scholarly journals Tungsten accumulates in the intervertebral disc and vertebrae stimulating disc degeneration and upregulating markers of inflammation and pain

2021 ◽  
Vol 41 ◽  
pp. 517-530
Author(s):  
MP Grant ◽  
CR VanderSchee ◽  
H Chou ◽  
A Bolt ◽  
LM Epure ◽  
...  
Keyword(s):  
Disc Degeneration ◽  
Intervertebral Discs ◽  
The Body ◽  
Nociceptive Neurons ◽  
Protein Gene Product ◽  
Markers Of Inflammation ◽  
Tumour Formation ◽  
Calcitonin Gene ◽  
Tnf Α ◽  
Military Applications

Tungsten is incorporated in many industrial goods, military applications and medical devices due to its ability to impart flexibility, strength and conductance to materials. Emerging evidence has questioned the safety of tungsten exposure as studies have demonstrated it can promote tumour formation, induce pulmonary disease and alter immune function. Although tungsten is excreted from the body it can accumulate in certain organs such as the brain, colon, liver, kidneys, spleen and bones, where most of the bioaccumulation occurs. Whether prolonged tungsten exposure leads to accumulation in other tissues is unknown. The present study demonstrated that mice exposed to 15 ppm sodium tungstate for 4 weeks in their drinking water showed comparable accumulation in both the bony vertebrae and intervertebral discs (IVDs). Lumbar IVD height was significantly reduced in tungsten-exposed mice and accompanied by decreased proteoglycan content and increased fibrosis. In addition to catabolic enzymes, tungsten also increased the expression of the inflammatory cytokines IL-1β and tumour necrosis factor (TNF)-α as well as the neurotrophic factors nerve growth factor (NGF) and brain-derived nerve factor (BDNF) in IVD cells. Tungsten significantly increased the presence of nociceptive neurons at the endplates of IVDs as observed by the expression of calcitonin gene-related peptide (CGRP) and anti-protein gene product 9.5 (PGP9.5) in endplate vessels. The present study provided evidence that tungsten may enhance disc degeneration and fibrosis as well as increase the expression of markers for pain. Therefore, tungsten toxicity may play a role in disc degeneration disease.

Soy and the exercise-induced inflammatory response in postmenopausal women

2010 ◽  
Vol 35 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Kristen M. Beavers ◽  
Monica C. Serra ◽  
Daniel P. Beavers ◽  
Matthew B. Cooke ◽  
Darryn S. Willoughby
Keyword(s):  
Inflammatory Response ◽  
Postmenopausal Women ◽  
Controlled Trial ◽  
Exercise Bout ◽  
The Body ◽  
Significant Group ◽  
Oxidative Defense ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Before And After

Aging is associated with increasing inflammation and oxidative stress in the body, both of which can have negative health effects. Successful attenuation of such processes with dietary countermeasures has major public health implications. Soy foods, as a source of high-quality protein and isoflavones, may improve such indices, although the effects in healthy postmenopausal women are not well delineated. A single-blind, randomized controlled trial was conducted in 31 postmenopausal women who were assigned to consume 3 servings of soy (n = 16) or dairy (n = 15) milk per day for 4 weeks. Parameters of systemic inflammation (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)) and the oxidative defense system (superoxide dismutase (SOD), glutathione peroxidase, cyclooxygenase-2) were measured post supplementation, before and after an eccentric exercise bout performed to elicit an inflammatory response. A significant group-by-time effect for plasma TNF-α was observed (p = 0.02), with values in the dairy group increased post supplementation and then decreasing into the postexercise period. Additionally, significant time effects were observed for plasma SOD (p < 0.0001) and IL-6 (p < 0.0001) in the postexercise period. Overall results from our study do not support the notion that 4 weeks of daily soy milk ingestion can attenuate systemic elevations in markers of inflammation or oxidative defense. However, data do suggest that the downhill-running protocol utilized in this study can be effective in altering systemic markers of inflammation and oxidative defense enzyme activity, and that the ingestion of soy may help prevent fluctuations in plasma TNF-α.

scholarly journals Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shaoyi Wang ◽  
Jianlu Wei ◽  
Jie Shi ◽  
Qiting He ◽  
Xiaocong Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Intervertebral Discs ◽  
Inflammatory Factors ◽  
Wild Type ◽  
Tnf Α

Background. Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. Objectives. The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. Methods. We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. Results. In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Conclusion. Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.

scholarly journals Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-κB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Haichao Yu ◽  
Guowei Hou ◽  
Jiankang Cao ◽  
Yanyu Yin ◽  
Yunpeng Zhao ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Nucleus Pulposus Cells ◽  
Mitochondrial Ros ◽  
Tnf Α

Intervertebral disc degeneration (IVDD), one of the most common clinical diseases worldwide, causes disc herniation and sciatica. Recent studies have identified the involvement of mitochondrial dysfunction, inflammatory responses, and extracellular matrix degradation in IVDD. Mangiferin is known to protect against various diseases by inhibiting oxidative stress, suppressing inflammation reaction, and relieving mitochondrial dysfunction. Whether mangiferin can alleviate IVDD remains to be elucidated. In the present study, human nucleus pulposus cells (HNPCs) and mouse intervertebral discs were cultured and stimulated with TNF-α, with or without treatment of mangiferin. Moreover, we established a rat needle puncture model and injected mangiferin into the intervertebral discs to verify its protective effect on IVDD. Furthermore, the activity of the NF-κB signaling pathway was tested in vitro. Our results indicated that mangiferin alleviated the inflammatory response and reversed the loss of major intervertebral disc components. Besides, mangiferin reduced reactive oxygen species production, ameliorated mitochondrial damage, and decreased the expression of apoptosis-related parameters in stimulation of TNF-α. In addition, mangiferin antagonized the activation of the NF-κB signaling pathway induced by TNF-α. Collectively, mangiferin antagonized mitochondrial ROS in NP cells and protected against IVDD by suppressing the activation of the NF-κB signaling pathway, which might provide a potential therapeutic instrument for IVDD.

scholarly journals Long wavelength light that improves aged mitochondrial function selectively increases cytokine expression in serum and the retina

2021 ◽  
Author(s):  
Harpreet Shinhmar ◽  
Chris Hogg ◽  
Glen Jeffery
Keyword(s):  
Mitochondrial Function ◽  
Light Exposure ◽  
Cytokine Expression ◽  
The Body ◽  
Long Wavelength ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Cellular Markers ◽  
Selective Increase ◽  
Wavelength Light

Aged mitochondrial function can be improved with long wavelength light exposure. This reduces cellular markers of inflammation and can improve system function from fly though to human. Here, we ask what impact 670nm light has on cytokine expression using a 40 cytokine array in blood serum and retina in C57Bl6 mice. There was a relatively uniform increase in cytokine expression between 3 and 12 months of age in serum and retina. 670nm exposure was delivered daily for a week in 12 month old mice. This shifted patterns of cytokine expression in both serum and retina inducing a selective increase with some in serum increasing >5 fold. Changes in retina were smaller. In serum there were major increases in IL-7, 6, 13, 16 and 23, also in TNF-α and CXCL 9 and 10. In retina the increases were found mainly in some IL (interleukins) and CXCLs (chemokines). A few cytokines were reduced by light exposure. Changes in serum cytokines implies that long wavelengths impacts systemically even to unexposed tissues deep in the body. In the context of wider literature, increased cytokine expression may be protective. However, their upregulation by light merits further analysis as cytokines upregulation can also be negative.

scholarly journals Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 735
Author(s):  
Laura Mihaela Trandafir ◽  
Elena Cojocaru ◽  
Mihaela Moscalu ◽  
Maria Magdalena Leon Constantin ◽  
Ingrith Miron ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Cortisol ◽  
Predictive Power ◽  
Pediatric Patients ◽  
The Body ◽  
Control Group ◽  
Homa Index ◽  
Obese Patients ◽  
Metabolic Markers ◽  
Markers Of Inflammation

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

scholarly journals Expression of miR-195 and its target gene Bcl-2 in human intervertebral disc degeneration and their effects on nucleus pulposus cell apoptosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xue-Lin Lin ◽  
Zhao-Yun Zheng ◽  
Qing-Shan Zhang ◽  
Zhen Zhang ◽  
You-Zhi An
Keyword(s):  
Cell Proliferation ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Target Gene ◽  
Blank Group ◽  
Tnf Α

Abstract Objective To investigate the expression of miR-195 and its target gene Bcl-2 in intervertebral disc degeneration (IVDD) and its effect on nucleus pulposus (NP) cell apoptosis. Methods The expressions of miR-195 and Bcl-2 in NP tissues of IVDD patients were quantified by qRT-PCR and western blotting, respectively. NP cells were divided into blank group, TNF-α group, TNF-α + miR-NC group, TNF-α + siBcl-2 group, and TNF-α + miR-195 inhibitors + siBcl-2 group. Cell proliferation was detected by MTT assay, cell apoptosis evaluated by flow cytometry, and mitochondrial membrane potential (MMP) tested by JC-1 staining. Moreover, the function of miR-195 on IVDD in vivo was investigated using a puncture-induced IVDD rat model. Results IVDD patients had significantly increased miR-195 expression and decreased Bcl-2 protein expression in NP tissues. The expression of miR-195 was negatively correlated with the expression of Bcl-2 in IVDD patients. Dual-luciferase reporter gene assay indicated that Bcl-2 was a target gene of miR-195. In comparison with blank group, TNF-α group showed decreased cell proliferation and MMP, increased cell apoptosis, upregulated expression of miR-195, Bax, and cleaved caspase 3, and downregulated Bcl-2 protein, while these changes were attenuated by miR-195 inhibitors. Additionally, siBcl-2 can reverse the protective effect of miR-195 inhibitors on TNF-α-induced NP cells. Besides, inhibition of miR-195 alleviated IVDD degeneration and NP cell apoptosis in the rat model. Conclusion MiR-195 was significantly upregulated in NP tissues of IVDD patients, and inhibition of miR-195 could protect human NP cells from TNF-α-induced apoptosis via upregulation of Bcl-2.

scholarly journals Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance

2021 ◽  
Vol 22 (11) ◽  
pp. 5648
Author(s):  
Takashi Yurube ◽  
Hiroaki Hirata ◽  
Masaaki Ito ◽  
Yoshiki Terashima ◽  
Yuji Kakiuchi ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Time Course ◽  
The Body ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Autophagic Flux ◽  
Static Compression ◽  
Notochordal Cell ◽  
Notochordal Cells ◽  
Rat Tail

The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (n = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (n = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (n = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.

scholarly journals Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-α-Induced Damage of Human Dermal Fibroblasts

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 514
Author(s):  
Sullim Lee ◽  
Giang Do Hoang ◽  
Daeyoung Kim ◽  
Ho Sueb Song ◽  
Sungyoul Choi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Dermal Fibroblasts ◽  
The Body ◽  
Hazardous Substances ◽  
Human Dermal Fibroblasts ◽  
Cutaneous Lesions ◽  
Matrix Metalloproteinase 1 ◽  
Tnf Α ◽  
Necrosis Factor

The skin is an important organ in the human body that protects the body from environmentally hazardous substances. Reactive oxygen species (ROS) cause inflammatory reactions and degradation of the extracellular matrix leading to skin aging and various cutaneous lesions. This study evaluated the potential of isoflavones isolated from Maclura tricuspidata fruit to prevent TNF-α-induced skin inflammation in normal human dermal fibroblasts (HDFs). It focused on alpinumisoflavone (AIF) that suppressed the accumulation of ROS and nitric oxide (NO) in tumor necrosis factor-alpha (TNF-α)-treated HDFs. AIF inhibited the TNF-α-induced increase in matrix metalloproteinase-1, decreased procollagen I α1, and suppressed pro-inflammatory mediators and pro-inflammatory cytokines, including NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8 that trigger inflammatory responses. AIF inhibited nuclear factor-κB and activating protein 1 mitogen-activated protein kinases that were increased by TNF-α stimulation. These results suggest that AIF may protect skin from aging and various cutaneous lesions.

scholarly journals Cutaneous Hypersensitivity as an Indicator of Visceral Inflammation via C-Nociceptor Axon Bifurcation

2020 ◽  
Author(s):  
Yehong Fang ◽  
Shu Han ◽  
Xiaoxue Li ◽  
Yikuan Xie ◽  
Bing Zhu ◽  
...  
Keyword(s):  
Body Surface ◽  
The Body ◽  
Visceral Organ ◽  
Deep Tissue ◽  
Nociceptive Neurons ◽  
Chemically Induced ◽  
Acute Gastritis ◽  
Cutaneous Hypersensitivity ◽  
Evans Blue Extravasation

Abstract Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure. Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion (DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation (colitis, urocystitis, and acute gastritis) rat models. In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from double-labeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.

Effects of Moringa Oleifera Leaf Polysaccharide on Growth Performance and Immune Response of Broiler Chickens

2021 ◽  
Author(s):  
Hosameldeen Mohamed Husien ◽  
JunJie Huang ◽  
WeiLong Peng ◽  
ShuMei Zheng ◽  
JinGui Li
Keyword(s):  
Immune Response ◽  
Growth Performance ◽  
Broiler Chickens ◽  
Moringa Oleifera ◽  
The Body ◽  
Feed Consumption ◽  
Feed Additive ◽  
Control Group ◽  
High Dose ◽  
Tnf Α

Abstract Moringa oleifera (MO) is a widely used as the nutritious and non-traditional feed supplementation containing kinds of bioactive substances. However, the enhancement effect of Moringa oleifera leaf Polysaccharide (MOLP) as a feed additive in broilers growth performance and immunity remains unclear. In this study, MOLP was obtained by water extraction and alcohol precipitation method, then purified with Trichloroacetic acid (TCA) assay. Chickens were randomly divided into 4 groups, to receive different doses of MOLP (0, 0.1, 0.2, 0.4g/kg) in feed for 3 weeks. The body weight gain (BWG) and feed consumption were recorded for feed conversion ratio (FCR) and average daily feed intake (ADFI) calculation. Broiler chickens were sacrificed and sampled on day 14, 21, 28 (D 14, D 21, and D 28) respectively. Serological indicators, including total protein (TP), albumin (ALB), globulin (GLO), and creatinine (CREA) were detected. ELISA kits were applied for detecting the levels of immunoglobulin A (IgA), immunoglobulin G (IgG), interleukin-2 (IL-2), and tumor necrosis factor (TNF-α). From D 21 to D 28, the results showed that middle dose of MOLP significantly increased BWG and ADFI as well as liver and bursa indexes when compared with the control group. In addition, TP and GLO were also increased (P<0.05). All MOLP treatments enhanced the serum concentrations of IgG and IL-2 (P<0.01). Furthermore, results of quantitative RT-PCR showed that high dose of MOLP treatment significantly increased (P<0.001) the mRNA expression levels of IL-2 and TNF-α of chickens relative to the control group. In conclusion, the results showed that MOLP supplementation contributed to improve growth performance and immune response in broiler chickens, and MOLP could be considered as a promising feed additive.

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