RESUMO
BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
Assuntos
Biomarcadores , Transtorno Bipolar , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/sangue , Biomarcadores/sangue , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/sangue , Fatores de Crescimento Neural/sangue , Antimaníacos/uso terapêuticoRESUMO
BACKGROUND: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. METHODS: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. RESULTS: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. CONCLUSION: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.
Assuntos
Autoanticorpos , Moléculas de Adesão Celular , Fatores de Crescimento Neural , Fenótipo , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Masculino , Feminino , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/imunologia , Fatores de Crescimento Neural/imunologia , Fatores de Crescimento Neural/sangue , Pessoa de Meia-Idade , Autoanticorpos/sangue , Idoso , Adulto , Citocinas/sangue , Nós Neurofibrosos/imunologia , Contactina 1/imunologiaRESUMO
OBJECTIVE: Mesencephalic astrocyte-derived neurotrophic factor (MANF) expressions are dramatically up-regulated in injured brain tissues, thereby conferring neurological protective effects. We intended to determine significance of serum MANF as a prognostic biomarker of intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study done from February 2018 to July 2021, 124 patients with new-onset primary supratentorial ICH were consecutively enrolled. Also, a group of 124 healthy individuals constituted controls. Their serum MANF levels were detected using the Enzyme-Linked Immunosorbent Assay. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were designated as the two severity indicators. Early neurologic deterioration (END) was referred to as an increase of 4 or greater points in NIHSS scores or death at post-stroke 24 h. Post-stroke 90-day modified Rankin scale (mRS) scores of 3-6 was considered as a poor prognosis. Serum MANF levels were analyzed using multivariate analysis with respect to its association with stroke severity and prognosis. RESULTS: Patients, in comparison to controls, displayed markedly elevated serum MANF levels (median, 24.7 versus 2.7 ng/ml; P < 0.001), and serum MANF levels were independently correlated with NIHSS scores (beta, 3.912; 95% confidence interval (CI), 1.623-6.200; VIF = 2.394; t = 3.385; P = 0.002), hematoma volumes (beta, 1.688; 95% CI, 0.764-2.612; VIF = 2.661; t = 3.617; P = 0.001) and mRS scores (beta, 0.018; 95% CI, 0.013-0.023; VIF = 1.984; t = 2.047; P = 0.043). Serum MANF levels significantly predicted END and poor 90-day prognosis with areas under receiver operating characteristic curve at 0.752 and 0.787 respectively. END and prognostic predictive abilities were similar between serum MANF levels and NIHSS scores plus hematoma volumes (all P > 0.05). Combination of serum MANF levels with NIHSS scores and hematoma volumes had significantly higher prognostic capability than each of them (both P < 0.05). Serum MANF levels above 52.5 ng/ml and 62.0 ng/ml distinguished development of END and poor prognosis respectively with median-high sensitivity and specificity values. Using multivariate analysis, serum MANF levels > 52.5 ng/ml predicted END with odds ratio (OR) value of 2.713 (95% CI, 1.004-7.330; P = 0.042) and > 62.0 ng/ml predicted a poor prognosis with OR value of 3.848 (95% CI, 1.193-12.417; P = 0.024). Using restricted cubic spline, there was a linear correlation between serum MANF levels and poor prognosis or END risk (both P > 0.05). Nomograms were well established to predict END and a poor 90-day prognosis. Under calibration curve, such combination models were comparatively stable (using Hosmer & Lemeshow test, both P > 0.05). CONCLUSION: Increased serum MANF levels after ICH, in independent correlation with disease severity, independently distinguished risks of END and 90-day poor prognosis. Therefore, serum MANF may be a potential prognostic biomarker of ICH.
Assuntos
Astrócitos , Hemorragia Cerebral , Fatores de Crescimento Neural , Acidente Vascular Cerebral , Humanos , Biomarcadores , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico , Hematoma , Prognóstico , Estudos Prospectivos , Fatores de Crescimento Neural/sangueRESUMO
BACKGROUND: Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration. METHODS: Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration. FINDINGS: The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect. INTERPRETATION: This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.
