Serum Growth Factors Research Articles

Increase in serum nerve growth factor but not intervertebral disc degeneration following whole-body vibration in rats

BackgroundLow 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. MethodsMale 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. FindingsThe 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. InterpretationThis study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.

Improvements in skin quality parameters in postmenopausal participants after use of topical growth factor serum.

Photodamage can induce skin aging processes that can be particularly concerning for postmenopausal women. Growth factors from hypoxic human fibroblast-conditioned media have demonstrated improvements in skin quality parameters. The aim of the study was to assess efficacy and tolerability of topical combination-treatment hypoxic growth factor serum (TNS A+) in postmenopausal women with moderate to severe facial photodamage. In this 12-week, open-label, single-center study, participants used TNS A+ serum twice daily. Postmenopausal women (40-65 years of age) with Fitzpatrick skin types I-VI and modified Griffiths scale scores 4-9 were eligible. Clinical and participant-reported assessments were evaluated at Weeks 6 and 12. Statistical significance was defined as p≤ 0.05. There were 17 enrolled participants. TNS A+ treatment demonstrated significant improvements from baseline in fine lines and wrinkles in periocular, forehead, and cheek areas at Week 12 and the perioral area at Weeks 6 and 12. Significant improvements from baseline in coarse lines and wrinkles were observed for the perioral area at Week 12 and periocular and cheek areas at Weeks 6 and 12. Improvements in overall photodamage, skin tone evenness, and tactile roughness were significantly greater at Weeks 6 and 12 versus baseline. Most participants reported TNS A+ made their skin look and feel smooth, soft, and rejuvenated; improved skin radiance; made lines and wrinkles less apparent; and improved skin texture. No treatment-related adverse events were reported. The TNS A+ regimen was well tolerated and provided significant improvements in skin quality in postmenopausal women with moderate to severe facial photodamage.

Cytokine profile in patients with atrophic gastritis in comorbidity with thyroid gland pathology

Background. Optimization of the management of patients with precancerous conditions of the stomach in comorbid pathology is an urgent task of gastroenterology. The purpose of the study: to evaluate the content of pro- and anti-inflammatory cytokines, as well as the level of vascular endothelial growth factor (VEGF) at different degrees of vascularization of the thyroid gland in patients with atrophic gastritis. Materials and methods. A study was conducted in 120 patients with atrophic gastritis and thyroid pathology. All of them underwent a sonological examination of the thyroid gland using an ultrasound scanner Toshiba Xario (Japan), which revealed poor vascularization of the parenchyma in 82 (68.3%) cases, moderate vascularization was diagnosed in 20 (16.7%) patients and marked— in 18 (15.0%). Quantitative content of cytokines (interleukins (IL) 8, 10, 18, tumor necrosis factorα), vascular endothelial growth factor in the blood serum was determined by immunoenzymatic assay using Vector-Best reagents. Results. Among patients with poor vascularization, only atrophic changes of the gastric mucosa were diagnosed in almost half— 39 (47.6%) people, while dysplastic changes of the gastric mucosa were found in a third of patients with marked vascularization. Intestinal metaplasia was detected in half of cases, regardless of the degree of vascularization of the thyroid parenchyma. Cytokine imbalance was found in patients with atrophic gastritis, with the greatest shift in case of marked vascularization of the thyroid parenchyma due to a 4-fold increase in the level of pro-inflammatory cytokines IL-8 (р<0.05) and by 1.7 times of IL-18 (p<0.05), with a simultaneous decrease in the content of the anti-inflammatory cytokine IL-10 by 3.2 times (p<0.05) compared to control indicators. The level of VEGF in the blood serum of patients with atrophic gastritis with moderate and marked vascularization of the thyroid parenchyma was significantly increased by 1.5 (p<0.05) and 1.7 times (p<0.05), respectively, compared to that of people with poor vascularization. Correlations were revealed between the degree of vascularization of the thyroid parenchyma and the level of IL-8 (r=0.491; p=0.031) and VEGF (r=0.444; p=0.019) in patients with atrophic gastritis. Conclusions. Patients with atrophic gastritis had a cytokine imbalance, which deepens as the vascularization of the thyroid gland increases that is possibly related to common pathogenetic mechanisms of the development of comorbid pathology.

