Regulatory emotional self-efficacy and self-compassion mediate anxiety, depression, body image distress and subjective well-being in women with polycystic ovary syndrome: A cross-sectional study.

AIMS: This study aims to investigate the mediating role of regulatory emotional self-efficacy and self-compassion in the relationship among anxiety, depression, body image distress and subjective well-being among women with polycystic ovary syndrome. DESIGN: A cross-sectional study. METHODS: The study recruited 510 women with polycystic ovary syndrome from a tertiary hospital affiliated with a university in Hunan Province, China. The study employed several tools to collect data, including the Generalized Anxiety Scale, the Patient Health Questionnaire-9, the Body Image States Scale, the Self-Compassion Scale, the Regulatory Emotional Self-Efficacy Scale and the Index of Well-being questionnaire. Data analysis was carried out using descriptive analysis, spearman correlation analysis, ordinary least squares regression and bootstrapping. RESULTS: The study's findings indicate that regulatory emotional self-efficacy and self-compassion both act as mediators in the connection between anxiety, depression, body image distress and subjective well-being among women with polycystic ovary syndrome. CONCLUSION: The study emphasizes the significance of regulatory emotional self-efficacy and self-compassion in promoting well-being among women with polycystic ovary syndrome. It also implies that interventions targeted at enhancing these factors could potentially enhance the subjective well-being of women affected by PCOS. IMPACT: Our study's primary contribution is to underscore the crucial mediating roles of regulatory emotional self-efficacy and self-compassion in the relationship among anxiety, depression, body image distress and subjective well-being. Our study indicates that clinical practitioners should prioritize improving the regulatory emotional self-efficacy and self-compassion of women with polycystic ovary syndrome, reducing their anxiety, depression and body image distress and improving their subjective well-being. REPORTING METHOD: This study was reported according to the Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution outside of participation in the actual study for purposes of data collection.

AQP8 Modulates Mitochondrial H2O2 Transport to Influence Glioma Proliferation.

BACKGROUND: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. MATERIALS AND METHODS: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. RESULT: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. CONCLUSIONS: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.

CPNE1, A Potential Therapeutic Target in Nasopharyngeal Carcinoma, Affects Cell Growth and Radiation Resistance.

The increased expression of Copine 1 (CPNE1) has been observed in various cancers, which promotes cell proliferation, apoptosis, and radio resistance. However, the potential mechanism of CPNE1 in nasopharyngeal carcinoma (NPC) remains elusive. Consequently, our objective was to investigate the role of CPNE1 in regulating proliferation and radio resistance of NPC. CPNE1 expression in NPC and normal patients were obtained from Cancer Genome Atlas (TCGA) database. An elevated CPNE1 was observed in NPC patients and cells (C666-1, SUNE-1, and HNE-1). Then, C666-1 and SUNE-1 cells were subjected to si-CPNE1 under different radiations (0-8 Gy). Cell growth and proliferation were measured by CCK8 and EDU assays, which demonstrated si-CPNE1 suppressed proliferation. Colony formation was performed to detect cell viability under different radiation therapy and survival curve of cell was plotted, which indicated that CPNE1 knockdown improved cell radiosensitivity. Additionally, flow cytometry showed silence of CPNE1 enhanced apoptosis rate in radiated cells. To further investigate the mechanisms of CPNE1 regulating NPC, the expression of activated phosphate Akt (p-Akt) was assessed through western blotting. We observed elevated p-Akt in si-CPNE1 transfected C666-1 and SUNE-1 cells. In conclusion, these results demonstrated that CPNE1 expression is elevated in nasopharyngeal carcinoma cells, and its silencing could attenuate nasopharyngeal carcinoma advancement and improve radiosensitivity to radiation therapy by controlling Akt activation.