Assuntos
Degeneração do Disco Intervertebral , Dor Lombar , Fatores de Crescimento Neural , Vibração , Animais , Masculino , Ratos , Degeneração do Disco Intervertebral/sangue , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/sangue , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Fatores de Crescimento Neural/sangue , Ratos Sprague-Dawley , Vibração/efeitos adversosRESUMO
BACKGROUND: Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. METHODS: A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. RESULTS: Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI (P = 0.019) and CHA2DS2-VASc score (P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF (P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF (P < 0.001). CONCLUSIONS: Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF.
Assuntos
Fibrilação Atrial , Remodelamento Atrial , Moléculas de Adesão Celular Neuronais , Fatores de Crescimento Neural , Acidente Vascular Cerebral , Tromboembolia , Idoso , Fibrilação Atrial/complicações , Moléculas de Adesão Celular Neuronais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Tromboembolia/diagnóstico , Tromboembolia/etiologiaRESUMO
Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein encoded by SERPINF1 and our previous study reported that PEDF may have antidepressant effects. As a key brain region regulating cognition, memory and emotion, the prefrontal cortex (PFC) has been studied extensively in major depressive disorder (MDD), but there are few reports on the relationship between PEDF and the PFC. In this study, enzyme-linked immunosorbent assay showed that the PEDF level was decreased in the plasma of MDD patients compared with that of healthy controls. Western blotting validated that the PEDF expression in the PFC was downregulated in the mouse chronic social defeat stress and rat chronic unpredictable mild stress models of depression. Correspondingly, normal mice overexpressing PEDF in the PFC showed depression-resistant phenotypes. We detected PFC metabolite levels by liquid chromatography-tandem mass spectrometry and found significant upregulation of 5-hydroxyindoleacetic acid, kynurenine, 5-hydroxytryptamine, ornithine and glutamine, and downregulation of 5-hydroxytryptophan, glutamic acid and aspartic acid in PEDF-overexpressing mice compared with control mice, in which no such changes were detected. Combined with the above findings, this provides an insight into a potential mechanism of the antidepressant effects of PEDF via the PFC, which may help to improve understanding of depression pathophysiology.
Assuntos
Depressão/sangue , Proteínas do Olho/metabolismo , Fatores de Crescimento Neural/metabolismo , Córtex Pré-Frontal/metabolismo , Serpinas/metabolismo , Estresse Psicológico/metabolismo , Adulto , Animais , Depressão/patologia , Regulação para Baixo , Proteínas do Olho/sangue , Proteínas do Olho/genética , Feminino , Ácido Glutâmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/genética , Fenótipo , Serpinas/sangue , Serpinas/genética , Estresse Psicológico/genética , Triptofano/metabolismoRESUMO
BACKGROUND/AIM: Multiple myeloma (MM) is characterized by high production of immunoglobulins resulting in a constant source of endoplasmic reticulum (ER)-stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified as a possible circulating biomarker that could help in monitoring ER-stress mediated diseases. MATERIALS AND METHODS: To assess the relevance of MANF in MM, we performed in silico and in vitro analysis in malignant cell lines including the myeloma cell line RPMI 8226. Serum MANF concentration was compared between healthy subjects (n=60), patients with MM (n=68), or those with monoclonal gammopathy of undetermined significance (MGUS) (n=73). RESULTS: MANF mRNA expression was upregulated in the RPMI 8226 cell line, and higher secretion of MANF was measured in RPMI 8226 supernatant. Serum MANF levels were not significantly different between MM or MGUS patients and those in age- and sex-matched healthy controls. CONCLUSION: MANF was not validated as a biomarker of interest in MM patients. Its potential implication in myeloma pathogenesis should be investigated.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Mieloma Múltiplo/metabolismo , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/genética , Estudos Retrospectivos , Adulto JovemRESUMO
