Mitochondrial plasticity, coordinated by fission and fusion, is crucial to ensure cellular functions. Mitochondrial fission is mediated by the GTPase Drp1 at the constriction site, which is proposed to be driven by the actin-myosin contractile force. However, the mechanism that propels constriction remains unclear, and the potential involvement of additional mechanisms in this process remains an open question. Here, using structured illumination microscopy, electron microscopy, and correlative light electron microscopy (CLEM), we show that the type III intermediate filament glial fibrillary acidic protein (GFAP) participates in mitochondria constriction and fission by interacting with Drp1. Remarkably, loss of GFAP results in hyperfused mitochondria under physiological and even Ca2+-induced mitochondrial fission conditions. Additionally, mutations in GFAP, the cause of Alexander disease, result in more Drp1 localized to GFAP and lead to significantly increased mitochondrial fissions. Taken together, these findings propose a role of type III intermediate filaments in mitochondrial division.

Abstract Interleukin-12 (IL-12) is a multifaceted cytokine primarily produced by antigen-activated dendritic cells, macrophages, and neutrophils. Its receptor is a composite of IL12RB1 and IL12RB2, and the union of these two subunits forms a high-affinity receptor complex proficient in mediating IL-12 signaling. As a pivotal regulator of innate and adaptive immunity, IL-12 plays a crucial role in steering the differentiation of naïve T cells into Th1 cells. It is renowned as a T cell stimulatory factor, fostering T cell proliferation. Furthermore, IL-12 has the capacity to augment the activation of cytotoxic lymphocytes and natural killer cells (NK), thereby enhancing interferon (IFN-γ) production. Empirical evidence consistently demonstrates that IL-12 synergistically exerts anti-tumor effects in conjunction with various immune cells, such as T cells and NK cells. Its effectiveness in preclinical studies has solidified IL-12 as an appealing drug target, leading to the development of activating antibodies, therapeutic IL-12 proteins, and tumor vaccines as potential treatments. To delve deeper into the functionality and therapeutic potential of IL-12, we have engineered a humanized mouse model, known as BALB/c-hIL12RB1/hIL12RB2. Notably, this model fully preserves the intracellular domains of mouse IL12RB1 and IL12RB2 proteins, ensuring the normal propagation of intracellular signaling. It also effectively expresses human IL12RB1 and IL12RB2. In vitro functional validation experiments have verified that BALB/c-hIL12RB1/hIL12RB2 mice can proficiently generate IFN-γ when induced by human IL-12. Furthermore, in vivo efficacy experiments have yielded compelling results. Intratumoral administration of human IL-12 mRNA in BALB/c-hIL12RB1/hIL12RB2 mice led to a significant suppression in the growth of CT26 tumors, culminating in complete tumor regression. Subsequent rechallenge experiments conducted after the discontinuation of treatment revealed no tumor recurrence, signifying the enduring inhibitory effect of hIL12 mRNA on mouse tumors. In conclusion, the development of BALB/c-hIL12RB1/hIL12RB2 mice stands as a robust model for advancing preclinical research in the realm of human IL-12 therapy. Citation Format: Yuan Fang, Huiyi Wang, Jun Xing, Lu Yang, Jing Zhao, Xiang Gao, Cunxiang Ju. BALB/c-hIL12RB1/hIL12RB2: A robust model for preclinical research in human IL-12 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4189.

This study investigated the rehabilitation effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training on children with mental retardation (MR). Through a randomized controlled trial design, 40 children aged 2–6 years with mental retardation were selected as study subjects and randomly divided into two groups: conventional treatment group and rTMS combined with cognitive training treatment group. The results showed that compared with the conventional treatment group, the rTMS combined with cognitive training treatment group exhibited more significant effects in improving children’s cognitive function, social adaptability, and quality of life. This study not only enriched the theoretical basis of rehabilitation treatment for children with mental retardation but also provided strong evidence support for clinical practice.

