Video
Drink It or Chew globalhumanhelp.orgve Mucus: Your Sinus, Chest \u0026 Lungs Will Love You! Dr. MandellResveratrol and respiratory health -
Especially in SSc-ILD. Balachandran and Adams, , can promote the occurrence of ILD. At present, preclinical studies have determined that some T cell subtypes are associated with fibrosis, such as Th2 and Th17, which promote fibrosis.
At present, the most studied ILD are IPF and SSc-ILD. The two diseases share similar common features, such as T cell profiles Th2, Th17, increased ratio of CD4 to CD8 T cells , T cell cytokine profiles IL-4, IL-5, IL, and IL of IPF, and IL-4, IL-5, IL-6, IL, IL, and IL in SSc-ILD Bagnato and Harari, In RA-ILD, like IPF and SSc-ILD, the expression of IL receptor was up-regulated, indicating that Th17 cell-mediated immunity was involved in the pathogenesis of ILD Wang et al.
These results indicated that the imbalance of T cell subsets might be involved in ILD formation. Recently, several studies have pointed to a possible role of B cells in IPF, RA, or ILD associated with connective tissue disease. Some studies have found that, compared with healthy people, the phenotype distribution of B cells in the peripheral blood of IPF patients is abnormal, and the percentage of plasmabytes in IPF patients is negatively correlated with forced vital capacity Xue et al.
The authors detected focal aggregates of CDpositive B cells in all IPF lung tissues using immunohistochemistry Xue et al.
Atkins et al. Recent studies have also found that the total peripheral blood B cell count is higher in patients with RA-ILD, but the frequency of memory B cells is lower. The mechanism may be that some of them selectively migrate to the lung tissue Shimizu et al. In some ILDs, B cell production of antibodies may play a key role.
For example, there is an association between antibodies, including anti-citrullinated protein antibodies ACPA and rheumatoid factor RF , and the risk of RA-ILD Katsumata et al. These results suggest that B cell-formed autoantibodies may be involved in the formation of ILD.
Previous studies have shown that NK cells play a key role in the pathogenesis of acute lung injury Liu et al. There are two different NK environments in human pulmonary fibrosis: one in the lung and the other in the peripheral blood. In pulmonary fibrosis, NK cells are thought to counteract the fibrotic activity of TGF-β by producing the anti-fibrotic mediator interferon-γ IFN-γ , thereby inducing anti-fibrotic signals in the lung Culley, As for NK cells in the peripheral blood, studies have found that the percentage and absolute number of NK cells in the peripheral blood of 11 IPF patients are both high Esposito et al.
These results suggest that NK cells may be involved in the formation of profibrotic, antifibrotic, and ILD conditions; however, further studies are needed. FIGURE 2. The related mechanism of ILD occurrence. Cytokines and growth factors, after binding to their corresponding receptors in immune cells or myofibroblasts, can be activated through different signal transduction pathways.
Activated immune cells can secrete a variety of cytokines. They further activate macrophages; T, B, and NK cells; and myofibroblasts. They are over-activated and can secrete pro-inflammatory and pro-fibrotic cytokines, which is the environment for the formation of inflammation and fibrosis in the lung.
Meanwhile, in different autoimmune diseases, B cells secrete corresponding antibodies, which are related to pulmonary fibrosis. In addition, IL-6 can activate myofibroblasts, causing them to undergo EMT and form ECM, which is deposited in the lung.
Eventually ILD is formed. TRAF6 activates TGF-β-activated kinase 1 TAK1 through Lyslinked polyubiquitination, which in turn is activated by phosphorylating MAP kinase kinases MKK MKK4, MKK3, and MKK6. MKKS further activate their downstream kinases JNK and p38, which can then phosphorylate their target transcription factors TF and regulate transcription Tzavlaki and Moustakas, In addition, TGF-β-induced ShcA tyrosine phosphorylation promotes Ras protein activation.
Studies have shown that TGF-β can also induce Sirtuin 1 activation and activate α -smooth muscle actin α-SMA Ma and Li, In addition, IL forms heterodimer complexes with its receptors ILRA and ILRC to recruit NF-κB activator 1 Act1 through SEFIR domain interactions.
Subsequently, Act1 binds to TRAF6 via its TRAF6 binding site, recruiting TRAF6 into the ILR complex Zhu and Qian, Act1 acts as E3 ubiquitin ligase to polymerize TRAF6.
In addition, heat shock protein HSP is also involved in ILD formation. HSP90 has been shown to directly regulate ERK through dissociation of the ERk-HSPCDC37 complex Erazo et al. HSP90 also regulates AKT, and activation of AKT pathway has been reported in different cells with different pathological functions for pulmonary fibrosis Colunga Biancatelli et al.
