The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder.

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.

The relationship between duration of abstinence and gray-matter brain structure in chronic methamphetamine users.

Background: Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g., sex, abstinence duration) can help clarify the clinical course of recovery.Objectives: We studied the effects of long-term methamphetamine abstinence on gray-matter volume. Our hypothesis was that smaller volume early in abstinence would precede long-term recovery.Methods: Individuals who used methamphetamine (≥100 g lifetime use, mandated to residential treatment for methamphetamine-positive urine; 40 men, 21 women), undergoing supervised abstinence (men: 12-400 days; women: 130-594 days), were compared to healthy controls (49 men, 36 women) using T1-weighted MRI. Volumes of orbitofrontal, anterior cingulate and parietal cortex, hippocampus, and striatum were measured using Freesurfer software. Associations of volumes with abstinence duration were tested in males and females separately because their abstinence times differed (121.5 ± 124.5 vs. 348.0 ± 128.6 days, p < 0.001); only males were studied in early abstinence. The General Linear Model was used to test effects of abstinence duration and group (methamphetamine users vs. controls).Results: In males, duration of abstinence was multivariate significant for gray-matter volumes (p = 0.017). Abstinence duration was associated with increases in volumes of the orbitofrontal and parietal cortices (ps = 0.031, 0.016) and hippocampi (ps = 0.044). Irrespective of abstinence, male methamphetamine users had smaller hippocampi than male controls (p = 0.008). Females showed no significant effects of group or abstinence.Conclusions: In males, abstinence from methamphetamine appears to result in volumetric increases in regions important for cognitive function, which may affect recovery during the course of treatment. Data from the period of early abstinence are required to evaluate volumetric changes in females.

Gray-matter structure in long-term abstinent methamphetamine users.

BACKGROUND: Previous studies of brain structure in methamphetamine users have yielded inconsistent findings, possibly reflecting small sample size and inconsistencies in duration of methamphetamine abstinence as well as sampling and analyses methods. Here we report on a relatively large sample of abstinent methamphetamine users at various stages of long-term abstinence. METHODS: Chronic methamphetamine users (n = 99), abstinent from the drug ranging from 12 to 621 days, and healthy controls (n = 86) received T1-weighted structural magnetic resonance imaging brain scans. Subcortical and cortical gray-matter volumes and cortical thickness were measured and the effects of group, duration of abstinence, duration of methamphetamine use and onset age of methamphetamine use were investigated using the Freesurfer software package. RESULTS: Methamphetamine users did not differ from controls in gray-matter volumes, except for a cluster in the right lateral occipital cortex where gray-matter volume was smaller, and for regions mainly in the bilateral superior frontal gyrui where thickness was greater. Duration of abstinence correlated positively with gray-matter volumes in whole brain, bilateral accumbens nuclei and insulae clusters, and right hippocampus; and with thickness in a right insula cluster. Duration of methamphetamine use correlated negatively with gray-matter volume and cortical thickness of a cluster in the right lingual and pericalcarine cortex. CONCLUSIONS: Chronic methamphetamine use induces hard-to-recover cortical thickening in bilateral superior frontal gyri and recoverable volumetric reduction in right hippocampus, bilateral accumbens nuclei and bilateral cortical regions around insulae. These alternations might contribute to methamphetamine-induced neurocognitive disfunctions and reflect a regional specific response of the brain to methamphetamine.

Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation.

Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation.

Low Concentration of Exogenous Carbon Monoxide Modulates Radiation-Induced Bystander Effect in Mammalian Cell Cluster Model.

During radiotherapy procedures, radiation-induced bystander effect (RIBE) can potentially lead to genetic hazards to normal tissues surrounding the targeted regions. Previous studies showed that RIBE intensities in cell cluster models were much higher than those in monolayer cultured cell models. On the other hand, low-concentration carbon monoxide (CO) was previously shown to exert biological functions via binding to the heme domain of proteins and then modulating various signaling pathways. In relation, our previous studies showed that exogenous CO generated by the CO releasing molecule, tricarbonyldichlororuthenium (CORM-2), at a relatively low concentration (20 µM), effectively attenuated the formation of RIBE-induced DNA double-strand breaks (DSB) and micronucleus (MN). In the present work, we further investigated the capability of a low concentration of exogenous CO (CORM-2) of attenuating or inhibiting RIBE in a mixed-cell cluster model. Our results showed that CO (CORM-2) with a low concentration of 30 µM could effectively suppress RIBE-induced DSB (p53 binding protein 1, p53BP1), MN formation and cell proliferation in bystander cells but not irradiated cells via modulating the inducible nitric oxide synthase (iNOS) andcyclooxygenase-2 (COX-2). The results can help mitigate RIBE-induced hazards during radiotherapy procedures.