Value and influencing factors of preoperative MRI evaluation for previous cesarean scar defect associated abnormal uterine bleeding in patients undergoing laparoscopic surgery. / æœ¯å‰ç£å ±æŒ¯è¯„ä»·è ¹è ”é•œæ‰‹æœ¯æ²»ç–—å‰–å®«äº§åˆ‡å£ç˜¢ç—•ç¼ºé™·ç›¸å ³å¼‚å¸¸å­å®«å‡ºè¡€çš„ä»·å€¼åŠå½±å“å› ç´ ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: As the cesarean section rate increases year by year, the treatment of previous cesarean scar defects (PCSD) poses a significant challenge. This study aims to evaluate the clinical value of preoperative magnetic resonance imaging (MRI) technology and analyze relevant influencing factors for patients with abnormal uterine bleeding (AUB) associated with cesarean scar defects who underwent laparoscopic surgery. METHODS: A retrospective cohort analysis was performed on women who underwent laparoscopic surgery for PCSD-related AUB at the Department of Gynecology, the Third Xiangya Hospital of Central South University from 2018 to 2022. A total of 57 patients who underwent laparoscopic surgery for the treatment of AUB associated with PCSD were divided into 2 groups based on their postoperative clinical cure status: The clinically-cured group (n=28, 49.1%) and the non-clinically-cured group (n=29, 50.9%). After a postoperative follow-up period of 3 months for all participants, logistic regression analysis was conducted to explore the correlation between the clinical cure rate of AUB associated with cesarean scar defects treated by laparoscopic surgery and various factors. These factors included patient age, clinical symptoms, obstetric history, history of cesarean section, basic clinical information, preoperative MRI parameters, and postoperative menstrual conditions. RESULTS: There were no significant differences in many aspects, including the patient's age at the time of previous cesarean section, number of pregnancy, time since the previous cesarean section, the uterus position assessed by preoperative T2 signal MRI, defect length, defect width, residual muscle layer thickness, adjacent uterine muscle layer thickness, and distance from the defect to the external cervical os between the 2 groups (all P>0.05). However, the time of onset of AUB symptoms (P=0.036, OR=1.019, 95% CI 1.002 to 1.038) and the depth of the defect on the preoperative MRI (P=0.010, OR=5.793, 95% CI 1.635 to 25.210) were identified as risk factors affecting the clinical cure rate. CONCLUSIONS: The time of onset of AUB symptoms and the depth of the defect on preoperative MRI are risk factors that influence the clinical cure rate of laparoscopic surgery for the treatment of AUB associated with PCSD, which could be helpful for evaluating the prognosis of disease.

Alteration of the N6-methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome.

OBJECTIVE: To explore the N6-methyladenosine (m6A) methylation abnormality of mRNAs and its potential roles in the mouse model of polycystic ovary syndrome (PCOS). METHODS: The mouse model of PCOS were induced by injecting dehydroepiandrosterone (DHEA), and confirmed by observing the morphological structures of ovarian follicles. Subsequently, m6A-tagged mRNAs were identified via m6A epitranscriptomic microarray and its potential functional pathways were predicted in KEGG database. The expression and modification levels of key mRNAs in the most enriched pathway were evaluated and compared using western blot and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR). RESULTS: Compared with the control group, 415 hypermethylated and downregulated mRNAs, 8 hypomethylated and upregulated mRNAs, and 14 hypermethylated and upregulated mRNAs were identified in the PCOS group (Fold change ≥ 1.5). Those mRNAs were mainly involved in insulin signaling pathway, type II diabetes mellitus, Fc epsilon RI signaling pathway, inositol phosphate metabolism, and GnRH secretion. In insulin signaling pathway, the expression levels of phosphorylated protein kinase B (p-AKT) were decreased, whereas that of upstream phosphorylated phosphatidylinositol 3-kinase (p-PI3K) were increased in PCOS group. Moreover, skeletal muscle and kidney-enriched inositol polyphosphate 5-phosphatease (SKIP), one of PIP3 phosphatases, was verified to be overexpressed, and Skip mRNAs were hypermethylated in PCOS group. CONCLUSION: The altered m6A modification of mRNAs might play a critical role in PCOS process. The PI3K/AKT pathway is inhibited in the mouse model of PCOS. Whether it is caused by the m6A modification of Skip mRNAs is worthy of further exploration.