(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4/5 seems to display contradictory and inconsistent conclusions.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Exercício Físico , Fatores de Crescimento Neural/sangue , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Regulação para CimaRESUMO
Objective: Adult growth hormone deficiency (AGHD) is a rare chronic inflammatory disease caused by damage to the pituitary gland and is accompanied by disorders of multiple metabolic pathways. By examining the correlation between the serum mesencephalic astrocyte-derived neurotrophic factor (MANF) levels of AGHD patients and those of normal controls, we hope to elucidate the close relationship among MANF, lipid metabolism and insulin resistance in AGHD and discuss the potential therapeutic value of MANF. Methods: This study included 101 AGHD patients and 100 healthy subjects matched for sex, age, height, and weight. Anthropometric parameters and biochemical indicators such as body mass index, waist circumference, hip circumference, serum MANF level, blood lipids and insulin level were measured. The above patients were also divided into several subgroups for correlation analysis based on indicators such as insulin resistance and BMI. Results: The serum circulating MANF content of AGHD patients was significantly lower than that of the normal control group (5.235 (0.507-17.62) ng/ml (n=101) vs. 10.30 (1.84-16.65) ng/ml (n=100); p<0.0001), and circulating MANF levels were linearly correlated with HOMA-IR in the AGHD population (R=0.481, P=0.0041). When MANF was at pathological concentrations (lower than the mean circulating MANF of normal controls), the lowest concentration tertile (OR=21.429 p<0.0001) had a significantly higher disease odds ratio, Framingham risk score and 10-year risk of atherosclerotic cardiovascular disease than the highest concentration tertile. Conclusions: MANF has a significant correlation with insulin resistance in the AGHD state. There is a strong correlation with abnormal glucose and lipid metabolism in the obese AGHD population. MANF is also a good assessment factor for the risk of cardiovascular disease in AGHD patients and has excellent therapeutic potential.
Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Transtornos do Crescimento/complicações , Fatores de Crescimento Neural/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
Biomarkers predict World Trade Center-Lung Injury (WTC-LI); however, there remains unaddressed multicollinearity in our serum cytokines, chemokines, and high-throughput platform datasets used to phenotype WTC-disease. To address this concern, we used automated, machine-learning, high-dimensional data pruning, and validated identified biomarkers. The parent cohort consisted of male, never-smoking firefighters with WTC-LI (FEV1, %Pred< lower limit of normal (LLN); n = 100) and controls (n = 127) and had their biomarkers assessed. Cases and controls (n = 15/group) underwent untargeted metabolomics, then feature selection performed on metabolites, cytokines, chemokines, and clinical data. Cytokines, chemokines, and clinical biomarkers were validated in the non-overlapping parent-cohort via binary logistic regression with 5-fold cross validation. Random forests of metabolites (n = 580), clinical biomarkers (n = 5), and previously assayed cytokines, chemokines (n = 106) identified that the top 5% of biomarkers important to class separation included pigment epithelium-derived factor (PEDF), macrophage derived chemokine (MDC), systolic blood pressure, macrophage inflammatory protein-4 (MIP-4), growth-regulated oncogene protein (GRO), monocyte chemoattractant protein-1 (MCP-1), apolipoprotein-AII (Apo-AII), cell membrane metabolites (sphingolipids, phospholipids), and branched-chain amino acids. Validated models via confounder-adjusted (age on 9/11, BMI, exposure, and pre-9/11 FEV1, %Pred) binary logistic regression had AUCROC [0.90(0.84-0.96)]. Decreased PEDF and MIP-4, and increased Apo-AII were associated with increased odds of WTC-LI. Increased GRO, MCP-1, and simultaneously decreased MDC were associated with decreased odds of WTC-LI. In conclusion, automated data pruning identified novel WTC-LI biomarkers; performance was validated in an independent cohort. One biomarker-PEDF, an antiangiogenic agent-is a novel, predictive biomarker of particulate-matter-related lung disease. Other biomarkers-GRO, MCP-1, MDC, MIP-4-reveal immune cell involvement in WTC-LI pathogenesis. Findings of our automated biomarker identification warrant further investigation into these potential pharmacotherapy targets.
