Progress of Exosomal MicroRNAs and Traditional Chinese Medicine Monomers in Neurodegenerative Diseases.

Exosomes, extracellular vesicles secreted by various cells, actively participate in intercellular communication by facilitating the exchange of crucial molecular information such as DNA, RNA, and lipids. Within this intricate network, microRNAs, endogenous non-coding small RNAs, emerge as pivotal regulators of post-transcriptional gene expression, significantly influencing the development of neurodegenerative diseases. The historical prominence of traditional Chinese medicine (TCM) in clinical practice in China underscores its enduring significance. Notably, TCM monomers, serving as active constituents within herbal medicine, assume a critical role in the treatment of neurodegenerative diseases, particularly in mitigating oxidative stress, inhibiting apoptosis, and reducing inflammation. This comprehensive review aims to delineate the specific involvement of exosomal microRNAs in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. Furthermore, the exploration extends to the application of TCM monomers, elucidating their efficacy as therapeutic agents in these conditions. Additionally, the review examines the utilization of exosomes as drug delivery carriers in the context of neurodegenerative diseases, providing a nuanced understanding of the potential synergies between TCM and modern therapeutic approaches. This synthesis of knowledge aims to contribute to the advancement of our comprehension of the intricate molecular mechanisms underlying neurodegeneration and the potential therapeutic avenues offered by TCcom interventions.

Effectiveness of Cold Therapy for Pain and Anxiety Associated with Chest Tube Removal: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effectiveness of cold therapy for pain and anxiety associated with chest tube removal. DESIGN: A Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Articles were searched from Cochrane Library, PubMed, Embase, CINAHL, ProQuest, Airiti Library, China National Knowledge Infrastructure, and the National Digital Library of Theses and Dissertations in Taiwan. REVIEW/ANALYSIS METHODS: Eight electronic databases were searched from inception to August 20, 2022. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of the included studies. Using a random-effects model, we calculated Hedges' g and its associated confidence interval to evaluate the effects of cold therapy. Cochrane's Q test and an I2 test were used to detect heterogeneity, and moderator and meta-regression analyses were conducted to explore possible sources of heterogeneity. Publication bias was assessed using a funnel plot, Egger's test, and trim-and-fill analysis. RESULTS: We examined 24 trials involving 1,821 patients. Cold therapy significantly reduced pain during and after chest tube removal as well as anxiety after chest tube removal (Hedges' g: -1.28, -1.27, and -1.80, respectively). Additionally, the effect size of cold therapy for reducing anxiety after chest tube removal was significantly and positively associated with that of cold therapy for reducing pain after chest tube removal. CONCLUSIONS: Cold therapy can reduce pain and anxiety associated with chest tube removal.

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.

A Review of Research on the Association between Neuron-Astrocyte Signaling Processes and Depressive Symptoms.

Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal-astrocyte signaling processes and depressive symptoms.

[Vitamin D level in umbilical cord blood of late preterm infants and the effect of vitamin D3 supplementation on the behavioral development of infants and young children: a prospective randomized controlled study]. / æ™šæœŸæ—©äº§å„¿è„è¡€ç»´ç”Ÿç´ Dæ°´å¹³åŠç»´ç”Ÿç´ D3è¡¥å å¯¹å©´å¹¼å„¿è¡Œä¸ºå‘è‚²çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D3 supplementation on the neurobehavioral development of infants and young children. METHODS: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group (n=52), insufficiency group (n=53), and deficiency group (n=56). Each group was further divided into subgroup A (vitamin D3 800 IU/d) and subgroup B (individualized vitamin D3 supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months. RESULTS: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group (P<0.05), and the insufficiency group had a significantly higher level of 25(OH)D than the deficiency group (P<0.05). In the deficiency group, subgroup B had a significantly higher level of 25(OH)D than subgroup A (P<0.05) at 3 months after birth. At the corrected ages of 10 months and 18 months, the insufficiency and deficiency groups had significantly lower scores of five functional areas of the Gesell Development Scale than the sufficiency group (P<0.05). Compared with the insufficiency group, the deficiency group had a significantly lower score of language at the corrected age of 10 months and a significantly lower score of gross motor at the corrected age of 18 months (P<0.05). Compared with subgroup A of the deficiency group, subgroup B had a significantly higher score of adaptive ability at the corrected age of 10 months and significantly higher scores of adaptive ability and response ability at the corrected age of 18 months (P<0.05). CONCLUSIONS: There is a significant difference in the level of 25(OH)D in umbilical cord blood in late preterm infants. Individualized vitamin D supplementation appears to be more effective for the treatment of vitamin D deficiency. Vitamin D level at birth and in early infancy has certain influence on neurobehavioral development.

Using phage-assisted continuous evolution (PACE) to evolve human PD1.

PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer therapies, including predictors of response, patient selection, and innate resistance. Thus, a competitive antagonist of native PD1/PDL1, with smaller size and lower side-effect, is required for future cancer therapies. In this study, we utilized a protein evolution system of phage-assisted continuous evolution (PACE) to evolve PD1 continuously. Our results indicated that the newly evolved PD1 bound to PDL1 with higher affinity. The interactome analysis further suggested that these evolved PD1s exhibited higher specificity with PDL1. Therefore, these evolved PD1s may be applied as a new tool for tumor immunotherapy.

Mechanisms and Effects of Health Coaching in Patients With Early-Stage Chronic Kidney Disease: A Randomized Controlled Trial.

PURPOSE: To examine the effects of health coaching on self-management and quality of life (QOL) in patients with chronic kidney disease (CKD) and to evaluate whether self-efficacy and patient activation mediate the effect of health coaching on self-management and QOL. DESIGN AND METHODS: A single-center, parallel-group, randomized controlled trial. A total of 108 patients with stages 1 to 3a CKD participated in the study. Participants were randomly assigned to a health-coaching intervention group or a usual care control group. Participants' QOL (World Health Organization Quality of Life Scale), self-management (CKD Self-Management instrument), patient activation (Patient Activation Measure), and self-efficacy (CKD Self-Efficacy instrument) were measured at baseline, immediately after, and 6 weeks after the intervention. FINDINGS: Health coaching improved QOL, self-management, patient activation, and self-efficacy at postintervention and at 12 weeks' follow-up. Health coaching had a significant indirect effect on QOL through improvements in patient activation. Health coaching exerted a significant indirect effect on self-management through improvements in self-efficacy and patient activation. CONCLUSIONS: The findings demonstrated that health coaching can effectively improve QOL and self-management. A health-coaching intervention can raise self-efficacy and activation levels through which self-management and QOL further improve. CLINICAL RELEVANCE: Health-coaching strategies can be used to assist patients with early-stage CKD in reaching their health goals and becoming activated in self-management of their diseases.

Psychometric Properties and Factorial Structure of Vietnamese Version of the Hypertension Self-care Profile Behavior Scale.

BACKGROUND: The Hypertension Self-care Profile Behavior (HTN-SCPB) scale is a self-report instrument with which a patient's self-care behavior can be assessed. However, its psychometric properties for adult patients with hypertension in Vietnam require clarification. OBJECTIVE: The aim of this study was to translate the HTN-SCPB scale into Vietnamese and to assess its psychometric properties. METHODS: The study included 220 adult patients with hypertension. To evaluate test-retest reliability, 133 participants were tested twice with a 3-week interval between tests. For construct validity, exploratory factor analysis was used to assess factor structure, and confirmatory factor analysis was used to evaluate the structural model fit of the scale. RESULTS: Reliability was confirmed by internal consistency (Cronbach α = 0.79) and test-retest reliability (intraclass correlation coefficient, 0.88). The Kaiser-Meyer-Olkin value was 0.75, and Bartlett's test of sphericity was significant (P < .001) and adequate for exploratory factor analysis. A 5-factor structure was obtained, and the factors were named as follows: "advanced self-management skills," "adverse health behaviors," "medication adherence," "diet-related knowledge regarding hypertension," and "information skills." Confirmatory factor analysis revealed that the model fit indices were acceptable (root-mean-square error of approximation, 0.07) or slightly less than the good fit values (comparative fit index, 0.85; incremental fit index, 0.85; goodness-of-fit index, 0.88; adjusted goodness-of-fit index, 0.84; and Tucker-Lewis index, 0.82). CONCLUSIONS: The Vietnamese HTN-SCPB scale had satisfactory validity and reliability for assessing self-care behaviors in patients with hypertension in Vietnam.

Effects of self-management programs on blood pressure, self-efficacy, medication adherence and body mass index in older adults with hypertension: Meta-analysis of randomized controlled trials.

AIM: To assess the effects of self-management interventions on systolic blood pressure, diastolic blood pressure, self-efficacy, medication adherence and body mass index in older adults with hypertension. BACKGROUND: Effective treatment of hypertension may require the practice of self-management behaviours. However, evidence on effects of self-management interventions on blood pressure, self-efficacy, medication adherence and body mass index in older adults with hypertension is lacking. DESIGN: A systematic review and meta-analysis. DATA SOURCES: CINAHL, Cochrane Library, Embase, Ovid-Medline, PubMed, Scopus, Web of Science and other sources were searched to October 2020. REVIEW METHODS: Data were analysed using Comprehensive Meta-Analysis 2.0 and quality assessment was done using ROB 2.0. The pooled effect sizes were reported as Hedges' g values with corresponding 95% confidence intervals using a random-effects model. RESULTS: Twelve randomized controlled trials met our inclusion criteria. The results revealed that self-management interventions significantly decreased blood pressure and increased self-efficacy and medication adherence in older adult patients with hypertension, with no significant effect on body mass index. CONCLUSIONS: Self-management interventions have considerable beneficial effects in older adults with hypertension. Health care providers should implement self-management interventions to strengthen the patient's role in managing their health.

Alternate healthy eating index and risk of depression: A meta-analysis and systemematic review.

Objective: The alternate healthy eating index has been associated with depression. However, results reported in the literature are inconsistent. The present meta-analysis determined the association between the AHEI or AHEI-2010 and depression in adults without chronic disease.Methods: Nine electronic databases and the reference lists of identified studies were systematically searched for studies published up to December 2016. Articles examining the association between depression and the AHEI or AHEI-2010 in adults were included.Results: We identified eight observational studies with 10 effect sizes involving a total of 38,360 participants. When both the AHEI and AHEI-2010 were considered, the dietary index score was associated with a significant reduction in depression risk (odds ratio OR=0.70, 95% confidence interval CI=0.57-0.87). However, the subgroup analysis indicated that the AHEI-2010 (OR=0.69, 95% CI=0.56-0.89), but not the AHEI (OR=0.60, 95% CI=0.30-1.17), was significantly associated with reduced odds of depression. The heterogeneity among the included studies was significantly high (Q=48.9, P<0.01, I2=81.60%).Discussion: Our findings suggest that the AHEI-2010 is associated with a reduction in depression risk. However, well-designed randomized controlled trials must be conducted to confirm the causal relationship between the AHEI-2010 and depression.

Quantitative analysis of multicomponents by single marker combined with HPLC fingerprint qualitative analyses for comprehensive evaluation of Aurantii Fructus.

The present study aimed to develop a strategy involving quantitative analysis of multicomponents by single marker in combination with high-performance liquid chromatography fingerprint qualitative analysis for performing the quality control of Aurantii Fructus. The content of 12 components (eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, meranzin, poncirin, naringenin, nobiletin, tangeretin, and auraptene) in samples was determined using reliable relative correction factors that were obtained using naringin as an internal reference standard. The new method demonstrated good applicability, and no significant differences were observed between the external standard method and the new method as determined by calculating standard method difference. Qualitative evaluation of samples was conducted using similarity analysis, hierarchical cluster analysis, and quality fluctuation analysis. Chromatographic fingerprint data were divided into three groups by similarity and hierarchical cluster analyses, and seven components may have a more significant impact on the quality of Aurantii Fructus in quality fluctuation analysis. Overall, the study suggests that the qualitative and quantitative analyses of multicomponents using quantitative analysis of multicomponents by single marker combined with chromatographic fingerprinting can be considered good quality criteria for performing quality control and providing technical support for the further pharmacological and pharmaceutical research of Aurantii Fructus.

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses.

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.

Factors influencing peritoneal dialysis patients' psychosocial adjustment.

AIMS AND OBJECTIVES: The specific aims of this study were as follows: (1) to describe psychosocial adjustment in adults with end-stage renal disease who underwent maintenance peritoneal dialysis; (2) to explore the influence of demographics, clinical variables, symptom distress and social support on psychosocial adjustment and (3) to determine predictive factors of psychosocial adjustment. BACKGROUND: Proper psychosocial adjustment is important for patients with end-stage renal disease to cope with multiple stressors of their disease and to balance their lives within the restrictions imposed by peritoneal dialysis treatment. Knowledge on psychosocial adjustment in patients receiving long-term peritoneal dialysis has been limited. DESIGN: The study was based on a predictive correlational design. METHOD: One hundred peritoneal dialysis patients were recruited from outpatient peritoneal dialysis clinics of a general hospital in Taipei, Taiwan. Data were collected with the study questionnaires, including the Physical Symptom Distress Scale, the Social Support Scale and the Psychosocial Adjustment to Illness Scale - self-report. RESULTS: The mean score on the Psychosocial Adjustment to Illness Scale was 359.7 (SD = 40.0), indicating that these participants were moderately struggling in adjusting to their illness. Symptom distress, family social support and financial status explained 38.3% of the variance in psychosocial adjustment (F3,96 = 21..5, p < 0.001). CONCLUSIONS: The level of psychosocial adjustment in peritoneal dialysis patients is suboptimal. Overall, the patients with high physical symptom distress, weak family social support and poor financial status reported deficient psychosocial adjustment to their illness. IMPLICATIONS FOR PRACTICE: The findings of this study are relevant to the understanding of preconditions that enable peritoneal dialysis patients to successfully adjust to the disease and its diverse consequences. Patients with insufficient income, higher symptom distress and less family social support have a greater risk of psychosocial maladjustment. Medical professionals may use these variables to identify higher risk groups for early intensive intervention.

Association Between Social Jetlag and Components of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: A mismatch between biological and social time, often referred to as social jetlag (SJL), can lead to inadequate sleep and activities or taking meals at times that do not align with our biological rhythms, increasing the risk of metabolic abnormalities. Although the association between sleep and metabolic syndrome (MetS) is well established, the effects of SJL on MetS and the components of MetS in adults remain unclear. PURPOSE: This study was designed to explore the relationship between SJL and MetS components in adults. METHODS: A systematic review and meta-analysis was conducted on studies registered in PubMed, Cochrane, Web of Science, and Embase between the inception of each database until November 15, 2023. We focused on studies designed to evaluate the relationship between SJL and either MetS or its components. Only studies using cross-sectional, prospective, or retrospective designs were considered for inclusion. The relationship between SJL and MetS was depicted as an odds ratio with a corresponding 95% confidence interval (CI). We determined the mean differences and 95% CIs to estimate the associations between SJL and MetS components. The Joanna Briggs Institute Critical Appraisal Checklist was used to evaluate the methodological rigor of the selected studies. Data were analyzed using RevMan software Version 5.4. RESULTS: The systematic review included 16 studies, with five analyzed via a meta-analysis covering four outcomes, each based on two to three studies. When comparing SJL of less than 1 hour with SJL of 2 hours or more, the latter showed a higher likelihood of MetS (pooled odds ratio: 1.52). Although a significant decrease in systolic blood pressure (pooled mean differences = -3.52 mmHg, 95% CI [-6.41, -0.64]) and a significant increase in waist circumference (pooled mean differences = 2.17 cm, 95% CI [0.61, 3.73]) were observed, the correlation between SJL and diastolic blood pressure failed to reach statistical significance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The meta-analysis conducted in this study found an association between SJL and MetS. Healthcare practitioners should prioritize the management of sleep quality and duration, especially for individuals exhibiting substantial SJL. Improving sleep can aid in controlling blood pressure and managing weight and should form part of MetS management strategies.

Higenamine exerts antidepressant effect by improving the astrocytic gap junctions and inflammatory response.

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.

Ginsenoside Rg1 treats ischemic stroke by regulating CKLF1/CCR5 axis-induced neuronal cell pyroptosis.

BACKGROUND: Ischemic stroke, a severe and life-threatening neurodegenerative condition, currently relies on thrombolytic therapy with limited therapeutic window and potential risks of hemorrhagic transformation. Thus, there is a crucial need to explore novel therapeutic agents for ischemic stroke. Ginsenoside Rg1 (Rg1), a potential neuroprotective agent, exhibits anti-ischemic effects attributed to its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Nevertheless, the precise underlying mechanism of action remains to be fully elucidated. PURPOSE: This study aimed to explore whether Rg1 exerts anti-ischemic stroke effects by inhibiting pyroptotic neuronal cell death through modulation of the chemokine like factor 1 (CKLF1)/ C-C chemokine receptor type 5 (CCR5) axis. METHODS: In this study, the MCAO model was used as an ischemic stroke model, and experimental tests were performed after 6 hours of ischemia. The anti-ischemic effect of Rg1 was examined by TTC staining, nissl-staining and neurobehavioral tests. In the in vitro experiments, PC12 cells were subjected to stimulation with CKLF1's mimetic peptide C27 to assess the potential of CKLF1 to induce focal neuronal cell death. Additionally, the impact of CKLF1 mimetic peptide C27, antagonistic peptide C19, and CCR5 inhibitor MVC on PC12 cells subjected to oxygen-glucose deprivation (OGD) and subsequently treated with Rg1 was investigated. In vivo, Rg1 treatment was examined by quantitative real-time PCR (qPCR), ELISA, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and co-immunoprecipitate (Co-IP) assays to perspective whether Rg1 treatment reduces CKLF1/CCR5 axis-induced pyroptotic neuronal cell death. In addition, to further explore the biological significance of CKLF1 in ischemic stroke, CKLF1-/- rats were used as the observation subjects in this study. RESULTS: The in vitro results suggested that CKLF1 was able to induce neuronal cells to undergo pyroptosis. In vivo pharmacodynamic results showed that Rg1 treatment was able to significantly improve symptoms in ischemic stroke rats. In addition, Rg1 treatment was able to inhibit the interaction between CKLF1 and CCR5 after ischemic stroke and inhibited CKLF1/CCR5 axis-induced pyroptosis. The results of related experiments in CKLF1-/- rats showed that Rg1 lost its therapeutic effect after CKLF1 knockdown. CONCLUSION: Our findings indicate that the activation of the NLRP3 inflammasome is initiated by the CKLF1/CCR5 axis, facilitated through the activation of the NF-κB pathway, ultimately resulting in the pyroptosis of neuronal cells. Conversely, Rg1 demonstrates the capability to mitigate neuronal cell damage following CKLF1-induced effects by suppressing the expression of CKLF1. Thus, CKLF1 represents a crucial target for Rg1 in the context of cerebral ischemia treatment, and it also holds promise as a potential target for drug screening in the management of ischemic stroke.

Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases.

Neuroinflammation is an innate and adaptive immune response initiated by the release of inflammatory mediators from various immune cells in response to harmful stimuli. While initially beneficial and protective, prolonged or excessive neuroinflammation has been identified in clinical and experimental studies as a key pathological driver of numerous neurological diseases and an accelerant of the aging process. Glycolysis, the metabolic process that converts glucose to pyruvate or lactate to produce adenosine 5'-triphosphate (ATP), is often dysregulated in many neuroinflammatory disorders and in the affected nerve cells. Enhancing glucose availability and uptake, as well as increasing glycolytic flux through pharmacological or genetic manipulation of glycolytic enzymes, has shown potential protective effects in several animal models of neuroinflammatory diseases. Modulating the glycolytic pathway to improve glucose metabolism and ATP production may help alleviate energy deficiencies associated with these conditions. In this review, we examine six neuroinflammatory diseases-stroke, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and depression-and provide evidence supporting the role of glycolysis in their treatment. We also explore the potential link between inflammation-induced aging and glycolysis. Additionally, we briefly discuss the critical role of glycolysis in three types of neuronal cells-neurons, microglia, and astrocytes-within physiological processes. This review highlights the significance of glycolysis in the pathology of neuroinflammatory diseases and its relevance to the aging process.

CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

The relationship between health-promoting behaviors and resilience in patients with chronic kidney disease.

This cross-sectional research study explored differences in health-promoting behavior and resilience among three groups of chronic kidney disease patients (high-risk, early chronic kidney disease; early CKD and pre-end stage renal disease; pre-ESRD) treated at the Nephrology outpatient clinic in northern Taiwan. A total of 150 CKD outpatients were interviewed using structured questionnaires including a CKD Health to Promote Lifestyle Scale, and resilience scale. We found that the pre-ESRD group had lower resilience than either high-risk or early CKD groups. Factors affecting pre-ESRD resilience were gender, occupational status, diabetes and health-promoting behaviors. Factors affecting resilience of the high-risk group included level of education and health-promoting behaviors while factors affecting resilience in the early CKD group involved whether they are employed and health promoting behaviors. A significant positive correlation was found between health promoting behavior and resilience in all study subjects. Multiple regression analysis found that factors which could effectively predict resilience in patients at high-risk for CKD were gender, whether the patient had a job, nutrition, self-actualization, and stress level, accounting for 69.7% of the variance. Therefore, nursing education should focus on health promotion advocacy throughout the life of not only patients but also their families.

Screening anti-fatigue components of American ginseng saponin by analyzing spectrum-effect relationship coupled with UPLC-Q-TOF-MS.

Background: American ginseng has an obvious anti-fatigue effect, but the effective material basis is still unclear. The spectrum-effect relationship is a scientific method that studies the correlations between chemical spectra and pharmacological effect. Objective: To reveal the real bioactive compounds in American ginseng saponin (AGS) based on a study of the underlying correlations between these compounds' occurrence in rat serum after their intake of AGS and the anti-fatigue effect of AGS. Methods: We utilized ultra-performance liquid chromatography (UPLC) with quadrupole and time-of-flight mass spectrometry (Q-TOF-MS) to analyze the extract of AGS and its constituents in serum after oral administration in rats. The anti-fatigue effect of AGS in rats was measured using the time weight-bearing swimming technique, the content of blood urea nitrogen, hepatic glycogen, and blood lactic acid. The relationship between the peak area values in fingerprints from rat serum and pharmacodynamic parameters of AGS was established using correlation analysis with partial least square regression (PLSR) method and gray correlation method. Results: We detected and identified 22 compounds from extract, and 8 prototype components from serum. Through PLSR and gray correlation method, it was found that the ginsenosides Re, Rb1, and Rb2 were significantly positively related to the pharmacodynamic data. Conclusions: Based on the spectrum-effect relationship, PLSR and gray correlation method can be used to screen for the anti-fatigue components available in AGS. Such an approach is of practical significance as it provides an effective means for exploring the material basis for the efficacy of American ginseng, particularly as an anti-fatigue agent.