The cognitive appraisal path of stroke knowledge, coping traits, family functioning and stigma among stroke patients: A moderated parallel mediation model.

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.

Ecological model of health behaviour of hypertensive stroke patients at the end of recovery period.

AIMS AND OBJECTIVES: This study aimed to construct a structural equation model guided by the ecological model to explore the factors influencing health behaviour among hypertensive stroke patients 6 months post-stroke. BACKGROUND: Health behaviour is important for recurrence prevention in hypertensive stroke patients. Moreover, previous studies have indicated that health behaviour at the end of the recovery period is of particular concern. The ecological model provides an integrated perspective for explaining the factors influencing health behaviour. DESIGN: A cross-sectional study guided by the STROBE. METHODS: A total of 121 hypertensive stroke patients were included to assess stroke knowledge, health belief, depression, family function, chronic illness resource and health behaviour. A structural equation model was used to explore the health behaviour's factors and pathways. RESULTS: In the final ecological model, sex, education level, depression and chronic illness resource directly affected health behaviour. Stroke knowledge directly affected health behaviour and indirectly affected health behaviour through health belief and chronic illness resource. Family function indirectly affected health behaviour through health belief, depression and chronic illness resource. Health belief affected health behaviour indirectly through depression and chronic illness resource. CONCLUSIONS: Hypertensive stroke patients' health behaviour is jointly and interactively influenced by stroke knowledge, health belief, depression, family function and chronic illness resource. In particular, chronic illness resource is an important mediator of health behaviour. RELEVANCE TO CLINICAL PRACTICE: For clinical practitioners, health behaviour of men and patients with low educational levels should be specifically focused on. Additionally, it is necessary to provide stroke knowledge, establish health beliefs, control depression emotion and improve family function. Furthermore, chronic illness resources should be improved particularly due to its important mediating role. PATIENT OR PUBLIC CONTRIBUTION: Participants completed demographic and disease-related questionnaires during hospitalisation and completed other questionnaires when returning to hospital at 6 months follow-up.

Comparisons of Stroke Knowledge and Health Behaviors in Patients With Hypertensive Stroke at Different Recurrence Risk Strata: The Comprehensive Reminder System Based on the Health Belief Model Study.

BACKGROUND: Risk factor management via behavioral change contributes substantially to secondary stroke prevention. The health belief model identified self-perceived risk as a significant factor in behavior change. In previous studies, people have tended to incorrectly estimate their risk of stroke. Little is known about the differences in stroke knowledge and health behaviors in patients who have had a stroke with different risks of stroke recurrence in China. OBJECTIVE: The aims of this study were to determine the accuracy of self-perceived risk of stroke recurrence and to compare stroke knowledge and health behaviors in patients with hypertensive stroke at different recurrence risk strata. METHODS: Baseline data from 174 patients in the Comprehensive Reminder System based on the Health Belief Model (CRS-HBM) study were used. Self-perceived risk was assessed via the susceptibility subcategory of the Short-Form Health Belief Model Scale, and actual risk was stratified using the Essen Stroke Risk Score. RESULTS: Only 27.0% of the patients estimated their risks of stroke recurrence accurately. Patients who perceived themselves to be at higher risk had better knowledge of warning signs. Compared with patients who underestimated their risk of stroke recurrence, those who accurately estimated or overestimated their risk less likely to smoke. CONCLUSIONS: Most patients incorrectly estimated their risk of stroke recurrence. Communicating with patients about their future risk of recurrent stroke may help improve their stroke knowledge and health behaviors. Implementation of the Comprehensive Reminder System based on the Health Belief Model focusing on risk education aimed at prevention of stroke recurrence is warranted in China.

Rosmarinic acid ameliorates acetaminophen-induced acute liver injury in mice via RACK1/TNF-α mediated antioxidant effect.

CONTEXT: Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. OBJECTIVE: This study explores the RA protective effect on APAP-induced ALI and its mechanism. MATERIALS AND METHODS: Sixty Kunming mice 6-8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. RESULTS: Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p < 0.05), AST (114.78 ± 19.87, 115.29 ± 31.91, 101.78 ± 21.85 U/L, p < 0.05), MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-α expression decreased. Moreover, the RACK1 and TNF-α levels were positively correlated with MDA (r = 0.8453 and r = 0.9391, p < 0.01). DISCUSSION AND CONCLUSIONS: Our findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-α pathway.

