Association between cancer health literacy and cancer-related behavior of residents in Shandong, China.

Health literacy is closely related to the incidence of major chronic diseases and its related behaviors such as cancer-related behaviors. This study explored how the cancer health literacy level affects cancer-related behaviors. About one to two villages from six cities of Shandong province were selected as sample areas. Professionals conducted face-to-face interviews with the participants. Finally, 1200 residents completed 1085 effective questionnaires. Data were analysed from a cross-sectional survey in 2019, which included 1085 residents in six cities/counties of Shandong province, China. The result showed that residents with high cancer health literacy were more likely to eat fruits and vegetables frequently, avoid eating moldy food and take exercise. Besides, they were more likely to engage in health education and have a higher willingness to pay for cancer screenings. Most residents in Shandong province have a basic level of cancer health literacy. Improving the cancer health literacy of the population can be an effective strategy to promote a healthier lifestyle, thereby reducing the incidence rates related to cancers.

Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans.

AIM: Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. METHODS AND RESULTS: Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. CONCLUSIONS: AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.

Health insurance as a moderator in the relationship between financial toxicity and medical cost-coping behaviors: Evidence from patients with lung cancer in China.

OBJECTIVE: This study investigates the relationship between financial toxicity and medical cost-coping behaviors (MCCB) in Chinese patients with lung cancer, with a particular focus on the moderating role of health insurance. METHODS: We surveyed 218 patients with lung cancer and assessed their Comprehensive Score for Financial Toxicity (COST) and self-reported MCCB. Patients were categorized into Urban Employee's Basic Medical Insurance (UEBMI) group and Urban-Rural Resident Basic Medical Insurance Scheme (URRBMI) groups by their medical insurance, and matched for socioeconomic, demographic, and disease characteristics via propensity score. RESULTS: Significant different characteristics were noted between UEBMI patients and URRBMI patients. Patients with UEBMI had higher COST scores but lower levels of MCCB compared to URRBMI patients in the original dataset. After data matching, multivariate logit regression analysis showed that better financial toxicity was associated with lower levels of MCCB (OR = 0.95, 95% CI: 0.92-0.99). Health insurance type did not have a direct association with cost-coping behaviors, but an interaction was observed between health insurance type and financial toxicity. Among patients with URRBMI, better financial toxicity was associated with lower levels of cost-coping behaviors (OR = 0.89, 95% CI: 0.83-0.95). Patients with UEBMI had a lower probability of engaging in any cost-coping behaviors in situations of worse financial toxicity compared to patients with URRBMI. CONCLUSION: The findings suggest that financial toxicity is correlated with MCCB in Chinese patients with lung cancer. The type of health insurance, specifically UEBMI and URRBMI, plays a moderating role in this relationship. Understanding these dynamics is essential for developing targeted interventions and policies to mitigate financial toxicity and improve patients' management of medical costs.

Dyadic coping in young and middle-aged women with gynecological cancer: a latent class analysis.

PURPOSE: Cancer is a shared stress that can cause psychosocial and emotional burdens for both patients and their partners. This study aimed to identify patterns of dyadic coping (DC) among young and middle-aged women with gynecological cancer and to assess between-group differences. METHODS: Between June 2021 and November 2021, patients with gynecological cancer who received therapy in a tertiary-grade hospital in Shandong, China, completed questionnaires including a demographic questionnaire, the Dyadic Coping Inventory, the PROMIS-Anxiety Short Form, the PROMIS-Depression Short Form, and the revised Conflict Tactics Scale and were classified into subtypes by latent class analysis. RESULTS: The sample consisted of 339 patients. Approximately one-third of the patients, especially cervical cancer patients, were exposed to varying degrees of DC issues. Three patterns were identified: class 1, middle-DC group (33.6%); class 2, low-DC group (32.2%); and class 3, high-DC group (34.2%). Postmenopausal patients were more likely to be included in class 1, while patients with cervical cancer were more likely to be included in class 2 (p < 0.05). Additionally, patients in class 2 were more likely to report insufficient emotional support (p < 0.05). A positive correlation was found for social relationship domains, and a negative correlation was found for anxiety and depression (p < 0.05). CONCLUSION: The findings indicated a high prevalence of DC in young and middle-aged women with gynecological cancer. Overall, participants scored in the low-to-middle range in terms of DC levels, and patients with cervical cancer and those with insufficient emotional support were more likely to report DC issues and require additional attention.