Upregulation of FAM50A promotes cancer development.

FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

Perioperative nutritional risk and its influencing factors in patients with oral cancer: a longitudinal study.

Introduction: We aimed to investigate the nutritional risk status and dynamic changes in patients with perioperative oral cancer at different stages and analyze the factors influencing nutritional risk and the correlation among body mass index, nutrition-related symptoms, and nutritional risk. Methods: In total, 198 patients with oral cancer who were hospitalized in the Head & Neck Surgery Departments of a tertiary cancer hospital in Hunan Province, China, from May 2020 to January 2021, were selected as participants. The Nutritional Risk Screening 2002 scale and Head and Neck Patient Symptom Checklist were used to assess patients on admission day, 7 days post-surgery, and 1 month post-discharge. Multivariate analysis of variance, paired t-test, and generalized estimating equation were used to analyze the trajectory and influencing factors of nutritional risk in patients with perioperative oral cancer. Spearman's correlation analysis was used to explore the correlation among body mass index, symptoms, and nutritional risk. Results: The nutritional risk scores of patients with oral cancer at the three time points were 2.30 ± 0.84, 3.21 ± 0.94, and 2.11 ± 0.84, respectively, and the differences were significant (p < 0.05). The incidences of nutritional risk were 30.3, 52.5, and 37.9%, respectively. The factors influencing nutritional risk included education level, smoking status, clinical stage, flap repair, and tracheotomy (ß = -0.326, 0.386, 0.387, 0.336, and 0.240, respectively, p < 0.05). Nutritional risk was negatively correlated with body mass index (rs = -0.455, p < 0.01) and positively correlated with pain, loss of appetite, sore mouth, bothersome smells, swallowing difficulty, taste changes, depression, chewing difficulty, thick saliva, and anxiety (rs = 0.252, 0.179, 0.269, 0.155, 0.252, 0.212, 0.244, 0.384, 0.260, and 0.157, respectively, p < 0.05). Conclusion: The incidence of nutritional risk in patients with perioperative oral cancer was high, and the trajectory of nutritional risk changed over time. Strengthening the nutritional monitoring and management of postoperative patients or those with low education level, advanced-stage cancer, flap repair, tracheotomy, and low body mass index; strengthening tobacco control management; and controlling nutrition-related discomfort symptoms in perioperative oral cancer patients are necessary.

Experience of mental health in women with Polycystic Ovary Syndrome: a descriptive phenomenological study.

Purpose: This study aims to investigate the experiences, emotional coping strategies, and help-seeking needs of women with PCOS from their perspective, considering common psychological issues such as stress, anxiety, and depression that are prevalent among individuals with PCOS. Materials and Methods: The study recruited 14 women with PCOS for semi-structured interviews between October and November 2022, using a descriptive phenomenology method design. The interviews were analyzed using NVivo 12 software. Results: Four themes and eleven subthemes were derived from the semi-structured interviews: (1) Negative Mental Health Status; (2) Four Patterns of Emotion Regulation; (3) The Psychological Double-Edged Sword: Family Social Network; (4) Strong Demands for Psychological Counseling and Lifestyle Guidance. Conclusion: The study suggests that interventions should focus on fostering internalized self-efficacy and emotional expression, promoting constructive familial support, and providing psychological counseling and lifestyle recommendations to alleviate psychological distress experienced by women with PCOS.

AQP8 may affect glioma proliferation and growth by regulating GSK-3ß phosphorylation and nuclear transport of ß-catenin.