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis.

Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF-ß1. RACK1 is the downstream target gene of TGF-ß1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS-2B cells were cultured and exposed to recombinant soluble human TGF-ß1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA-challenged mice, as well as TGF-ß1-induced apoptosis and EMT of BEAS-2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF-ß1 up-regulated EMT related protein levels (N-cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF-ß1-induced N-cadherin and Snail up-regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF-ß1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF-ß1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

Effects of a Comprehensive Reminder System Based on the Health Belief Model for Patients Who Have Had a Stroke on Health Behaviors, Blood Pressure, Disability, and Recurrence From Baseline to 6 Months: A Randomized Controlled Trial.

BACKGROUND: The health behaviors and blood pressure control of patients with hypertension who have had a stroke are unsatisfactory. A protocol of a comprehensive reminder system has been published, and the results of 3 months of implementation have demonstrated improved patient health behaviors and blood pressure control. The continuity of the intervention effect on these variables after 3 months was not clear. OBJECTIVE: The aim of this study was to determine the impact of a comprehensive reminder system intervention on health behaviors, medication adherence, blood pressure, disability, and stroke recurrence in patients with hypertension who have had a stroke from baseline to 6 months after discharge. METHOD: A multicenter, assessor-blinded, randomized controlled trial was conducted with 174 patients with hypertension who have had a stroke. The intervention consisted of health belief education, a calendar handbook, weekly short message services, and telephone interviews. Data were collected at baseline and at 3 and 6 months after discharge. RESULTS: Repeated-measures analysis of variance and single-effect analysis revealed that, compared with the control group, improvements of health behaviors, medication adherence, blood pressure, and disability of participants in the intervention group were superior. From 3 to 6 months after discharge, these trends remained or continually improved, whereas a downward trend was observed in the control group. There were only 2 stroke recurrences within 6 months, and no statistically significant difference between groups was found. CONCLUSION: The comprehensive reminder system improved patients' health behaviors and medication adherence and reduced blood pressure and disability; the effect extended to 6 months after discharge.

Factors influencing health behaviour, blood pressure control, and disability in hypertensive ischaemic stroke patients after a comprehensive reminder intervention.

AIMS: To test prospective pathways of a Comprehensive Reminder System based on the Health Belief Model (CRS-HBM), stroke knowledge, health belief in health behaviour, blood pressure (BP) control, and disability in hypertensive ischaemic stroke patients at 6-month postdischarge. DESIGN: A nested cohort study design. METHODS: Data were derived from a randomized controlled trial evaluating the effects of the intervention (N = 174, performed during February 2015 - March 2016). Data were collected by questionnaires and analysed in structural equation modelling in Mplus software. RESULTS: The proposed model provided a good fit to the data. This model accounted for 51.5% of the variance in health behaviour, 34.1% in BP control, and 5.7% in modified Rankin Scale score at 6-month postdischarge. The CRS-HBM had: (a) direct positive effect (ß = .391, p < .001) and indirect positive effects (ß = .186, p = .002) on health behaviour; (b) direct positive effect (ß = .356, p < .001) and indirect positive effects (ß = .183, p = .009) on BP control; and (c) indirect negative effect (ß = -.146, p = .008) on disability. Being female was linked to better health behaviour. Higher education predicted higher level of stroke knowledge and health belief. CONCLUSIONS: The CRS-HBM can not only directly but also indirectly improve patients' health behaviours by improving their health knowledge or health belief. Better health behaviour can improve patients' BP control and reduce disability. Therefore, nurses need to pay more attention to not only patients' health knowledge but also their health belief when providing education. IMPACT: The CRS-HBM intervention accounted for 51.5% of variance in health behaviour, 34.1% in BP control, and 5.7% in modified Rankin Scale score at 6-month postdischarge. This research can help nurses improve health education strategies in postdischarge and community contexts to achieve better health results.

Association Between Medication Adherence and Admission Blood Pressure Among Patients With Ischemic Stroke.

