Forskolin improves experimental autoimmune encephalomyelitis in mice probably by inhibiting the calcium and the IL-17-STEAP4 signaling pathway.

Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system. Forskolin (FSK) is a plant-derived diterpene with excellent immunomodulatory properties and has not been systematically reported for treating MS. This study investigated the therapeutic effects of FSK on cellular and animal MS models and preliminarily explored related mechanisms. The results showed that FSK suppressed the inflammatory response, reduced the expression of STEAP4, and relieved iron deposition in BV-2 cells pretreated by LPS at the cellular level. Meanwhile, at the animal level, FSK treatment halted the progression of experimental autoimmune encephalomyelitis (EAE), alleviated the damage at the lesion sites, reduced the concentration of proinflammatory factors in peripheral blood, and inhibited the immune response of peripheral immune organs in EAE mice. Besides, FSK treatment decreased the expression of STEAP4 in the spinal cord and effectively restored the iron balance in the brain, spinal cord, and serum of EAE mice. Further investigation showed that FSK can reduce IL-17 expression, prevent the differentiation of TH17 cells, and inhibit the calcium signaling pathway. Thus, these results demonstrate that FSK may have the potential to treat MS clinically.

Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.

In this review, we have discussed the invasive and non-invasive treatment options for Parkinson's Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.

Correlations between non-suicidal self-injury and problematic internet use among Chinese adolescents: a systematic review and meta-analysis.

Background: Non-Suicidal Self-Injury (NSSI) has continued to be a major issue for public health worldwide, especially among teenagers. Studies have found a certain correlation between NSSI and Problematic Internet Use (PIU). However, this relationship is still unclear among Chinese adolescents, a specific population. Hence, a meta-analysis was carried out on observational studies to explore the connection between NSSI and PIU in Chinese teenagers, aiming to provide more clarity on the correlation. Methods: To identify the link between NSSI and PIU, we scoured seven digital repositories until November 16, 2023. Employing a random-effects meta-analysis framework, we delved into the association between NSSI and PIU. Additionally, we carried out subgroup evaluations to scrutinize variables including geographical location, age demographics, research methodology, diagnostic instruments, gender, and variables controlled for confounding, like symptoms of depression. For amalgamating data, STATA software (version 16) was deployed. Results: In this analysis, we included 15 research papers encompassing a collective sample of 137,166 individuals. Our findings revealed a significant positive association between NSSI and PIU within the adolescent population in China, with an Odds Ratio (OR) of 2.02 and a 95% Confidence Interval (CI) ranging from 1.73 to 2.37. Notably, this correlation was markedly stronger in specific subgroups: adolescents from China's Western regions exhibited an OR of 4.22 (95% CI: 3.44, 5.18); middle school attendees had an OR of 2.09 (95% CI: 1.92, 2.28); those diagnosed with concurrent depression disorders showed an OR of 2.32 (95% CI: 1.98, 2.73); and female adolescents demonstrated an OR of 2.49 (95% CI: 2.26, 2.75), highlighting the nuanced dynamics of this relationship. Conclusion: This meta-analysis indicates that PIU among adolescents is associated with an increased risk of NSSI. Our findings underscore the importance of targeting specific populations, including those in the western region of China, middle school students, adolescents with comorbid depression disorders, and female adolescents, who may be at higher risk of PIU and subsequently NSSI. These results emphasize the need for tailored interventions and preventive strategies to address these intertwined issues effectively. Systematic review registration: PROSPERO, identifier CRD42024496579.

Safety of Exposure to 0.2 T and 4 Hz Rotating Magnetic Field: A Ten-Month Study on C57BL/6 Mice.

Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.

Palliative effect of rotating magnetic field on glucocorticoid-induced osteonecrosis of the femoral head in rats by regulating osteoblast differentiation.

With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced invivo rat model, and an MPS-induced invitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH.

Anti-ulcerative colitis effect of rotating magnetic field on DSS-induced mice by modulating colonic inflammatory deterioration.

Ulcerative colitis (UC) is a prevalent inflammatory disorder that emerges in the colon and rectum, exhibiting a rising global prevalence and seriously impacting the physical and mental health of patients. Significant challenges remain in UC treatment, highlighting the need for safe and effective long-term therapeutic approaches. Heralded as a promising physical treatment, the rotating magnetic field (RMF) demonstrates safety, stability, manageability, and efficiency. This study delves into RMF's potential in mitigating DSS-induced UC in mice, assessing disease activity indices (DAI) and pathological alterations such as daily body weight, fecal occult blood, colon length, and morphological changes. Besides, several indexes have been detected, including serum concentrations of pro-inflammatory cytokines (IL6, IL-17A, TNF-α, IFN-γ) and anti-inflammatory cytokines (TGF-ß, IL-4, IL-10), the ratio of splenic CD3+, CD4+, and CD8+ T cells, the rate of apoptotic colonic cells, the expression of colonic inflammatory and tight junction-associated proteins. The results showed that RMF had beneficial effects on the decrease of intestinal permeability, the restoration of tight junctions, and the mitigation of mitochondrial respiratory complexes (MRCs) by attenuating inflammatory dysfunction in colons of DSS-induced UC model of mice. In conclusion, this study demonstrates that RMF attenuates colonic inflammation, enhances colonic tight junction, and alleviates MRCs impairment by regulating the equilibrium of pro-inflammatory and anti-inflammatory cytokines in UC mice, suggesting the potential application of RMF in the clinical treatment of UC.

Rotating magnetic field improved cognitive and memory impairments in a sporadic ad model of mice by regulating microglial polarization.

Neuroinflammation, triggered by aberrantly activated microglia, is widely recognized as a key contributor to the initiation and progression of Alzheimer's disease (AD). Microglial activation in the central nervous system (CNS) can be classified into two distinct phenotypes: the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. In this study, we investigated the effects of a non-invasive rotating magnetic field (RMF) (0.2T, 4Hz) on cognitive and memory impairments in a sporadic AD model of female Kunming mice induced by AlCl3 and D-gal. Our findings revealed significant improvements in cognitive and memory impairments following RMF treatment. Furthermore, RMF treatment led to reduced amyloid-beta (Aß) deposition, mitigated damage to hippocampal morphology, prevented synaptic and neuronal loss, and alleviated cell apoptosis in the hippocampus and cortex of AD mice. Notably, RMF treatment ameliorated neuroinflammation, facilitated the transition of microglial polarization from M1 to M2, and inhibited the NF-кB/MAPK pathway. Additionally, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice. In cellular experiments, RMF promoted the M1-M2 polarization transition and enhanced amyloid phagocytosis in cultured BV2 cells while inhibiting the TLR4/NF-кB/MAPK pathway. Collectively, these results demonstrate that RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway. These findings suggest the promising therapeutic applications of RMF in the clinical treatment of AD.

Correlations between negative life events and suicidal ideation among Chinese adolescents: a meta-analysis.

Background: Suicide ideation (SI) has become a serious social issue worldwide, and research has found a certain correlation between negative life events (NLE) and SI. Nevertheless, this relationship is still not clear among Chinese adolescents, a special population. Hence, this investigation performed a meta-analysis of observational research on the correlation between NLE and SI among adolescents in China, to further clarify the association. Methods: We performed an extensive search on seven electronic databases starting from their establishment until March 10, 2023. The research mainly focused on cross-sectional studies conducted on samples of Chinese adolescents. To examine the association between NLE and SI, a meta-analysis model using random effects was utilized. To investigate moderating factors such as age, region, assessment tools for SI, and year of publication, subgroup and meta-regression analyses were performed. The AHRQ evaluated the quality of the study. The synthesis of data was conducted utilizing STATA software (version 16). Results: Ultimately, a total of 30 cross-sectional studies were selected for this analysis, including 39,602 individuals in the participant sample. The results showed that NLE was moderately positively correlated with SI among Chinese adolescents (r = 0.29, 95% CI: 0.26, 0.32). In addition, this relationship was moderated by regional differences and the measurement tool used for SI. Studies conducted in Western China showed a higher correlation coefficient than those conducted in Eastern and Central China. Moreover, research conducted with the SSIOSS demonstrated a stronger correlation coefficient compared to studies utilizing the BSI-CV or other assessment instruments. Conclusion: This meta-analysis indicates that NLE is linked to SI in Chinese teenagers, especially those residing in Western regions of China. Identifying and intervening in NLE and associated risk factors are crucial to prevent suicide within this demographic.

Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions.

Ankylosing spondylitis (AS) is clinically characterized by bone fusion that is induced by the pathological formation of extra bone. Unfortunately, the fundamental mechanism and related therapies remain unclear. The loss of SHP-2 (encoded by Ptpn11) in CD4-Cre;Ptpn11f/f mice resulted in the induction of AS-like pathological characteristics, including spontaneous cartilage and bone lesions, kyphosis, and arthritis. Hence, this mouse was utilized as an AS model in this study. As one of the basic physical fields, the magnetic field (MF) has been proven to be an effective treatment method for articular cartilage degeneration. In this study, the effects of a rotating magnetic field (RMF; 0.2 T, 4 Hz) on an AS-like mouse model were investigated. The RMF treatment (2 h/d, 0.2 T, 4 Hz) was performed on AS mice from two months after birth until the day before sampling. The murine specimens were subjected to transcriptomics, immunomics, and metabolomics analyses, combined with molecular and pathological experiments. The results demonstrated that the mitigation of inflammatory deterioration resulted in an increase in functional osteogenesis and a decrease in dysfunctional osteolysis due to the maintenance of bone homeostasis via the RANKL/RANK/OPG signaling pathway. Additionally, by regulating the ratio of CD4+ and CD8+ T-cells, RMF treatment rebalanced the immune microenvironment in skeletal tissue. It has been observed that RMF interventions have the potential to alleviate AS, including by decreasing pathogenicity and preventing disease initiation. Consequently, RMF, as a moderately physical therapeutic strategy, could be considered to alleviate the degradation of cartilage and bone tissue in AS and as a potential option to halt the progression of AS.

Antitumor effect and mechanism of FZD7 polypeptide vaccine.

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

Investigations on the Changes of Serum Proteins in Rabbits after Trimeresurus stejnegeri Venom Injection via Mass Spectrometry-Based Proteomics.

Purpose: There are few studies on protein phosphorylation in the process of snake poisoning. The purpose of this study was to investigate the toxic mechanism of Trimeresurus stejnegeri at the protein level by determining the differential expression of phosphorylated proteins in rabbits after poisoning using proteomics. Methods: The Trimeresurus stejnegeri venom model in rabbits was established by intramuscular injection of 20 mg/kg venom. The serum was collected and the differential expression of phosphorylated proteins in the serum was determined by the iTRAQ technology, TiO2 enriched phosphorylated peptides, and the mass spectrometry analysis. The functional analysis was conducted using ClueGO software and the related mechanism was evaluated by the network analysis of biological interaction. The expression level of related proteins was determined by the Western blotting assay. Results: Compared to the control group, 77 differentially expressed proteins were observed in the model group. These proteins were closely associated with the complement and agglomerate cascade signaling pathways, the HIF signaling pathway, the pentose phosphate pathway, and the cholesterol metabolism signaling pathway. According to the results of network analysis, TF and SCL16A1 were determined as the core proteins, which were identified by the Western blotting assay. Conclusion: The present study provided valuable phosphorylation signal transduction resources for investigating the toxic mechanism and the therapies for Trimeresurus stejnegeri poisoning.