Nerve Growth Factor Levels Research Articles

Melancholic Depression Is Accompanied by Increased Level of Nerve Growth Factor in Blood Serum

Melancholic Depression Is Accompanied by Increased Level of Nerve Growth Factor in Blood Serum

The Role of Breast Milk Neurotrophin Levels in Infantile Colic Pathogenesis: A Cross-Sectional Case-Control Study.

Objective: Immaturity of the digestive tract and enteric nervous system is a widely accepted theory for infantile colic (IC) etiopathogenesis. The study aimed to show whether neurotrophins that are necessary for normal functioning and development of the gastrointestinal system have a role in the pathogenesis of IC. Materials and Methods: The IC group (n = 75) comprising the mothers of infants with IC and the control group (n = 75) were included to this cross-sectional case-control study. Brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and nerve growth factor (NGF) levels of breast milk samples were evaluated by immunosorbent analysis method. Results: The mean age of infants with IC was 7.3 ± 2.8 weeks, while the mean age of the control group was 8.1 ± 2.9 weeks (p = 0.110). No significant difference was found between the breast milk BDNF, GDNF, CNTF, and NGF levels of two groups (p = 0.941, p = 0.510, p = 0.533, p = 0.839, respectively). Conclusions: This is the first report comparing the neurotrophin levels of the breast milk samples taken from the mothers of infants with and without IC. The study demonstrated that breast milk neurotrophin levels of the mothers did not differ significantly between the infants with and without IC.

Multidisciplinary team collaboration impact on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke.

This study aimed to study the impact of multidisciplinary team collaboration on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke. For this purpose, 200 post-stroke hemiplegic patients admitted from March 2022 to February 2023 were selected and randomly divided into a control group (100) and an observation group (100). The control group was given routine nursing care, while the observation group was given a multidisciplinary team collaboration model. The neurotroph in [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)] and nutritional status [hemoglobin (HGB), serum albumin (ALB), transferrin (TRF)] of patients were compared before and after the intervention on the second day of admission and on the 30th day of intervention. The FUGL Meyer (FM) motor function assessment scale, NIHSS National Institutes of Health Stroke Scale, and the Specialized Quality of Life Scale (SS-QIL) for stroke patients were used to assess limb motor function, balance function, degree of neurological impairment, and life quality. Results showed that before intervention, there was no statistically significant difference in the levels of NGF, BDNF, IGF-1, HGB, ALB, TRF, limb motor function, balance function, neurological deficits, and quality of life scores between the two (P>0.05); After intervention, the levels of NGF, BDNF, IGF-1, HGB, ALB, and TRF in the observation group were significantly higher (P<0.05); The FM and SS-QOL of patients in the observation group were significantly higher (P<0.05); The NIHSS score of patients in the observation group was significantly lower (P<0.05). In conclusion, multidisciplinary team cooperation can significantly improve the level of neurotrophin, reduce the degree of nerve defect, and promote the recovery of limb function, balance function and life quality for stroke patients with hemiplegia.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study

ObjectivesPrevious studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). MethodsWe conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. ResultsThe results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016–1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (β-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81–0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696–0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057–1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049–1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024–1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05–1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044–1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. ConclusionsThis study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation

BackgroundSleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD.MethodsA mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis.ResultsThe mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD.ConclusionThe current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.

Sex differences in lower urinary tract function in mice with or without spinal cord injury.

We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

An in silico study of protein-protein interactions and design of novel peptides for TrkA in ameloblastoma

Ameloblastoma is a benign odontogenic jawbone tumor. The binding of Nerve growth factor (NGF) to receptor tyrosine kinase A (TrkA) promotes cell survival, proliferation, and differentiation via PI3K/AKT and Ras/MAPK signaling. Although the exact cause of ameloblastoma remains unknown, elevated levels of NGF and TrkA expression in ameloblastoma are associated with aggressive tumor behavior and poor patient outcomes. It is previously demonstrated that His 4, Arg 9, and Glu 11 residues of NGF made crucial interactions with the TrkA subunit. The main aim of our present study to develop potential therapeutic strategies by identifying promising peptide candidates. The objectives include starting with a detailed in silico analysis to identify a crucial peptide sequence of NGF that is bound by TrkA, creating a library of novel peptides from the identified peptide sequence through a single-point mutation on interacting residues (His 4, Arg 9, and Glu 11), and selecting the top peptides based on docking score, interactions analysis, and desirable pose analysis. The study ultimately designed a hybrid peptide candidate through the simultaneous and continuous mutation of the top residues, resulting in a peptide that exhibited a more specific interaction with TrkA, blocking the binding site and preventing the interaction between NGF and TrkA. Communicated by Ramaswamy H. Sarma

Cdk5 activation promotes Cos-7 cells transition towards neuronal-like cells.

Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear. Cdk5 kinase activity was measured by [γ-32P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa. P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression. p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.

Mechanism of propofol-induced apoptosis in neonatal rat oligodendrocytes

To explore the molecular mechanism of propofol-induced apoptosis in oligodendrocytes. Fortyfive neonatal (7 days old) SD rats were randomized into 3 groups (n=15) for a single intraperitoneal injection of saline (control), long chain fat emulsion, or propofol (50 mg/kg). Eight hours after the injection, the rats were examined for mRNA and protein expressions of caspase-3, caspase-8, and caspase-9 in the brain tissues using qPCR and Western blotting, and the expression levels of nerve growth factor (NGF) mRNA and P-PI3K/P-PAkt were also detected. Compared with those in the control group, the neonatal rats with propofol injection showed significantly up-regulated mRNA and protein expressions of caspase-3, caspase-8, and caspase-9 in the brain tissue (P<0.05) with significantly down-regulated expressions of NGF mRNA and P-PI3K/P-PAkt (P<0.05). Propofol induces apoptosis in oligodendrocytes by activating the caspase family protein members involved in triggering cell apoptosis and inhibiting the anti-apoptosis mechanism.

Neuroprotective Activity of Premna latifolia on Streptozotocin Induced Diabetic Neuropathy in Rats

The leaves of plant Premna latifolia Lam are traditionally used for treating diabetes and related complications. Presently ethanolic extract of leaves of plant P. latifolia explored for the neuroprotective potential in rat model of streptozotocin induced diabetic neuropathy. The intra-peritoneal route administered streptozotocin 60 mg/kg body weight to induce experimental diabetes, then treatment were not given for two weeks to develop diabetic complications. After two weeks of induction, animals were treated with extract 100 and 200 mg/kg per day for the duration of five weeks. The neuroprotective effect was assessed using Eddy’s hot plate and tail immersion method. Also, measuring blood sugar and cytokines cause inflammations like interleukins, tumor necrosis factor and a neurotrophin in the sciatic nerve. Thiobarbituric acid reactive substances reduced glutathione and activity levels of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase measured in the sciatic tissue. Extract normalizes blood glucose in diabetic neuropathy rats brought on by streptozotocin. The diabetic neuropathy rats show significant reductions in the period when the tail retracts and the paws are licked or jumped. In these rats pro-inflammatory cytokines level in sciatic nerve was significantly high. In addition, the oxidative stress bio-markers level altered significantly in sciatic nerve tissue. Diabetic neuropathy-developing rats treated with extract for five weeks reduce the levels of nerve growth factor, oxidative stress indicators, and pro-inflammatory cytokines rise in the sciatic nerve tissue. Ethanolic extract of P. latifolia possesses neuroprotective action in streptozotocin-induced diabetic neuropathy.

Integrating plasma metabolomics and gut microbiome to reveal the mechanisms of Huangqi Guizhi Wuwu Decoction intervene diabetic peripheral neuropathy