Currently, the treatment of acute ischemic stroke is still limited. In clinical studies, the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on stroke risk is controversial. This preclinical study was conducted to determine whether canagliflozin, a SGLT2 inhibitor, has neuroprotective effects on ischemic stroke and the underlying mechanisms. The middle cerebral artery occlusion (MCAO) model was established in Sprague Dawley rats, and canagliflozin was administered by gavage before reperfusion. Canagliflozin treatment significantly reduced infarct volume, improved neurological deficits, lessened brain edema, alleviated neuronal damage and reduced apoptosis. SGLT2 inhibitors which are commonly used in the clinic have different degrees of affinity for SGLT1 and SGLT2 receptors, the expression levels of SGLT1 and SGLT2 were detected using immunofluorescence in the cortex and hippocampus. SGLT2 was barely detectable in these regions regardless of MCAO or canagliflozin treatment or not. The SGLT1 expression levels were significantly elevated in the cortex and hippocampus after MCAO, and further significantly reduced by canagliflozin administration. In vitro experiments, the oxygen-glucose deprivation/reoxygenation (OGD/R) model of the HT-22 mouse hippocampal neurons was established. Canagliflozin treatment increased cell viability and attenuated lactate dehydrogenase (LDH) release. Additionally, canagliflozin activated AMP-activated protein kinase (AMPK) and subsequently inhibited apoptosis in a SGLT1 inhibition dependent manner. The present study shows that canagliflozin could attenuate cerebral ischemia-reperfusion injury in experimental ischemic stroke via SGLT1/AMPK signaling, leading to anti-apoptotic effects in neuron. These findings might serve as evidence for the further application of canagliflozin in the treatment of acute ischemic stroke.

Recent studies have shown the in vitro neuro-protective functions of atmospheric pressure plasma (APP) against multiple pathological injuries during ischaemic stroke (IS). However, whether APP treatment exerts a therapeutic effect on a rat IS model remains unclear. Here, on the basis of needle-to-ring dielectric barrier discharge, an atmospheric pressure plasma jet (APPJ) was designed, with the Helium as the working gas which was driven by a sinusoidal voltage. Then, the treatment conditions were optimised for IS rat model treatment and the characteristics of this APPJ were further diagnosed. Subsequently, the rat IS model was established through 90 min middle cerebral artery occlusion (MCAO), and plasma was intermittently inhaled by rats via the nasal cavity for a 2 min period at 60 min of MCAO process. The therapeutic effects of this plasma jet device were then evaluated using biomedical analyses. According to our results, intermittent APP inhalation in the MCAO rats increased the serum NO content, improved the neurological function, enhanced regional cerebral blood flow, lowered brain infarction, and reduced the cell apoptosis in brain tissues of MCAO rats. Collectively, our data provides a novel potential strategy for IS treatment by using atmospheric-pressure plasma inhalation.

Previous studies suggest the potential efficacy of neuroprotective effects of gaseous atmospheric-pressure plasma (APP) treatment on neuronal cells. However, it remains unclear if the neuroprotective properties of the gas plasmas benefit the ischemic stroke treatment, and how to use the plasmas in the in vivo ischemic stroke models. Rats were subjected to 90 min middle cerebral artery occlusion (MCAO) to establish the ischemic stroke model and then intermittently inhaled the plasma for 2 min at 60 min MCAO. The regional cerebral blood flow (CBF) was monitored. Animal behavior scoring, magnetic resonance imaging (MRI), 2,3,5-triphenyltetrazolium chloride (TTC) staining, and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic efficacy of the gas plasma inhalation on MCAO rats. Intermittent gas plasma inhalation by rats with experimental ischemic stroke could improve neurological function, increase regional CBF, and decrease brain infarction. Further MRI tests showed that the gas plasma inhalation could limit the ischemic lesion progression, which was beneficial to improve the outcomes of the MCAO rats. Post-stroke treatment with intermittent gas plasma inhalation could reduce the ischemic lesion progression and decrease cerebral infarction volume, which might provide a new promising strategy for ischemic stroke treatment.

Physico-chemical and biological effects of atmospheric pressure plasmas (APPs) find numerous applications in biotechnology, medicine, and other fields. Recent studies revealed APPs’ potential for ischemic stroke treatment through the protection of neuronal cells from injuries. However, the mechanisms of the plasma neuroprotection effects still remain unknown. This study reveals the key mechanisms of APP plasma jet (APPJ) enabled reduction of neuronal cell death caused by oxygen and glucose deprivation (OGD) under stroke-relevant conditions. Plasma reduced OGD induced apoptosis of SH-SY5Y neuronal cells is based on reactive oxygen and nitrogen species production and on nitric oxide related activation of the cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase G (PKG) pathway, followed by the Bcl-2/Bax level modulation and caspase3/9 activity inhibition. In addition, the protective effect of APPJ treatment on OGD injured SH-SY5Y cells could be abolished by cGMP pathway inhibitor LY83583 pretreatment. Collectively, our findings highlight that the mechanism of the neuroprotection effects of the plasma treatment is closely related to the intracellular cGMP/PKG pathway, which provide experimental and theoretical references for future studies on plasma medicine.