The receptor-associated JAK is then activated and phosphorylates the tyrosine residue in the tail of its receptor cell to form p-JAK. These phosphorylations act as docking sites for STAT and bind to them via its SH2 domain, which phosphorylates STAT and is activated by tyrosine phosphorylation to form p-STAT, which subsequently becomes a dimer and translocations from the cytoplasm to the nucleus, where they act as transcription factors Montero et al.
Thus, STATs are activated by JAKs and transferred from cytoplasm to nucleus, and then bind to specific DNA sequences to direct gene transcription, resulting in increased expression of pro-inflammatory cytokines TNF-α and IL-1β and pro-fibrotic cytokine IL-6 in the lung Yang et al.
In the lung, the above cytokines and growth factors are activated in immune cells through the above signal transduction pathways, resulting in the expression of pro-inflammatory, pro-fibrosis genes and α -SMA Ma and Li, , thus activating more immune cells including macrophages, T cells, B cells, and NK cells and lung fibroblasts Figure 2.
T cells and NK cells release pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, and IL and pro-fibrotic cytokines IL-6 Figure 2 Alesci et al. In addition to releasing cytokines, B cells can also differentiate into plasma cells and secrete ACPA, anti-SCL70 antibodies Bellamri et al.
Moreover, positive feedback amplifies the above signaling pathways and promotes the occurrence of pulmonary inflammation and fibrosis Lescoat et al. Lung fibroblasts can induce self-proliferation or mesenchymal transformation through the pathway, resulting in abnormal expression of α -SMA and EMC components, thus causing fibroblasts to lose differentiation and obtain mesenchymal phenotype of myofibroblasts, ultimately leading to ILD formation Duchemann et al.
RSV can enter cells by a variety of means e. passive diffusion, endocytosis, or via transporters and bind to specific receptors, such as the integrin receptor alphavβ3 Delmas and Lin, ; Ho et al.
It helps regulate innate and adaptive immunity, such as macrophages, B cells, T cells, and NK cells, thereby inhibiting overactivation of cells, reducing the production of pro-inflammatory or pro-fibrotic factors, and controlling the progression of ILD.
Effects of RSV on immune cells Table 2. The development of autoimmune diseases may result in damage to one or more body tissues or organs. Autoimmune diseases disorders of immune cells in the body, which cause immune cells to overactivate and produce a large number of inflammatory factors, such as TNF-α, IFN-γ, and IL-1β.
Overstrong immune response can simultaneously attack different organs or tissues, leading to local or systemic immune response, such as RA, amyotrophic lateral sclerosis ALS , PsO, SLE, IBD, etc. RSV is a well-studied substance known for its effects on a large number of chronic diseases and its numerous therapeutic benefits, including anti-regulatory immunity, anti-inflammatory, etc.
In autoimmune diseases, RSV can inhibit synovial macrophages, reduce angiogenesis, leukocyte and lymphocyte recruitment, fibroblast proliferation and protease secretion, especially in RA, and thus inhibit cartilage and bone destruction at pus formation sites Oliveira et al.
It can also inhibit the differentiation of T lymphocytes into Th2 and Th17, and reduce the activation of B cells and the production of autoantibodies Oliveira et al. Cytokines are also closely related to autoimmune diseases.
For example, macrophages increase the recruitment of neutrophils at the site of inflammation through the activation of NF-κB, and produce related cytokines IFN-γ, TNF-α, IL, IL, and IL, etc. In experimental animals, When IL-6, TNF-α and other disorders occur, they are sufficient to cause destructive arthritis Oliveira et al.
RSV not only inhibited TNF-α and IL-1β-induced NF-κB activation, but also activated SIRT1 and inhibited RelA acetylation in mice with arthritis. In addition, the expression of NF-κB-induced inflammatory factors such as TNF-α, IL-1β, IL-6, metalloproteinase MMP -1 and MMP3 is decreased Yamamoto and Gaynor, It can also reduce the mRNA expression levels of IL17 and IL19, reduce the thickness of animal skin and improve the damage caused by psoriasis Malaguarnera, In addition, RSV reduced mRNA expression levels of IL-6, TNF-α, IFN-γ, JAK, and STAT when treating inflammatory mice Yang et al.
Therefore, RSV may have some efficacy in the treatment of autoimmune diseases by regulating the immune system and interfering with multiple cellular and molecular processes see Table 3.
Epithelial interstitial transformation EMT is an important factor in the development of pulmonary fibrosis Tian et al.