Ethnopharmacological relevanceHuangqi Guizhi Wuwu Decoction (HGWD) is a classic traditional Chinese herbal formula from “Synopsis of Golden Chamber,” which is used to treat blood stagnation and has been used for alleviating diabetic peripheral neuropathy (DPN) in the clinic. However, the mechanisms of HGWD intervention DPN are still to be discovered. Aim of the studyThis study aims to explore the mechanism of HGWD intervention DPN by integrating plasma metabolomics and gut microbiome. Materials and methodsBKS Cg-m+/+Leprdb/J (db/db) mice with DPN were at 16 weeks of age. The indices of DPN phenotypes in db/db mice, pathomorphology of the sciatic nerve, intraepithelial nerve fibers (IENF) of the foot pad, levels of blood lipids and oxidative stress, and inflammatory reaction were used to appraise the HGWD efficacy. Finally, the pharmacological mechanisms of HGWD intervening DPN were explored by metabolomics and 16S rRNA gene sequencing. ResultsHGWD reversed DPN phenotypes in db/db mice, improved peripheral nerve structure, ameliorated the level of blood lipids and nerve growth factor in plasma, enhanced antioxidant capacity, and alleviated inflammatory responses. Plasma metabolomics disclosed that HGWD remarkably regulated the unusual levels of thirty-seven metabolites involved in sphingolipid metabolism, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and amino acid biosynthesis pathways. The gut microbiome showed that nine bacteria were highly correlated with the efficacy of HGWD in DPN. Integrating analysis of microbiome and metabolomics demonstrated that the interaction of four bacteria with four metabolic pathways might be the significant mechanism of HGWD intervention in DPN. ConclusionsThe mediation of gut microbiota and plasma metabolism may be the potential mechanism of HGWD ameliorating DPN in db/db mice. The interaction of Lactobacillus, Alloprevotella, Bacteroides, and Desulfovibio with four metabolic pathways might be the critical mechanism for HGWD treating DPN.

Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation.

Cranial irradiation (IR) negatively regulates hippocampal neurogenesis and causes cognitive dysfunctions in cancer survivors, especially in pediatric patients. IR decreases proliferation of neural stem/progenitor cells (NSPC) and consequently diminishes production of new hippocampal neurons. Memantine, an NMDA receptor antagonist, used clinically to improve cognition in patients suffering from Alzheimer's disease and dementia. In animal models, memantine acts as a potent enhancer of hippocampal neurogenesis. Memantine was recently proposed as an intervention to improve cognitive impairments occurring after radiotherapy and is currently under investigation in a number of clinical trials, including pediatric patients. To date, preclinical studies investigating the mechanisms underpinning how memantine improves cognition after IR remain limited, especially in the young, developing brain. Here, we investigated whether memantine could restore proliferation in the subgranular zone (SGZ) or rescue the reduction in the number of hippocampal young neurons after IR in the juvenile mouse brain. Mice were whole-brain irradiated with 6 Gy on postnatal day 20 (P20) and subjected to acute or long-term treatment with memantine. Proliferation in the SGZ and the number of young neurons were further evaluated after the treatment. We also measured the levels of neurotrophins associated with memantine improved neural plasticity, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). We show that acute intraperitoneal treatment with a high, non-clinically used, dose of memantine (50 mg/kg) increased the number of proliferating cells in the intact brain by 72% and prevented 23% of IR-induced decrease in proliferation. Long-term treatment with 10 mg/kg/day of memantine, equivalent to the clinically used dose, did not impact proliferation, neither in the intact brain, nor after IR, but significantly increased the number of young neurons (doublecortin expressing cells) with radial dendrites (29% in sham controls and 156% after IR) and enhanced their dendritic arborization. Finally, we found that long-term treatment with 10 mg/kg/day memantine did not affect the levels of BDNF, but significantly reduced the levels of NGF by 40%. These data suggest that the enhanced dendritic complexity of the hippocampal young neurons after treatment with memantine may contribute to the observed improved cognition in patients treated with cranial radiotherapy.

Plasma calcitonin gene-related peptide and nerve growth factor as headache and pain biomarkers in recently deployed soldiers with and without a recent concussion.

