Evaluation of the therapeutic effects of rehabilitation therapy on patients with amyotrophic lateral sclerosis-a meta-analysis.

Objective: To investigate the effect of rehabilitation therapy on the global function, respiratory function, and quality of life in patients with amyotrophic lateral sclerosis (ALS). Methods: PubMed, Web of Science, and The National Library of Medicine (NLM) were systematically searched and the search period was between the date of database establishment and December 31, 2023. The outcome measures finally analyzed included the ALS functional rating scale/revised (ALSFRS/ALSFRS-R), forced vital capacity percentage predicted (FVC%), fatigue severity scale (FSS), and maximal expiratory pressure (MEP). Results: A total of 13 randomized controlled trials (RCTs) were included, and 5 outcome measures were pooled and analyzed. A total of 657 patients with ALS were enrolled, with 299 in the experimental group (rehabilitation therapy, such as resistance training, endurance training, aerobic training, respiratory muscle training, and standard rehabilitation therapy) and 358 in the control group (conventional interventions, such as simple joint movements or daily stretching). The ALSFRS scores were better in the experimental group than in the control group at 0-4 months (MD = 3.36, 95% CI: 0.82, 5.91, Z = 2.59, p = 0.009) and at 5-8 months (MD = 5.00, 95% CI: -2.42, 7.58, Z = 3.80, p < 0.001). Moreover, the ALSFRS-R scores of the experimental group was better than that of the control group at 5-8 months (MD = 2.83, 95% CI: 1.21, 4.45, Z = 3.42, p < 0.001) and 9-12 months (MD = 1.87, 95% CI: -0.37, 4.11, Z = 1.63, p = 0.10). It was also found that the MEP value of the experimental group was significantly better than that of the control group after intervention (MD = 18.49, 95% CI: 1.47, 35.50, Z = 2.13, p = 0.03). However, there were no significant differences in FVC% value and FSS scores at 0-5 months and 6-12 months between the two groups. Conclusion: Rehabilitation therapy is helpful in improving the short-, medium-, and long-term global function score of patients with ALS, with positive effects on respiratory function.

MicroRNA-16 inhibits the lipopolysaccharide-induced inflammatory response in nucleus pulposus cells of the intervertebral disc by targeting TAB3.

INTRODUCTION: A variety of inflammatory mediators are produced by the degenerative human intervertebral disc (IVD) tissues spontaneously, suggesting their role in the development of intervertebral disc degeneration (IDD). Our present study was designed to investigate the regulatory effect of microRNA-16 (miR-16) on the lipopolysaccharide (LPS)-induced inflammatory response in nucleus pulposus (NP) cells of the IVD. MATERIAL AND METHODS: NP cells were treated with LPS to induce inflammatory responses. The expression of miRNA and genes was determined by qRT-PCR. Western blot and an ELISA kit were used to detect the proteins and protein expression, respectively. A dual luciferase reporter assay was applied to identify the correlation between a miRNA and a gene, and to test nuclear factor-κB (NF-κB) activity. RESULTS: The results suggested that miR-16 positively regulated the mRNA and protein expression of extracellular matrix (ECM) genes (including aggrecan and collagen II) in NP cells, while it was negatively correlated with ECM degrading enzymes (including MMP3, MMP13, ADAMTS4, ADAMTS5) and related genes of nitric oxide (NO) reaction. Further studies revealed that miR-16 could oppositely regulate NF-κB and MAPK pathways by directly mediating their upstream gene TAB3. CONCLUSIONS: Our study suggested that, in NP cells of the IVD, miR-16 could exert inhibitory effects on the LPS-induced inflammatory response through NF-κB and MAPK pathways by directly mediating TAB3. In this way, miR-16 would play a protective role against LPS-induced IDD and inflammation. Therefore, miR-16 may be a novel therapeutic target for the inhibit of the ECM in the IVD.

Elevated Serum Levels of Monocyte Chemotactic Protein-1/Chemokine C-C Motif Ligand 2 are Linked to Disease Severity in Patients with Fibromyalgia Syndrome

Background: Elevated levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 have been identified in fibromyalgia patients. Aims: To examine the potential association among serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 with disease severity of fibromyalgia. Study Design: Cross-sectional study. Methods: Seventy-nine female patients with fibromyalgia and 75 healthy normal controls were included in our study. Serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 were detected by enzyme-linked immune sorbent assays. The existence of tender points was evaluated based on the standardized manual tender point examination. Pressure pain thresholds at the knees, and bilateral trapezius muscles were measured with an algometer. A visual analog scale and the Revised Fibromyalgia Impact Questionnaire were utilized to assess the degree of pain and functional abilities. Results: Serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 were significantly greater in patients with fibromyalgia compared with healthy controls (151.6±31.9 pg/mL vs 103.3±25.2 pg/mL, p<0.001). Patients with severe fibromyalgia had significantly higher serum levels of chemokine C-C motif ligand 2 than patients with mild and moderate fibromyalgia (173.1±21.9 pg/mL vs 151.0.0±35.1 pg/mL, p=0.01). Patients with moderate fibromyalgia revealed markedly augmented serum levels of chemokine C-C motif ligand 2 compared with patients with mild fibromyalgia (151.0±35.1 pg/mL vs 133.3±23.9 pg/mL, p=0.03). Serum levels of chemokine C-C motif ligand 2 were positively associated with tender point scores (r=0.455, p<0.001). In addition, serum levels of chemokine C-C motif ligand 2 were positively associated with pressure pain thresholds in both knees and bilateral trapezius muscles (knees: r=-0.349, p=0.002; trapezius muscles: r=-0.318, p=0.004). Finally, we found elevated serum levels of chemokine C-C motif ligand were also positively associated with the visual analog scale (r=0.368, p=0.001), and the Fibromyalgia Impact Questionnaire score (r=0.401, p<0.001). Conclusion: Elevated serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 are linked to disease severity of fibromyalgia. Therapeutic interventions inhibiting monocyte chemotactic protein-1/chemokine C-C motif ligand 2 in fibromyalgia deserve additional studies.

Cyclic enzymatic amplification method for highly sensitive detection of nuclear factor-kappa B.

Effective detection of the intracellular expression level of transcription factors is important for biological research and medical diagnosis. This study proposes a rapid and simple fluorescence sensing strategy for highly sensitive detection of a transcription factor, nuclear factor-kappa B (NF-κB). NF-κB binds to double-stranded DNA duplex, one of which is then protected from Exonuclease III (Exo III) digestion. An Exo III-mediated hydrolysis cycle on TaqMan probes is then triggered to achieve highly sensitive detection of NF-κB. This method can detect NF-κB with concentration as low as 45.6 pM. Furthermore, sequence-specific binding of NF-κB to DNA provides good selectivity. This method can be used for the direct quantification of nuclear proteins extracted from cells. More importantly, by simply replacing the sequence of the probe binding site, this method can also be used for reliable quantification of other DNA-binding proteins and is thus a universal sensing protocol. This strategy can be a powerful technology in the areas of disease diagnosis and pharmaceutical research.

Prognostic significance of CDC25C in lung adenocarcinoma: An analysis of TCGA data.

OBJECTIVE: Cell division cycle 25C (CDC25C) is involved in the regulation of the G2/M phase transition and is associated with various cancers, including non-small cell lung cancer. We evaluated its prognostic value in lung adenocarcinoma (LUAD) based on data from The Cancer Genome Atlas (TCGA). METHODS: Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate relationships between clinical-pathologic features and CDC25C expression. Cox regression analyses and the Kaplan-Meier method were used to evaluate factors contributing to prognosis. Gene set enrichment analysis (GSEA) was performed. RESULTS: High CDC25C expression in LUAD was associated with a high tumor extent (odds ratio (OR) = 2.23 (1.52-3.29), P < 0.001), regional lymph node invasion (OR = 2.18 (1.48-3.22), P < 0.001), OR = advanced stage (OR = 2.47 (1.72-3.59), P < 0.001), and poor status (OR = 1.87 (1.19-2.96), P = 0.007). A univariate analysis showed that high CDC25C expression is associated with a short overall survival (OS) (HR: 1.873; 95% CI: 1.385-2.535; P < 0.001) and poor progression-free survival (HR: 1.503; 95% CI: 1.173-1.926; P = 0.0012). In a multivariate analysis, high CDC25C expression was associated with poor OS (HR = 2.193; CI: 1.394-3.452, P = 0.001). GSEA showed the enrichment of cell cycle, apoptosis, p53-dependent G1 DNA damage response, S-phase, mitotic M-M G1 phases, and FA-mediated cell death in the CDC25C high-expression phenotype. CONCLUSIONS: CDC25C predicts poor prognosis in LUAD and may function in cell cycle regulation and FAS-mediated apoptosis.

MiR-214 Regulates the Human Hair Follicle Stem Cell Proliferation and Differentiation by Targeting EZH2 and Wnt/ß-Catenin Signaling Way In Vitro.

miR-214 plays a major role in the self-renewal of skin tissue. However, whether miR-214 regulates the proliferation and differentiation of human hair follicle stem cells (HFSCs) is unknown. Primary HFSCs were isolated from human scalp skin tissue, cultured, and identified using flow cytometry. An miR-214 mimic and inhibitor were constructed for transfection into HFSCs. The MTS and colony formation assays examined cell proliferation. Immunofluorescence detected the localization and expression levels of TCF4, ß-catenin, and differentiation markers. Luciferase reporter and TOP/FOP Flash assays investigated whether miR-214 targeted EZH2 and regulated the Wnt/ß-catenin signaling pathway. Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2), Wnt/ß-catenin signaling-related proteins, and HFSC differentiation markers in cells subjected to miR-214 transfection. miR-214 expression was remarkably decreased during the proliferation and differentiation of HFSCs into transit-amplifying (TA) cells. Downregulation of miR-214 promotes the proliferation and differentiation of HFSCs. Overexpression of miR-214 led to decreased expression of EZH2, ß-catenin, and TCF-4, whereas downregulation of miR-214 resulted in increased expression of EZH2, ß-catenin, and TCF-4 as well as TA differentiation markers. Immunofluorescence assay revealed that inhibiting miR-214 triggered the entry of ß-catenin and TCF-4 into the nucleus. The luciferase reporter and TOP/FOP Flash assays demonstrated that miR-214 directly targets EZH2 and affects Wnt/ß-catenin signaling. The miR-214/EZH2/ß-catenin axis could be considered a candidate target in tissue engineering and regenerative medicine for HFSCs.