroptosis regulators using Mann-Whitney U test in the proteome data from Clinical Proteomic Tumor Analysis Consortium (CPTAC). We next analyzed the effect of mutation on protein abundance. A multivariate Cox model was constructed to identify the prognostic signature. RESULTS: In this study, we systemically portrayed the proteogenomic landscape of ferroptosis regulators in GBM. We observed that some mutation-specific ferroptosis regulators, such as down-regulated ACSL4 in EGFR-mutated patients and up-regulated FADS2 in IDH1-mutated patients, were linked to the inhibited ferroptosis activity in GBM. To interrogate the valuable treatment targets, we performed the survival analysis and identified five ferroptosis regulators (ACSL3, HSPB1, ELAVL1, IL33, and GPX4) as the prognostic biomarkers. We also validated their efficiency in external validation cohorts. Notably, we found overexpressed protein and phosphorylation abundances of HSPB1 were poor prognosis markers for overall survival of GBM to inhibit ferroptosis activity. Alternatively, HSPB1 showed a significant association with macrophage infiltration levels. Macrophage-secreted SPP1 could be a potential activator for HSPB1 in glioma cells. Finally, we recognized that ipatasertib, a novel pan-Akt inhibitor, could be a potential drug for suppressing HSPB1 phosphorylation, inducing ferroptosis of glioma cells. CONCLUSION: In summary, our study characterized the proteogenomic landscape of ferroptosis regulators and identified that HSPB1 could be a candidate target for ferroptosis-inducing therapy strategy for GBM.

Nifuroxazide inhibits the growth of glioblastoma and promotes the infiltration of CD8 T cells to enhance antitumour immunity.

INTRODUCTION: Glioblastoma is a primary intracranial tumour with extremely high disability and fatality rates among adults. Existing diagnosis and treatment methods have not significantly improved the overall poor prognosis of patients. Nifuroxazide, an oral antibiotic, has been reported to act as a tumour suppressor in a variety of tumours and to participate in the process of antitumour immunity. However, whether it can inhibit the growth of glioma is still unclear. METHODS: We explored the potential mechanism of nifuroxazide inhibiting the growth of glioblastoma cells through in vitro and in vivo experiments. RESULTS: nifuroxazide can inhibit the proliferation of glioblastoma cells, promote G2 phase arrest, induce apoptosis, and inhibit epithelial-mesenchymal transition through the MAP3K1/JAK2/STAT3 pathway. Similarly, clinical sample analysis confirmed that MAP3K1 combined with STAT3 can affect the prognostic characteristics of patients with glioma. In addition, nifuroxazide can drive the M1 polarization of microglioma cells, inhibit the expression of CTLA4 and PD-L1 in tumour cells, and promote the infiltration of CD8 T cells to exert antitumour effects. Combination treatment with PD-L1 inhibitors can significantly prolong the survival time of mice. CONCLUSION: we found that nifuroxazide can inhibit the growth of glioblastoma and enhance antitumour immunity. Thus, nifuroxazide is an effective drug for the treatment of glioblastoma and has great potential for clinical application.

Analysis of differentially expressed microRNAs in bovine mammary epithelial cells treated with lipoteichoic acid.

Mastitis is one of the most common diseases of dairy cattle and can be caused by physical stress, chemicals and microbial infection. Staphylococcus aureus is the most common pathogens that induce mastitis in dairy cattle. In this study, bovine mammary epithelial cells (BMECs) were treated either with lipoteichoic acid (LTA, 30 µg/ml) or 1 × phosphate-buffer saline (PBS, control) and RNA-Seq was applied to explore the effect of LTA on the expression microRNAs (miRNAs) in BMECs. Compared to the control group, 43 miRNAs were significantly up-regulated and eight miRNAs were significantly down-regulated. Additionally, 724 genes were significantly up-regulated and 13 genes were significantly down-regulated in LTA group relative to the control group. Bta-miR-196a, bta-miR-2285aj-5p, bta-miR-143, bta-miR-2433, bta-miR-2284f and bta-miR-2368-3p were selected from 51 differentially expressed miRNAs and are discussed in this manuscript. Target gene prediction revealed that the target genes of these six miRNAs were all differentially expressed, including MT1E, SPDYA, FGL1, TLR2, PAPOLG, ZDHHC17 and SMC4. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the target genes with differentially expressed miRNAs were enriched in mitogen-activated protein kinase (MAPK) signalling pathway, rheumatoid arthritis and cancer. Therefore, the results of this study provided new evidences for the molecular mechanism of LTA-induced mastitis, which may provide new targets for the diagnosis and treatment of mastitis in dairy cattle.