PURPOSE: The purpose of this work is to examine the impact of AQP8 on the proliferation and development of human glioma cell lines A172 and U251 and to determine if aquaporin 8 (AQP8) is associated with GSK-3ß phosphorylation and nuclear transport of ß-catenin in the Wnt signaling pathway. METHODS: AQP8 knockdown cell lines were constructed using a CRISPR/Cas9 double vector lentivirus infection. SAM/dCas9 was used to construct AQP8 overexpression cell lines and the CV084 lentivirus vector was used to construct AQP8 rescue cell lines. AQP8 and its mRNA, and phosphorylated GSK-3ß, ß-catenin, and other related proteins, were detected using western blot and qRT-PCR. Glioma cell apoptosis was detected using Hoechst 33342 dye. The migration of glioma cells was discovered using a wound healing assay. ß-catenin localization in cells was detected using immunofluorescence staining. RESULTS: The proliferative and migratory capacities of A172 and U251 cells were significantly enhanced after AQP8 overexpression. The Wnt signaling pathways appeared to have higher levels of phosphorylated GSK-3ß and ß-catenin, and a rise in the fluorescence intensity ratio of ß-catenin in the nucleus and cytoplasm, which suggests that ß-catenin translocated into the nucleus, while AQP8 knockdown produced the opposite effect. Further, overexpression of AQP8 in AQP8 knockdown cell lines rescued the reduction of related protein levels caused by AQP8 knockdown. CONCLUSION: High AQP8 expression promotes proliferation and growth of glioma cells, a process associated with phosphorylation of GSK-3ß and nuclear translocation of ß-catenin.

p53 inhibits the Urea cycle and represses polyamine biosynthesis in glioma cell lines.

Glioma is the most common malignant tumor of the central nervous system. The urea cycle (UC) is an essential pathway to convert excess nitrogen and ammonia into the less toxic urea in humans. However, less is known about the functional significance of the urea cycle in glioma. p53 functions as a tumor suppressor and modulates several cellular functions and disease processes. In the present study, we aimed to explore whether p53 influences glioma progression by regulating the urea cycle. Here, we demonstrated the inhibitory impact of p53 on the expression of urea cycle enzymes and urea genesis in glioma cells. The level of polyamine, a urea cycle metabolite, was also regulated by p53 in glioma cells. Carbamoyl phosphate synthetase-1 (CPS1) is the first key enzyme involved in the urea cycle. Functionally, we demonstrated that CPS1 knockdown suppressed glioma cell proliferation, migration and invasion. Mechanistically, we demonstrated that the expression of ornithine decarboxylase (ODC), which determines the generation of polyamine, was regulated by CPS1. In addition, the impacts of p53 knockdown on ODC expression, glioma cell growth and aggressive phenotypes were significantly reversed by CPS1 inhibition. In conclusion, these results demonstrated that p53 inhibits polyamine metabolism by suppressing the urea cycle, which inhibits glioma progression.

Geranylgeranylacetone-induced heat shock protein70 expression reduces retinal ischemia-reperfusion injury through PI3K/AKT/mTOR signaling.

Retinal ischemia-reperfusion (I/R) injury is a common pathophysiological stress state connected to various diseases, including acute glaucoma, retinal vascular obstruction, and diabetic retinopathy. Recent studies have suggested that geranylgeranylacetone (GGA) could increase heat shock protein70 (HSP70) level and reduce retinal ganglion cells (RGCs) apoptosis in a rat retinal I/R model. However, the underlying mechanism remains unclear. Moreover, the injury caused by retinal I/R includes not only apoptosis but also autophagy and gliosis, and the effects of GGA on autophagy and gliosis have not been reported. Our study established a retinal I/R model by anterior chamber perfusion pressuring to 110 mmHg for 60 min, followed by 4 h of reperfusion. The levels of HSP70, apoptosis-related proteins, GFAP, LC3-II, and PI3K/AKT/mTOR signaling proteins were determined by western blotting and qPCR after treatment with GGA, HSP70 inhibitor quercetin (Q), PI3K inhibitor LY294002, and mTOR inhibitor rapamycin. Apoptosis was evaluated by TUNEL staining, meanwhile, HSP70 and LC3 were detected by immunofluorescence. Our results demonstrated that GGA-induced HSP70 expression significantly reduced gliosis, autophagosome accumulation, and apoptosis in retinal I/R injury, indicating that GGA exerted protective effects on retinal I/R injury. Moreover, the protective effects of GGA mechanistically relied on the activation of PI3K/AKT/mTOR signaling. In conclusion, GGA-induced HSP70 overexpression has protective effects on retinal I/R injury by activating PI3K/AKT/mTOR signaling.