Glioma is the most common and malignant cancer of the central nervous system, and the prognosis is poor. Metabolic reprogramming is a common phenomenon that plays an important role in tumor progression including gliomas. Searching the representative process among numerous metabolic processes to evaluate the prognosis aside from the glycolytic pathway may be of great significance. A novel prediction signature was constructed in the present study based on gene expression. A total of 1027 glioma samples with clinical and RNA-seq data were used in the present study. Lasso-Cox, gene set variation analysis, Kaplan-Meier survival curve analysis, Cox regression, receiver operating characteristic curve, and elastic net were performed for constructing and verifying predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. This signature was found to be stable in prognostic prediction in the Chinese Glioma Genome Atlas Network and the Cancer Genome Atlas databases. The possible mechanism was also explored, revealing that the aforementioned signature was closely related to DNA replication and ATP binding. In summary, a prognosis prediction signature for patients with glioma based on five genes was constructed and showed great potential for clinical application.

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD). Long noncoding RNAs regulate gene expression and participate in many biological processes. However, the role of long noncoding RNAs in LID is not well understood. In the present study, we examined the lncRNA transcriptome profile of a rat model of PD and LID by RNA sequence and got a subset of lncRNAs, which were gradually decreased during the development of PD and LID. We further identified a previously uncharacterized long noncoding RNA, NONRATT023402.2, and its target genes glutathione S-transferase omega (Gsto)2 and prostaglandin E receptor (Ptger)3. All of them were decreased in the PD and LID rats as shown by quantitative real-time PCR, fluorescence in situ hybridization and western blotting. Pearson’s correlation analysis showed that their expression was positively correlated with the dyskinesia score of LID rats. In vitro experiments by small interfering RNA confirmed that slicing NONRATT023402 inhibited Gsto2 and Ptger3 and promoted the inflammatory response. These results demonstrate that NONRATT023402.2 may have inhibitive effects on the development of PD and LID.

Objective:To study the expression of ubiquitin-specific protease 25 (USP25) in the temporal cortex of the kainic acid (KA) induced epilepsy rat model.Methods:Fifty-two male SD rats were randomly divided into the epilepsy model group ( n=39) and sham-operated control group ( n=13) with the random number table. The epilepsy model group was established by injecting KA into the amygdala, then the epileptic rats were randomly divided into 3 groups according to the modeling success time: 1 day for acute period, 7 days for latent period and 30 days for chronic period (13 rats in each group). Those rats were sampled at the end of observation. Rats in the control group were injected with normal saline into the amygdala and sampled together with those in the experimental group. Immunohistochemistry and immunofluorescence double labeling was used to test USP25 expression and its co-expression with neurons (NeuN) and astrocytes (GFAP). Quantitative real-time PCR and Western blot were used to assess the change of USP25 in the temporal cortex of rats. Results:In the ipsilateral temporal cortex, the positive cells of co-expression of USP25 and NeuN were increased in the later stage of epilepsy in the epilepsy model group, and the expression levels of USP25 mRNA and protein in different stages of epilepsy varied significantly ( F= 25.48 and 7.68 respectively, both P<0.05). Compared with the control group (mRNA level: 1.00±0.36, protein level: 1.00±0.46), the expression of USP25 in the latent group (mRNA level: 10.80±4.82, protein level: 1.88±0.32) and the chronic group (mRNA level: 12.97±4.48, protein level: 1.92±0.26) were increased significantly (all P<0.05). In the contralateral temporal cortex, the expression levels of USP25 mRNA and protein in different stages of epilepsy also varied significantly ( F=86.86 and 6.65 respectively, both P<0.05). Conclusions:The increased expression of USP25 in the temporal cortex after the latent period has suggested that the deubiquitination pathway is involved in the chronic pathological process of temporal lobe epilepsy.

Glioblastoma (GBM) is the most common and malignant cancer of the central nervous system, and radiotherapy is widely applied in GBM treatment; however, the sensitivity to radiotherapy varies in different patients. To solve this clinical dilemma, a radiosensitivity prediction signature was constructed in the present study based on genomic methylation. In total, 1044 primary GBM samples with clinical and methylation microarray data were involved in this study. LASSO-COX, GSVA, Kaplan-Meier survival curve analysis, and COX regression were performed for the construction and verification of predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. Via the integration analysis of methylation and the survival data of primary GBM, a novel prognostic and radiosensitivity prediction signature was constructed. This signature was found to be stable in prognosis prediction in the TCGA and CGGA databases. The possible mechanism was also explored, and it was found that this signature is closely related to DNA repair functions. Most importantly, this signature could predict whether GBM patients could benefit from radiotherapy. In summary, a radiosensitivity prediction signature for GBM patients based on five methylated probes was constructed, and presents great potential for clinical application.

Brain edema is a common and serious complication of ischemic stroke with limited effective treatment. We previously reported that methylene blue (MB) attenuated ischemic brain edema in rats, but the underlying mechanisms remained unknown. Aquaporin 4 (AQP4) in astrocytes plays a key role in brain edema. We also found that extracellular signal-regulated kinase 1/2 (ERK1/2) activation was involved in the regulation of AQP4 expression in astrocytes. In the present study, we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), MB (3 mg/kg, for 30 min) was infused intravenously through the tail vein started immediately after reperfusion and again at 3 h after ischemia (1.5 mg/kg, for 15 min). Brain edema was determined by MRI at 0.5, 2.5, and 48 h after tMCAO. The decreases of apparent diffusion coefficient (ADC) values on diffusion-weighted MRI indicated cytotoxic brain edema, whereas the increase of T2 MRI values reflected vasogenic brain edema. We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO. In addition, MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO. In a cell swelling model established in cultured rat astrocyte exposed to glutamate (1 mM), we consistently found that MB (10 μM) attenuated cell swelling, AQP4 increases and ERK1/2 activation. Moreover, the ERK1/2 inhibitor U0126 (10 μM) had the similar effects as MB. These results demonstrate that MB improves brain edema and astrocyte swelling, which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway, suggesting that MB may be a potential choice for the treatment of brain edema.

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 β, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-β pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.

患者,女,27岁.就诊日期:2019年10月21日.主诉:口咽干燥5月余.现病史:5个月前因膝盖疼痛,于网上发现偏方可服用曼陀罗籽治疗,自购曼陀罗籽1包(约50 g),每日取5～8 g用开水冲泡后饮水,服至第3天时,突感头晕、恶心,站立时摔倒,后出现昏迷、肢体轻微抽搐症状.急送至北京某三甲医院治疗,予洗胃排毒,新斯的明、毛果芸香碱解毒等治疗,患者神志转清醒,住院治疗1周后出院.出院后自觉口干、咽干严重,每次进餐均需饮水,夜间需多次起床饮水才能再次入睡,于北京协和医院就诊,行抗核抗体等免疫相关检查未见异常.西医诊断:中毒性唾液腺分泌障碍.服用营养神经西药(具体药物不详)治疗1个月未见好转,后停用.

Most studies regarding plasma biomedicine applications mainly focus on the oxidative and/or nitrative stress on bacteria, cancer cells, and other treatment objects. In this study, we evaluate the protective effect of appropriate atmospheric pressure plasma jet (APPJ) treatments on oxygen and glucose deprivation (OGD)-induced neural cell apoptosis, which is a major pathological process during ischemic stroke, based on the physiological functions of NO. Results show that APPJ treatment reduces the OGD-induced apoptosis by weakening typical OGD injury consequences including loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytoplasm, lower antiapoptotic Bcl-2 expression, and upregulating the proapoptotic protein Bax. Furthermore, APPJ increased intracellular NO production, which is closely related to the cytoprotective effect of APPJ.

BACKGROUND AND AIMS:Cancer has become the second most serious disease threatening human health, followed by cardiovascular diseases. This study aimed to quantitatively estimate the mortality, morbidity, and analyze the trends of 29 cancer groups in 195 countries/regions between 1990 and 2017.METHODS:Detailed information of 29 cancer groups were collected from the Global Burden of Disease (GBD) study in 2017 and age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) of 29 cancer groups were calculated based on gender, age, region, and country. Trend analyses were conducted for major cancer types.RESULTS:In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. The ASDR and ASIR of cancer in males were about 1.5 times those of females. Breast cancer showed the highest mortality rate in females in 2017. Individuals aged over 50 are at high risk of developing cancer and the number of cases and deaths in this age group accounted for more than 80% of all cancers in all age groups. Asia has the heaviest cancer burden due to its large population density. Different cancers in varied countries globally have their own characteristics. The ASDR and ASIR of some major cancers demonstrated changes from 1990 to 2017.CONCLUSIONS:Analyses of these data provided basis for future investigations to the common etiological factors, leading to the occurrence of different cancers, the development of prevention strategies based on local characteristics, socioeconomic and other conditions, and the formulation of more targeted interventions.

Objective To compare the behavioral manifestations, electroencephalogram ( EEG ) monitoring and hippocampal pathological changes in two rat epilepsy models induced by kainic acid ( KA) injected into hippocampus and amygdala respectively. Methods Male adult Sprague-Dawley rats(n=24) were randomly divided into hippocampus model group ( n=9 ) , amygdala model group ( n=9 ) and control group (n=6). Two epilepsy models were established by kainic acid (0. 6 μg,1. 0 μg/μl) stereotactically injected into hippocampus CA3 region (hippocampus model) or amygdala (amygdala model). The status epilepticus ( SE ) of rats was observed by behavioral manifestations and EEG monitoring. Following successful modeling, those rats were randomly divided into 3 groups, including 1-day ( acute phase) , 7-day ( latent phase) and 30-day ( chronic phase) post SE groups ( n=3 in each group) . Rats in the control group were injected with an equal volume of saline in the hippocampal CA3 or amygdala. Immunohistochemistry&nbsp;was used for observing the pathological changes of neuron (NeuN), astrocyte (GFAP) and microglia (Iba1) in the rat hippocampus. Results Behavioral and EEG monitoring showed that rats from both models had typical seizure behaviors and EEG characteristics in the acute and chronic phases. However, there were different seize types and onset time between the 2 models in the acute phase. The hippocampus model group had partial seizures at 63. 33 ± 4. 41 min post KA injection with intermittent generalized tonic-clonic seizures. Multi-phase spikes were recorded in acute phase. Amygdala model group had severe generalized tonic-clonic seizures at 28. 67 ± 3. 48 min post KA injection, and the main cortical EEG form was sharp wave rhythm. Immunohistochemical staining revealed gradual hippocampal neuron death from acute to chronic phases in both models, which resulted in serious neuronal loss. Meanwhile, the aggravation of astrocyte proliferation and accumulation of microglia occurred in hippocampus in both models. Remarkably, compared with hippocampus model, the amygdala model in chronic phase had more neuronal loss in CA1 region ( 10. 83 ± 1. 52 vs. 22. 43 ± 5. 16, P<0. 01) and CA4 region (12. 87 ± 2. 13 vs. 25. 81 ± 4. 60, P <0. 05), more astrocyte proliferation in CA1 region (61. 20 ± 7. 33 vs. 14. 65 ± 0. 12, P<0. 01) and CA4 region (76. 73 ± 5. 40 vs. 43. 01 ± 1. 35, P<0. 01) as well as more widespread accumulation of microglia in CA1 region (13. 70 ± 3. 88 vs. 1. 08 ± 0. 01, P<0. 01). Conclusions Our results have indicated that both rat epilepsy models simulated human temporal lobe epilepsy. The differences in the behavior, EEG performances and particularly pathological changes of hippocampus between two models should be taken into consideration in the future study.

患者,女,63 岁.就诊日期:2019 年 4 月 17 日.主诉:持续背痛、喘憋 1 月余.现病史:1 月前因连续缝被子 3 d 后出现持续性后背疼痛,疼痛性质为胀痛,位置固定在双侧肩胛骨内侧,服用布洛芬等止痛药物后无缓解,夜间不能入睡,在当地医院行拔罐、理疗等治疗后症状未改善,2 d 后出现严重喘憋、不能平卧,双手持物困难,当地医院建议至北京就诊.后至北京某三甲医院就诊,考虑为冠心病、呼吸衰竭,完善相关检查后肺部影像学检查提示双侧膈肌上抬,考虑膈神经麻痹可能,诊断为膈神经麻痹,予吸氧,口服维生素 B12 治疗后无明显缓解,后至我院针灸科就诊.

Atmospheric pressure plasma jet (APPJ) has shown excellent potential prospects in biomedical applications, based on the production of reactive oxygen species and reactive nitrogen species (RNS) from APPJ emissions. The current research focused on the protective effect of APPJ on oxygen and glucose deprivation (OGD)-induced cell death in both the H9C2 cardiac myoblast cell line, a frequently used cardiac cell line in cardioprotective studies, and primary neonatal rat cardiomyocytes (NRCMs). Cells were treated with APPJ for different durations, cultured for 6h and then subjected to OGD for 18h before their use in assays. We found that APPJ treatment could maintain H9C2 cell viability and reduce cell apoptosis in a dose-dependent manner in cells subjected to the OGD conditions. To confirm the cardioprotective effect of APPJ on primary NRCM, we first identified the 'safe dose' of APPJ treatment by evaluating the cytotoxicity of APPJ on primary NRCMs in normal culture conditions. Under the 'safe dose' of APPJ treatment, we also found that the APPJ treatment could maintain NRCM viability under OGD conditions and reduce CK-MB and cTnI release from cardiomyocytes. Further studies revealed that the cytoprotective effect of APPJ may be related to NO production induced by APPJ treatment. Our results gave the first evidence of the cardiotoxicity and cytoprotective effect of APPJ on cardiomyocytes against OGD injury, and furthermore, contributed to new insights into the potential medical applications of plasma in cardiovascular diseases.