The objective of this study was to characterize the utility of calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) as potential biomarkers for headache and pain disorders in the post-military deployment setting. The need to improve recognition, assessment, and prognoses of individuals with posttraumatic headache or other pain has increased interest in the potential of CGRP and NGF as biomarkers. The Warrior Strong Study (NCT01847040) is an observational longitudinal study of United States-based soldiers who had recently returned from deployment to Afghanistan or Iraq from 2009 to 2014. The present nested cross-sectional analysis uses baseline data collected from soldiers returning to Fort Bragg, North Carolina. In total, 264 soldiers (mean (standard deviation [SD] age 28.1 [6.4] years, 230/264 [87.1%] men, 171/263 [65.0%] White) were analyzed. Mean (SD) plasma levels of CGRP were 1.3 (1.1) pg/mL and mean levels of NGF were 1.4 (0.4) pg/mL. Age was negatively correlated with NGF (-0.01 pg/mL per year, p = 0.007) but was not associated with CGRP. Men had higher mean (SD) CGRP plasma levels than women (1.4 95% confidence interval [CI; 1.2] vs. 0.9 95% CI [0.5] pg/mL, p < 0.002, Kruskal-Wallis test). CGRP levels were lower in participants who had a headache at the time of the blood draw (1.0 [0.6] pg/mL vs. 1.4 [1.2] pg/mL, p = 0.024). NGF was lower in participants with continuous pain (all types; 1.2 [0.4] vs. 1.4 [0.4] pg/mL, p = 0.027) and was lower in participants with traumatic brain injury (TBI) + posttraumatic headache (PTH) versus TBI without PTH (1.3 [0.3] vs. 1.4 [0.4] pg/mL, p = 0.021). Otherwise, CGRP and NGF were not associated with migraine-like headache, TBI status, or headache burden as measured by the number of medical encounters in crude or adjusted models. In this exploratory study, plasma levels of NGF and CGRP showed promise as biomarkers for headache and other types of pain. These findings need to be replicated in other cohorts.

Melancholic Depression is Followed by the Increased Serum Nerve Growth Factor Level

The aim of the work was to investigate the nerve grown factor (NGF) level in the blood serum in patients with melancholic depression (MD). The investigated group consists of 23 patients. At admission in the clinic (before any antidepressive treatment) the NGF concentration in patient’s serum was 278.28 ± 43.68 pg/mL that was significantly higher in comparison with controls 239.51 ± 22.15 pg/mL, (p 0.05), respectively. It is supposed, that the increased NGF level in serum of the MD patients can be connected with the impairment of the functioning of the brain-blood barrier and the increase of its permeability for the NGF.

Effect of Tirofiban Combined with Neurointerventional Therapy on Neurological Function of Patients with Acute Cerebral Infarction

Objective: To analyze the effect of tirofiban combined with neurointerventional therapy on neurological function of patients with acute cerebral infarction. Methods: 70 patients with acute cerebral infarction admitted between January 2022 and January 2023 were selected as research objects, and patients were divided into control group (neurological interventional therapy) and experimental group (tirofiban combined with neurointerventional therapy) according to the computerized grouping method. The treatment outcomes of both groups were compared. Results: The efficacy of the treatment in the experimental group was 94.9%, which was significantly higher that of the control group control group at 77.14% (P &lt; 0.05). Before treatment, there was no difference in the National Institutes of Health Stroke Scale and Barthel Index between the control group and the experimental group (P &lt; 0.05); after treatment, the NIHSS score of the experimental group was lower than that of the control group, and the BI score was higher than that of the control group (P &lt; 0.05). Before treatment, there was no difference in the levels of high-sensitivity C-reactive protein (hs-CRP) and neuron-specific enolase (NSE) between the control group and the experimental group (P &lt; 0.05); after treatment, the levels of hs-CRP and NSE in the experimental group were lower than those in the control group (P &lt; 0.05). Before treatment, there was no difference in the levels of carbon monoxide (CO), endothelin (ET), nerve growth factor (NGF), and myelin basic protein (MBP) between the control group and the experimental group (P &lt; 0.05); after treatment, the levels of CO and NGF in the experimental group were higher than those in the control group, and the levels of ET and MBP were lower than those in the control group, with statistical significance (P &lt; 0.05). Conclusion: Tirofiban combined with neurointervention is effective in treating acute cerebral infarction. It can not only control the development of the disease, but also improve the patients’ neurological function and the quality of life.

Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels.

Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.

Synthesis and secretion of Nerve Growth Factor is regulated by Nitric Oxide in bladder cells in vitro under a hyperglycemic environment

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 μM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 μM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2′-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome.

