A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression.

Maladaptive changes of nerve injury-associated genes in dorsal root ganglia (DRGs) are critical for neuropathic pain genesis. Emerging evidence supports the role of long noncoding RNAs (lncRNAs) in regulating gene transcription. Here we identified a conserved lncRNA, named nerve injury-specific lncRNA (NIS-lncRNA) for its upregulation in injured DRGs exclusively in response to nerve injury. This upregulation was triggered by nerve injury-induced increase in DRG ELF1, a transcription factor that bound to the NIS-lncRNA promoter. Blocking this upregulation attenuated nerve injury-induced CCL2 increase in injured DRGs and nociceptive hypersensitivity during the development and maintenance periods of neuropathic pain. Mimicking NIS-lncRNA upregulation elevated CCL2 expression, increased CCL2-mediated excitability in DRG neurons, and produced neuropathic pain symptoms. Mechanistically, NIS-lncRNA recruited more binding of the RNA-interacting protein FUS to the Ccl2 promoter and augmented Ccl2 transcription in injured DRGs. Thus, NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathic pain management.

Relationship between brain-derived neurotrophic factor and immune function during dietary supplement treatment of elderly with Alzheimer's dementia.

BACKGROUND AND AIM: The objective of the present study was to investigate the relationships among pro-brain-derived neurotrophic factor (BDNF) and mature BDNF and immune functioning during aloe polymannose multinutrient complex (APMC) treatment in persons with moderate to severe Alzheimer's dementia (AD). MATERIALS AND METHODS: An open-label trial of 12 months was used to execute the study. Thirty-four adults with AD were enrolled and consumed four teaspoons/day of APMC for 12 months. Subjects were assessed at baseline and 12 months follow-up for proBDNF and BDNF and cytokines, growth factors, T-cell and B-cell subsets, and complete blood count to measure immune functioning. All biomarkers were intercorrelated. RESULTS: Several relationships were identified between proBDNF, BDNF, and BDNF/proBDNF ratio and immune function at 12 months, particularly BDNF with vascular endothelial growth factor (VEGF) (r=0.55, P=0.03), epidermal growth factor (EGF) (r=0.74, P=0.001), and CD95+CD3+ (%) (r=-0.64, P=0.03) and proBDNF with VEGF (r=0.64, P=0.02), EGF (r=0.86, P<0.001), and CD16+56+ (%) (r=-0.78, P<0.01). Other correlations were noted for various immune function variables with BDNF, proBDNF, and/or BDNF/proBDNF ratio at baseline and 12 months. Dichotomizing subjects on BDNF above and below 5000 pg/mL revealed additional relationships with platelets and neutrophils. CONCLUSIONS: The associations between BDNF and proBDNF and various immune markers, such as VEGF, EGF, and CD95+CD3+ ratio, provide insight into the link between neurological function and the immune system. These relationships were even stronger in response to APMC treatment, which lends support to previous findings showing improved immune function after dietary supplementation. RELEVANCE FOR PATIENTS: AD patients have conventional treatment options with limited efficacy for counteracting the deleterious effects of the disease on neurological function. The link between neurological and immune function has been understudied in this population. Overall, our results showed a significant beneficial relationship between immune and neurological function, particularly in response to 12 months of treatment with an all-natural polysaccharide-based dietary supplement that is a known immunomodulator. Thus, the use of this dietary supplement may benefit these patients by simultaneously improving immune and neurological function.

The effect of dietary supplementation on brain-derived neurotrophic factor and cognitive functioning in Alzheimer's dementia.

BACKGROUND AND AIM: The objective of the present study was to investigate the effect of an aloe polymannose multinutrient complex (APMC) on pro brain-derived neurotrophic factor (BDNF) and mature BDNF in persons with moderate to severe Alzheimer's dementia. METHODS: A 12-month open-label trial was utilized to evaluate the effect of the APMC on proBDNF and BDNF and their relationship to cognitive functioning. Thirty-four adults were enrolled and consumed 4 teaspoons/day of APMC for 12 months. Subjects were assessed at baseline and twelve months follow-up for proBDNF and BDNF and with a neuropsychological battery to measure cognitive functioning. Cognitive functioning was correlated with proBDNF and BDNF. RESULTS: Few adverse effects were reported. While proBDNF (baseline M = 6,108.9, SD = 854.9 and 12 months M = 5,799.2, SD = 573.4; p = 0.57) and BDNF (baseline M = 5,673.8, SD = 3,342.3 and 12 months M = 6,312.9, SD = 2,830.9; p = 0.29) did not significantly change, the correlations between the ADAS-cog total score and BDNF (r = -0.53, p = 0.04) and BDNF/proBDNF ratio (r = -0.58, p = 0.05) became statistically significant after 12 months of dietary supplementation. Other correlations were noted for various cognitive functioning assessments and BDNF and/or BDNF/proBDNF ratio at both baseline and 12 months. CONCLUSIONS: These findings suggest that the relationship between cognitive functioning and BDNF and BDNF/proBDNF ratio improved in response to consumption of a dietary supplement in persons with Alzheimer's dementia, which is consistent with our previous findings on cognitive functioning. RELEVANCE FOR PATIENTS: Overall, our results showed modest improvements in clinical outcomes for a disease that otherwise has no standard conventional approach to treatment with proven efficacy.

Physical Exposures, Work Tasks, and OSHA-10 Training Among Temporary and Payroll Construction Workers.

OBJECTIVE: We characterize and compare the self-reported physical exposures, work tasks, and OSHA-10 training in a non-probabilistic sample of temporary and payroll construction workers. METHODS: In June 2016, a total of 250 payroll and temporary general laborers employed at Florida construction sites completed a survey at the job site as part of the falls reported among minority employees (FRAME) study. RESULTS: Workers employed through temp agencies (57.1%) were significantly more likely to report moving or lifting materials more than 100 pounds than payroll workers (38.5%; P < 0.01). Temporary construction workers with 10-hour OSHA training (22.2%) spent significantly less time with intense hand use/awkward hand posture than temporary workers without 10-hour OSHA training (46.9%; P = 0.048). CONCLUSIONS: Temp construction workers with OSHA 10-hour training reported less hazardous physical postures than workers without the same training.