Effect of forsythoside A on the transcriptional profile of bovine mammary epithelial cells challenged with lipoteichoic acid.

Mastitis is a common disease of the dairy cattle, which affects the development of the dairy industry and leads to huge economic losses. Forsythoside A (FTA) has anti-inflammatory, antioxidant, antiviral and anti-apoptotic effects. However, the therapeutic effect and molecular mechanism of FTA on dairy cow mastitis remain unclear. In this study, bovine mammary epithelial cells (BMECs) were stimulated with lipoteichoic acid (LTA), a key virulence factor of Staphylococcus aureus (S. aureus), to construct in vitro models, and then treated with FTA. Subsequently, the differentially expressed genes (DEGs) in different groups were determined by RNA sequencing (RNA-Seq) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse the possible function of the DEGs, real-time quantitative PCR (RT-qPCR) was used to verify whether the expression levels of these DEGs were consistent with RNA-Seq results. The results showed that cell division cycle 20B (CDC20B), endothelial cell surface expressed chemotaxis and apoptosis regulator (ECSCR), complement factor H-related 5 (CFHR5) and phospholipase A2 group IVA (PLA2G4A) were down-regulated after FTA treatment. In contrast, Kruppel-like factor 15 (KLF15) and Metallothionein 1E (MT1E) were up-regulated. These DEGs are involved in processes such as apoptosis, inflammation and development of cancer. This study provides valuable insights into the transcriptome changes in BMECs after FTA treatment. Further analysis may help identify the underlying molecular mechanisms.

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux.

The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

Genome Instability-Associated Long Non-Coding RNAs Reveal Biomarkers for Glioma Immunotherapy and Prognosis.

Genome instability is a hallmark of tumors and is involved in proliferation, invasion, migration, and treatment resistance of many tumors. However, the relationship of genome instability with gliomas remains unclear. Here, we constructed genome instability-derived long non-coding RNA (lncRNA)-based gene signatures (GILncSig) using genome instability-related lncRNAs derived from somatic mutations. Multiple platforms were used to confirm that the GILncSig were closely related to patient prognosis and clinical characteristics. We found that GILncSig, the glioma microenvironment, and glioma cell DNA methylation-based stemness index (mDNAsi) interacted with each other to form a complex regulatory network. In summary, this study confirmed that GILncSig was an independent prognostic indicator for patients, distinguished high-risk and low-risk groups, and affected immune-cell infiltration and tumor-cell stemness indicators (mDNAsi) in the tumor microenvironment, resulting in tumor heterogeneity and immunotherapy resistance. GILncSig are expected to provide new molecular targets for the clinical treatment of patients with gliomas.

The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma.

Glioma is a malignant tumor with a high fatality rate, originating in the central nervous system. Even after standard treatment, the prognosis remains unsatisfactory, probably due to the lack of effective therapeutic targets. The family of transmembrane proteins (TMEM) is a large family of genes that encode proteins closely related to the malicious behavior of tumors. Thus, it is necessary to explore the molecular and clinical characteristics of newly identified oncogenes, such as transmembrane protein 60 (TMEM60), to develop effective treating options for glioma. We used bioinformatic methods and basic experiments to verify the expression of transmembrane protein 60 in gliomas and its relationship with 1p and 19q (1p19q) status, isocitrate dehydrogenase (IDH) status, patient prognosis, and immune cell infiltration using public databases and clinical samples. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to detect co-expressed genes. Thus, we inhibited the expression of transmembrane protein 60 to observe the proliferation and activity of glioma LN229 cells. We found transmembrane protein 60 was significantly upregulated in glioma compared with that in normal brain tissue at the mRNA. In the subgroups of World Health Organization high grade, isocitrate dehydrogenase wildtype, 1p and 19q non-codeletion, or isocitrate dehydrogenase wild combined with 1p and 19q non-codeletion, the expression of transmembrane protein 60 increased, and the prognosis of glioma patients worsened. In the transmembrane protein 60 high expression group, infiltration of immune cells and stromal cells in the tumor microenvironment increased, tumor purity decreased, and immune cells and pathways were activated. The immune cells mainly included regulatory T-cell, gamma delta T-cell, macrophages M0, neutrophils, and CD8+ T-cells. Overexpression of co-inhibitory receptors (CTLA4, PDL1 and CD96) may promote the increase of depletion of T-cell, thus losing the anti-tumor function in the transmembrane protein 60 high expression group. Finally, we found that transmembrane protein 60 silencing weakened the viability, proliferation, and colony formation of glioma LN229 cells. This is the 0 report on the abnormally high expression of transmembrane protein 60 in glioma and its related clinical features, such as tumor microenvironment, immune response, tumor heterogeneity, and patient prognosis. We also found that transmembrane protein 60 silencing weakened the proliferation and colony formation of glioma LN229 cells. Thus, the new oncogene transmembrane protein 60 might be an effective therapeutic target for the clinical treatment of glioma.