Assuntos
Proteínas do Olho/sangue , Lesão Pulmonar , Aprendizado de Máquina , Fatores de Crescimento Neural/sangue , Doenças Profissionais , Ataques Terroristas de 11 de Setembro , Serpinas/sangue , Adulto , Biomarcadores/sangue , Bombeiros , Humanos , Exposição por Inalação/estatística & dados numéricos , Estudos Longitudinais , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/epidemiologia , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Doenças Profissionais/sangue , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To compare the effects of 12-week high-intensity interval training (HIIT) and vigorous-intensity continuous training (VICT) on cognitive function, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors in overweight and obese elderly individuals. METHODS: Twenty-nine physically inactive older adults (18 males and 11 females) with a mean age of 64.8 ± 3.9 years were randomly divided into a control group (CON, n = 9), an HIIT group (4 × 3 min at 90% VO2max interspersed with 3 min at 60% VO2max, n = 10) and a VICT group (25 min at 70% VO2max, n = 10) and submitted to 12 weeks of training. Cognitive function questionnaires, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors were determined at baseline and post training. RESULTS: Twelve weeks of HIIT and VICT improved the VO2max (4.19 ± 2.21 and 1.84 ± 1.63 mL/kg/min, respectively, p = 0.005), sit-and-reach distance (8.7 ± 3.0 and 7.8 ± 3.8 cm, p = 0.033), choice reaction time (- 0.115 ± 0.15 and - 0.09 ± 0.15 s, p = 0.004) and one-leg stand time (4.4 ± 3.4 and 4.2 ± 4.0 s, p < 0.001) of the elderly participants. The serum concentrations of brain-derived neurotrophic factor (375.5 ± 247.9 and 227.0 ± 137.1 pg/ml, p = 0.006), nerve growth factor (33.9 ± 16.7 and 23.3 ± 14.5 pg/ml, p = 0.037), neurotrophin-3 (24.2 ± 9.33 and 16.3 ± 5.91 pg/ml, p = 0.006) and neurotrophin-4 (10.4 ± 3.8 and 7.8 ± 5.0 pg/ml, p = 0.029) increased significantly in the HIIT and VICT groups after training. In addition, compared to VICT, HIIT significantly increased VO2max and the serum neurotrophin-3 concentration. Serum concentrations of the neurotransmitters acetylcholine, dopamine and serotonin trended upward with training. No significant change was observed in the cognitive function questionnaire scores (p > 0.05). CONCLUSION: HIIT is suitable for elderly adults and is more effective than VICT for improving VO2max and serum neurotrophin-3 concentrations. CHINESE CLINICAL TRIAL REGISTRY NUMBER: No. ChiCTR1900022315, date of registration: 4 April 2019.
Assuntos
Treinamento Intervalado de Alta Intensidade , Fatores de Crescimento Neural/sangue , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Aptidão Física/fisiologiaRESUMO
Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.
Assuntos
Autoanticorpos , Moléculas de Adesão Celular , Fatores de Crescimento Neural , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/imunologia , Neuromielite Óptica/epidemiologia , PrevalênciaRESUMO
AIM: Little is known about whether overhydration (OH), measured using bioimpedance assay (BIA), is associated with CKD progression in patients with type 2 diabetes mellitus (T2DM). We hypothesised that OH was a predictor, and pigment epithelium-derived factor (PEDF) was a modifiable risk factor of CKD progression. METHODS: We conducted a prospective cohort study of 1,065 patients with clinically euvolemic T2DM who attended the diabetes centre in a tertiary hospital or primary care clinic. CKD progression was defined as a combination of the worsening of the KDIGO defined CKD category by eGFR and a ≥25% decline in eGFR compared to baseline. RESULTS: Patients with T2DM in the highest tertile of OH and relative OH (OH/ extracellular water > 7%) were positively associated with CKD progression (hazard ratio [HR] 1.45 [95% confidence interval (CI) 1.14-1.85; p = 0.003 and HR 1.29 [95%CI 1.05-1.59; p = 0.017]). There were positive associations between PEDF and CKD progression (ß = 1.10; p = 0.001) and between OH and CKD progression (ß = 0.21; p = 0.036). OH remained positively associated with CKD progression mediated by PEDF. CONCLUSIONS: OH is an independent risk factor for CKD progression in patients with T2DM. Our study supports the novel definition of PEDF as a positive mediator between OH and CKD progression.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/complicações , Proteínas do Olho/sangue , Falência Renal Crônica/patologia , Fatores de Crescimento Neural/sangue , Serpinas/sangue , Desequilíbrio Hidroeletrolítico/complicações , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Even though major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are among the most prevalent and incapacitating mental illnesses in the world, their diagnosis still relies solely on the characterization of subjective symptoms (many of which are shared by multiple disorders) self-reported by patients. Thus, the need for objective measures that aid in the detection of and differentiation between psychiatric disorders becomes urgent. In this paper, we explore the potential of neurosteroids and neurotrophic proteins as biomarkers for MDD and PTSD. Circulating levels of the GABAergic neuroactive steroid, allopregnanolone, are diminished in MDD and PTSD patients, which corroborates the finding of depleted neurosteroid levels observed in animal models of these disorders. The neurotrophic protein, brain-derived neurotropic factor (BDNF), is also reduced in the periphery and in the brain of MDD patients and depressed-like animals that express lower neurosteroid levels. Although the role of BDNF in PTSD psychopathology seems less clear and merits more research, we propose a causal link between allopregnanolone levels and BDNF expression that could function as a biomarker axis for the diagnosis of both MDD and PTSD.
Assuntos
Transtorno Depressivo Maior/diagnóstico , Fatores de Crescimento Neural/análise , Neuroesteroides/análise , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Animais , Biomarcadores/análise , Biomarcadores/sangue , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Humanos , Fatores de Crescimento Neural/sangue , Neuroesteroides/sangue , Pregnanolona/análise , Pregnanolona/sangue , Transtornos de Estresse Pós-Traumáticos/sangueRESUMO
PURPOSE: This study was conducted to determine the relationship between mesencephalic astrocyte-derived neurotrophic factor (MANF) and lipid metabolism with or without type 2 diabetes mellitus (T2DM). METHODS: Human serum samples were collected from 58 normal controls (NC), 40 subjects with hyperlipidemia (HLD) without T2DM, and 42 subjects with HLD and T2DM. Their MANF levels were detected using an enzyme-linked immunosorbent assay (ELISA). Subgroup analysis was performed in the group with HLD and T2DM based on fasting blood glucose (FBG) > 8.22 vs. FBG ≤ 8.22. Furthermore, the relationship between MANF levels and lipid indices was analyzed. RESULTS: Serum MANF levels were found to be significantly higher in the HLD group, both with and without T2DM (5.62 (3.59-7.11) and 4.21 (2.87-6.11)), both P < 0.001, than in the NC (2.81(1.81-4.01). MANF levels were higher in those with FBG > 8.22 than that in those with FBG ≤ 8.22. In addition, in the HLD without T2DM group, MANF levels were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and age, while LDL-C and age were independently related to MANF levels. The area under the curve (AUC) in the ROC analysis of MANF for the diagnosis of HLD without T2DM and HLD with T2DM was 0.709 and 0.841, respectively (P < 0.001). CONCLUSION: Serum MANF levels increased in the HLD with or without T2DM groups and was associated with lipid and glucose metabolism. MANF may be a useful marker for predicting the development of dyslipidemia in T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Hiperlipidemias , Metabolismo dos Lipídeos , Fatores de Crescimento Neural/sangue , Fatores Etários , LDL-Colesterol , Glucose/metabolismo , HumanosRESUMO
Sympathetic activation may trigger acute coronary syndromes. We examined the relation between circulating neurotrophic factors and hemostatic risk factors of atherothrombotic cardiovascular disease at baseline and in response to acute mental stress to establish a brain-heart link. In 409 black and white South Africans, brain-derived neurotrophic factor (BDNF) and fibrinolytic measures were assessed at baseline. Glial cell-derived neurotrophic factor (GDNF), S100 calcium-binding protein (S100B), von Willebrand factor (VWF), fibrinogen and D-dimer were assessed at baseline and 10 min after the Stroop test. Neurotrophins were regressed on hemostatic measures adjusting for demographics, comorbidities, cardiometabolic factors and health behaviors. Higher baseline BDNF was associated with greater stress-induced increase in fibrinogen (p = 0.003) and lower D-dimer increase (p = 0.016). Higher baseline S100B was significantly associated with higher baseline VWF (p = 0.031) and lower fibrinogen increase (p = 0.048). Lower baseline GDNF was associated with higher baseline VWF (p = 0.035) but lower VWF increase (p = 0.001). Greater GDNF (p = 0.006) and S100B (p = 0.042) increases were associated with lower VWF increase. All associations showed small-to-moderate effect sizes. Neurotrophins and fibrinolytic factors showed no significant associations. The findings support the existence of a peripheral neurothrophin-hemostasis interaction of small-to-moderate clinical relevance. The implications for atherothrombotic cardiovascular disease need further exploration.
Assuntos
Doenças Cardiovasculares/sangue , Fatores de Crescimento Neural/sangue , Adulto , População Negra , Feminino , Fibrinogênio/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de von Willebrand/metabolismoRESUMO
CONTEXT: Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain. OBJECTIVE: This work aimed to quantify RBP4, PEDF, and clusterin in paired serum and CSF samples of patients undergoing neurological evaluation. METHODS: A total of 268 patients (109 male, 159 female) were included. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay in duplicate. RESULTS: RBP4 was abundant in serum (mean, 31.9â ±â 24.2 µg/mL). The serum concentrations were approximately 145 times higher than in CSF (CSF to serum RBP4 ratio, 8.2â ±â 4.3â ×â 10-3). PEDF was detectable in serum (mean, 30.2â ±â 11.7 µg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to serum PEDF ratio, 42.3â ±â 15.6â ×â 10-3). Clusterin serum concentrations were abundant with mean levels of 346.0â ±â 114.6 µg/mL, which were approximately 40 times higher than CSF levels (CSF to serum clusterin ratio, 29.6â ±â 23.4â ×â 10-3). RBP4 and PEDF serum levels correlated positively with CSF levels, which were increased in overweight/obese patients and in type 2 diabetic patients. The CSF concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF correlated positively with inflammatory parameters. In detail, only RBP4 showed the kinetics and associations that are mandatory for a putative mediator of the fat-brain axis. CONCLUSION: RBP4, PEDF, and clusterin are permeable to the BBB and increase with the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis.
Assuntos
Clusterina , Proteínas do Olho , Fatores de Crescimento Neural , Proteínas Plasmáticas de Ligação ao Retinol , Serpinas , Adipocinas/sangue , Adipocinas/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/metabolismo , Clusterina/sangue , Clusterina/líquido cefalorraquidiano , Estudos de Coortes , Proteínas do Olho/sangue , Proteínas do Olho/líquido cefalorraquidiano , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/líquido cefalorraquidiano , Proteínas Plasmáticas de Ligação ao Retinol/líquido cefalorraquidiano , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Serpinas/sangue , Serpinas/líquido cefalorraquidiano , Adulto JovemRESUMO
Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges' g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges' g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges' g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges' g = - 0.795; 95% CI = - 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges' g = 0.182; 95% CI = - 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.
Assuntos
Transtorno do Espectro Autista/sangue , Fatores de Crescimento Neural/sangue , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Fator de Crescimento Neural/sangue , Neurotrofina 3/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity.