Oerskovia flava sp. nov., a deoxynivalenol (DON)-degrading actinomycete isolated from the rhizosphere soil of long-term continuous cropping cucumber.

The deoxynivalenol (DON)-degrading bacterium JB1-3-2 T was isolated from a rhizosphere soil sample of cucumber collected from a greenhouse located in Zhenjiang, Eastern China. The JB1-3-2 T strain is a Gram-stain-positive, nonmotile and round actinomycete. Growth was observed at temperatures between 15 and 40 ℃ (optimum, 35 ℃), in the presence of 15% (w/v) NaCl (optimum, 3%), and at pH 3 and 11 (optimum, 7). The major cellular fatty acids identified were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. Genome sequencing revealed a genome size of 4.11 Mb and a DNA G + C content of 72.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the JB1-3-2 T strain was most closely related to type strains of the Oerskovia species, with the highest sequence similarity to Oerskovia turbata NRRL B-8019 T (98.2%), and shared 98.1% sequence identity with other valid type strains of this genus. Digital DNA‒DNA hybridization (dDDH) and average nucleotide identity (ANI) showed 21.8-22.2% and 77.2-77.3% relatedness, respectively, between JB1-3-2 T and type strains of the genus Oerskovia. Based on genotypic, phylogenetic, chemotaxonomic, physiological and biochemical characterization, Oerskovia flava, a novel species in the genus Oerskovia, was proposed, and the type strain was JB1-3-2 T (= CGMCC 1.18555 T = JCM 35248 T). Additionally, this novel strain has a DON degradation ability that other species in the genus Oerskovia do not possess, and glutathione-S-transferase was speculated to be the key enzyme for strain JB1-3-2 T to degrade DON.

Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

Nocardioides limicola sp. nov., an alkaliphilic alkane degrading bacterium isolated from oilfield alkali-saline soil.

A Gram-stain-positive, rod-shaped, non-spore-forming, alkane degrading bacterium, designated DJM-14T, was isolated from oilfield alkali-saline soil in Heilongjiang, Northeast China. On the basis of 16 S rRNA gene sequencing, strain DJM-14T was shown to belong to the genus Nocardioides, and related most closely to Nocardioides terrigena KCTC 19,217T (95.53% 16 S rRNA gene sequence similarity). Strain DJM-14T was observed to grow at 25-35 °C, pH 7.0-11.0, in the presence of 0-6.0% (w/v) NaCl. The predominant respiratory quinone was MK-8 (H4) and LL-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major fatty acids were identified as iso-C16:0 and C18:1 ω9c. It contained diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the polar lipids. The genome (3,722,608 bp), composed of 24 contigs, had a G + C content of 69.6 mol%. Out of the 3667 predicted genes, 3618 were protein-coding genes, and 49 were ncRNAs. Digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) of strain DJM-14T against genomes of the type strains of related species in the same family ranged between 18.7% and 20.0%; 68.8% and 73.6%, respectively. According to phenotypic, genotypic and phylogenetic data, strain DJM-14T represents a novel species in the genus Nocardioides, for which the name Nocardioides limicola sp. nov. is proposed and the type strain is DJM-14T (= CGMCC 4.7593T, =JCM 33,692T). In addition, novel strains were able to grow with n-alkane (C24-C36) as the sole carbon source. Multiple copies of alkane 1-monooxygenase (alkB) gene, as well as alcohol dehydrogenase gene and aldehyde dehydrogenase gene involved in the alkane assimilation were annotated in the genome of type strain DJM-14T.

Hepatocellular carcinoma­cavernous hemangioma collision tumor: A case report.

Collision tumors consisting of hepatocellular carcinoma (HCC) and cavernous hemangioma (CH) are rare and the clinicopathological characteristics or cause of the tumors remain unclear. The present study reports the case of a 71-year-old male patient who was admitted to Sunshine Union Hospital (Weifang, China) due to a liver mass found during a routine physical examination. computed tomography scans showed a main lesion of ~4.0×4.2×3.5 cm in segment IV of the patient's liver and a nodule of ~2.4×2.2×1.3 cm in the lower-left part of the lesion, which was clearly demarcated from the main lesion. The capsule of the lesion was found to be intact during the operation performed to remove the tumor. The final patient diagnosis was of a HCC-CH collision tumor based on pathology. The patient underwent follow-up for 6 months after surgery and no recurrence was observed.