TMEM2 Combined with IDH and 1p19q in Refining Molecular Subtypes for Predicting Survival of Patients with Glioma.

Gliomas are common intracranial tumors with high morbidity and mortality in adults. Transmembrane protein 2 (TMEM2) is involved in the malignant behavior of solid tumors. TMEM2 regulates cell adhesion and metastasis as well as intercellular communication by degrading nonprotein components of the extracellular matrix. This study aimed to evaluate the relationship between TMEM2 expression levels and glioma subtypes or patient prognosis. Our findings revealed that TMEM2 expression was abnormally upregulated in high-grade glioma. Moreover, combining TMEM2, the status of isocitrate dehydrogenase (IDH) and 1p19q, we subdivided molecular subtypes with significant differences in survival. Patients in the MT-codel-low subgroup had better prognosis than those in the WT-no-codel-high subgroup, who fared the worst. Additionally, correlation analysis of TMEM2 and immune cell infiltration indicated an altered tumor microenvironment (TME) and cell redistribution in the TMEM2 high-expression subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that focal adhesion and PI3K-Akt signaling pathways were enriched in the TMEM2-expressing group. In conclusion, aberrant TMEM2 expression can be used as an independent prognostic marker for refining glioma molecular subtyping and accurate prognosis. These findings will improve rational decision making to provide individualized therapy for patients with glioma.

Clinical Value of TXNDC12 Combined With IDH and 1p19q as Biomarkers for Prognosis of Glioma.

Background: Glioma is the primary malignant tumor of the central nervous system and presents high mortality and disability rates under existing treatment measures. Thioredoxin domain-containing 12 (TXNDC12) has been shown to play an important role in various malignant tumors. Therefore, we explored the clinicopathological characteristics of TXNDC12 in glioma to bring to light new ideas in its treatment. Methods: We obtained data packages related to TXNDC12 expression status in gliomas from public databases. We analyzed glioma TXNDC12 expression and patient survival status and validated the above results using glioma specimens from our institution. Next, we analyzed the value of TXNDC12 in combination with 1p19q and isocitrate dehydrogenase (IDH) on the prognosis of glioma by regression model and receiver operating characteristic curve (ROC). Finally, we explored the function of related genes by GO analysis and KEGG analysis. Results: Compared with normal brain tissue, the expression of TXNDC12 in glioma cells, regarding both mRNA and protein levels, was significantly upregulated. The survival time of patients with high-expression of TXNDC12 in glioma cells was shortened. In the World Health Organization pathological classification, IDH status, 1p19q status, and IDH combined with 1p19q subgroups, the expression of TXNDC12 increased with the deterioration of the above indicators. Tumor local immune analysis showed that the immune cell infiltration in TXNDC12 high-expressing glioma tissue increased, the tumor purity was reduced. GO and KEGG analyses indicated that TXNDC12 may be involved in the malignant prognosis of glioma through glycosylation and antigen processing and presentation. Conclusion: We showed that TXNDC12 is significantly highly expressed in gliomas. This high expression predicts the poor prognosis of glioma patients and is related to the gliomas' local immune microenvironment. As a tumor-related gene, TXNDC12 may be used as a new prognostic judgment molecule.

A novel lncRNA, RPL34-AS1, promotes proliferation and angiogenesis in glioma by regulating VEGFA.

Purpose: Brain gliomas are the most common primary malignant tumors of the central nervous system and one of the leading causes of death in patients with intracranial tumors. The lncRNA RPL34-AS1 is significantly upregulated in glioma tissues. However, the biological function of RPL34-AS1, especially in proliferation in glioma, remains unclear. Methods: The role of RPL34-AS1 in proliferation and angiogenesis in glioma cells was investigated using the LN229, U87, and U251 glioma cell lines. The levels of RPL34-AS1 were detected using real-time quantitative reverse transcription polymerase chain reaction. CCK-8 and colony formation assays were performed to determine the role of RPL34-AS1 in proliferation and survival, and its role in angiogenesis was assessed by an endothelial tube formation assay. Changes in protein levels were assessed by western blotting. Results: RPL34-AS1 was upregulated in glioma tissues and was correlated with tumor grade. RPL34-AS1 expression was also higher in glioma cells than in normal astrocytes. Knockdown of RPL34-AS1 blocked glioma cell proliferation by inhibiting angiogenesis. This effect occurred through decreased ERK/AKT signaling. Conclusions: This study suggests that RPL34-AS1 affects cell proliferation and angiogenesis in glioma and therefore may potentially serve as a valuable diagnostic and prognostic biomarker and therapeutic target in patients with glioma.

Effects of triptolide on radiosensitivity of human glioma cells and its mechanism.

PURPOSE: To study the effect of triptolide (TP) on radiosensitivity of human glioma U251 cells and its mechanism, so as to provide new ideas and methods for the radiotherapy of glioma. METHODS: U251 cells were treated with 10, 50, 100 nmol/L TP at different concentrations and irradiated with 0, 2, 4, 6, 8 Gy X-ray. The radiosensitivity of cells in each group were detected by MTT. U251 cells were then divided into control group, 10 nmol/L TP group, 4 Gy radiation group, 10 nmol/L TP + 4 Gy radiation group. The formation ability of U251 cells in each group was detected by colony formation assay. Flow cytometry was used to detect cell cycle and apoptosis in each group. Western blot was used to detect the changes of PI3K/Akt signal pathway in each group. RESULTS: When 10, 50, 100 nmol/L TP were combined with 2, 4, 6, 8 Gy X-ray, the proliferation inhibition rate of U251 cells in each group increased significantly (p<0.05); compared with 10 nmol/L TP alone group and 4 Gy radiation alone group, the colony formation ability rate of U251 cells in 10 nmol/L TP + 4Gy radiation combined group decreased significantly (p<0.05), the cell cycle was blocked in G1 phase, and the apoptosis rate was significantly reduced (p<0.05). The level of p-pi3k and p-Akt decreased significantly (p<0.05). CONCLUSION: Triptolide could significantly increase the radiosensitivity of human glioma U251 cells and play a role by inhibiting the PI3K/Akt signal pathway.

Long noncoding RNA SNHG12 is a potential diagnostic and prognostic biomarker in various tumors.

BACKGROUND: Tumors are the second most common cause of death in humans worldwide, second only to cardiovascular and cerebrovascular diseases. Although methods and techniques for the treatment of tumors continue to improve, the effect is not satisfactory. These may lack effective therapeutic targets. This study aimed to evaluate the value of SNHG12 as a biomarker in the prognosis and clinical characteristics of various cancer patients. METHODS: We analyzed SNHG12 expression and plotted the survival curves of all cancer samples in the TCGA database using the GEPIA tool. Then, we searched for eligible papers up to April 1, 2019, in databases. Next, the data were extracted from studies examining SNHG12 expression, overall survival and clinicopathological features in patients with malignant tumors. We used Review Manager 5.3 and Stata 15 software to analyze the statistical data. RESULTS: In the TCGA database, abnormally high expression of SNHG12 in tumor samples indicates that the patient has a poor prognosis. Results of meta-analysis is that SNHG12 high expression is related to low overall survival (HR = 2.72, 95% CI = 1.95-3.8, P < 0.00001), high tumor stage (OR = 3.94, 95% CI = 2.80-5.53, P < 0.00001), high grade (OR = 2.04, 95% CI = 1.18-3.51, P = 0.01), distant metastasis (OR = 2.20, 95% CI = 1.40-3.46, P = 0.0006), tumor size (OR = 2.79, 95% CI = 1.89-4.14, P < 0.00001), and lymph node metastasis (OR = 2.66, 95% CI = 1.65-4.29, P < 0.0001). CONCLUSIONS: Our study confirmed that the high expression level of SNHG12 is closely related to the clinicopathological characteristics and prognosis of patients and is a new predictive biomarker for various cancer patients.

Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy.

The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

Analysis of miRNA expression changes in bovine endometrial stromal cells treated with lipopolysaccharide.