Deep learning strategies with CReToNeXt-YOLOv5 for advanced pig face emotion detection.

This study underscores the paramount importance of facial expressions in pigs, serving as a sophisticated mode of communication to gauge their emotions, physical well-being, and intentions. Given the inherent challenges in deciphering such expressions due to pigs' rudimentary facial muscle structure, we introduced an avant-garde pig facial expression recognition model named CReToNeXt-YOLOv5. The proposed model encompasses several refinements tailored for heightened accuracy and adeptness in detection. Primarily, the transition from the CIOU to the EIOU loss function optimized the training dynamics, leading to precision-driven regression outcomes. Furthermore, the incorporation of the Coordinate Attention mechanism accentuated the model's sensitivity to intricate expression features. A significant innovation was the integration of the CReToNeXt module, fortifying the model's prowess in discerning nuanced expressions. Efficacy trials revealed that CReToNeXt-YOLOv5 clinched a mean average precision (mAP) of 89.4%, marking a substantial enhancement by 6.7% relative to the foundational YOLOv5. Crucially, this advancement holds profound implications for animal welfare monitoring and research, as our findings underscore the model's capacity to revolutionize the accuracy of pig facial expression recognition, paving the way for more humane and informed livestock management practices.

Exogenous carbon monoxide promotes GPX4-dependent ferroptosis through ROS/GSK3ß axis in non-small cell lung cancer.

The gas therapy is drawing increasing attention in the treatment of many diseases including cancer. As one of gas signaling molecules, carbon monoxide (CO) has been proved to exert anti-cancer effects via triggering multiple cell death types, such as autophagy, apoptosis and necrosis. Here, we showed that low concentration CO delivered from CO-releasing molecule 3 (CORM-3) effectively induced ferroptosis, known as a novel proinflammatory programmed cell death, in vitro and in vivo. Mechanistically, we found that CO triggered ferroptosis by modulating the ROS/GSK3ß/GPX4 signaling pathway, resulting in the accumulation of lipid hydroperoxides and the occurrence of ferroptosis. We think our findings provide novel insights into the anti-cancer mechanisms of CO, and suggest that CO could potentially be exploited as a novel ferroptosis inducer for cancer treatment in the future.

GAP-43 Induces the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Retinal Ganglial-Like Cells.

Optic neuritis (ON) is a common neurological disease, and the transplant of retinal ganglion cells (RGCs) has been thought as a promising strategy for improving the injury of the optic nerve system. Bone mesenchymal stem cells (BMSCs) have the potential to differentiate into neural cells. Several studies have indicated that GAP-43 is related with the regeneration of nerve cells, while the effect of GAP-43 on inducing BMSC differentiation remains unclear. In this study, the BMSCs were separated from the rats and identified with flow cytometry assay. The GAP-43 expressed vectors were transfected into the BMSCs, and the biomarkers of RGCs such as PAX6, LHX2, and ATOH7 were used to observe by qRT-PCR. Moreover, the effect of GAP-43-induced BMSCs (G-BMSCs) on ON improvement was also verified with rat models, and the activity of MAPK pathway was measured with western blot. Here, it was found that GAP-43 could obviously promote the differentiation of BMSCs, and increased PAX6, LHX2, ATOH7, BRN3A, and BRN3B were observed in the process of cell differentiation. Moreover, it was also found that G-BMSCs significantly increased the abundances of NFL and NFM in G-BMSCs, and GAP-43 could also enhance the activity of MAPK pathways in BMSCs. Therefore, this study suggested that GAP-43 could induce the differentiation of bone marrow-derived mesenchymal stem cells into retinal ganglial cells.

miR-223-3p Regulates NLRP3 to Inhibit Proliferation and Promote Apoptosis of ONG Cells.