Multi-omics analysis of lung tissue metabolome and proteome reveals the therapeutic effect of Shegan Mahuang Decoction against asthma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan Mahuang Decoction (SMD) is a classic traditional Chinese medicine (TCM) formula for asthma treatment, but the anti-asthma mechanism of SMD is still not fully studied. AIMS OF THE STUDY: In this study, we established an ovalbumin (OVA)-induced asthma rat model and treated it with SMD to observe its anti-asthma effect and explore the related mechanism. MATERIALS AND METHODS: We evaluated the anti-inflammatory effect of SMD via testing the levels of immunoglobulin E (IgE), C-reactive protein (CRP), interleukin-4 (IL-4), interleukin-6 (IL-6) in serum and performing the hematoxylin-eosin (H&E) staining of lung tissue slices. We analyzed the variations of metabolites and proteins in the lung tissue of different groups using liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics and TMT-based proteomics approaches. The metabolic biomarkers and differentially expressed proteins (DEPs) were picked, and the related signal transduction pathways were also investigated. In addition, the key proteins on the signaling pathway were validated through western blotting (WB) experiment to reveal the anti-asthma mechanism of SMD. RESULTS: The results showed that the SMD could significantly reduce the serum levels of IgE, CRP, IL-4, and IL-6 and attenuate the OVA-induced pathological changes in lung tissue. A total of 34 metabolic biomarkers and 84 DEPs were screened from rat lung tissue, which were mainly associated with lipid metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, the excessive production of reactive oxygen species (ROS), and lysosome pathway. Besides, SMD could inhibit the myeloid differentiation factor 88 (MyD88)/inhibitor of kappa B kinase (IKK)/nuclear factor-kappa B (NF-κB) signaling pathway to exhibit anti-inflammatory activities. CONCLUSIONS: SMD exhibited a therapeutic effect on asthma, which possibly be exerted by inhibiting the MyD88/IKK/NF-κB signaling pathway.

Targeting ABCA12-controlled ceramide homeostasis inhibits breast cancer stem cell function and chemoresistance.

Cancer stem cells (CSCs) drive tumor growth, metastasis, and chemoresistance. While emerging evidence suggests that CSCs have a unique dependency on lipid metabolism, the functions and regulation of distinct lipid species in CSCs remain poorly understood. Here, we developed a stem cell factor SOX9-based reporter for isolating CSCs in primary tumors and metastases of spontaneous mammary tumor models. Transcriptomic analyses uncover that SOX9high CSCs up-regulate the ABCA12 lipid transporter. ABCA12 down-regulation impairs cancer stemness and chemoresistance. Lipidomic analyses reveal that ABCA12 maintains cancer stemness and chemoresistance by reducing intracellular ceramide abundance, identifying a CSC-associated function of ABCA subfamily transporter. Ceramide suppresses cancer stemness by inhibiting the YAP-SOX9 signaling pathway in CSCs. Increasing ceramide levels in tumors enhances their sensitivity to chemotherapy and prevents the enrichment of SOX9high CSCs. In addition, SOX9high and ABCA12high cancer cells contribute to chemoresistance in human patient-derived xenografts. These findings identify a CSC-suppressing lipid metabolism pathway that can be exploited to inhibit CSCs and overcome chemoresistance.

Exploring the in vitro anti-inflammatory activity of gross saponins of Tribulus terrestris L. fruit by using liquid chromatography-mass spectrometry-based cell metabolomics approach.