Digs out and characterization of the resistance gene accountable to soybean mosaic virus in soybean (Glycine max (L.) Merrill).

KEY MESSAGE: A putative candidate gene conferring resistance to SMV strain SC1 was identified on chromosome 2, and the linked marker was validated in soybean cultivars Soybean mosaic, caused by the soybean mosaic virus, is the most common disease in soybean and a significant impediment to soybean production in the Huanghuai and Yangtze River regions of China. Kefeng No.1, a soybean cultivar, showed high resistance to soybean mosaic virus strain (SC1) collected from Huanghuai and Yangtze River regions. Genetic analysis based on the Mendelian genic population derived from the cross Kefeng No.1 × Nannong 1138-2 revealed that Kefeng No.1 possesses a single dominant gene. Furthermore, genetic fine-mapping using an F2 population containing 281 individuals delimited resistant gene to a genomic region of 186 kb flanked by SSR markers BS020610 and BS020620 on chromosome 2. Within this region, there were 14 genes based on the Williams 82 reference genome. According to sequence analysis, six of the 14 genes have amino acid differences, and one of these genes is the Rsv4 allele designated as Rsc1-DR. The functional analysis of candidate genes using the bean pod mottle virus (BPMV)-induced gene silencing (VIGS) system revealed that Rsc1-DR was accountable for Kefeng No.1's resistance to SMV-SC1. Based on the genome sequence of Rsc1-DR, an Insertion/Deletion (InDel) molecular marker, JT0212, was developed and genotyped using 100 soybean cultivars, and the coincidence rate was 89%. The study enriched our understanding of the SMV resistance mechanism. The marker developed in this study could be directly used by the soybean breeders to select the genotypes with favorable alleles for making crosses, and also it will facilitate marker-assisted selection of SMV resistance in soybean breeding.

The Integrated Analysis Identifies Three Critical Genes as Novel Diagnostic Biomarkers Involved in Immune Infiltration in Atherosclerosis.

Atherosclerosis (AS), a chronic inflammatory disease of the blood vessels, is the primary cause of cardiovascular disease, the leading cause of death worldwide. This study aimed to identify possible diagnostic markers for AS and determine their correlation with the infiltration of immune cells in AS. In total, 10 serum samples from AS patients and 10 samples from healthy subjects were collected. The original gene expression profiles of GSE43292 and GSE57691 were downloaded from the Gene Expression Omnibus database. Least absolute shrinkage and selection operator regression model and support vector machine recursive feature elimination analyses were carried out to identify candidate markers. The diagnostic values of the identified biomarkers were determined using receiver operating characteristic assays. The compositional patterns of the 22 types of immune cell fraction in AS were estimated using CIBERSORT. RT-PCR was performed to further determine the expression of the critical genes. This study identified 17 differentially expressed genes (DEGs) in AS samples. The identified DEGs were mainly involved in non-small cell lung carcinoma, pulmonary fibrosis, polycystic ovary syndrome, glucose intolerance, and T-cell leukemia. FHL5, IBSP, and SCRG1 have been identified as the diagnostic genes in AS. The expression of SCRG1 and FHL5 was distinctly downregulated in AS samples, and the expression of IBSP was distinctly upregulated in AS samples, which was further confirmed using our cohort by RT-PCR. Moreover, immune assays revealed that FHL5, IBSP, and SCRG1 were associated with several immune cells, such as CD8 T cells, naïve B cells, macrophage M0, activated memory CD4 T cells, and activated NK cells. Overall, future investigations into the occurrence and molecular mechanisms of AS may benefit from using the genes FHL5, IBSP, and SCRG1 as diagnostic markers for the condition.