After parturition, bovine uterine stromal cells are often exposed to complex bacterial and viral stimuli owing to epithelial cell rupture, resulting in an inflammatory response. In this study, we used an in vitro model to study the response of bovine endometrial stromal cells to inflammatory mediators and the associated regulated microRNAs in response to lipopolysaccharide. Lipopolysaccharide (LPS) is a bacterial wall component in gram-negative bacteria that causes inflammation upon immune recognition, which is used to create in vitro inflammation models. Thus, we used high-throughput RNA sequencing to identify miRNAs that may have an anti-inflammatory role in the LPS-induced inflammatory response. Two groups of bovine uterine cells were treated with phosphate buffer saline (PBS) and LPS, respectively. Compared with the control (PBS) group, the LPS-treated group had 219 differentially expressed miRNAs, of which 113 were upregulated, and 106 were downregulated. Gene ontology enrichment analysis revealed that the target genes of differentially expressed miRNAs were significantly enriched in several activities, such as transferase activity, small molecule binding, and protein binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the target genes of differential miRNAs were significantly enriched in fluid shear stress and atherosclerosis, MAPK signaling pathway, TNF signaling pathway. By analyzing differentially expressed miRNAs, we found that miR-200c, miR-1247-3p, and let-7b are directly related to the inflammatory response. For instance, miR-200c target genes (MAP3K1, MAP4K3, MAPKAPK5, MAP3K8, MAP3K5) and let-7b target genes (CASP3, IL13, MAPK8, CXCL10) were significantly enriched in the MAPK and IL-17 signaling pathways, respectively. In summary, our research provides insight into the molecular mechanism underlying LPS-induced inflammation in vitro, which may unveil new targets for the treatment of endometritis.

Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells.

Bovine endometrial stromal cells (bESCs) are exposed to a complex environment of bacteria and viruses due to the rupture of epithelial cells after delivery. Inflammatory responses are elicited by the activation of host pattern recognition receptors through pathogen-related molecules such as lipopolysaccharides (LPS) on the cell membrane. Forsythoside A (FTA) is a major active constituent of Forsythia suspensa (Thunb.) Vahl. is a flowering plant widely employed as a traditional Chinese herbal medicine to treat various inflammatory diseases such as nephritis, eye swelling, scabies, ulcers, and mastitis; however, the molecular mechanisms underlying its therapeutic effects on bovine endometritis are still unclear. The aim of this study was to explore the role of miRNA and the mechanisms underlying the protective activity of FTA on the inflammation of bovine endometrial stromal cells induced by LPS. Based on previous research, we isolated and cultured bESCs in vitro and categorized them into LPS and LPS+FTA groups with three replicates. Upon reaching 80% confluence, the bESCs were treated with 0.5 µg/mL of LPS or 0.5 µg/mL of LPS + 100 µg/mL of FTA. We, then, performed high-throughput sequencing (RNA-Seq) to investigate the effects of FTA on LPS-stimulated primary bESCs and their underlying mechanisms. We identified 167 miRNAs differentially expressed in the LPS groups; 72 miRNAs were up-regulated, and 95 were down-regulated. Gene ontology enrichment analysis revealed that differentially expressed microRNA (DEGs) were most enriched during the cellular metabolic process; they were mostly located intracellularly and participated in protein, enzyme, and ion binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were most enriched in the mitogen-activated protein kinase, tumor necrosis factor, and Interleukin-17 signaling pathways. These results reveal the complex molecular mechanism involved in the FTA and provide a basis for future studies of bovine endometritis treatment with traditional Chinese medicine monomer.

Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide.

Endometritis adversely affects the ability of cattle to reproduce and significantly reduces milk production. The is mainly composed of epithelial and stromal cells, and they produce the first immune response to invading pathogens. However, most of the epithelial cells are disrupted, and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. Many bacteria and toxins start attacking stromal cell due to loss of epithelium, which stimulates Toll-like receptor (TLRs) on stromal cells and causes upregulated expression of cytokines. Understanding the genome-wide characterization of bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine endometrial stromal cells (BESCs) treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing. Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in the LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P < 0.05 by DESeq. Gene Ontology (GO) enrichment analysis revealed that DEGs were most enriched in interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in the TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, NF-κB signaling pathway, and chemokine signaling pathway. The results of this study unraveled BESCs affected with LPS transcriptome profile alterations, which may have a significant effect on treatment inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.