Our previous studies confirmed the efficacy of gross saponins of Tribulus terrestris L. fruit in treating cerebral ischemia. This study aimed to investigate the related mechanisms in vitro. The lipopolysaccharide-induced BV2 cells model was constructed and treated with gross saponins at different concentrations to explore its anti-inflammatory activity. The cell metabolite changes were tracked by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, and the metabolic biomarkers and related metabolic pathways were analyzed. Molecular biochemistry analysis was further used to verify the relevant inflammatory pathways. The results showed that the saponins reduced nitric oxide release and the secretion of tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 from lipopolysaccharide-induced BV2 cells. Metabolic perturbations occurred in lipopolysaccharide-treated BV2 cells, which could be reversed by drug treatment via mainly regulating glycerophospholipid metabolism, tryptophan metabolism, purine metabolism pathways, etc. The western blot analysis demonstrated that saponin could suppress the activation of the inflammatory-related signaling pathway. The present study explored the in vitro anti-inflammatory mechanism of gross saponins of Tribulus terrestris L. fruit using an LC-MS-based cell metabolomics approach, which confirms the great potential of LC-MS for drug efficacy evaluation and can be applied in other herbal medicine-related analyses.

A SOX9-B7x axis safeguards dedifferentiated tumor cells from immune surveillance to drive breast cancer progression.

How dedifferentiated stem-like tumor cells evade immunosurveillance remains poorly understood. We show that the lineage-plasticity regulator SOX9, which is upregulated in dedifferentiated tumor cells, limits the number of infiltrating T lymphocytes in premalignant lesions of mouse basal-like breast cancer. SOX9-mediated immunosuppression is required for the progression of in situ tumors to invasive carcinoma. SOX9 induces the expression of immune checkpoint B7x/B7-H4 through STAT3 activation and direct transcriptional regulation. B7x is upregulated in dedifferentiated tumor cells and protects them from immunosurveillance. B7x also protects mammary gland regeneration in immunocompetent mice. In advanced tumors, B7x targeting inhibits tumor growth and overcomes resistance to anti-PD-L1 immunotherapy. In human breast cancer, SOX9 and B7x expression are correlated and associated with reduced CD8+ T cell infiltration. This study, using mouse models, cell lines, and patient samples, identifies a dedifferentiation-associated immunosuppression mechanism and demonstrates the therapeutic potential of targeting the SOX9-B7x pathway in basal-like breast cancer.

Clinicopathological significance and prognostic implications of Ube2v1 expression in colorectal cancer.

The present study aimed to investigate the expression of ubiquitin-conjugating enzyme E2 variant 1 (Ube2v1) in colorectal cancer (CRC) and its clinical significance. The differential expression of Ube2v1 in CRC tissues and normal intestinal tissues, as well as the association between Ube2v1 expression and the prognosis of patients with CRC were analyzed using bioinformatics analyses. TIMER database analysis revealed higher Ube2v1 expression in CRC tissues than in normal intestinal tissues. Cancerous and normal tissues collected retrospectively from 37 cases of CRC between July, 2022 and June, 2023 were analyzed for Ube2v1 expression using immunohistochemistry, and the associations between Ube2v1 expression and the clinical pathological features of patients with CRC were analyzed. Ube2v1 expression was associated with lymph node metastasis in patients with CRC (P<0.05). However, bioinformatics analysis using the GEPIA2 and HPA database revealed that Ube2v1 was not associated with the overall survival of patients with CRC. On the whole, the present study demonstrates that due to its high expression and association with lymph node metastasis, Ube2v1 may serve as a potential target for the treatment of CRC.

Ectopic gastric mucosa in the submucosa of the stomach: A case report.

Under normal circumstances, gastric mucosa only exists within the stomach. However, in certain situations, gastric mucosal tissue may undergo ectopia, commonly occurring in the esophagus and intestine, with rare occurrences within the stomach itself. A comprehensive literature review was performed to understand the distinct characteristics of ectopic gastric mucosa (EGM) in the stomach and investigate a rare incident of this disease, providing an in-depth analysis of the clinical, histopathologic, and differential diagnostic findings. The case was a 47-year-old man with acid reflux, heartburn, abdominal distension, and diarrhea (5-10 times daily) for >10 years. A gastroscope indicated a submucosal protuberance lesion in the gastric body that felt hard with biopsy forceps. A well-defined nodule under the mucosal muscle was revealed microscopically, composed of epithelial elements and no atypia. Immunohistochemical staining demonstrated similar EGM expression patterns compared with normal gastric mucosa. The present case report highlights the importance of accurate EGM diagnosis and understanding.