Upregulation of TUBG1 expression promotes hepatocellular carcinoma development.

Tubulin γ-1 (TUBG1) is a highly conserved component of the centrosome and its deregulation is involved in the development of several types of cancer. However, the role of TUBG1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TUBG1 was upregulated in human HCC cells and tissues and that TUBG1 upregulation was associated with promoter hypomethylation in HCC tissues. TUBG1 knockdown suppressed the proliferation, invasion, and migration of HCC cells. While TUBG1 expression was positively correlated with CD4 + memory T lymphocyte infiltration, it was negatively correlated with CD4 + regulatory T-cell infiltration in human HCC tissues. Furthermore, TUBG1 expression was positively correlated with the expression of genes involved in cell division. Noticeably, high expression of TUBG1 was associated with poor prognosis in patients with HCC. Overall, our findings revealed that TUBG1 promotes hepatocarcinogenesis by increasing proliferation, invasion, and migration of HCC cells and may regulate T lymphocyte infiltration. The current findings provide important insights into TUBG1 regulation in HCC, which could provide new therapeutic targets for hepatocarcinoma which has a very high incidence and mortality rate worldwide.

Resveratrol Enhances the Anti-Cancer Effects of Cis-Platinum on Human Cervical Cancer Cell Lines by Activating the SIRT3 Relative Anti-Oxidative Pathway.

Background: Cervical cancer exerts considerable mortality in the world. The combinations of chemotherapy with cis-platinum were the first-line treatment in late-stage cervical cancer but may cause severe adverse effects. Resveratrol (RES, 3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin, and it showed anti-cancer effects but with low toxicity and side effects. Herein, we examined the anti-cancer effects of cis-platinum combined with RES in human cervical cancer cell lines. Methods: The antiproliferative effect was examined by cell counting and short-term MTT assay. Cell apoptosis was detected. The cell cycle distribution was determined by flow cytometry. Intracellular reactive oxygen species and mitochondrial transmembrane potential change were observed and calculated by confocal microscopy. The Si-RNA interference of SIRT3 in cancer cells was performed. Protein expression was checked by Western blotting. Results: RES inhibited the growth of SiHa cell lines, and it significantly enhanced the cis-platinum-induced cell apoptosis and cell cycle arresting in 48 h. The activation of the SIRT3 relative anti-oxidative pathway was proved to be the reason for the enhanced anti-cancer effects of cis-platinum and RES combination. Si-RNA interference of SIRT3 compromised the anti-cancer effect of cis-platinum and RES combination. Furthermore, the silencing of SIRT3 RNA inhibited the expression of the anti-oxidant enzyme (MnSOD, GPx, SOD-1, and CAT) and decreased the generation of H2O2 in the cis-platinum and RES combination group. Conclusion: RES enhances the anti-cancer effects of cis-platinum on SiHa cells by activating the SIRT3 relative anti-oxidative pathway. RES may act as a potential synergistic agent and be useful in the treatment of cervical cancer.

Effect of cryopreservation on A172 and U251 glioma cells infected with lentiviral vectors designed for CRISPR/Cas9-mediated aquaporin-8 knock-out.