Some studies have found that the activation of NF-κB is an effective inducer of EMT activation, suggesting a close relationship between pulmonary fibrosis, inflammation and EMT Chua et al.
In autoimmune diseases, some cytokines, such as IFN-γ, TNF-α, IL, and IL-6, are associated with ILD Montero et al. In addition, it has been found that JAK-STAT pathway plays an important role in early alveolitis and the development of ILD Banerjee et al. In RA-ILD mouse models, intraperitoneal injection of a JAK inhibitor tofacitinib improved symptoms and inhibited the progression of ILD Sendo et al.
RSV can not only reduce the levels of NF-κB and JAK-STAT, but also reduce the levels of IFN-γ, TNF-α, IL, and other cytokines, so RSV may have the potential to treat ILD, especially auto-immune-related ILD.
ILD is associated with decreased lung function, and complications can lead to rapid deterioration of the clinical course of ILD patients. In the past few years, two anti-fibrosis drugs pirfenidone and Nidanib have been approved for the treatment of ILD patients, but there are associated adverse reactions, including gastrointestinal adverse reactions, fatigue, weight loss, etc.
Morrow et al. More and more studies confirm that RSV is an ideal treatment for ILD. Fagone et al. Inflammatory cell infiltration, congestion and edema are reduced Liu et al. In addition, Li et al. found that RSV targeted TAK1, significantly inhibited TAK1 activation, inhibited alveolar macrophages in alveoli, and reduced lung inflammation and pulmonary fibrosis in mice Li et al.
In bleomycin-induced EMT-related pulmonary fibrosis, SIRT1 expression is decreased, and the expression of type I collagen and α -SMA is increased Rong et al. After RSV treatment, SIRT1 expression is increased, which reduces alveolar epithelial cell damage, fibroblast proliferation, collagen deposition and pulmonary fibrosis, and is related to lung protection Ma and Li, A recent study evaluated the effect of RSV on RA-ILD.
the expression of JAK and STAT were significantly reduced in lung tissue and decreased the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β.
Meanwhile, it can promote the production of anti-inflammatory factor IL and reduce lung inflammation Colunga Biancatelli et al. In addition, the authors found that RSV improved pulmonary pathology reduced inflammatory cell infiltration, reduced collagen deposition, significantly thinner alveolar wall thickness and reduced fibrosis degree Colunga Biancatelli et al.
In ILD, HSP90 expression was increased, and HSP90 ATPase activity was increased in fibroblasts isolated from fibrotic lung injury Sontake et al. HSP90 may also contribute to the development of pulmonary fibrosis through IL-6, as HSP90 mediates activation of the nuclear factor kappa light chain enhancer in the B cell NF-κB dependent inflammatory pathway, promoting IL-6 production Bohonowych et al.
In IPF, alveolar epithelial type II cells promote pulmonary fibrosis through HSPAKT signaling Chen et al. In SSc-ILD patients, HSP90 was overexpressed, and HSP90 could promote the persistence of myoblasts in pulmonary fibrosis by enhancing TGF-β signal transduction pathway Štorkánová et al.
In RA-ILD, IFN-γ produced by T cells stimulated by anti-citrullinated HSP90 indicated a TH1 immune response, and thus participated in the development of ILD Chen et al. In addition, inhibition of HSP90 has an effective antifibrotic effect in vitro and in mouse pulmonary fibrosis models Koh et al.
The use of HSP90 inhibitors showed that inhibition of HSP90 can down-regulate the expression of AKT, ERK, and NF-κB, regulate the stability of TGF-β receptor, and interfere with the Smad and non-Smad P-ERK TGF-β signaling cascade. Thus, EMT is reduced and cell proliferation, formation of fibrotic mediators and ECM are reduced Schumacher et al.
Studies have shown that RSV can inhibit HSP90 Liu et al. Therefore, RSV may have similar effects as an inhibitor of HSP HSP90 may be the target of RSV, which can inhibit signal transduction pathways, reduce cytokine levels and play the role of anti-fibrosis, so as to achieve the purpose of treating ILD.
However, there is still a lack of relevant research, and more studies are expected to further confirm. In conclusion, RSV inhibits different signaling pathways and immune cells, and therefore has therapeutic potential for treating ILD.
In general, RSV ingestion is generally well tolerated. In animal models, RSV has been shown to be non-irritating and genotoxic to the skin and eyes. This preliminarily proves that RSV is non-toxic and safe. However, some studies have found that RSV has certain side effects.
When rats were treated with 1. This indicates that high dose RSV has certain toxicity Hebbar et al. When RSV was administered simultaneously to rats at 0.