Ultrasound-guided quadratus lumborum block: a powerful way for reducing postoperative pain.

Ultrasound-guided quadratus lumborum block (QLB) has been gradually carried out in clinical practice. However, some clinical evidence is contradictory, and no studies have summarized and described these results. The authors reviewed the anatomical characteristics of QLB and summarized the advantages and disadvantages of four puncture methods, so as to facilitate the clinical application of QLB.

Methylation of KRAS by SETD7 promotes KRAS degradation in non-small cell lung cancer.

Oncogenic KRAS mutations are a key driver for initiation and progression in non-small cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity remain largely unclear. Here, we show that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysines 182 and 184. SETD7-mediated methylation of KRAS leads to degradation of KRAS and attenuation of the RAS/MEK/ERK signaling cascade, endowing SETD7 with a potent tumor-suppressive role in NSCLC, both in vitro and in vivo. Mechanistically, RABGEF1, a ubiquitin E3 ligase of KRAS, is recruited and promotes KRAS degradation in a K182/K184 methylation-dependent manner. Notably, SETD7 is inversely correlated with KRAS at the protein level in clinical NSCLC tissues. Low SETD7 or RABGEF1 expression is associated with poor prognosis in lung adenocarcinoma patients. Altogether, our results define a tumor-suppressive function of SETD7 that operates via modulating KRAS methylation and degradation.

Glioblastoma with a primitive neuronal component: A case report.

The present study describes a rare case of glioblastoma with a primitive neuronal component (GBM-PNC), and provides an in-depth analysis of the clinical, pathological and differential diagnostic findings. A comprehensive literature review was conducted to enhance the understanding of GBM-PNC, revealing its distinct characteristics and prognostic implications. A 57-year-old woman presented with acute onset headache, nausea and vomiting, leading to the identification of an intracranial mass through magnetic resonance imaging. Surgical resection revealed the coexistence of a glial component and a PNC within the tumor. Immunohistochemical analysis detected the expression of glial fibrillary acidic protein in the glial component and synaptin in the PNC. The pathological diagnosis confirmed the presence of GBM-PNC. Gene detection analysis revealed no mutations in isocitrate dehydrogenase (IDH)1 and IDH2, and neurotrophic tyrosine kinase receptor-1 (NTRK1), NTRK2 and NTRK3 genes. GBM-PNC is characterized by a propensity for recurrence and metastasis, with a low 5-year survival rate. The present case report highlights the importance of accurate diagnosis and comprehensive characterization of GBM-PNC to guide treatment decisions and improve patient outcomes.

Association Between Gastric Antral Cross-sectional Area and Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy.

OBJECTIVE: To explore the predictive value of gastric antral cross-sectional area (CSA) in the occurrence of postoperative nausea and vomiting (PONV) by analysing the association between gastric antral CSA measured by ultrasound and frequency of PONV after laparoscopic cholecystectomy. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Anaesthesiology, The First Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, from October 2021 to February 2022. METHODOLOGY: Gastric antral ultrasound (US) was performed in 266 patients undergoing laparoscopic cholecystectomy (LC) before anaesthesia induction, after it, and after surgery. The data obtained were used to evaluate the relationship between gastric antral CSA and PONV. RESULTS: The gastric antral CSA in Semi-recumbent decubitus (SRD) position >398.85 mm2 (AUC=0.623) highly indicated the occurrence of PONV. In addition, the subject performance characteristic curve of a binary logistics retrospective model for predicting PONV (AUC=0.805) highly indicated the occurrence of PONV. CONCLUSION: Gastric US assessment of gastric antral CSA might change the current assessment model of PONV risk. This study showed that the gastric antral CSA in the SRD position after anaesthesia induction and a binary logistics retrospective model could be used to predict the occurrence of PONV, which could be helpful to adjust intraoperative and postoperative interventions and accelerate the recovery of patients. KEY WORDS: Postoperative nausea and vomiting, Gastric ultrasound, Gastric cross-sectional area, Perioperative period.

