ABSTRACT
Lung diseases have complex pathogenesis and treatment challenges, showing an obvious increase in the rate of diagnosis and death every year. Therefore, elucidating the mechanism for their pathogenesis and treatment ineffective from novel views is essential and urgent. Methyltransferase-like 3 (METTL3) is a novel post-transcriptional regulator for gene expression that has been implicated in regulating lung diseases, including that observed in chronic conditions such as pulmonary fibrosis (PF), pulmonary arterial hypertension (PAH), and chronic obstructive pulmonary disease (COPD), as well as acute conditions such as pneumonia, severe acute respiratory syndrome coronavirus 2 infection, and sepsis-induced acute respiratory distress syndrome. Notably, a comprehensive summary and analysis of findings from these studies might help understand lung diseases from the novel view of METTL3-regulated mechanism, however, such a review is still lacking. Therefore, this review aims to bridge such shortage by summarising the roles of METTL3 in lung diseases, establishing their interrelationships, and elucidating the potential applications of METTL3 regarding diagnosis, treatment, and prognosis. The analysis collectively suggests METTL3 is contributable to the onset and progression of these lung diseases, thereby prospecting METTL3 as a valuable biomarker for their diagnosis, treatment, and prognosis. In conclusion, this review offers elucidation into the correlation between METTL3 and lung diseases in both research and clinical settings and highlights potential avenues for exploring the roles of METTL3 in the respiratory system.
ABSTRACT
Breast cancer (BC) is a highly prevalent malignancy worldwide, with complex pathogenesis and treatment challenges. Research reveals that methyltransferase-like 3 (METTL3) is widely involved in the pathogenesis of several tumors through methylation of its target RNAs, and its role and mechanisms in BC are also extensively studied. In this review, we aim to provide a comprehensive interpretation of available studies and elucidate the relationship between METTL3 and BC. This review suggests that high levels of METTL3 are associated with the pathogenesis, poor prognosis, and drug resistance of BC, suggesting METTL3 as a potential diagnostic or prognostic biomarker and therapeutic target. Collectively, this review provides a comprehensive understanding of how METTL3 functions through RNA methylation, which provides a valuable reference for future fundamental studies and clinical applications.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Methyltransferases , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Drug Resistance, Neoplasm/genetics , Methyltransferases/metabolism , Methyltransferases/genetics , Methyltransferases/antagonists & inhibitors , Biomarkers, Tumor/metabolism , Prognosis , Molecular Targeted Therapy , AnimalsABSTRACT
Hypoxia-ischaemia (HI) can induce the death of cerebrovascular constituent cells through oxidative stress. Hydrogen is a powerful antioxidant which can activate the antioxidant system. A hypoxia-ischaemia brain damage (HIBD) model was established in 7-day-old SD rats. Rats were treated with different doses of hydrogen-rich water (HRW), and brain pericyte oxidative stress damage, cerebrovascular function and brain tissue damage were assessed. Meanwhile, in vitro-cultured pericytes were subjected to oxygen-glucose deprivation and treated with different concentrations of HRW. Oxidative injury was measured and the molecular mechanism of how HRW alleviated oxidative injury of pericytes was also examined. The results showed that HRW significantly attenuated HI-induced oxidative stress in the brain pericytes of neonatal rats, partly through the Nrf2-HO-1 pathway, further improving cerebrovascular function and reducing brain injury and dysfunction. Furthermore, HRW is superior to a single-cell death inhibitor for apoptosis, ferroptosis, parthanatos, necroptosis and autophagy and can better inhibit HI-induced pericyte death. The liver and kidney functions of rats were not affected by present used HRW dose. This study elucidates the role and mechanism of hydrogen in treating HIBD from the perspective of pericytes, providing new theoretical evidence and mechanistic references for the clinical application of hydrogen in neonatal HIE.
Subject(s)
Animals, Newborn , Brain , Hydrogen , Hypoxia-Ischemia, Brain , Oxidative Stress , Pericytes , Rats, Sprague-Dawley , Animals , Pericytes/drug effects , Pericytes/metabolism , Hydrogen/pharmacology , Hypoxia-Ischemia, Brain/pathology , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/drug therapy , Rats , Oxidative Stress/drug effects , Brain/pathology , Brain/drug effects , Brain/metabolism , NF-E2-Related Factor 2/metabolism , Apoptosis/drug effects , Disease Models, Animal , Antioxidants/pharmacologyABSTRACT
Non-small cell lung cancer (NSCLC) is a malignant cancer that with high incidence, recurrence, and mortality rates in human beings, posing significant threats to human health. Moreover, effective early diagnosis of NSCLC remains limited primarily by the lack of accurate biomarkers. Therefore, there is an urgent need to understand the mechanisms underlying NSCLC pathogenesis and treatment failure. Methyltransferase-like 3 (METTL3) is a prototypical member of a family of which its members transfer methyl groups. It has been implicated in modulating the pathogenesis of NSCLC, as well as conferring resistance to NSCLC therapeutics. The targeting of METTL3 for NSCLC treatment has been reported. However, the relationship between METTL3 and NSCLC remains to be demonstrated. In this review, we discuss relevant interrelationships by summarising the studies on METTL3 in NSCLC pathogenesis, therapeutic resistance, and clinical applications. Current research suggests that the upregulation of METTL3 expression propels the tumorigenesis, progression, and treatment resistance of NSCLC. Therefore, we propose that METTL3 is an excellent candidate biomarker for NSCLC diagnosis and prognosis. Therapeutic targeting of METTL3 has significant potential for NSCLC treatment. This review provides a summary of the association between METTL3 and NSCLC, which would be a valuable reference for both basic and clinical research.
ABSTRACT
BACKGROUND: The benefits of partner support have been well documented for maternal and child health and wellbeing. Chinese women who practice traditional postpartum rituals may lack support during the confinement and often rely heavily on their partners. Currently, there is no validated measure to assess postpartum partner support in China. AIM: To translate the Postpartum Partner Support Scale (PPSS) into Chinese, evaluate its psychometric properties and assess postpartum support among Chinese women. METHODS: The PPSS was translated into Chinese using a validated process and administered to 428 postpartum women residing in the city of Quanzhou in the Fujian Province in China between September 2021 and July 2022. RESULTS: Reliability analysis demonstrated a Cronbach's α coefficient of 0.97, a split-half coefficient of 0.93, and a retest correlation coefficient of 0.91 (p < 0.01). The item analysis and content validity results fell within the recommended range, with no items requiring deletion. Exploratory factor analysis revealed the extraction of a single common factor, which accounted for 74.05% of the cumulative variance. Confirmatory factor analysis yielded a χ2/df ratio of 1.48 and an RMSEA value of 0.05. Several demographic variables were associated with significantly lower levels of postnatal partner support including older maternal and paternal age, lower maternal education, higher household income, fair relationship with in-law family, female infant sex, and premature birth. CONCLUSION: The Chinese version of the PPSS exhibited good reliability and validity providing evidence that it may be suitable for evaluating partner support among postpartum women in China.
Subject(s)
Postpartum Period , Psychometrics , Social Support , Humans , Female , Adult , Reproducibility of Results , China , Psychometrics/methods , Psychometrics/instrumentation , Surveys and Questionnaires , Postpartum Period/psychology , Pregnancy , TranslatingABSTRACT
Background: Public health emergencies impose unique challenges on pregnant women, affecting their physiological, psychological, and social wellbeing. This study, focusing on the context of the corona virus disease in 2019 (COVID-19) pandemic in China, aims to comprehensively explore the experiences of pregnant women amidst diverse public health crises. Herein, we investigate the health education needs of pregnant Chinese women in regard to public health emergencies to provide a scientific foundation for the development of targeted health education strategies. Objective: The study described in this article aims to explore the health education needs of pregnant Chinese women in the context of public health emergencies specifying the types of emergencies of pandemics and to provide a scientific basis for targeted health education interventions. Methods: Thirteen pregnant women were purposively selected, and the rationale for this sample size lies in the qualitative nature of the study, seeking in-depth insights rather than generalizability. Data collection involved semi-structured interviews, and the Colaizzi, which is a structured qualitative technique used to extract, interpret, and organize significant statements from participant descriptions into themes, providing a comprehensive understanding of their lived experiences. Results: The analysis yielded six prominent themes encompassing the following areas: I. Personal protection and vaccine safety; II. Knowledge of maternal health; III. Knowledge of fetal health; IV. Knowledge of childbirth; V. Knowledge of postpartum recovery; and VI. Knowledge sources of health education for pregnant women and their expectations of healthcare providers. Theme I was analyzed with two sub-themes (needs for personal protection knowledge, vaccine safety knowledge needs); Theme II was analyzed with three sub-themes (nutrition and diet, exercise and rest, sexual life); Theme III was analyzed with three sub-themes (medications and hazardous substances, pregnancy check-ups, and fetal movement monitoring); Theme IV was analyzed with three sub-themes (family accompaniment, analgesia in childbirth, and choice of mode of delivery); Theme V was analyzed with one sub-theme (knowledge of postnatal recovery); Theme VI was analyzed with one sub-theme (expectations of Healthcare providers). Sub-themes within each main theme were identified, offering a nuanced understanding of the multifaceted challenges faced by pregnant women during public health emergencies. The interrelation between sub-themes and main themes contributes to a holistic portrayal of their experiences. Conclusion: The study emphasizes the need for healthcare professionals to tailor health education for pregnant women during emergencies, highlighting the role of the Internet in improving information dissemination. It recommends actionable strategies for effective health communication, ensuring these women receive comprehensive support through digital platforms for better health outcomes during public health crises.
Subject(s)
COVID-19 , Health Education , Pregnant Women , Public Health , Qualitative Research , Humans , Female , Pregnancy , China , Adult , Pregnant Women/psychology , SARS-CoV-2 , Emergencies/psychology , PandemicsABSTRACT
Objective: This study aims to investigate the clinical efficacy of biomimetic physiotherapy combined with manipulation therapy in the management of female myofascial pelvic pain syndrome (MPPS). Methods: A total of 120 patients diagnosed with MPPS at our hospital from June 2018 to June 2021 were included. All patients had a history of sexual activity, met the diagnostic criteria for female chronic pelvic pain, and exhibited pelvic floor muscle and myofascial trigger points in gynecological examinations. Based on treatment methods, patients were categorized into a control group (n=64, treated with biomimetic physiotherapy) and an experimental group (n=56, treated with biomimetic physiotherapy plus manipulation therapy). Pre- and post-treatment assessments in both groups included pelvic floor muscle surface electromyogram, Visual Analogue Scale (VAS) score, pelvic floor muscle tenderness score, and pelvic floor muscle strength. Results: After treatment, in the control group, the mean values of pre-resting potential and post-resting potential declined significantly, from (9.58±2.22) to (4.06±0.77) and from (8.18±1.78) to (3.56±0.61), respectively. In the experimental group, these values decreased from (9.61±2.77) to (3.15±0.58), and from (8.16±1.78) to (2.79±0.59). The VAS score exhibited a noteworthy decrease from (6.18±1.00) to (3.15±0.56) in the control group and from (6.20±1.13) to (2.04±0.68) in the experimental group. The pelvic floor muscle tenderness score decreased from (8.14±0.86) to (3.78±0.77) in the control group and from (7.91±1.03) to (1.93±0.80) in the experimental group. Furthermore, the percentage of patients whose pelvic floor muscle strength increased from Subject(s)
Myofascial Pain Syndromes
, Pelvic Pain
, Physical Therapy Modalities
, Humans
, Female
, Myofascial Pain Syndromes/therapy
, Adult
, Pelvic Pain/therapy
, Middle Aged
, Pelvic Floor/physiopathology
, Pain Measurement
, Treatment Outcome
, Combined Modality Therapy
ABSTRACT
Most patients with myopia have dry eye, which has been shown to adversely affect ocular symptoms, myopia progression, and quality of life in patients with myopia. Needle prickling has been shown to be effective in providing symptom relief in patients with myopia and dry eye. Press needle is a long-lasting, easy-to-operate, and inexpensive traditional Chinese medicine treatment. The standard practice of needle insertion is very important for the treatment of myopia and dry eye. The specific steps include selecting the appropriate acupoints, piercing them with appropriate needles, and fixing them in the skin or subcutaneously at the acupoints, burying them for 2 days, resting for 1 day; the course of treatment lasts for 2 weeks. Specifically, the following indicators were assessed: uncorrected visual acuity and the ocular surface disease index. This article will explain how to standardize the operation of a press needle in the treatment of myopia and dry eye.
Subject(s)
Acupuncture Therapy , Dry Eye Syndromes , Medicine, Chinese Traditional , Myopia , Humans , Dry Eye Syndromes/therapy , Myopia/therapy , Medicine, Chinese Traditional/methods , Acupuncture Therapy/methods , Acupuncture Therapy/instrumentation , NeedlesABSTRACT
Transfer RNAs (tRNAs) can regulate cell behavior and are associated with neurological disorders. Here, we aimed to investigate the expression levels of tRNAs in oligodendrocyte precursor cells (OPCs) and their possible roles in the regulation of brain white matter injury (WMI). Newborn Sprague-Dawley rats (postnatal day 5) were used to establish a model that mimicked neonatal brain WMI. RNA-array analysis was performed to examine the expression of tRNAs in OPCs. psRNAtarget software was used to predict target mRNAs of significantly altered tRNAs. Gene ontology (GO) and KEGG were used to analyze the pathways for target mRNAs. Eighty-nine tRNAs were changed after WMI (fold change absolute ≥1.5, P â <â 0.01), with 31 downregulated and 58 upregulated. Among them, three significantly changed tRNAs were identified, with two being significantly increased (chr10.trna1314-ProTGG and chr2.trna2771-ProAGG) and one significantly decreased (chr10.trna11264-GlyTCC). Further, target mRNA prediction and GO/KEGG pathway analysis indicated that the target mRNAs of these tRNAs are mainly involved in G-protein coupled receptor signaling pathways and beta-alanine metabolism, which are both related to myelin formation. In summary, the expression of tRNAs in OPCs was significantly altered after brain WMI, suggesting that tRNAs may play important roles in regulating WMI. This improves the knowledge about WMI pathophysiology and may provide novel treatment targets for WMI.
Subject(s)
RNA, Transfer , Rats, Sprague-Dawley , White Matter , Animals , RNA, Transfer/metabolism , RNA, Transfer/genetics , White Matter/metabolism , White Matter/pathology , Rats , Animals, Newborn , Oligodendrocyte Precursor Cells/metabolism , Brain Injuries/metabolism , Brain Injuries/genetics , Brain Injuries/pathology , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Depression is the leading cause of health-related disability. A proportion of depression cases begin in childhood and increase dramatically during adolescence. This systematic review and meta-analysis aimed to estimate the global prevalence of depression or depressive symptoms in children and adolescents and explore the temporal and regional distribution of depression or depressive symptoms. METHODS: This systematic review and meta-analysis identified peer-reviewed literature published through April 8, 2023, using the MEDLINE, Embase and APA PsycINFO databases, supplemented by reverse reference searches. Observational studies published in English and based on validated instruments with prevalence data on depression or depressive symptoms in children and adolescents aged ≤18 years were eligible. Random-effects meta-analysis and meta-regression analysis were performed using R software. RESULTS: This systematic review and meta-analysis included a total of 96 studies (29 countries, 528,293 participants) published between 1989 and 2022. The pooled prevalence of mild-to-severe, moderate-to-severe, and major depression were 21.3 % (95%CI, 16.7 %-26.7 %), 18.9 % (95%CI, 14.6 %-24.2 %), and 3.7 % (95%CI, 2.7 %-5.1 %) respectively. Meta-regression analysis showed that from 1989 to 2022, the prevalence of mild-to-severe and moderate-to-severe depression increased over time (P = 0.002, P = 0.034, respectively), but the prevalence of major depression did not change significantly (P = 0.636). LIMITATIONS: Only English articles were included. There was significant heterogeneity across the included studies. The studies included were mostly based on self-report scales to assess depressive symptoms. CONCLUSION: In this systematic review, about one in five children and adolescents globally suffered from depression or had depressive symptoms, and this proportion was increasing over time.
Subject(s)
Depression , Humans , Child , Adolescent , Depression/epidemiology , Depression/psychology , Prevalence , Global Health/statistics & numerical data , Male , Female , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychologyABSTRACT
Several studies have highlighted the functional indispensability of methyltransferase-like 3 (METTL3) in the reproductive system. However, a review that comprehensively interprets these studies and elucidates their relationships is lacking. Therefore, the present work aimed to review studies that have investigated the functions of METTL3 in the reproductive system (including spermatogenesis, follicle development, gametogenesis, reproductive cancer, asthenozoospermia and assisted reproduction failure). This review suggests that METTL3 functions not only essential for normal development, but also detrimental in the occurrence of disorders. In addition, promising applications of METTL3 as a diagnostic or prognostic biomarker and therapeutic target for reproductive disorders have been proposed. Collectively, this review provides comprehensive interpretations, novel insights, potential applications and future perspectives on the role of METTL3 in regulating the reproductive system, which may be a valuable reference for researchers and clinicians.
Subject(s)
Methyltransferases , RNA , Male , Humans , Methyltransferases/genetics , Spermatogenesis/genetics , Reproduction/genetics , GenitaliaABSTRACT
Methyltransferase-like 3 (METTL3), a component of the RNA N6-methyladenosine (m6A) modification with a specific catalytic capacity, controls gene expression by actively regulating RNA splicing, nuclear export, stability, and translation, determines the fate of RNAs and assists in regulating biological processes. Studies conducted in recent decades have demonstrated the pivotal regulatory role of METTL3 in liver disorders, including hepatic lipid metabolism disorders, liver fibrosis, nonalcoholic steatohepatitis, and liver cancer. Although METTL3's roles in these diseases have been extensively investigated, the regulatory network of METTL3 and its potential applications remain unexplored. In this review, we provide a comprehensive overview of the roles and mechanisms of METTL3 implicated in these diseases, establish a regulatory network of METTL3, evaluate the potential for targeting METTL3 for diagnosis and treatment, and discuss avenues for future development and research. We found relatively upregulated expressions of METTL3 in these liver diseases, demonstrating its potential as a diagnostic biomarker and therapeutic target.
Subject(s)
Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Methyltransferases/genetics , Liver Cirrhosis , Catalysis , RNAABSTRACT
Methyltransferase-like 3 (METTL3) is the most well-known element of N6-methyladenosine modification on RNAs. METTL3 deposits a methyl group onto target RNAs to modify their expression, ultimately regulating various physiological and pathological events. Numerous studies have suggested the significant role of METTL3 in endocrine dysfunction and related disorders. However, reviews that summarize and interpret these studies are lacking. In this review, we systematically analyze such studies, including obesity, type 2 diabetes mellitus (T2DM), T2DM-induced diseases, pancreatic cancer, and thyroid carcinoma. This review indicates that METTL3 contributes remarkably to the endocrine dysfunction and progression of obesity, T2DM, T2DM-induced diseases, pancreatic cancer, and thyroid carcinoma. In conclusion, this review provides a comprehensive interpretation of the mechanism via which METTL3 functions on RNAs and regulates various endocrine dysfunction events and suggest potential associated correlations. Our review, thus, provides a valuable reference for further fundamental studies and clinical applications.
Subject(s)
Diabetes Mellitus, Type 2 , Pancreatic Diseases , Thyroid Neoplasms , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Diabetes Mellitus, Type 2/genetics , RNA , Endocrine System/metabolism , ObesityABSTRACT
BACKGROUND: Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported. METHODS: Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-α and interleukin-1ß were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin-eosin staining. RESULTS: We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. In vivo assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation. CONCLUSIONS: This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.
Subject(s)
Acute Lung Injury , Macrophages, Alveolar , Animals , Mice , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/genetics , Lipopolysaccharides/pharmacology , Acute Lung Injury/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , Lung/metabolism , Inflammation/pathologyABSTRACT
OBJECTIVE: To determine the effects of rehabilitation therapy combined with neuromuscular electrical stimulation (NES) on cognitive dysfunction and ability to perform activities of daily living (ADLs) of stroke patients. METHODS: The clinical data of 100 stroke patients treated in the Second Affiliated Hospital of Soochow University from February 2019 to August 2021 were retrospectively analyzed. According to the therapeutic regimen, the patients given rehabilitation therapy combined with NES were assigned to a study group (n=52) and those given rehabilitation therapy alone were assigned to a control group (n=48). The treatment efficacy in the two groups was evaluated, and the levels of plasma cortisol (Cor) and neuropeptide Y (NPY), neurological function, motor function, balance ability, swallowing function, cognitive function, negative emotions, and quality of life (QoL) after therapy were evaluated. The maximum amplitude of surface electromyography (sEMG) and swallowing time were compared between the two groups. RESULTS: The study group yielded significantly better efficacy than the control group (P<0.05). Before therapy, there were no significant differences between the two groups in Cor and NPY levels, neurological function, motor function, balance ability, swallowing function, cognitive function, sEMG, swallowing time or negative emotions (P>0.05). After therapy, the above all indices all greatly improved, with more notso in the study group. In addition, after therapy, the study group had significantly better QoL indexes than the control group. CONCLUSION: Rehabilitation therapy combined with NES is effective in treating stroke. It can substantially ameliorate the cognitive dysfunction, prognosis and QoL in patients.
ABSTRACT
Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, we show that brief activation of protocerebral anterior medial DANs (PAM-DANs) or inhibition of a pair of dorsal posterior medial (DPM) neurons during the first few hours of memory consolidation impairs 24 h LTM. Interestingly, sleep deprivation elevates the neural activity of PAM-DANs and DPM neurons, and brief thermos-activation of PAM-DANs or inactivation of DPM neurons results in sleep loss and fragmentation. Pharmacological rescue of sleep after this manipulation restores LTM. A specific subset of PAM-DANs, PAM-α1 that synapse onto DPM neurons specify the microcircuit that links sleep and memory. PAM-DANs, including PAM-α1, form functional synapses with DPM neurons mainly via Dop1R1 receptor to inhibit DPM. Our data suggest that the post-training activity of PAM(-α1)-DPM microcircuit, especially during memory consolidation, plays an essential role in maintaining the sleep necessary for LTM consolidation, providing a new cellular and circuit basis for the complex relationship between sleep and memory.
ABSTRACT
Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of ß-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/ß-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/ß-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/ß-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/ß-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.
ABSTRACT
Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers' attention and emerged as a potential therapeutical target for the treatment of various diseases. In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings. Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.
Subject(s)
Endocannabinoids , Humans , Endocannabinoids/metabolism , Receptors, Cannabinoid/metabolismABSTRACT
Objective: This study aims to investigate the occurrence of maternal postpartum depression (PPD) during menstruation and analyze the influencing factors and risk prediction modeling of maternal PPD in Chinese puerperal women of sitting the month. Methods: A total of 286 mothers were selected using convenience sampling, who came for a routine postpartum follow-up visit were surveyed, including face-to-face, telephone, and online. They completed questionnaires including the basic profile questionnaire, Postpartum Partner Support Scale (PPSS), Edinburgh PPD Scale (EPDS), Parenting Self-Efficacy Scale (SICS), and Simple Coping Style Questionnaire (SCSQ), who were advised to complete the survey alone, in private, reducing the impact of husband's presence on the quality of the questionnaire. Variables showing statistical significance in the one-way analysis were further analyzed using logistic regression analysis. The predictive value of the logistic regression model was analyzed using the Receiver Operating Characteristic Curve (ROC), and the predictive reliability was expressed as the area under the ROC [Area Under the Curve (AUC)]. Results: The total score of PPD was 7.78 ± 4.57, and 22 people (7.69%) experienced depression during the postpartum period. PPD was found to be correlated with postpartum partner support, positive coping, negative coping, and parenting self-efficacy, with correlation coefficient values of -0.63, 0.62, 0.56, and - 0.70, respectively (all p < 0.05). Logistic regression analysis revealed that postpartum partner support and parenting self-efficacy were independent factors influencing PPD, with odds ratios (95% confidence intervals) of 0.76 (0.61 ~ 0.94) and 0.83 (0.75 ~ 0.93), respectively both p < 0.05.The area under the curve, sensitivity, and specificity for postpartum partner support and parenting self-efficacy were 1.00 (95% confidence intervals 0.99 ~ 1.00), 99.24, and 90.91%. Conclusion: Postpartum partner support and parenting self-efficacy independently predict the occurrence of PPD. Healthcare professionals and maternal families should prioritize timely attention to maternal partner support and parenting issues to reduce the occurrence of PPD.