Analysis of cytokine gene polymorphisms in patients with chronic diffusional liver diseases in Perm krai

Aim. To estimate the concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (interleukin, IL-6), vascular endothelial growth factor (VEGF) in blood serum and to analyze the polymorphism of TNF-α cytokine genes in region 308G / A (rs1800629), IL-6 in region 174G / C (rs1800795) and VEGFA in region 634G / C (rs2010963) in patients with chronic diffuse liver diseases (CDLD) living in the Perm region. Materials and methods. In 193 patients with CDLD and 90 healthy donors, the concentration of cytokines in the blood serum was studied by ELISA and the analysis of cytokine gene polymorphism by PCR was performed. Results. In patients with CDLD, the concentration of pro-inflammatory cytokines TNF-α, IL-6 and the level of VEGF in the blood serum were significantly higher than in the control (p <0.001, respectively), while the maximum level of inflammation markers was noted in liver cirrhosis, and VEGF production - in chronic hepatitis C. Comparative analysis of single nucleotide polymorphisms of cytokine genes showed significant differences in the occurrence of the GA and AA genotypes of the TNF-α gene (G-308A), the carriage of the CG variant of the IL-6 gene (C-174G), as well as the C allele and CC homozygote for marker VEGF (G-634C), which in the population of patients with CDLD in the Perm region were recorded significantly more often than in the cohort of donors, which allows us to consider them as genetic markers of the risk of developing CDLD. Conclusion. An increase in the concentration of pathogenetically significant cytokines TNF-α, IL-6 and VEGF in liver diseases can develop against the background of gene polymorphisms of these molecules. Genetic markers can be used to assess the risk of developing and progression of CDLD.

Role of rTMS and Expression Levels of Serum Growth Factors Along with Neurophysiological Markers in Ischemic Stroke Recovery: A Double Blind, Parallel Group, Sham Controlled Randomized Study

Role of rTMS and Expression Levels of Serum Growth Factors Along with Neurophysiological Markers in Ischemic Stroke Recovery: A Double Blind, Parallel Group, Sham Controlled Randomized Study

Evaluation of the dynamics of changes in the quantitative content of neuron growth factor (Beta-NGF) in the blood serum of patients who have suffered an ischemic stroke under the influence of complex physical rehabilitation

The article is devoted to the study of dynamic of changes in the quantitative content of neuron growth factor (Beta-NGF) in the blood serum of patients who have suffered ischemic stroke under the influence of complex physical rehabilitation. 116 patients in the recovery period of ischemic stroke (IS) (from 3 to 6 months) were examined. The average age of the patients was 61.4±0.53 years. During the study all patients were divided into two groups depending on the type of rehabilitation treatment. Group 1 consisted of 66 patients who received standard drug therapy aimed at secondary prevention during the entire period of the study and undergoing a course of complex physical rehabilitation. Group 2 consisted of 50 patients who received only standard drug therapy as part of secondary IS prevention. The control group included 30 practically healthy persons of the appropriate age and subjects who, according to the anamnesis and neuroimaging data, had no signs of a previous IS. The average age of the control group was 61.07±0.75 years. Beta-NGF was determined in 22 patients of group 1 and group 2 before the beginning of inpatient treatment and after its completion. This study was also conducted once for 10 people from the control group. The analysis of the results showed a significant decrease in the content of Beta-NGF in blood serum in patients with IS in the recovery period, which, in our opinion, may be associated with hypoxic damage to the brain tissue. In favor of this, data indicate the presence of a strong correlation between the level of Beta-NGF content and MMSE indicators. Also, the obtained data suggest that a significant decrease in the level of Beta-NGF content can be an indicator of the presence of type 2 diabetes. Significantly higher quantitative content of Beta-NGF in blood serum and statistically significant differences in dynamic changes during the study in patients of the first group indicate that physical rehabilitation can contribute to an increase in the content of Beta-NGF and thus cause a positive effect on the restoration of functions impaired as a result of a brain catastrophe.

Effect of Bicalutamide Combined with Docetaxel on Serum PSA and VEGF Levels in Patients with Advanced Prostate Carcinoma

Objective To investigate the effect of bicalutamide combined with docetaxel on the levels of prostate-specific antigen (PSA) in serum and vascular endothelial growth factor (VEGF) in patients with advanced prostate carcinoma (PCa). Methods The clinical data of 103 patients with advanced PCa at our hospital between Feb. 2020 and Feb. 2021 were retrospectively analyzed, the 90 of whom screened by inclusion and exclusion criteria were finally chosen as research objects. They were divided into a control group and an experimental group according to the order of admission, with 45 cases in each group. The control group was treated with conventional treatment, while the experimental group underwent the combination of bicalutamide and docetaxel, and the clinical indices of the two groups were compared. Results After treatment, the serum indices in the experimental group were remarkably lower than those in the control group (P < 0.001), with remarkably lower incidence of toxic and side effects (P < 0.05) and higher Expanded Prostate Cancer Index Composite (EPIC) scores (P < 0.001) in the experimental group than in the control group. Conclusion The implementation of bicalutamide combined with docetaxel in patients with advanced PCa is effective in reducing the inflammatory expression and improving quality of life and has a higher safety profile. Compared with conventional treatment, this method is of high application value, and further studies will help establish a better solution for such patients.

LEDGF is a new growth factor in fetal serum

Fetal serum supports the immortal growth of mammalian cell lines in culture while adult serum leads to the terminal differentiation and death of cells in culture. Many of the proteins in fetal serum that support the indefinite division and growth of cancerous cell lines remain obscure. The peptides and proteins of fetal versus adult serum were analyzed by liquid chromatography, nano electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Three batches of fetal serum contained the Alpha Fetoprotein marker while adult serum batches did not. Insulin (INS), and insulin-like growth factor (ILGF), fibroblast growth factor (FGF), epidermal growth factor (EGF) and platelet derived growth factor (PDGF) were increased in fetal serum. New fetal growth factors including MEGF, HDGFRP and PSIP1 and soluble growth receptors such as TNFR, EGFR, NTRK2 and THRA were discovered. Addition of insulin or the homeotic transcription factor PSIP1, also referred to as Lens Epithelium Derived Growth Factor (LEDGF), partially restored the rounded phenotype of rapidly dividing cells but was not as effective as fetal serum. Thus, a new growth factor in fetal serum, LEDGF/PSIP1, was directly observed by tandem mass spectrometry and confirmed by add back experiments to cell culture media alongside insulin.

Apolipoprotein C3 and circulating mediators of preadipocyte proliferation in states of lipodystrophy

Adipogenesis is a complex process controlled by intrinsic and extrinsic factors that regulate preadipocyte proliferation, adipogenic capacity and maturation of metabolic function. Here we show that insulin and IGF-1 receptors are essential for mature adipocyte survival and that deletion of both IR and IGF1R specifically in fat using a tamoxifen inducible-AdipoQ-Cre (Ai-DKO) leads to rapid and severe loss of adipocytes in all depots, associated with a metabolic syndrome characterized by hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver, and pancreatic beta cell proliferation. In this model, this pathological phenotype reverses over a few weeks, in large part, due to preadipocyte proliferation and adipose tissue regeneration. Incubation of preadipocytes with serum from the Ai-DKO mice in vitro stimulates cell proliferation, and this effect can be mimicked by conditioned media from liver slices of Ai-DKO mice, but not by media of cultured Ai-DKO adipocytes, indicating a hepatic origin of the growth factor. Proteomic analysis of serum reveals apolipoprotein C3 (APOC3), a protein secreted by liver, as one of the most upregulated proteins in the Ai-DKO mice. In vitro, purified and delipidated APOC3 stimulates preadipocyte proliferation, however, knockdown of hepatic APOC3 in vivo in Ai-DKO mice is not sufficient to block adipose regeneration. Thus, lipodystrophy is associated with presence of increased preadipocyte-stimulating growth factors in serum. Our study indicates that APOC3 is one contributing factor to preadipocyte proliferation, however, other still-unidentified circulating growth factors are also likely present in Ai-DKO mice. Identification of these factors may provide a new approach to regulation of adipose mass in health and disease.

Abstract P3070: Distinct Inflammatory Milieu In Patients With Right Heart Failure

Introduction: Right heart failure (RHF) is associated with worse clinical outcomes in patients with heart failure (HF) and pulmonary hypertension. Previous studies have shown elevated circulating proinflammatory cytokines in patients with HF; however, no study has compared the inflammatory signature in patients with RHF to those with HF and preserved right ventricular (RV) function. Hypothesis: We predicted that patients with RHF would have a distinct inflammatory milieu compared to normal and HF patients. Methods: We recruited adult patients undergoing right heart catheterization (RHC) and excluded those with a history of transplant, autoimmune disease, malignancy, or infection. Patients underwent blood sampling during RHC and were classified into normal, HF, and RHF cohorts a priori . We then performed multiplex protein assay on serum targeting cytokines, chemokines, and growth factors. Results: A total of 43 patients were included. HF and RHF patients had similar demographics and cardiac indices, but the RHF cohort had elevated markers of congestion characterized by higher right atrial pressure and creatinine, and a trend towards higher bilirubin (Figure). Patients with RHF had elevated levels of select proinflammatory cytokines, chemokines, and growth factors. Of the factors measured, VEGF-A, soluble CD163, and CXCL12 were predictive of all-cause mortality and LVAD/transplant-free survival. Conclusion: Patients with RHF have a distinct proinflammatory signature compared to those with preserved RV function. VEGF-A, soluble CD163, and CXCL12 predicted clinical outcomes in an advanced HF population.

Correlation of VEGF Expression with Serous Effusion in Multiple Myeloma Patients

To investigate the expression level of vascular endothelial growth factor (VEGF) in serum of patients with multiple myeloma (MM) and its possible clinical significance. 68 patients with MM who were admitted to The First Affiliated Hospital of Bengbu Medical College from July 2019 to June 2020 were collected. The expression level of VEGF was detected by VEGF enzyme-linked immunosorbent assay, the correlation of VEGF expression with serous effusion in MM was explored, and the relationship between VEGF expression level and clinical features and prognosis of patients with MM was analyzed. The positive rate of VEGF was 36.76% (25/68) in 68 patients with MM, 10 cases (58.82%, 10/17) were VEGF positive in 17 MM patients with serous effusion. The expression level of VEGF in patients with positive serous effusion was significantly higher than that in patients with negative serous effusion (P<0.05); the expression level of VEGF in MM patients of the newly diagnosed and untreated group was significantly higher than that in the remission group after treatment (P<0.05), but there was no significant difference in the expression level of VEGF between the newly diagnosed group and the refractory/relapsed (R/R) group (P>0.05). Among 68 patients with MM, 48 patients underwent FISH examination, 28 cases had normal karyotype (58.33%), and 20 cases had abnormal karyotype (41.67%). The abnormal karyotype was mainly IgH rearrangement, with a total of 10 cases (20.83%); other cases: 1q21+, del (13q14), del (17p13) were 3 cases (6.25%), 2 cases (4.17%), 7 cases (14.58%), respectively. Compared with VEGF- group, the incidence of IgH rearrangement and del (17p13) in VEGF+ group was higher [IgH rearrangement: 35% vs 10.71%, P=0.043; del(17p13): 30% vs 3.57%, P=0.011]. Compared with negative serous effusion group, the incidence of del (17p13) in positive serous effusion group was higher (31.25% vs 6.25%, P=0.021). The proportion of patients with positive VEGF and serous effusion was 14.71% (10/68), and the proportion of patients with negative VEGF and negative serous effusion was 52.94% (36/68). There was a correlation between serous effusion and VEGF expression (r=0.264, P=0.029). The prognosis of MM patients with serous effusion is poor, and the expression of VEGF in serum of these patients is significantly high. The increased VEGF may be involved in the occurrence and development of serous effusion.