Nerve Growth Factor and Angiotensin Converting Enzyme 2 Levels in Children with Neurodevelopmental Disorders

Objective Neurodevelopmental disorders (NDDs) are the most common psychiatric disorders in childhood, and there are many factors in their etiology. In recent years, many biomarkers have been studied to elucidate the etiology of these disorders. In this study, it was aimed to investigate the levels of nerve growth factor (NGF) and angiotensin converting enzyme 2 (ACE2) in attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). Methods The study included 74 children with NDDs (the number of patients in ADHD, ASD and ID groups were 24, 25 and 25 respectively) and 30 healthy controls (HCs). Serum NGF and ACE2 levels were studied with ELISA kits, also complete blood count (CBC), levels of fasting glucose and serum lipids were assessed. Results ACE2 levels were found to be lower in NDD group than HCs in girls. In boys with ASD, triglyceride levels were significantly higher than other groups. Also a positive correlation was found between ACE2 and NGF levels when all sample assessed together. Conclusions This study is a premise for investigating ACE2 and NGF in NDDs. The role of these markers in ADHD, ASD, ID and other NDDs and their associations with gender should be assessed by studies in which both larger sample groups and more disorders.

Brain-derived neurotrophic factor and nerve growth factor expression in endometriosis: A systematic review and meta-analysis.

Endometriosis is diagnosed by laparoscopic surgery. The availability of biomarkers can help understand the pathophysiology and aid in the diagnosis of the condition. In this context, this review aimed to examine levels of expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are increased amongst patients with endometriosis and if they can serve as a potential biomarker. PubMed, CENTRAL, Scopus, Web of Science, and Embase databases were searched for studies comparing BDNF or NGF levels amongst endometriosis patients and controls. Data were pooled for serum and tissue levels of BDNF and NGF. Ten fulfilled the inclusion criteria. On comparing BDNF levels, it was noted that endometrial tissue had significantly higher expression of BDNF levels as compared to controls (SMD: 1.73 95% CI: 0.64, 2.82 I2=89%). Similarly, the meta-analysis found significantly higher serum levels of BDNF in endometriosis patients as compared to controls (SMD: 1.66 95% CI: 0.73, 2.59 I2=95%). Pooled analysis showed significantly increased levels of NGF in endometrial tissue as compared to controls (SMD: 4.15 95% CI: 0.11, 8.18 I2=98%) but with unstable results on sensitivity analysis. Only one study showed higher levels of NGF in serum amongst endometriosis patients. Limited data shows higher expression of BDNF in endometrial lesions and increased serum levels of BDNF in endometriosis patients. Similar results were noted for NGF but with very scarce data. Further research is needed to establish BDNF and NGF as suitable biomarkers for the disease.

Investigation of the protective effect of anzer propolis in cerebral ischemia-reperfusion injury.

Globally, stroke is the leading cause of disability and death. With the use of thrombolytic therapy, reperfusion injury, and its consequences came to the fore. We aimed to find out how anzer propolis, which can only be obtained in Turkey's Eastern Black Sea region, affected ischemia-reperfusion injury using biochemical and histological techniques. 32 female Wistar albino rats were divided into 4 groups, including a control group. Three of the groups underwent 30 minutes of induced ischemia via clamping of the common carotid artery, followed by ischemia-reperfusion injury through the release of the clamp. One group received no treatment, another received oral administration of 100 mg/kg of anzer propolis one hour before surgery, and the third group received oral administration of 40 mg/kg of acetylsalicylic acid just before surgery. Histopathological examination assessed apoptosis and tissue necrosis, while serum and brain tissue were evaluated for levels of nerve growth factor (NGF), Interlokin 1β (IL-1β), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAS), and total oxidant capacity (TOS). Anzer propolis and acetylsalicylic acid significantly reduced hyperemia in vessels, vacuolization in neurons, glial cell infiltration, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. The anzer propolis group had the highest NGF levels. The anzer propolis and acetylsalicylic acid groups had lower levels of TNF-a and IL-6 in the brain tissue than the ischemia-reperfusion group, while TAS levels were higher. The findings obtained in this study suggest that anzer propolis has a neuroprotective effect against ischemia-reperfusion injury and will have beneficial effects on neurodegeneration. We believe our findings will contribute to the clinical treatment of ischemia-reperfusion injury.