Isolation and Identification of Porcine Bone Marrow Mesenchymal Stem Cells and their Derived Extracellular Vesicles.

With the development of stem cell therapy in translational research and regenerative medicine, bone marrow mesenchymal stem cells (BM-MSCs), as a kind of pluripotent stem cells, are favored for their instant availability and proven safety. It has been reported that transplantation of BM-MSCs is of great benefit to repairing injured tissues in various diseases, which might be related to modulating the immune and inflammatory responses via paracrine mechanisms. Extracellular vesicles (EVs), featuring a double-layer lipid membrane structure, are considered to be the main mediators of the paracrine effects of stem cells. Recognized for their crucial roles in cell communication and epigenetic regulation, EVs have already been applied in vivo for immunotherapy. However, similar to its maternal cells, most of the studies on the efficacy of transplantation of EVs still remain at the level of small animals, which is not enough to provide essential evidence for clinical translation. Here, we use density-gradient centrifugation to isolate bone marrow cells (BMC) from porcine bone marrow at first, and get porcine BM-MSCs (pBM-MSCs) by cell culture subsequently, identified by the results of observation under the microscope, induced differentiation assay, and flow cytometry. Furthermore, we isolate EVs derived from pBM-MSCs in cell supernatant by ultracentrifugation, proved by the techniques of transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting successfully. Overall, pBM-MSCs and their derived EVs can be isolated and identified effectively by the following protocols, which might be widely used in pre-clinical studies on the transplantation efficacy of BM-MSCs and their derived EVs.

Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices.

The left ventricular assist device (LVAD) is often used in the treatment of heart failure. However, 4% to 9% implanted LVAD will have thrombosis problem in one year, which is fatal to the patient's life. In this work, an interventional sonothrombolysis (IST) method is developed to realize the thrombolysis on LVAD. A pair of ultrasound transducer rings is installed on the shell of LVAD, and drug-loaded microbubbles are injected into the LVAD through the interventional method. The microbubbles are adhere on the thrombus with the coated thrombus-targeted drugs, and the thrombolytic drugs carried by the bubbles are brought into the thrombus by the cavitation of bubbles under the ultrasound. In a proof-of-concept experiment in a live sheep model, the thrombus on LVAD is dissolved in 30 min, without damages on LVADs and organs. This IST exhibits to be more efficient and safer compared with other thrombolysis methods on LVAD.

Tartary buckwheat extract alleviates alcohol-induced acute and chronic liver injuries through the inhibition of oxidative stress and mitochondrial cell death pathway.

Alcohol use disorder (AUD) is an enormous public health problem that poses significant social, medical, and economic burdens. Under AUD, the liver is one of the most adversely affected organs. As current therapies and protective drugs for AUD-mediated liver injury are very limited, the prevention and therapy of alcoholic liver disease are urgently needed. The present study aims to investigate the beneficial effects of tartary buckwheat extract (TBE), the important component of Maopu tartary buckwheat liquor, on both alcoholic-induced acute and chronic liver injuries. We show that the TBE administration, similar to curcumin, significantly reduces the elevated serum aspartate aminotransferase and alanine aminotransferase levels, improves liver index, alleviates the elevated contents of hepatic malondialdehye, and restores the decreased contents of hepatic glutathione both in acute and chronic liver injuries in alcohol-exposed rats. Furthermore, histopathological analyses show that a medium dose of TBE (16.70 ml/kg body weight) alleviates hepatocyte morphology changes in both acute and chronic alcohol exposure models. We also show the protective effects of TBE on the cell death rates of alcohol-exposed primary cultured hepatocytes, HepG2 hepatoma, and Huh 7 hepatoma cells. Furthermore, we demonstrate that TBE exerts hepatoprotection partly through inhibiting the mitochondrial cell death pathway by reducing cytochrome c release, caspase-9 and -3 activities, and the number of TUNEL-positive cells. These effects of TBE were accompanied by enhanced levels of Bcl-2 and Bcl-xL and autophagic cell death pathway by reducing Beclin-1 expression, as well as through promoting its anti-oxidant capacity by suppressing reactive oxygen species production. This study demonstrates, for the first time, the protective effect of TBE against alcohol-induced acute and chronic liver injury in vivo and in vitro. Given the dietary nature of tartary buckwheat, pueraria, lycium barbarum, and hawthorn, the oral intake of TBE or liquor contained TBE, e.g., Maopu Tartary buckwheat liquor, compared with pure liquor consumption alone, may have the potential to alleviate alcoholic-induced liver injuries.