The Important Role of TaohongSiwu Decoction in Gut Microbial Modulation in Response to High-Salt Diet-Induced Hypertensive Mice

TaohongSiwu decoction (THSWD), a traditional Chinese recipe, has been widely used to treat hypertension since ancient times. However, the mechanisms of its action are still unclear. Herein, we aimed to explore the gut microbial activity of THSWD in high-salt diet-induced hypertensive mice. Eight percent high-salt (NaCl) diet was used to induce hypertension for 4 weeks in a mouse model. Meanwhile, THSWD was used to intervene in the high-salt diet-induced mice, and the efficacy was evaluated by different parameters. Here, we found that THSWD significantly restored blood pressure compared with the model group. Moreover, THSWD effectively protected endothelial function by significantly upregulating the level of nitric oxide (NO) and downregulating the level of endothelin-1 (ET-1), angiotensin I (AngI), and vascular endothelial growth factor (VEGF) in serum compared with the model group. Notably, THSWD significantly upregulated the relative abundance of Dubosiella and downregulated that of Cyanobium_PCC-6307 and DNF00809 at the genus level compared with the model group. The results of PCA and microbial distance calculation further exhibited that THSWD treatment resulted in significant regulation of the microbial community. Furthermore, compared with the model group, THSWD increased the level of vitamin k2 (VK2) in serum. These findings indicate that THSWD could protect blood pressure and endothelial function by regulating gut microbiota and promoting microbial metabolite VK2. These results show the important role of THSWD in regulating the gut microbiota in response to high-salt diet-induced mice.

Correlation of serum Insulin-Like Growth Factor one with acne severity

Background and Objectives: Acne is a common chronic inflammatory skin condition; Acne could present as inflammatory or non-inflammatory lesion. Acne can be varied in severity from patient to another, generally, it can present in mild, moderate or severe degree. Excessive production of sebum by sebaceous glands in the skin contributes in acne formation. One of the factors associated with the production of sebum is Insulin-Like Growth Factor in serum. Current study tries to find any association between acne severity and serum Insulin-Like Growth Factor. Method: On a sample of 40 female patients with acne, aged 14-26 years at the outpatient clinic as a cross sectional study. Serum IGF-1 level was compared to their acne severity across three groups, mild, moderate and severe acne. Global acne grading system was used to classify the acne severity. Results: Median levels of IGF-1 were 208.09 ng/ml. Mean serum level of IGF-1 is 254.53ng/ml, 200.03ng/ml and 172.39ng/ml in severe, moderate and mild acne respectively. Acne severity strongly associated with serum level of IGF-1 which is statistically significant. No significantly association between serum level of Insulin-Like Growth Factor and the age of patients was found. Likewise, the severity degree of acne has no association with body mass index Conclusion: There is a direct relationship between mean level of IGF-1 in patients with AV with degree of their acne severity

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C.

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.

PERSONALIZED APPROACHES TO TREATMENT OF COMPLEX CEREBRAL ARTERIOVENOUS MALFORMATIONS

Background . Cerebral AVMs are not static congenital lesions, but can grow, recur, and appear de novo after complete resection, embolization, or radiosurgery. Understanding the complex molecular biology of AVMs is critical to predicting their behavior during treatment and improving treatment outcomes. Objective . To study the dynamics of angiogenesis factors in the process of cerebral AVM embolization in order to develop a strategy for their personalized treatment. Methods . The study included 314 patients with AVM who received surgical treatment at the Department of Brain Vascular Surgery of the Polenov Neurosurgical Research Institute. Determined the level of vascular endothelial growth factor (VEGF), angiopoietin-2 (ANG-2) and matrix metalloproteinase-9 (MMP-9) in blood serum before and 24 hours after endovascular embolization using enzyme-linked immunosorbent assay (Personal Lab, Adaltis, Italy). Results . 48.4 % of primary patients with AVM showed an increase in VEGF, MMP-9, ANG-2. A high level of VEGF and MMP-9 demonstrated AVM III grades according to SpetzlerMartin, AVM with a hemorrhagic flow type, with a deep drainage pattern, with afferents from the external carotid artery. The return to control values of all elevated growth factors after total embolization confirms the lack of potency for AVM recurrence. The absence of a decrease in aniogenesis factors after radical, according to angiographic criteria, embolization is a sign of subtotal AVM shutdown. A personalized concept of embolization in patients with a high risk of growth and recurrence has been formulated.

HbA1c and Serum Level of VEGF in Diabetic Retinopathy Patients

Objective: This study aims to determine whether HbA1c level has a correlation with vascular endothelial growthfactor (VEGF) serum level in diabetic retinopathy (DR) patients.Methods: This is an analytical cross-sectional study of patients with DR due to type 2 diabetes, with a purposivesampling technique. Patients were grouped into non-proliferative DR (NPDR) and proliferative DR (PDR). HbA1cand VEGF serum levels were assessed by taking the patient’s venous blood.Results: A total of 82 samples were included, in which the mean HbA1c levels were 8.17% ± 1.91% and the medianVEGF levels were 85.78 ng/L (range 38.23-149.43 ng/L). A total of 23 out of 35 NPDR patients were female (65.7%),while 29 out of 47 PDR patients were male (61.7%). Approximately 61.7% of PDR patients had a DM duration ofmore than 10 years, while 62.9% of NPDR patients had DM duration of less than 10 years. There was an increasein the mean of HbA1c levels in the PDR group compared to NPDR, although it was not statistically significant (p =0.214), and there was no difference in the median VEGF levels of the two groups. Spearman’s correlation analysisrevealed no correlation between HbA1 and VEGF levels in diabetic retinopathy, in both the NPDR and PDRgroups (correlation coefficient 0.183 and -0.022 respectively).Conclusion: No statistically significant correlation was found between HbA1c and VEGF serum levels in diabeticretinopathy patients. In this study poor glycemic control were not proven for their implications for VEGFprogression. VEGF serum levels may not be used as a marker of DR severity.

Changes and Significance of Cytokines in Serum of Rabbits with Acute Pulmonary Embolism

Objective:To observe the changes of cytokines in serum of rabbits with acute pulmonary embolism, and to provide scientific basis for clinical treatment of the disease.Methods: The animal models of pulmonary embolism were established in 26 healthy rabbits by autologous thrombus reinfusion and normal saline injection, and the serum levels of cytokines (TNF-α, IL-1β, HGF) in the two groups were monitored by enzyme-linked immunosorbent assay.Results: The expression levels of serum inflammatory cytokines (TNF-α, IL-1β) increased in both groups of rabbits within 1-3 hours of the acute stage of embolism, but the expression levels of serum inflammatory cytokines in experimental group of rabbits with pulmonary embolism caused by thrombosis increased more obviously；There was no significant change in serum HGF of rabbits before and after embolization in group B. The serum HGF content of experimental rabbits at 1h, 3h, 12h, 24h and 48h after embolization was significantly higher than that before embolization.And in the acute stage of embolism (1-12 hours), it showed a gradual upward trend.Conclusion: The expression level of serum growth factor is different in different acute stages of pulmonary embolism. Detecting serum cytokines in rabbits with acute pulmonary embolism is of great reference significance for improving clinical diagnosis.

Previous biological therapy and impairment of the IFN-γ/IL-10 axis are associated with low immune response to 17DD-YF vaccination in patients with spondyloarthritis

Yellow fever (YF) vaccination is known to induce a suboptimal response in patients with autoimmune diseases (AIDs). To date, few studies have focused on the performance of 17DD-YF vaccination in patients with spondyloarthritis (SpA). In general, patients with SpA are young and have less comorbidities than other patients with AIDs, and frequently receive biological disease-modifying antirheumatic drugs (DMARDs) that may impact their response to vaccines. Taking this background information, the present study aimed to investigate whether the use of biological DMARDs, even after planned washout, or disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), would impact the overall performance of planned 17DD-YF primary vaccination in patients with SpA. For this purpose, 74 subjects were enrolled in a prospective study, including adult patients with SpA (SpA; n = 51) and a healthy control (HC; n = 23) group. Analysis of YF specific neutralizing antibodies test (PRNT), along with YF viremia and the levels of serum chemokines, cytokines, and growth factors were performed at distinct time points (D0, D3, D4, D5, D6, D7, D14, and D28). The BASDAI scores were evaluated at D0 and D180. Data demonstrated that overall, the SpA group presented lower PRNT titers and seropositivity rates as compared to the HC group (GeoMean = 112 vs. 440; 73% vs. 96%, respectively). In SpA subgroup analyses, previous biological DMARDs (BIO-IT) led to a lower PRNT titers (BIO-IT 79, 95% CI [39–150] vs. without biological DMARDs [non-BIO-IT] 159, 95% CI [94–267], p < 0.001). The non-BIO-IT group achieved a response similar to the HC group (81% vs. 96%, p = 0.112), whereas the BIO-IT group had a lower seroconversion rate (64% vs. 96% HC, p = 0.007). The BASDAI was not associated with PRNT levels and did not change after 6 months of follow-up. No differences in YF viremia were observed amongst subgroups. Higher baseline levels of serum biomarkers were observed in the BIO-IT group vs. the non-BIO-IT group, as well as in those with a BASDAI ≥ 4 vs. those with a BASDAI < 4. Increasing levels of several biomarkers were observed in SpA, especially in the BIO-IT and BASDAI ≥ 4 subgroups throughout the timeline kinetics, with impairment/disturbance in the IFN-γ/IL-10 axis around the peak of viremia (D5). Altogether, these findings suggested that the use of biological DMARDs impacts the response to the 17DD-YF vaccine, even after planned washout. Therefore, previous biological DMARD therapy, the inflammatory status prior vaccination, and impairment of the IFN-γ/IL-10 axis at the peak of viremia may determine the immunogenicity of 17DD-YF vaccination in patients with SpA.

Antirheumatoid Arthritic Effects of Sabia parviflora Wall. Leaf Extracts via the NF-κB Pathway and Transient Receptor Potential Protein Family.

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou, Sabia parviflora Wall. provides antiviral properties against hepatitis, eliminates wind and dampness, and exhibits anti-inflammatory and pain relief properties. It has also been shown to treat rheumatoid arthritis (RA) and other diseases. However, the pharmacodynamic mechanism of S. parviflora Wall. for RA has not been reported. In this study, we identified the effective compounds of S. parviflora Wall. leaves against RA and discussed the mechanism against complete Freund’s adjuvant-induced arthritis (AIA) based on inflammatory proteins and transient receptor potential (TRP) proteins. S. parviflora Wall. leaf extracts (0.64 g/kg, 0.32 g/kg, and 0.16 g/kg, once daily) were given orally for 21 days. On the 15th day of complete Freund’s adjuvant-induced RA, the effects of this medicine on RA rats were investigated. S. parviflora Wall. extracts increased body weight, decreased foot swelling, and reduced thymus and spleen indices in model rats. Most of pannus in the synovial tissue of RA rats disappeared upon treatment, and the local inflammatory cells were greatly reduced when given the fraction of n-butanol (0.64 g/kg/d, 0.32 g/kg/d, and 0.16 g/kg/d) of 70% alcohol-soluble fraction of S. parviflora Wall. leaves. In addition, the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-15 (IL-15), and vascular endothelial growth factor (VEGF) in the RA rat serum was inhibited. The active compounds inhibited the expression of TNF-α, IL-1β, IL-6, IL-10, IL-15 and nuclear factor kappa-Bp65 (NF-κBp65) inflammatory protein and TRP protein transient receptor potential melastatin-5 (TRPM-5) and transient receptor potential channel-6 (TRPC-6), to reduce the expression of VEGF in synovial tissue of RA rats and relieve redness and edema. High-performance liquid chromatography identified six flavonoids and three triterpenoid saponins as active compounds. These findings suggest S. parviflora Wall. leaves may play a role in RA treatment by inhibiting the release of inflammatory factors as well as participating in the inflammatory protein expression in the NF-κB pathway and TRP protein family.

Serum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen’s d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.