Among the three existing targeted gene editing technologies, zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9), the latter is widely used owing to its simplicity, efficiency, and low cost. Here, we routinely infected A172 and U251 cells with lentiviral vectors, in which aquaporin-8 (AQP8) was knocked out using CRISPR/Cas9. Our results indicated that cryopreservation did not significantly alter the viral infection efficiency, but influenced AQP8 expression in the infected cells at both protein and mRNA levels compared with the non-cryopreserved samples. Further, AQP8 expression at protein and mRNA levels in recovered cryopreserved infected cells did not significantly differ from those in the blank and negative controls, indicating that the lentivirus was still infectious at low temperatures. However, it failed to release the AQP8-targeting guide RNA in the infected cells, or the guide RNA was released, but underwent changes that caused it to malfunction in the cells with CRISPR/Cas9-mediated AQP8 knock-out. Our findings possibly provide some insights into the reliability of lentiviruses as CRISPR/Cas9 vectors.

ER Stress is Involved in Mast Cells Degranulation via IRE1α/miR-125/Lyn Pathway in an Experimental Intracerebral Hemorrhage Mouse Model.

The degranulation of mast cells accounts for the development of neuroinflammation following intracerebral hemorrhage (ICH). Inhibition of IRE1α, a sensor signaling protein related to endoplasmic reticulum stress, has been shown to exert anti-inflammatory effects in several neurological diseases. The objective of this study was to investigate the effects of IRE1α inhibition on mast cells degranulation in an ICH mouse model and to explore the contribution of miR-125/Lyn pathway in IRE1α-mediated mast cells degranulation. Male mice were subjected to ICH by intraparenchymal injection of autologous blood. STF083010, an inhibitor of IRE1α, was administered intranasally at 1 h after ICH induction. AntimiR-125 was delivered by intracerebroventricular (i.c.v.) injection prior to ICH induction to elucidate the possible mechanisms. Western blot analysis, immunofluorescence staining, neurological test, hematoma volume, brain water content, toluidine blue staining and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were performed. Endogenous phosphorylated IRE1α (p-IRE1α), tryptase, interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α) and tryptase mRNA were increased in time dependent manner while miR-125b-2-3p was decreased after ICH. Inhibition of IRE1α, with STF083010, remarkably reduced brain water content, improved neurological function, decreased hematoma volume, upregulated the expression of miR-125b-2-3p, decreased the number of mast cells, and downregulated the protein expression of Lyn kinase, XBP1s (spliced X-box binding protein-1), tryptase, IL-17A and TNF-α. The downregulation of Lyn kinase, tryptase, IL-17A, TNF-α, and decreased mast cells number were reversed by antimiR-125. The present findings demonstrate that IRE1α inhibition attenuates mast cells degranulation and neuroinflammation, at least partially, through IRE1α/miR-125/Lyn signaling pathway after ICH.

Clemastine Rescues Chemotherapy-Induced Cognitive Impairment by Improving White Matter Integrity.

With the improvement of cancer treatment techniques, increasing attention has been given to chemotherapy-induced cognitive impairment through white matter injury. Clemastine fumarate has been shown to enhance white matter integrity in cuprizone- or hypoxia-induced demyelination mouse models. However, whether clemastine can be beneficial for reversing chemotherapy-induced cognitive impairment remains unexplored. In this study, the mice received oral administration of clemastine after chemotherapy. The open-field test and Morris water maze test were used to evaluate their anxiety, locomotor activity and cognitive function. Luxol Fast Blue staining and transmission electron microscopy were used to detect the morphological damage to the myelin. Demyelination and damage to the mature oligodendrocytes and axons were observed by immunofluorescence and western blotting. Clemastine significantly improved their cognitive function and ameliorated white matter injury in the chemotherapy-treated mice. Clemastine enhanced myelination, promoted oligodendrocyte precursor cell differentiation and increased the neurofilament 200 protein levels in the corpus callosum and hippocampus. We concluded that clemastine rescues cognitive function damage caused by chemotherapy through improving white matter integrity. Remyelination, oligodendrocyte differentiation and the increase of neurofilament protein promoted by clemastine are potential strategies for reversing the cognitive dysfunction caused by chemotherapy.

Neuroglobin expression and function in the temporal cortex of bilirubin encephalopathy rats.

Bilirubin encephalopathy (BE) is a neurological syndrome in newborns, mainly caused by neuronal injury due to excessive oxidative stress produced by unconjugated bilirubin (UCB). Neuroglobin (NGB) can protect the brain by removing oxidative stress species, but its expression and significance in BE are not clear. To address this question, the neonatal BE model was established by injecting UCB into the cerebellomedullary cistern of 7-day-old SD rats. Rats were divided into a sham and BE 6 hr group, BE 12 hr group, BE 24 hr group, and BE 7 d group according to UCB action times. Hematoxylin/eosin and Nissl staining, and electron microscopy were employed to observe the pathological and ultrastructural changes of nerve cells in each group. Immunofluorescence staining was used to detect NGB expression sites and cell types. Western blotting and quantitative PCR served to detect NGB expression and test the mitochondrial apoptosis signal pathway. The results confirm that UCB can lead to pathological damage and ultrastructural changes in rats' temporal cortex, increasing the expression of apoptosis-related proteins Bax, Bcl-2, Cyt c, Caspase-3, and neuronal NGB. UCB promotes NGB expression with an increase in action time and reach a peak at 12 hr. In summary, brain damage induced by UCB will cause an increase in NGB expression, the increasing NGB can inhibit neuron apoptosis in early BE phases. Therefore, promoting the expression of endogenous NGB, to act as a neuroprotective agent may be a potential treatment strategy for BE.

[Comparative analysis of electroacupuncture, metformin and their combination on cognitive function and senile plaques of cerebral cortex and hippocampus in APP/PS1 mice].

OBJECTIVE: To compare the effect of electroacupuncture (EA), metformin and EA plus metformin on the cognitive ability and senile plaques (SPs) in cerebral cortex and hippocampus of Alzheimer's disease (AD) mice, so as to explore a better treatment method for AD. METHODS: Twenty-four male APP/PS1 mice were randomly divided into model, metformin (medication), EA and EA+medication groups, with 6 mice in each group. Other 6 male wild C57 mice were used as the control group. EA (2 Hz, 1.0 mA) was applied to "Baihui" (GV20) and "Shenshu" (BL23) for 15 min, once a day, for 4 weeks, with 1 day's off every week. The mice of the medication group received gavage of metformin (300 mg·kg-1·d-1) once a day for 4 weeks. Morris water maze tests were used to assess the cognitive function of mice. H.E. staining was used to observe the histopathological changes of neurons in the cortex and hippocampus. Immunohistochemical method was used to observe the cerebral cortex and hippocampal SPs. The expression levels of SPs formation-related proteins: ß-site amyloid precursor protein cleaving enzyme 1(ßACE1) and insulin-degrading enzyme (IDE) in the cortex and hippocampus were detected by Western blot. RESULTS: Compared with the control group, the escape latency, number of SPs and the expression of ßACE1 in the cortex and hippocampus were ob-viously increased (P<0.01), and the times of platform quadrant crossing and the expression of IDE protein were markedly decreased in the model group (P<0.01). In comparison with the model group, the escape latency, and the number of SPs and expression of ßACE1 proteins in the cortex and hippocampus in the 3 treatment groups were significantly down-regulated (P<0.01), while the times of platform quadrant crossing, and the expression of IDE protein in both cortex and hippocampus of the three treatment groups were considerably up-regulated (P<0.01). Comparison among the three treatment groups showed that the therapeutic effect of EA+medication was significantly superior to that of medication and simple EA in down-regulating the escape latency, the number of SPs and expression of ßACE1 in the cortex and hippocampus (P<0.01), and in up-regulating the times of the platform quadrant crossing, and expression of IDE protein in both cortex and hippocampus (P<0.01). No significant differences were found between the simple medication and simple EA in all the indexes mentioned above (P>0.05). CONCLUSION: EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of ßACE1 and up-regulating the expression of IDE. The therapeutic effects of EA plus metformin are apparently better than those of simple EA and simple metformin.

Small Interfering RNA Targeting DMP1 Protects Mice Against Blood-Brain Barrier Disruption and Brain Injury After Intracerebral Hemorrhage.

Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment.