Roles of prostaglandins in immunosuppression.

Prostaglandins (PGs) play a crucial and multifaceted role in various physiological processes such as intercellular signaling, inflammation regulation, neurotransmission, vasodilation, vasoconstriction, and reproductive functions. The diversity and biological significance of these effects are contingent upon the specific types or subtypes of PGs, with each PG playing a crucial role in distinct physiological and pathological processes. Particularly within the immune system, PGs are essential in modulating the function of immune cells and the magnitude and orientation of immune responses. Hence, a comprehensive comprehension of the functions PG signaling pathways in immunosuppressive regulation holds substantial clinical relevance for disease prevention and treatment strategies. The manuscript provides a review of recent developments in PG signaling in immunosuppressive regulation. Furthermore, the potential clinical applications of PGs in immunosuppression are also discussed. While research into the immunosuppressive effects of PGs required further exploration, targeted therapies against their immunosuppressive pathways might open new avenues for disease prevention and treatment.

Inhibition of 15-hydroxyprostaglandin dehydrogenase protects neurons from ferroptosis in ischemic stroke.

Ischemic stroke is an acute serious cerebrovascular disease with high mortality and disability. Ferroptosis is an important regulated cell death (RCD) in ischemic stroke. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a degrading enzyme of prostaglandin E2 (PGE2), is shown to regulate RCD such as autophagy and apoptosis. The study aimed to determine whether 15-PGDH regulates ferroptosis and ischemic stroke, and further the exact mechanism. We demonstrated that overexpression of 15-PGDH in the brain tissues or primary cultured neurons significantly aggravated cerebral injury and neural ferroptosis in ischemic stroke. While inhibition of 15-PGDH significantly protected against cerebral injury and neural ferroptosis, which benefits arise from the activation of the PGE2/PGE2 receptor 4 (EP4) axis. While the impact of 15-PGDH was abolished with glutathione peroxidase 4 (GPX4) deficiency. Then, 15-PGDH inhibitor was found to promote the activation of cAMP-response element-binding protein (CREB) and nuclear factor kappa-B (NF-κB) via the PGE2/EP4 axis, subsequently transcriptionally upregulate the expression of GPX4. In summary, our study indicates that inhibition of 15-PGDH promotes the activation PGE2/EP4 axis, subsequently transcriptionally upregulates the expression of GPX4 via CREB and NF-κB, and then protects neurons from ferroptosis and alleviates the ischemic stroke. Therefore, 15-PGDH may be a potential therapeutic target for ischemic stroke.

HSP90 and Noncoding RNAs.

Heat shock protein 90 (HSP90) family is a class of proteins known as molecular chaperones that promote client protein folding and translocation in unstressed cells and regulate cellular homeostasis in the stress response. Noncoding RNAs (ncRNAs) are defined as RNAs that do not encode proteins. Previous studies have shown that ncRNAs are key regulators of multiple fundamental cellular processes, such as development, differentiation, proliferation, transcription, post-transcriptional modifications, apoptosis, and cell metabolism. It is known that ncRNAs do not act alone but function via the interactions with other molecules, including co-chaperones, RNAs, DNAs, and so on. As a kind of molecular chaperone, HSP90 is also involved in many biological procedures of ncRNAs. In this review, we systematically analyze the impact of HSP90 on various kinds of ncRNAs, including their synthesis and function, and how ncRNAs influence HSP90 directly and indirectly.

Molecular chaperones in stroke-induced immunosuppression.

Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome. Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections, such as urinary tract infections and stroke-associated pneumonia, worsening prognosis. Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains, refolding misfolded proteins, and targeting misfolded proteins for degradation. Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones, cochaperones, and their associated pathways. This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.

Relationship between Severity of Lumbar Spinal Stenosis and Ligamentum Flavum Hypertrophy and Serum Inflammatory Factors.

Objective: This study is aimed at investigating the correlation between lumbar spinal stenosis (LSS) severity, ligamentum flavum hypertrophy, and the upregulation of inflammatory markers. Methods: From March 2019 and May 2022, eighty-five inpatients with LSS were enlisted as the study's research group, while sixty-five patients hospitalized for lumbar intervertebral disc herniation over the same time period served as the study's control group. Moreover, mild, moderate, and severe subgroups of patients were created within the research population based on their LSS severity. The ligamentum flavum thickness and the positive expression rates of TNF-α, TGF-ß1, and IL-1α were compared between the study group and the control group. The levels of TNF-α, TGF-ß1, and IL-1α that were found to be positively expressed were compared between the mild, moderate, and severe groups. Patients with LSS had their ligamentum flavum thickness and their positive expression rates of TNF-α, TGF-ß1, and IL-1α analyzed using Spearman correlation analysis. We evaluated the diagnostic utility of the positive expression rates of IL-α1, TGF-ß1, and TNF-α and ligamentum flavum thickness in distinguishing the severity of LSS using a receiver operating characteristic (ROC) curve. Results: The rates of both lower limb pain (40.00%) and intermittent claudication (80.00%) in the LSS group were higher than those in the lumbar disc herniation group (15.38%, 12.31%), with statistical significance (P < 0.05). However, no substantial disparity was observed in left lower limb pain, right lower limb pain, low back pain, lower limb sensation, muscle strength, and reflex abnormalities between the two groups (P > 0.05). Positive expressions of TGF-ß1, TNF-α, and IL-1α and thicker ligamentum flavum were more prevalent in the LSS group than in the lumbar intervertebral disc herniation group. All indexes were significantly (P < 0.05) higher in the moderate stenosis group than in the severe stenosis group. Additionally, the thickness of the ligamentum flavum and the positive expression rates of TNF-α, TGF-ß1, and IL-1α were higher in the mild and moderate stenosis groups than in the severe stenosis group. The expression levels of TNF-α, TGF-ß1, and IL-1α were favorably linked with ligamentum flavum thickness (P < 0.05). ROC curve analysis showed that the thickness of ligamentum flavum, the expression of IL-1α, the expression of TGF-ß1, and the expression of TNF-α could effectively diagnose mild, moderate, and severe LSS (P < 0.05). Conclusion: Ligamentum flavum hypertrophy and positive expression rates of IL-1α, TGF-ß1, and TNF-α are closely linked to LSS, which can effectively identify mild, moderate, and severe LSS.

Effect of Penetration Electroacupuncture Combined with Intermediate Frequency Electrotherapy, Facial Acupoint Massage, and Cervical Reduction on Facial Nerve Function and Curative Effect of Senile Refractory Facial Paralysis.

Objective: This study aimed to explore the curative effects on senile refractory facial paralysis treated by penetration electroacupuncture combined with intermediate frequency electrotherapy, facial acupoint massage, and cervical reduction on facial nerve. Methods: 106 elderly patients with intractable facial paralysis that were retrospectively analyzed were all admitted from January 2019 to June 2020. The 106 patients were evenly divided into 2 groups according to the treatment method. The control group was treated with penetration electroacupuncture, while the observation group was treated with penetration electroacupuncture plus intermediate frequency electrotherapy + facial acupoint massage + cervical reduction treatment. Then, House-Brackmann (H-B) facial nerve function evaluation, RPA score, TCM syndrome score, disease remission rate, and incidence of adverse events were evaluated and compared between the two groups. Results: After 4 weeks of treatment, the H-B facial nerve function grading in the observation group was better than that in the control group (P < 0.05). And the disease remission rate after 1 week, 2 weeks, and 4 weeks of treatment was higher than that in the control group (P < 0.05). Meanwhile, the TCM syndrome score and RPA score after 2 weeks and 4 weeks of treatment were better than that in the control group (P < 0.05). Conclusion: For the elderly patients with refractory facial paralysis, the application of the combined treatment that penetration electroacupuncture + medium frequency electrotherapy + facial acupoint massage + cervical adjustment can significantly improve the facial nerve function and reduce various diseases, and the effect of this combined treatment plan is more significant than that of penetration electroacupuncture treatment.

How child maltreatment impacts internalized/externalized aggression among Chinese adolescents from perspectives of social comparison and the general aggression model.

BACKGROUND: Child maltreatment is believed to have a tight correlation with adolescent problem behaviors, and one of them is aggression. According to different attack targets, aggression can be divided into internalized aggression (attack oneself) and externalized aggression (attack others), both of which are negatively influenced by child maltreatment. However, little is known about the potential mechanisms of the effect from child maltreatment to internalized/externalized aggression. OBJECTIVE: Based on the perspectives of social comparison and the general aggression model, the present study examined the mediating effects of benign envy, malicious envy and self-control between child maltreatment and internalized/externalized aggression. PARTICIPANTS AND SETTING: 1951 adolescents (49 % girls, Mage = 12.93 years, SD = 2.54) from mainland China were recruited. METHODS: Based on the retrospective self-reporting of five questionnaires, structural equation modeling and bootstrap estimation procedure were adopted to identify the mediating effects of benign envy, malicious envy and self-control. RESULTS: The structural model fitted well [χ2 (178, 1951) = 1601.176, p < .001; RMSEA = 0.064; SRMR = 0.076; CFI = 0.913]. Benign envy (95 % CI [0.013, 0.002], [-0.040, -0.079]), malicious envy (95 % CI [0.044, 0.024], [0.363, 0.241]) and self-control (95 % CI [0.025, 0.005], [0.264, 0.166]) played a significant mediating role between child maltreatment and internalized/externalized aggression. CONCLUSION: Benign envy, malicious envy and self-control played an important mediating role between child maltreatment and internalized/externalized aggression, which may provide a theoretical basis for future interventions to reduce adolescent problem behaviors, paying more attention to the improvement of emotion regulation and self-control.

Orthogonal design to sift the optimal parameter of Neiguan acupuncture for cerebral infarction.

The individual difference and non-repeatability in acupuncture have not only restricted the development of acupuncture, but have also affected the specificity of acupoints. The present study used instruments to control needle depth, lifting and thrusting frequency, and the duration of acupuncture. Effects of the quantified acupuncture were observed at Neiguan (PC6) with different stimulation parameters. A frequency of 1, 2, or 3 Hz and duration of 5, 60, or 180 seconds were used to observe cerebral blood flow and ratio of infarct volume recovery. Results showed that stimulation at Neiguan with a frequency of 1 Hz and long duration of 180 seconds or 2/3 Hz and long duration of 5/60 seconds significantly increased cerebral blood flow and decreased the ratio of infarct volume. Interactions between frequency and duration play a critical role in quantified acupuncture therapy.