Risk Factors Associated with Precancerous Lesions of Esophageal Squamous Cell Carcinoma: a Screening Study in a High Risk Chinese Population.

Background: Esophageal squamous cell carcinoma (ESCC) has been having a high mortality rate in China. Most patients are diagnosed in advanced stages, leading to the poor prognosis and low 5-year survival rate. Detection of precancerous lesions or early cancers is the key to improving this situation. Although previous studies have identified some risk factors for ESCC, they rarely paid attention to the premalignant esophageal lesions. We thus initiated a population-based screening study aiming to assess risk factors associated with esophageal precancerous lesions (EPLs) in a high risk Chinese population. Methods: From September 2013 to July 2015, we screened residents aged 40-69 years from 53 randomly selected communities in Feicheng, China (n = 5076). Each participant went through questionnaire interview, physical examination, endoscopy and biopsy. Using logistic regression, we compared participants with EPLs to that with normal esophageal mucosa for finding potential risk factors of EPLs. Results: A total of 570 participants were diagnosed with EPLs. We observed no association between EPLs and tobacco smoking or alcohol consumption in unadjusted or adjusted model. In the adjusted model, the OR (95% CI) was 1.84 (1.18-2.89) for people of drinking shallow-well water comparing to people who was drinking tap-water. In a comparison of participants with good oral health, the ESD/ESCC ORs (95% CI) for those with very poor or poor oral health, were 1.78 (1.28-2.49) and 1.58 (1.16-2.15) respectively. However, no statistical significance was observed after adjustment. Moreover, cereal straw heating (OR= 1.74, 95% CI: 0.90-3.36, P=0.099) may lead to increased risk of EPLs. Conclusion: In Feicheng population, tobacco smoking or alcohol consumption may not be risk factors of EPLs. Low-quality drinking water raised the EPLs risk. Bad house heating materials, such as cereal straw, may lead to high EPLs risk.

Structural, functional and histological features of a novel ischemic heart failure model.

There is still no satisfactory large-animal model of ischemic heart failure (IHF) with ideal survival rate and model time. The aim of this study is to explore a novel chronic IHF model in swine. 23 healthy Ba-Ma miniature pigs were included. Pigs in the experimental group underwent multiple strategic ligations on side branches of the left anterior descending (LAD) and circumflex coronary arteries. One week later, sequential intervention occlusion of the distal end of the LAD trunk was performed. In the experimental groups, LV end-diastolic (LVEDV) and end-systolic volume (LVESV) gradually increased starting at 4 weeks post operation. At 12 WPO, LVEDV increased from 45.0 ± 2.9 ml at baseline to 110.0 ± 9.8 ml and LVESV increased from 17.0 ± 1.4 ml at baseline to 42.0 ± 3.6 ml. Meanwhile, left ventricular ejection fraction significantly decreased from 73.8 ± 4.2 % at baseline to 31.0 ± 2.5%. According to histomorphometric assessment, viable cells were observed in infarction lesions, indicating the model has replicated the structural and functional features of chronic IHF.

Construction and application of service quality evaluation system in the preclinical research on cardiovascular implant devices.

BACKGROUND: Services for the preclinical development and evaluation of cardiovascular implant devices (CVIDs) is a new industry. However, there is still no indicator system for quality evaluation. Our aim is to construct a service for quality evaluation system for the preclinical research and development of CVIDs based on Fuzzy Analytical Hierarchy Process (FAHP). METHODS: First, we reviewed the related literature to identify and select possible factors. Second, we developed an analytic hierarchy process framework. Third, we developed a questionnaire based on pairwise comparisons and invited 10 experienced specialists to rate these factors. We then used FAHP to compute the weights of these factors and prioritize them. Finally, to demonstrate the effectiveness of the proposed indicator system, a case study was performed as a practical example. RESULTS: Four main indicators (professionalism, functionality, stability and security) and 15 subindicators were selected to form the service evaluation system based on literature review and expert's proposals. According to the weight calculation data, the order of primary indicators by importance, is professionalism (0.6457), security (0.1193), functionality (0.0958) and stability (0.0596) in sequence. Top five secondary indices are personnel's technical ability, facility and equipment attractiveness, data auditability, confidentiality capability and professional service procedures. In the case study, FW's final actual effectiveness value was 0.9076, which is the same as the actual situation. CONCLUSION: The indicator system established in this study is comprehensive, reasonable, reliable and with strong practicality. It is worth popularizing and applying. The implementation of this evaluation system can provide measurable evidence for service demander and a way to improve service quality for suppliers.

The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin in targeting brain injury and liver damage and in maintaining bone health.

Melatonin is a neurohormone associated with sleep and wakefulness and is mainly produced by the pineal gland. Numerous physiological functions of melatonin have been demonstrated including anti-inflammation, suppressing neoplastic growth, circadian and endocrine rhythm regulation, and its potent antioxidant activity as well as its role in regeneration of various tissues including the nervous system, liver, bone, kidney, bladder, skin, and muscle, among others. In this review, we summarize the recent advances related to the multiple protective roles of melatonin receptor agonists, melatonin and N-acetylserotonin (NAS), in brain injury, liver damage, and bone health. Brain injury, including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and newborn perinatal hypoxia-ischemia encephalopathy, is a major cause of mortality and disability. Liver disease causes serious public health problems and various factors including alcohol, chemical pollutants, and drugs induce hepatic damage. Osteoporosis is the most common bone disease in humans. Due in part to an aging population, both the cost of care of fracture patients and the annual fracture rate have increased steadily. Despite the discrepancy in the pathophysiological processes of these disorders, time frames and severity, they may share several common molecular mechanisms. Oxidative stress is considered to be a critical factor in these pathogeneses. We update the current state of knowledge related to the molecular processes, mainly including anti-oxidative stress, anti-apoptosis, autophagy dysfunction, and anti-inflammation as well as other properties of melatonin and NAS. Particularly, the abilities of melatonin and NAS to directly scavenge oxygen-centered radicals and toxic reactive oxygen species, and indirectly act through antioxidant enzymes are disscussed. In this review, we summarize the similarities and differences in the protection provided by melatonin and/or NAS in brain, liver and bone damage. We analyze the involvement of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2), and melatonin receptor 1C (MT3) in the protection of melatonin and/or NAS. Additionally, we evaluate their potential clinical applications. The multiple mechanisms of action and multiple organ-targeted properties of melatonin and NAS may contribute to development of promising therapies for clinical trials.

Sevoflurane inhibits the progression of ovarian cancer through down-regulating stanniocalcin 1 (STC1).

BACKGROUND: Ovarian cancer is one of the leading causes of female death worldwide, with a poor prognosis of advanced patients. Sevoflurane, a volatile anesthetic commonly used in clinical operations, has been reported to have anti-cancer activity against some tumors. In the present study, we aimed to investigate the effects of sevoflurane on the progression of ovarian cancer and its potential mechanism. METHODS: The effects of sevoflurane on ovarian cancer cell viability, proliferation, migration, invasion, cell cycle, and apoptosis were determined by functional experiments in vitro. Gelatin zymography assay was performed to examine MMP9 activity. In vivo, sevoflurane was injected into mice of transplantation tumor with SKOV3 cells or with pcDNA-STC1 treated SKOV3 cells. RESULTS: We found that sevoflurane inhibited the viability of SKOV3 and OVCAR3 cells in a dose-dependent manner, and colony formation assay revealed that sevoflurane inhibited ovarian cancer cell colony-formation abilities. Additionally, sevoflurane could induce cell cycle arrest and promote cell apoptosis in SKOV3 and OVCAR3 cells. Moreover, sevoflurane reduced the migration and invasion abilities of SKOV3 and OVCAR3 cells, as well as the MMP-9 activity. Furthermore, sevoflurane down-regulated the expression of stanniocalcin 1 (STC1), and up-regulation of STC1 could reverse the inhibitory effects of sevoflurane on cell proliferation and invasion. In vivo, sevoflurane significantly inhibited the tumor growth, which was be reversed by STC1 overexpression. CONCLUSION: These data reveal an anti-cancer activity of sevoflurane on the growth and invasion of ovarian cancer, which may be through down-regulating STC1. Sevoflurane may serve as a potential anti-cancer agent in ovarian cancer therapy.

The characteristics of a porcine mitral regurgitation model.

The porcine mitral regurgitation (MR) model is a common cardiovascular animal model. Standardized manufacturing processes can improve the uniformity and success rate of the model, and systematic research can evaluate its potential use. In this study, 17 pigs were divided into an experimental group (n=11) and a control group (n=6). We used a homemade retractor to cut the mitral chordae via the left atrial appendage to establish a model of MR; the control group underwent a sham surgery. The model animals were followed for 30 months after the surgery. Enlargement and fibrosis of the left atrium were significant in the experimental group compared with those in the control group, and left atrial systolic function decreased significantly. In addition, model animals showed preserved left ventricular systolic function. There were no differences in left atrial potential or left ventricular myocardial fibrosis between the two groups. Atrial fibrillation susceptibility in the experimental group was higher than that in the control group. Our method enables the simple and effective production of a MR model with severe reflux that can be used for pathophysiological studies of MR, as well as for the development of preclinical surgical instruments and their evaluation. This model could also be used to study atrial fibrillation and myocardial fibrosis but is not suitable for studies of heart failure.

Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation.

Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission. Our previous studies proved that the inhibition of Drp1 may help attenuate traumatic brain injury (TBI)-induced functional outcome and cell death through maintaining normal mitochondrial morphology and inhibiting activation of apoptosis. However, the molecular mechanisms of Drp1 after TBI remain poorly understood. In this study, we investigated the role of mitochondrial division inhibitor 1 (Mdivi-1), a small molecule inhibitor of Drp1, in underlying mechanisms of general autophagy and mitochondria autophagy (mitophagy) after experimental TBI. In vivo, we found that autophagosomes accumulated in cortical neurons at 24h after TBI, owing to the enhanced autophagy indicated by the accumulation of LC3 and the decrease of p62; but Mdivi-1 reversed the enhancement. Mdivi-1 also alleviated the number of LC3 puncta and TUNEL-positive structures in cells, indicating that autophagy maybe involved in Mdivi-1's anti-apoptosis effects. Then, the expression level of mitochondrial dynamics related and mitophagy related proteins was assessed using the isolated mitochondria. The results showed that TBI-induced mitochondrial fission (represented by Drp1), mtDNA concentration down-regulation and PTEN induced putative kinase 1 (PINK1)-Parkin mediated mitophagy activation were all inhibited by Mdivi-1. In addition, TBI-induced blood-brain barrier (BBB) disruption and matrix metalloproteinases (MMP)-9 expression up-regulation were inhibited following Mdivi-1 treatment. In vitro, Mdivi-1 significantly alleviated the scratch injury-induced cell death, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production and ATP reduction in primary cortical neurons (PCNs). Additionally, the lysosome inhibitor chloroquine (CQ) abrogated the Mdivi-1-induced decrease in autophagosomes accumulation and cell death at 24h both in the basal state and under the conditions of scratch cell injury. Together, these data demonstrate that Mdivi-1 mitigates TBI-induced BBB disruption and cell death at least in part by a mechanism involving inhibiting autophagy dysfunction and mitophagy activation.

A comparative study of the characterization of miR-155 in knockout mice.

miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models.

miR-155 regulates high glucose-induced cardiac fibrosis via the TGF-ß signaling pathway.

Cardiac fibrosis, as a pathological process, plays an important role in various cardiac diseases. microRNA-155 (miR-155) is one of the most important miRNAs, and previous studies have shown that it is a regulatory factor in various fibrotic diseases. However, the mechanism by which miR-155 affects myocardial fibrosis remains unclear. In this study, we aim to establish the biological function of miR-155 in myocardial fibrosis induced by diabetes in mice. We used normal C57BL/6 wild type (WT) and miR-155 knockout (KO) mice to establish the diabetic model by intraperitoneal injection of streptozotocin, and we utilized echocardiography to evaluate the cardiac function at 30 and 60 days post-modeling. Hematoxylin-eosin (HE) and sirius-red (SR) staining were used to evaluate the degree of myocardial lesions. Furthermore, we extracted cardiac fibroblasts (CFs) from the WT mice and transfected them with miR-155 inhibitors, mimics and negative control siRNAs to analyze the specific mechanism involved in the development of myocardial fibrosis. The results showed that miR-155 deficiency could prevent cardiac fibrosis induced by diabetes in mice and also that attenuated collagen synthesis is induced by high glucose (HG) in CFs. We found that miR-155 regulated cardiac fibrosis via the TGF-ß1-Smad 2 signaling pathway. These findings suggest that miR-155 may be a therapeutic target for preventing cardiac fibrosis induced by diabetes.

Autophagy is associated with cell fate in the process of macrophage-derived foam cells formation and progress.

BACKGROUND: Autophagy participates in plaque formation and progression; however, its association with foam cells' fate is unknown. To investigate autophagy features and its effect on the fate of different-stage macrophage foam cells (FCs). Different-stage FCs were obtained through incubation of THP-1 macrophages (THP-M) with oxidized low-density lipoprotein LDL (oxLDL, 80 µg/mL) for various durations (0-72 h). Autophagy in THP-1 macrophage FCs and in apoE-/- mice was regulated by Rapamycin (80 ug/mL) or 3-MA (10 mM). Lipid droplet accumulation, LC3 I/II, P62 expression level, and autophagic flux were measured. Vascular ultrasound, TUNEL, IHC, and DHE staining were used to detect the artery plaques in apoE-/- mice. RESULTS: In early-stage FCs, the amount of autophagosomes gradually increased, and autophagic flux intensity accelerated, but in mid-late stage FCs, autophagic flux was suppressed. For early stage FCs, treatment with autophagy activator rapamycin markedly decreased intracellular lipid content and prevented them from transforming into foam cells, while the autophagy inhibitor 3-MA considerably increased the intracellular lipid-droplet accumulation. During the process of foam cell development, upregulating autophagy not only reduced intracellular lipid-droplet accumulation, but also inhibited cell apoptosis through clearing dysfunctional mitochondria and lowering intracellular ROS level. The in vivo experiments produced consistent results that rapamycin administration in apoE-/- mice reduced the death rate of macrophages and delayed plaque progression. CONCLUSIONS: The fate of macrophage FCs was associated with autophagy. Early autophagy enhancement inhibits the formation and progression of macrophage FCs and prevents atherosclerosis.