MLL3 loss drives metastasis by promoting a hybrid epithelial-mesenchymal transition state.

Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) is crucial to metastatic seeding and outgrowth. However, the mechanisms governing the hybrid EMT state remain poorly defined. Here we showed that deletion of the epigenetic regulator MLL3, a tumour suppressor frequently altered in human cancer, promoted the acquisition of hybrid EMT in breast cancer cells. Distinct from other EMT regulators that mediate only unidirectional changes, MLL3 loss enhanced responses to stimuli inducing EMT and mesenchymal-epithelial transition in epithelial and mesenchymal cells, respectively. Consequently, MLL3 loss greatly increased metastasis by enhancing metastatic colonization. Mechanistically, MLL3 loss led to increased IFNγ signalling, which contributed to the induction of hybrid EMT cells and enhanced metastatic capacity. Furthermore, BET inhibition effectively suppressed the growth of MLL3-mutant primary tumours and metastases. These results uncovered MLL3 mutation as a key driver of hybrid EMT and metastasis in breast cancer that could be targeted therapeutically.

Gastric inverted hyperplastic polyp: A case report.

Inverted hyperplastic polyp (IHP) is a rare disease characterized by the downward growth of proliferative mucosal components into the submucosal layer. It is often misdiagnosed as other submucosal tumors and accurate diagnosis requires pathological examination. Most patients with IHP have no clinical symptoms and some have non-specific symptoms, such as abdominal distension, abdominal pain and even anemia. IHP is treated via endoscopic mucosal resection or endoscopic sub-mucosal section. The present study reported a case of IHP and discussed its clinical manifestations, clinicopathological diagnosis, differential diagnosis and treatment to improve our understanding of the disease.

Phosphodiesterase 4D contributes to angiotensin II-induced abdominal aortic aneurysm through smooth muscle cell apoptosis.

Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.

Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis: a multi-omics study with drug exploration.

Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics, and currently used drugs cannot reverse the disease progress. Worse still, there are still challenges to be addressed to fully decipher the intricated pathogenesis. Thus, specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed. In this work, multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents. By utilizing an unbiased and time-resolved analysis of the transcriptome, proteome and phosphoproteome of a silicosis mouse model, we have verified the significant differences in transcript, protein, kinase activity and signaling pathway level during silicosis progression, in which the importance of essential biological processes such as macrophage activation, chemotaxis, immune cell recruitment and chronic inflammation were emphasized. Notably, the phosphorylation of EGFR (p-EGFR) and SYK (p-SYK) were identified as potential therapeutic targets in the progression of silicosis. To inhibit and validate these targets, we tested fostamatinib (targeting SYK) and Gefitinib (targeting EGFR), and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis. Overall, our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe -/- mice through the integrin αVß5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, ß-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVß5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

TMZ magnetic temperature-sensitive liposomes-mediated magnetothermal chemotherapy induces pyroptosis in glioblastoma.

Glioblastoma (GBM) is the most fatal and common type of primary malignant tumors in central nervous system. Chemotherapy drugs are difficult to reach the encephalic region effectively due to blood-brain barrier (BBB), but functional nanoparticle drug carriers can help to solve the problem. Herein, we developed a controllable drug carrier called temozolomide magnetic temperature-sensitive liposomes (TMZ/Fe-TSL) to investigate its feasibility and molecular mechanisms on GBM. Our research found TMZ/Fe-TSL exposed to alternating magnetic field (AMF) could induce significantly GBM cell death and promote the production of ROS. It also showed that the expression of NLRP3, CASP1 and N-GSDMD was upregulated compared to the control group, while the expression of CASP3 showed a reverse change. The results indicated that TMZ/Fe-TSL exposed to the AMF was capable of inducing GBM cells death. And the way and mechanisms of cell death may involve in ROS and pyroptosis, but not apoptosis.