BACKGROUND: Poor medication adherence is one of the most important factors underlying uncontrolled blood pressure, and ensuing hypertension is the leading risk factor for stroke. However, the influence of prestroke medication nonadherence on the admission blood pressure of patients with hypertension who have had an ischemic stroke remains unclear. OBJECTIVE: The aims of this study were to explore the influence of medication nonadherence on the admission blood pressure of patients with hypertension who have had an ischemic stroke and to analyze the reasons for medication nonadherence preceding stroke. METHODS: A sample population of 301 patients with hypertension who have had an ischemic stroke was recruited. A questionnaire was used to investigate sociodemographic data and reasons for nonadherence. The 4-item Medication Adherence Scale was used to investigate prestroke medication adherence. Blood pressure was measured upon patient admission. Logistic regression analysis was used to identify factors influencing adherence. RESULTS: In this cohort, 80.73% of the patients exhibited uncontrolled blood pressure on admission, and 26.58% had undiagnosed hypertension. Of the patients aware of their diagnosis, 75.11% were nonadherent and 10.40% had never used antihypertensive medicines. Uncontrolled admission blood pressure was positively influenced by medication nonadherence. The main causes of nonadherence included forgetfulness (58.08%), lack of belief in the need for long-term antihypertensive treatment (27.27%), and no awareness of the importance of long-term medication (24.75%). CONCLUSIONS: Stroke education in China should focus on patients' poor understanding of the importance for sustained antihypertensive medication adherence to improve blood pressure control and prevent stroke.

The Efficacy of a Comprehensive Reminder System to Improve Health Behaviors and Blood Pressure Control in Hypertensive Ischemic Stroke Patients: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The health behaviors of hypertensive stroke patients in China are not satisfactory. In this study, we tested the effect of a Health Belief Model Comprehensive Reminder System on health behaviors and blood pressure control in hypertensive ischemic stroke patients after occurrence and hospital discharge. METHODS: A randomized, parallel-group, assessor-blinded experimental design yielded participation of 174 hospitalized hypertensive ischemic stroke patients. The intervention consisted of face-to-face and telephone health belief education, a patient calendar handbook, and weekly automated short-message services. Data were collected at baseline and 3 months after discharge. RESULTS: Three months after discharge, the intervention group showed statistically, significantly better health behaviors for physical activity, nutrition, low-salt diet, and medication adherence. The intervention group also had statistically, significantly decreased systolic blood pressure and increased blood pressure control rate. Smoking and alcohol use behaviors were not affected. CONCLUSION: At 3 months, use of the Comprehensive Reminder System based on the Health Belief Model, yielded improvement in most health behaviors and blood pressure control in hypertensive ischemic stroke patients. Continued implementation of this intervention protocol is warranted to determine the long-term effect. Smoking and alcohol use behaviors need to be targeted with a different intervention.

Screening of lipase inhibitors from Scutellaria baicalensis extract using lipase immobilized on magnetic nanoparticles and study on the inhibitory mechanism.

Scutellaria baicalensis is a traditional Chinese medicinal plant possessing a wide variety of biological activities. In this work, lipase immobilized on magnetic nanoparticles (LMNPs) was used as solid phase extract absorbent for screening of lipase inhibitors from this plant. Three flavonoids were found to bind to LMNPs and were identified as baicalin, wogonin, and oroxylin A by liquid chromatography-mass spectrometry (HPLC-MS). Their IC50 values were determined to be 229.22 ± 12.67, 153.71 ± 9.21, and 56.07 ± 4.90 µM, respectively. Fluorescence spectroscopy and molecular docking were used to probe the interactions between these flavonoids and lipase. All the flavonoids quenched the fluorescence of lipase statically by forming new complexes, implying their affinities with the enzyme. The thermodynamic analysis suggested that van der Waals force and hydrogen bond were the main forces between wogonin and lipase, while hydrophobic force was the main force for the other two flavonoids. The results from a molecular docking study further revealed that all of them could insert into the pocket of lipase binding to a couple of amino acid residues.

The effectiveness of a comprehensive reminder system in the secondary prevention of hypertensive ischaemic stroke: randomized controlled trial protocol.

AIM: The aim of this study was to determine whether the Comprehensive Reminder System based on the Health Belief Model improves health belief, health behaviours, medication adherence and blood pressure control as a means of decreasing the rate of stroke recurrence among hypertensive ischaemic stroke. BACKGROUND: Hypertensive patients having experienced recent ischaemic strokes are at high risk for stroke recurrence. Several trials attempted to improve secondary stroke prevention via patient education, however, patient outcomes remained poor. Long-term follow-up studies regarding secondary stroke prevention are limited. DESIGN: A multi-centre, 12-month, assessor-blinded, parallel-group, randomized controlled longitudinal trial. METHODS: Hypertensive patients having experienced an ischaemic stroke are the target population. The intervention consists of health belief education, a calendar handbook, a weekly automated short-message service and four telephone follow-up interviews. Outcomes will be assessed at baseline and at 3, 6 and 12 months following discharge. The primary outcome is blood pressure control. The secondary outcomes include health belief, health behaviours and medication adherence. The clinical endpoint is the rate of stroke recurrence. DISCUSSION: Although many efforts to improve secondary stroke prevention have been undertaken, research indicates that improvements remain possible and warranted. This research protocol based on the Health Belief Model will improve our understanding of stroke education and transitional care needed in China and with the world-wide target population.

Effectiveness of Goal-Setting Telephone Follow-Up on Health Behaviors of Patients with Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND: Adopting healthy behaviors is critical for secondary stroke prevention, but many patients fail to follow national guidelines regarding diet, exercise, and abstinence from risk factors. Compliance often decreases with time after hospital discharge, yet few studies have examined programs promoting long-term adherence to health behaviors. Goal setting and telephone follow-up have been proven to be effective in other areas of medicine, so this study evaluated the effectiveness of a guideline-based, goal-setting telephone follow-up program for patients with ischemic stroke. METHODS: This was a multicenter, assessor-blinded, parallel-group, randomized controlled trial. Ninety-one stroke patients were randomized to either a control group or an intervention group. Intervention consisted of predischarge education and 3 goal-setting follow-up sessions conducted by phone. Data were collected at baseline and during the third and sixth months after hospital discharge. RESULTS: Six months after discharge, patients in the intervention group exhibited significantly higher medication adherence than patients in the control group. There were no statistically significant differences in physical activity, nutrition, low-salt diet adherence, blood pressure monitoring, smoking abstinence, unhealthy use of alcohol, and modified Rankin Scale (mRS) scores between the 2 groups. CONCLUSIONS: Goal-setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence. However, the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline-recommended targets.

Compound danshen tablet ameliorated aß25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.

BACKGROUND: Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aß25-35-induced cognitive impairment in mice. METHODS: Mice were randomly divided into 5 groups: the control group (sham operated), the Aß25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aß25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aß25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. RESULTS: The results showed that Aß25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aß25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. CONCLUSION: These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.

Stroke prevention knowledge and prestroke health behaviors among hypertensive stroke patients in mainland China.

BACKGROUND AND OBJECTIVES: Individuals with hypertension are at risk of stroke, and patients with stroke histories are at risk of experiencing another stroke. At this time, however, only a few studies have reported on stroke prevention knowledge and health behaviors among hypertensive patients who have had an initial stroke. The purpose of this study was to determine stroke prevention knowledge and health behaviors and to analyze the association between these 2 variables among hypertensive stroke patients who have had an initial stroke. SUBJECTS AND METHODS: With the use of a descriptive correlational design, a sample of 112 hypertensive stroke patients was recruited from the departments of neurology of 3 hospitals in Guangzhou, China. Each patient completed 2 reliable, validated questionnaires, the Stroke Prevention Knowledge Questionnaire and the Health Promoting Lifestyle Profile II. Data were collected during patients' hospital admission for stroke, within 2 days of stroke onset, and before they received stroke education. Pearson correlation coefficient was used to examine the correlations between the study variables. Multiple stepwise regression analysis was used to predict both the level of knowledge relating to stroke prevention and health behaviors. RESULTS AND CONCLUSIONS: The participants showed a relatively low level of stroke prevention knowledge and a moderate level of engagement in healthy behaviors. Pearson correlation coefficient between these 2 variables was 0.423 (P < .001). The results of multiple regression analysis showed that stroke prevention knowledge was positively influenced by education level; health behaviors were positively influenced by both gender and stroke prevention knowledge. Findings suggest that male hypertensive patients and those with a lower education level need targeted stroke education. Because knowledge was unrelated to behavior with respect to smoking, alcohol use, and low-salt diet, behavioral interventions should be explored to address these important risk factors among patients at risk for stroke.

Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis.

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.

Rosmarinic acid against cognitive impairment via RACK1/HIF-1α regulated microglial polarization in sepsis-surviving mice.

Microglial polarization modulation has been considered the potential therapeutic strategy for relieving cognitive impairment in sepsis survivors. Rosmarinic acid (RA), a water-soluble polyphenolic natural compound, processes a strong protective effect on various types of neurological disorders including Parkinson's disease, depression, and anxiety. However, its role and potential molecular mechanisms in sepsis-associated cognitive impairment remain unclear. To investigate the preventive and therapeutic effect of RA on sepsis-associated cognitive impairment and elucidate the potential mechanism of RA on regulating microglial polarization, we established a CLP-induced cognitive impairment model in mice and a lipopolysaccharide-induced microglia polarization cell model in BV-2. RACK1 siRNA was designed to identify the potential molecular mechanism of RACK1 on microglial polarization. The preventive and therapeutic effect of RA on cognitive impairment followed by PET-CT and behavioral tests including open-field test and tail suspension test. RACK1/HIF-1α pathway and microglial morphology in the hippocampus or BV-2 cells were measured. The results showed that RA significantly ameliorated the CLP-induced depressive and anxiety-like behaviors and promoted whole-brain glucose uptake in mice. Moreover, RA markedly improved CLP-induced hippocampal neuron loss and microglial activation by inhibiting microglial M1 polarization. Furthermore, experiments showed RACK1 was involved in the regulation of LPS-induced microglial M1 polarization via HIF-1α, and RA suppressed lipopolysaccharide or sepsis-associated microglial M1 polarization via RACK1/HIF-1α pathway (rescued the decrease of RACK1 and increase of HIF-1α). Taken together, RA could be a potential preventive and therapeutic medication in improving cognitive impairment through RACK1/HIF-1α pathway-regulated microglial polarization.

Azithromycin suppresses TGF-ß1-related epithelial-mesenchymal transition in airway epithelial cells via targeting RACK1.

Transforming growth factor-ß1 (TGF-ß1) associated epithelial-mesenchymal transition (EMT) contributes to multiple respiration diseases via Smad or MAPKs pathway. Our previous study has demonstrated that the typical macrolide antibiotic, azithromycin (AZM) played a notable anti-EMT role in ovalbumin (OVA)-challenged mice. However, the precise mechanism of AZM on TGF-ß1 mediated EMT in bronchial epithelial cells is still unclear. The purpose of this study was to elucidate whether azithromycin targeting RACK1 inhibits TGF-ß1 mediated EMT in vitro. The results showed that AZM significantly inhibited the expression of RACK1 and the activation of the downstream JNK, ERK, and Smad3 signaling pathways, thereby suppressing the migration of bronchial epithelial cells and reversing the TGF-ß1-induced EMT. The effect of AZM on TGF-ß1 mediated EMT in vitro is dependent on the dose of AZM. Although RACK1 has been shown to regulate IRE1α expression with siRACK1 transfection, there was no direct interaction between IRE1α and AZM. On the contrary, weak interaction between AZM and RACK1 was predicted with molecular docking. In summary, AZM targets RACK1 to trigger downstream JNK, ERK, and Smad3 signaling pathways and is an effective anti-EMT drug for bronchial epithelial cells in a dose-dependent manner.

Effects of a digital learning platform on health behaviours in stroke patients from baseline to 6 months after discharge: a randomized controlled trial.

AIMS: Improving the health behaviour can help prevent stroke recurrence. The existing health education interventions require more human resource. There is a lack of constructing a low-cost, highly universal, and easy-to-use stroke secondary prevention platform based on the existing medical resources. METHODS AND RESULTS: This was a randomized controlled trial to test the effects of a digital learning platform on the health knowledge, beliefs, and behaviours of stroke patients from baseline to 6 months after discharge. The control group received routine health education while the intervention group received health belief education during hospitalization and used a digital learning platform for 6 months after discharge. The health knowledge was assessed by The Stroke Health Knowledge Questionnaire, health beliefs by The Short Form Health Belief Model Scale for Stroke Patients, and health behaviours by the Stroke Health Behavior Scale. A total of 90 patients were included: 45 each in the intervention group and the control group, of whom 38 and 37 completed the study, respectively. At 6 months after discharge, (1) the health knowledge score of the intervention group was insignificantly higher than that of the control group, (2) the health belief score of the intervention group was significantly higher than that of the control group, and (3) the intervention group had higher health behaviour scores especially in physical activity than that of the control group. Other health behaviour dimensions have time effect, but not significant. CONCLUSIONS: The digital learning platform can improve health behaviours of stroke patients 6 months after discharge, especially in physical activity. REGISTRATION: ChiCTR1800019936.

rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice.

Ferroptosis plays a critical role in LPS-induced acute lung injury and is modulated by endoplasmic reticulum stress (ERS). As a typical ER stress-responsive protein, recently mesencephalic astrocyte-derived neurotrophic factor (MANF) has been demonstrated to attenuate LPS-induced acute lung injury (ALI) through repressing macrophage activation. However, whether MANF exerts a preventive role on ferroptosis and excess ER stress remains unclear. Here, we first built a protein-protein interaction (PPI) network to obtain potential interacting proteins related to MANF through STRING and GeneMANIA. Then, male C57BL/6J mice were used to build a model of LPS-induced lung injury. Two days before LPS injection, the tail vein injected recombinant murine MANF (rmMANF) at 750 µg/kg. Twenty-four hours after the LPS injection, the histopathological changes and damage in the lung tissues were detected and scored by HE staining and TUNEL assay, respectively. Endogenous MANF levels, oxidative stress markers (GSH, SOD, CAT, and MDA), ERS markers (GRP78, PERK, and ATF4), and the ferroptosis markers (iron, GPX4, and 4-HNE) in the lung tissues were measured by IHC, western blotting, and commercial kits. Our results showed that LPS induced significant lung injury to the increase in MPO, MDA, and 4-HNE, a decrease in GPX4 and GSH, SOD, CAT, and total iron accumulation in LPS-exposed mice. Simultaneously, GRP78/PERK/ATF4 pathway was notably activated by LPS, accompanied by the down-regulation of MANF. Furthermore, rmMANF pretreatment markedly prevented LPS-induced lung tissue injury and ferroptosis characteristics with the increased GPX4 level in sepsis mice. Finally, we found that LPS-induced oxidative stress and activation of the GRP78/PERK/ATF4 pathway were significantly restrained by rmMANF pretreatment, except for endogenous MANF level. Overall, rmMANF pretreatment can prevent sepsis-associated lung injury by inhibiting ER stress-induced ferroptosis in mice.

Relationship of family function and pre-hospital delay among Chinese patients with recurrent ischaemic stroke and the mediation effect of stigma.

AIMS: Pre-hospital delay refers to the time span from the onset of symptoms to arrival at a hospital ≥ 3 h and is the main limitation of stroke reperfusion therapies. Family factors and stroke-related stigma may influence pre-hospital delay. However, few studies have confirmed the influence of stigma on pre-hospital delay or explored the relationships between family function, stigma, and pre-hospital delay among patients with recurrent stroke. This study aimed to explore the relationship between family function and pre-hospital delay among patients with recurrent stroke and examine the mediation role of stigma in this relationship. METHODS AND RESULTS: A cross-sectional study was performed at the neurology departments of two hospitals in Guangzhou, China between July 2021 and April 2022. A total of 115 patients with recurrent stroke completed questionnaires and were included in the analysis. Data were collected using the Short Form Family Assessment Device, the Stroke Stigma Scale, and the Stroke Knowledge Questionnaire. Spearman's correlation and a structural equation model were used for data analysis. Family function directly influenced pre-hospital delay [ß=0.27, P = 0.033, 95%CI = (0.02-0.51)] and indirectly influenced pre-hospital delay [ß=0.17, P = 0.038, 95%CI = (0.02-0.34)] through stigma. Moreover, stigma partially mediated the effect of family function on pre-hospital delay. CONCLUSION: Family function and stigma directly and indirectly influenced pre-hospital delay among patients with recurrent stroke. Future health education and interventions need to focus on strengthening and improving emotional support from family members to improve family function and reduce stigma, thereby reducing pre-hospital delay among patients with recurrent stroke.