Objective: Optic nerve glioma (ONG) is a rare disease, defined as a WHO grade I tumor, which affects the visual pathway. The objective of this study was to investigate the expression of miR-223-3p in ONG as well as its function and regulation in ONG cell lines. Methods: qRT-PCR assays were used to measure miR-223-3p expression in ONG tissues and cell lines. After overexpression of miR-223-3p in Hs683 and WERI-Rb-1 cell lines, CCK-8 and EdU assays were performed to examine cell proliferation, and flow cytometry was used to assess apoptosis. Dual luciferase assays were utilized to identify the target binding to miR-223-3p and NLRP3. Rescue assays were carried out to investigate the regulatory mechanism of miR-223-3p acting through NLRP3. Nude mouse tumorigenesis assays were established to verify the effect of miR-223-3p on ONG growth. Results: miR-223-3p was weakly expressed in both ONG tissues and cell lines. miR-223-3p inhibited the proliferative ability of Hs683 and WERI-Rb-1 cell lines and promoted apoptosis. In addition, there was binding between miR-223-3p and NLRP3. Simultaneous overexpression of NLRP3 and miR-223-3p partially counteracted the role of miR-223-3p in the cell lines. Lastly, miR-223-3p inhibited ONG growth. Conclusion: miR-223-3p plays an inhibitory role in ONG development by regulating NLRP3 to inhibit the proliferation of ONG cells and promote apoptosis.

miR-216b-5p Inhibited the Progression of Experimental Optic Neuritis via Downregulating FAS.

Objective: Present study mainly explored the effect of miR-216b-5p on experimental optic neuritis and mechanism. Methods: Female C57BL/6 mice were utilized to establish the EAE model. miR-216b-5p expression was measured by RT-qPCR. Protein expression was evaluated via western blot. Inflammatory infiltration score was analyzed by HE staining. Visual function was assessed by measuring the OKR. Flow cytometry assay was conducted to measure the percentage of IL-17 cells. ELISA was utilized to evaluate the immune factor. Results: The EAE mouse model was successfully established. The EAE score of mice began to increase in EAE group after 11 days of MOG35-55 and CFA immunization. The degree of inflammatory cell infiltration in EAE mice was higher than that in normal mice. Compared with normal mice, the number of microglia and astrocytes was raised in EAE mice. miR-216b-5p expression was obviously declined and FAS expression was obviously raised in EAE. Compared with NC group, demyelination scores and axonal loss were markedly declined in miR-216b-5p mimic group. IL-17A concentration and the percentage of IL-17 cells were obviously declined in miR-216b-5p mimic group. FAS was predicted to be regulated by miR-216b-5p by TargetScan, and luciferase reporter assay confirmed this prediction. In addition, overexpression of FAS exacerbated experimental optic neuritis by promoting the inflammatory response and Th17 cell differentiation, and miR-216b-5p reversed this effect. Conclusions: miR-216b-5p downregulated FAS and inhibited the progression of experimental optic neuritis via promoting the inflammatory response and Th17 cell differentiation.

Disruption of regional homogeneity in the brains of chronic methamphetamine users.

Previous studies have reported evidence supporting structural and functional alterations in the brains of methamphetamine (MA) users. The aim of the present study was to extend current knowledge regarding brain function(s) in MA users by examining regional homogeneity (ReHo). Chronic MA users (51 male, 46 female), who were undergoing supervised abstinence for 12 to 621 days, and 79 healthy controls (43 male, 36 female) underwent resting-state functional brain magnetic resonance imaging. Voxel-wise whole-brain scale group differences in ReHo were examined. The mean ReHo values of significant clusters were extracted, and linear regression was used to identify factors that contributed to these mean ReHo values. MA users exhibited lower ReHo values in the left orbital part of the inferior frontal gyrus extending to the left insula and left temporal pole, left amygdala, and left fusiform gyrus. MA users also exhibited greater ReHo values in the bilateral pre- and postcentral gyri and right cerebellum. Characteristics of MA use, including duration, duration of abstinence from MA, and age at onset of MA use, demonstrated no reliable contribution to ReHo of the significant clusters. Findings of the present study demonstrated that chronic MA use was associated with regional specific disruption of ReHo, which is relatively independent of structural and functional alterations and, apparently, does not recover after relatively long-term abstinence. This disruption may underlie overall neurocognitive deficits in MA users, which is difficult to recover.

Golgi Phosphoprotein 3 Mediates Radiation-Induced Bystander Effect via ERK/EGR1/TNF-α Signal Axis.

The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation.

Golgi Phosphoprotein 3 Confers Radioresistance via Stabilizing EGFR in Lung Adenocarcinoma.

PURPOSE: Radioresistance is a major cause of treatment failure in tumor radiation therapy, and the underlying mechanisms of radioresistance are still elusive. Golgi phosphoprotein 3 (GOLPH3) has been reported to associate tightly with cancer progression and chemoresistance. Herein, we explored whether GOLPH3 mediated radioresistance of lung adenocarcinoma (LUAD) and whether targeted suppression of GOLPH3 sensitized LUAD to radiation therapy. METHODS AND MATERIALS: The aberrant expression of GOLPH3 was evaluated by immunohistochemistry in LUAD clinical samples. To evaluate the association between GOLPH3 and radioresistance, colony formation and apoptosis were assessed in control and GOLPH3 knockdown cells. γ-H2AX foci and level determination and micronucleus test were used to analyze DNA damage production and repair. The rescue of GOLPH3 knockdown was then performed by exogenous expression of small interfering RNA-resistant mutant GOLPH3 to confirm the role of GOLPH3 in DNA damage repair. Mechanistically, the effect of GOLPH3 on regulating stability and nuclear accumulation of epidermal growth factor receptor (EGFR) and the activation of DNA-dependent protein kinase (DNA-PK) were investigated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation. The role of GOLPH3 in vivo in radioresistance was determined in a xenograft model. RESULTS: In tumor tissues of 33 patients with LUAD, the expression of GOLPH3 showed significant increases compared with those in matched normal tissues. Knocking down GOLPH3 reduced the clonogenic capacity, impaired double-strand break (DSB) repair, and enhanced apoptosis after irradiation. In contrast, reversal of GOLPH3 depletion rescued the impaired repair of radiation-induced DSBs. Mechanistically, loss of GOLPH3 accelerated the degradation of EGFR in lysosome, causing the reduction in EGFR levels, thereby weakening nuclear accumulation of EGFR and attenuating the activation of DNA-PK. Furthermore, adenovirus-mediated GOLPH3 knockdown could enhance the ionizing radiation response in the LUAD xenograft model. CONCLUSIONS: GOLPH3 conferred resistance of LUAD to ionizing radiation via stabilizing EGFR, and targeted suppression of GOLPH3 might be considered as a potential therapeutic strategy for sensitizing LUAD to radiation therapy.

The effect of capsule tension ring on posterior capsule opacification: A meta-analysis.

BACKGROUND: Posterior capsule opacification is one of the most common complications after cataract surgery. Studies have suggested that the introduction of a capsule tension ring might play a critical role in the prevention of capsule opacification, yet quantitative evidence is still lacking. This work consists of a meta-analysis on available data in order to explore the influence of a capsule tension ring on posterior capsule opacification. METHODS: A comprehensive review of the literature on capsule tension ring and posterior capsule opacification was carried out using the Embase, Pubmed, Web of Science, and Cochrane electronic databases. The selected studies included randomized controlled trials, retrospective studies and prospective studies published before June 2020. The studies of interest were selected by two reviewers independently from the included studies. Odds ratios (ORs) and standardized mean differences (SMD) were used in order to assess the association. A fixed-effects model or a random-effects model was applied to combine data according to heterogeneities. Sensitivity analysis was used to assess the heterogeneity of the studies. Publication bias was estimated using the Egger test. Statistical analysis was performed using the stata15.1 software. RESULTS: The meta-analysis included in total 8 studies involving 379 cases and 333 controls. There was a statistically significant difference of Nd:YAG laser capsulotomy rate (OR=0.241, 95% CI: 0.145, 0.400 I2=42.1%) between the capsule tension ring group and the control group, indicating that the tension ring reduced the Nd:YAG laser capsulotomy rate. Further studies with continuous data also revealed that the use of capsule tension ring was associated with a lower posterior capsule opacification score (SMD = -1.402, 95% CI: -2.448, -0.355 I2=95.0%). The sensitivity analysis suggested that the result of the re-combined analysis did not change notably, indicating that the result was reliable and stable. Both pooled analysis showed no evidence of publication bias. CONCLUSION: The findings of this meta-analysis confirmed that capsule tension ring might reduce capsule opacification. Further studies should be made to validate the result.

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells.

BACKGROUND: Acquired radioresistant cells exhibit many characteristic changes which may influence cancer progression and further treatment options. The purpose of this study is to investigate the changes of radioresistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells on both phenotypic and molecular levels. METHODS: We established an acquired radioresistant cell line from its parental NF639 cell line (HER2-positive) by fractionated radiation and assessed changes in cellular morphology, proliferation, migration, anti-apoptosis activity, basal reactive oxygen species (ROS) level and energy metabolism. RNA-sequencing (RNA-seq) was also used to reveal the potential regulating genes and molecular mechanisms associated with the acquired changed phenotypes. Real-time PCR was used to validate the results of RNA-seq. RESULTS: The NF639R cells exhibited increased radioresistance and enhanced activity of proliferation, migration and anti-apoptosis, but decreased basal ROS. Two main energy metabolism pathways, mitochondrial respiration and glycolytic, were also upregulated. Furthermore, 490 differentially expressed genes were identified by RNA-seq. Enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed many differently expressed genes were significantly enriched in cell morphology, proliferation, migration, anti-apoptosis, antioxidation, tumor stem cells and energy metabolism and the signaling cascades such as the transforming growth factor-ß, Wnt, Hedgehog, vascular endothelial growth factor, retinoic acid-inducible gene I (RIG-I)-like receptor, Toll-like receptor and nucleotide oligomerization domain (NOD)-like receptor were significantly altered in NF639R cells. CONCLUSIONS: In clinical radiotherapy, repeat radiotherapy for short-term recurrence of breast cancer may result in enhanced radioresistance and promote malignant progression. Our research provided hints to understand the tumor resistance to radiotherapy de novo and recurrence with a worse prognosis following radiotherapy.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of COVID-19: a multicenter retrospective cohort study of 4086 cases in China.

To establish an effective nomogram for predicting in-hospital mortality of COVID-19, a retrospective cohort study was conducted in two hospitals in Wuhan, China, with a total of 4,086 hospitalized COVID-19 cases. All patients have reached therapeutic endpoint (death or discharge). First, a total of 3,022 COVID-19 cases in Wuhan Huoshenshan hospital were divided chronologically into two sets, one (1,780 cases, including 47 died) for nomogram modeling and the other (1,242 cases, including 22 died) for internal validation. We then enrolled 1,064 COVID-19 cases (29 died) in Wuhan Taikang-Tongji hospital for external validation. Independent factors included age (HR for per year increment: 1.05), severity at admission (HR for per rank increment: 2.91), dyspnea (HR: 2.18), cardiovascular disease (HR: 3.25), and levels of lactate dehydrogenase (HR: 4.53), total bilirubin (HR: 2.56), blood glucose (HR: 2.56), and urea (HR: 2.14), which were finally selected into the nomogram. The C-index for the internal resampling (0.97, 95% CI: 0.95-0.98), the internal validation (0.96, 95% CI: 0.94-0.98), and the external validation (0.92, 95% CI: 0.86-0.98) demonstrated the fair discrimination ability. The calibration plots showed optimal agreement between nomogram prediction and actual observation. We established and validated a novel prognostic nomogram that could predict in-hospital mortality of COVID-19 patients.

Mendelian randomization analyses of genetically predicted circulating levels of cytokines with risk of breast cancer.

To determine whether genetically predicted circulating levels of cytokines are associated with risk of overall breast cancer (BC), estrogen receptor (ER)-positive and ER-negative BC, we conducted two-sample MR analyses using data from the most comprehensive genome-wide association studies (GWAS) on cytokines in 8293 Finnish participants and the largest BC GWAS from the Breast Cancer Association Consortium (BCAC) with totally 122,977 BC cases and 105,974 healthy controls. We systematically screened 41 cytokines (of which 24 cytokines have available instruments) and identified that genetically predicted circulating levels (1-SD increase) of MCP1 (OR: 1.08; 95% CIs: 1.03-1.12; P value: 3.55 × 10-4), MIP1b (OR: 1.02; 95% CIs: 1.01-1.04; P value: 2.70 × 10-3) and IL13 (OR: 1.06; 95% CIs: 1.03-1.10; P value: 3.33 × 10-4) were significantly associated with increased risk of overall BC, as well as ER-positive BC. In addition, higher levels of MIP1b and IL13 were also significantly associated with increased risk of ER-negative BC. These findings suggest the crucial role of cytokines in BC carcinogenesis and potential of targeting specific inflammatory cytokines for BC prevention.

Cold atmospheric plasma induces GSDME-dependent pyroptotic signaling pathway via ROS generation in tumor cells.

Cold atmospheric plasma (CAP) has been proposed as a novel promising anti-cancer treatment modality. Apoptosis and necrosis have been revealed in CAP-induced cell death, but whether CAP induces pyroptosis, another kind of programmed cell death is still unknown. In the present study, we first reported that CAP effectively induced pyroptosis in a dose-dependent manner in Gasdermin E (GSDME) high-expressed tumor cell lines. Interestingly, the basal level of GSDME protein was positively correlated with the sensitivity to CAP in three selected cancer cell lines, implying GSDME might be a potential biomarker of prognosis in the forthcoming cancer CAP treatment. Moreover, our study revealed that CAP-induced pyroptosis depended on the activation of mitochondrial pathways (JNK/cytochrome c/caspase-9/caspase-3) and the cleavage of GSDME but not Gasdermin D (GSDMD). ROS generation induced by CAP was identified to initiate the pyroptotic signaling. These results complemented our knowledge on CAP-induced cell death and provide a strategy to optimize the effect of CAP cancer treatment.