The immediate effects of iTBS on the muscle activation pattern under challenging balance conditions in the patients with chronic low back pain: A preliminary study.

Background: The patients with chronic low back pain (CLBP) showed impaired postural control, especially in challenging postural task. The dorsolateral prefrontal cortex (DLPFC) is reported to involve in the complex balance task, which required considerable attentional control. The effect of intermittent theta burst stimulation (iTBS) over the DLPFC to the capacity of postural control of CLBP patients is still unknown. Methods: Participants diagnosed with CLBP received a single-session iTBS over the left DLPFC. All the participants completed the postural control tasks of single-leg (left/right) standing before and after iTBS. The activation changes of the DLPFC and M1 before and after iTBS were recorded by functional near-infrared spectroscopy (fNIRS). The activation pattern of the trunk [transversus abdominis (TrA), superficial lumbar multifidus (SLM)] and leg [tibialis anterior (TA), gastrocnemius medialis (GM)] muscles including root mean square (RMS) and co-contraction index (CCI) during single-leg standing were measured by surface electromyography (sEMG) before and after the intervention. The paired t-test was used to test the difference before and after iTBS. Pearson correlation analyses were performed to test the relationship between the oxyhemoglobin concentration and sEMG outcome variables (RMS and CCI). Results: Overall, 20 participants were recruited. In the right-leg standing condition, compared with before iTBS, the CCI of the right TrA/SLM was significantly decreased (t = -2.172, p = 0.043), and the RMS of the right GM was significantly increased (t = 4.024, p = 0.001) after iTBS. The activation of the left DLPFC (t = 2.783, p = 0.012) and left M1 (t = 2.752, p = 0.013) were significantly decreased and the relationship between the left DLPFC and M1 was significant after iTBS (r = 0.575, p = 0.014). Correlation analysis showed the hemoglobin concentration of M1 was negatively correlated with the RMS of the right GM (r = -0.659, p = 0.03) and positively correlated between CCI of the right TrA/SLM (r = 0.503, p = 0.047) after iTBS. There was no significant difference in the brain or muscle activation change in the left leg-standing condition between before and after iTBS. Conclusion: Intermittent theta burst stimulation over the left DLPFC seems to be able to improve the muscle activation pattern during postural control ability in challenging postural task, which would provide a new approach to the treatment of CLBP.

Leptin is upregulated in epididymitis and promotes apoptosis and IL-1ß production in epididymal epithelial cells by activating the NLRP3 inflammasome.

Epididymitis, one of the most common urological disease, is a significant cause of male infertility. Leptin is capable of modulating both reproduction and immune response. We analyzed the serum and seminal plasma levels of leptin in infertile patients with or without chronic epididymitis. Experimental epididymitis models were generated by administrating 200 µg Lipopolysaccharide (LPS) to Sprague-Dawley rats. The expression of leptin in epididymis were detected using qPCR, Western blots 6-72 h after injection, and using immunohistochemistry 72 h after injection. Besides, rat epididymal epithelial cells were isolated as an in vitro model and were treated with leptin (5-40 ng/ml, 6-48 h), LPS (1ug/ml, 6 h), and NLRP3 inflammasome inhibitor MCC950 (10 µM, 2 h). Cell Counting Kits-8 assay and Annexin V/PE assay were used to evaluate cell viability and apoptosis. Quantitive PCR and ELISA assay were used to detected inflammatory cytokines interleukin-1beta (IL-1ß) production. Western Blots were used to detect molecular related to cell apoptosis, IL-1ß maturation, and NLRP3 inflammasome. We found that patients with chronic epididymitis presented a significantly higher level of seminal plasma leptin and correlated declined sperm progressive motility. Leptin and leptin receptor expression in epididymis was significantly upregulated 24 h after LPS administration both in mRNA and protein level, and highly expressed in the epididymis epithelium 72 h after LPS administration. In epididymal epithelial cells, leptin reduced cell viability and promoted apoptosis in a concentration-dependent manner via cleavage of caspase-9, caspase-3, and PARP. Leptin enhanced the LPS-induced production of IL-1ß, which was associated with increased IL-1ß maturation and caspase-1 activation. Furthermore, NLRP3 inhibitor MCC950 attenuated the effects of leptin or co-treatment with LPS on NLRP3, ASC expression, IL-1ß maturation, and caspase-1 activation, which indicated that leptin promotes IL-1ß production via activating the NLRP3 inflammasome. These data suggested that leptin may act as a potential evaluation and treatment target for epididymitis and male subfertility.

Comprehensive transcriptome analysis based on RNA sequencing identifies critical genes for lipopolysaccharide-induced epididymitis in a rat model.

Epididymitis is a commonly diagnosed disease associated with male infertility. However, little is known about the molecules that are involved in its development. This study was to identify critical genes associated with lipopolysaccharide-induced epididymitis and analyze the molecular mechanism of epididymitis through RNA sequencing. Experimental epididymitis models were generated by administering male Sprague-Dawley rats' lipopolysaccharide. A total of 1378 differentially expressed genes, including 531 upregulated and 847 downregulated genes, were identified in the epididymitis model rats compared with those in sham-operated rats by RNA sequencing. Functional enrichment analyses suggested that the upregulated genes were markedly enriched in inflammation-related biological processes, as well as in the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interactions, complement and coagulation cascades, and in the chemokine signaling pathway. Four downregulated genes (collagen type XXVIII alpha 1 chain [Col28α1], cyclin-dependent kinase-like 1 [Cdkl1], phosphoserine phosphatase [Psph], and fatty acid desaturase 2 [Fads2]) and ten upregulated genes (CCAAT/enhancer-binding protein beta [Cebpß], C-X-C motif chemokine receptor 2 [Cxcr2], interleukin 11 [Il11], C-C motif chemokine ligand 20 [Ccl20], nuclear factor-kappa-B inhibitor alpha [Nfkbiα], claudin 4 [Cldn4], matrix metallopeptidase 9 [Mmp9], heat shock 70 kDa protein 8 [Hspa8], intercellular cell adhesion molecule-1 [Icam1], and Jun) were successfully confirmed by real-time polymerase chain reaction. Western blot demonstrated that CDKL1 was decreased, while MMP9 and NFKBIA were increased in the experimental model group compared with those in the sham-operated group. Our study sheds new light on the understanding of the early response of the epididymis during bacterial epididymitis.