The toxicity of RSV to target organs remains to be further studied. In human subjects, a daily RSV dose of mg has been reported to be safe for a 60 kg person Moon et al. However, some adverse effects have been reported, and high dose RSV intake appears to have negative effects on metabolic status, endothelial health, inflammation, and cardiovascular markers in human patients Ramírez-Garza et al.
In a recent meta-analysis of 18 studies included, adverse reactions occurred in two studies Zhang et al. Adverse events occurred in three of the five patients. In the RSV group, one patient with a history of fatty liver disease developed asymptomatic and mild elevated alanine aminotransferase, another patient developed diarrhea and mild hypoglycemia, and one patient developed mild cellulitis at the biopsy site Goh et al.
In another study, which administered RSV mg once daily plus losartan Therefore, more in vivo studies involving animal models are necessary, and more clinical trials of RSV in humans are needed to verify its efficacy and safety, especially before it can be considered for therapeutic or prophylactic use in humans.
ILD is one of the most important factors that directly affect the quality of life of patients. Long-term use of immunosuppressant and antifibrotic drugs can lead to many inevitable side effects. In addition, current drug treatments are still insufficient to reduce ILD progression and mortality worldwide.
Bioactive natural ingredients derived from natural herbs may provide additional benefits in the prevention and treatment of ILD and represent an important source of new drug screening and development. It is also a potential and beneficial candidate for combination with other clinical antifibrosis agents.
It also indicated that the related derivatives of RSV and the extracted compounds may also be able to treat ILD.
Oral and intravenous radioisotope labeling of 14C RSVS suggests that the stage of biotransformation is a rate-limiting factor in RSV bioavailability. Therefore, targeted delivery of RSV to desired tissues or increased stability of RSV in vivo through the development of slow release systems are critical for improving bioavailability Santos et al.
In addition, RSVS have been reported to have synergistic therapeutic effects when combined with other bioactive ingredients and micronutrients, giving RSVS a more stable chemical structure, higher solubility, and easier absorption in the small intestine Williamson and Manach, The drug dosage of RSV in the treatment of ILD is still unclear, as the dosage used in different studies varies.
If clinical studies of RSV dose gradient Settings exist, deeper mechanisms of therapeutic effect may be clearly understood. Future studies should further explore the effects of different drug doses of RSV on treatment and the deeper mechanism, and open a new window for the treatment of ILD.
Although the results of most studies on polyphenols have proved promising, further research on animals and humans is warranted. By extensively evaluating the biological activity, efficacy, safety and appropriate dose of RSV, and determining specific molecular targets and structure-activity relationships, it provides a new way for clinicians to treat ILD.
RH and XH wrote the manuscript. YTY and YY collected the references. JL reviewed and revised the manuscript. All authors read and approved the final manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Alesci, A. Resveratrol and immune cells: A link to improve human health. Molecules 27 2 , PubMed Abstract CrossRef Full Text Google Scholar. Aquino-Galvez, A. MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility.
Atkins, S. Arthritis Rheum. Bagnato, G. Cellular interactions in the pathogenesis of interstitial lung diseases. Balachandran, S. Interferon-γ-induced necrosis: An antitumor biotherapeutic perspective. Interferon Cytokine Res. Banerjee, S. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: Current and future prospects.
Drugs 77 5 , — Bao, L. Resveratrol ameliorates fibrosis in rheumatoid arthritis-associated interstitial lung disease via the autophagy-lysosome pathway. Molecules 27 23 , Bellamri, N. Alteration of human macrophage phenotypes by the anti-fibrotic drug nintedanib.
Bellaye, P. Synergistic role of HSP90α and HSP90β to promote myofibroblast persistence in lung fibrosis. Bohonowych, J. Extracellular Hsp90 mediates an NF-κB dependent inflammatory stromal program: Implications for the prostate tumor microenvironment.
Prostate 74 4 , — Camont, L. Lung aging, characterized by airspace enlargement and decreasing lung function, is a significant risk factor for chronic human lung diseases. The study is published online in the journal Thorax. Resveratrol RSL , a chemical found in red wine, is an antimicrobial chemical substance produced by plants to protect against infection and stress-related changes.
It has previously been shown to support muscle metabolism when delivered orally. RSL prophylaxis by inhalation was a novel measure taken by the research team as a potential approach for slowing age-related deterioration of lung function and structure by preserving alveolar epithelial type 2 cells AEC2 which line alveoli the tiny air sacs in the lungs through which the exchange of oxygen and carbon dioxide takes place and produce surfactant which is vital for efficient breathing.
In healthy young adults, breathing is an essential, efficient process, but natural aging of the lung occurs at a steady and irreversible rate, as measured by a decline in lung function. This natural deterioration leads to a significantly reduced quality of life, over a time frame dependent on genetic and environmental factors.
Previous studies showed that resveratrol offered protective effects on cardiovascular system via upregulating nuclear factor erythroid-2 related factor 2 Nrf-2 and thioredoxin-1 Trx-1 [ 30 , 31 ].
As a member of transcription factor, Nrf-2 was shown to play a critical coordinator as regulating the redox balance and protecting cells against oxidative and inflammatory lesions[ 32 ]. Our study firstly showed that hypoxia exposure reduced expression of both Nrf-2 and Trx-1 in vivo and in vitro , and resveratrol treatment significantly reversed the lowered expression of both proteins.
On the other hand, our data showed that resveratrol also decreased general ROS production in cultured PASMCs. Similarly, resveratrol reduced H 2 O 2 production in PASMCs culture supernatant. Hypoxia-inducible factors HIFs play important roles in response to hypoxia, in which HIF-1 α is the key factor modulating kinds of downstream genes transcription during the progression of HPH[ 36 , 37 ].
The prevailing view of HIF-1 α increase under hypoxia condition is mainly due to its decrease of oxygen-dependent degradation, and increase of oxygen-independent protein synthesis[ 38 ]. However, a recent study showed that besides hypoxia, NO and ROS can also activate HIF-1α production[ 39 ].
In the current study, ROS and HIF-1 α were both shown to be significantly decreased by resveratrol administration in vivo and in vitro. Moreover, HIF-1 α inhibition by its inhibitor KC7F2 suppressed the proliferation of PASMCs induced by hypoxia.
Though the relationship between ROS and HIF-1 α needs to be further explored, the present data intimated that resveratrol prevention of development of HPH is partially ascribed to decrease of ROS and HIF-1α.
In this study, hypoxia exposure induced HIF-1 α expression in vivo and in vitro , and hypoxia condition also resulted in increase of phosphorylated AKT and ERK expression in cultured PASMCs. Resveratrol treatment significantly inhibited both pathways, through which decreased the expression of HIF-1 α.
The suppression of VEGF, a downstream gene of HIF-1 α, verified those results. Those data were consistent with the previous study and advanced the mechanisms underlying the protective effects of resveratrol. Conclusively, our results showed that treatment with resveratrol prevented the development of pulmonary hypertension induced by chronic hypoxia.
Those demonstrated anti-proliferation, anti-inflammation, and anti-oxidant actions of resveratrol may answer for its protective effects on HPH. These data may suggest potential clinical application of resveratrol on treating HPH. HIF: hypoxia inducible factor; HPH: hypoxia-induced pulmonary hypertension; NO: nitric oxide; PASMC: pulmonary arterial smooth muscle cell; RVHI: right ventricle hypertrophy index.
Resveratrol is kindly gifted from Xi'an YiLe Bio-Tech laboratory. The authors thank reviewers for English language checking and editing of the paper. This study was supported by the National Natural Science Foundation of China grants: , and the Project of Natural Science Foundation Research of Shaanxi Province grant: JM Shigematsu S, Ishida S, Hara M.
et al. Free Radic Biol Med. Csiszar A, Smith K, Labinskyy N. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am J Physiol Heart Circ Physiol. Clark D, Tuor UI, Thompson R.
Protection against recurrent stroke with resveratrol: endothelial protection. PLOS ONE. Carrizzo A, Puca A, Damato A. Resveratrol improves vascular function in patients with hypertension and dyslipidemia by modulating NO metabolism.
Stef G, Csiszar A, Lerea K. Resveratrol inhibits aggregation of platelets from high-risk cardiac patients with aspirin resistance.
J Cardiovasc Pharmacol. El-Mowafy AM, Alkhalaf M, El-Kashef HA. Resveratrol reverses hydrogen peroxide-induced proliferative effects in human coronary smooth muscle cells: a novel signaling mechanism.
ARCH MED RES. Garcia P, Schmiedlin-Ren P, Mathias JS. Resveratrol causes cell cycle arrest, decreased collagen synthesis, and apoptosis in rat intestinal smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. Hong SW, Jung KH, Zheng HM. The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats.
ARCH PHARM RES. Jiang L, Gu Y, Ye J. Resveratrol prevents hepatic steatosis induced by hepatitis C virus core protein. Zhang W, Xue J, Ge M. Resveratrol attenuates hepatotoxicity of rats exposed to arsenic trioxide.
FOOD CHEM TOXICOL. Gupta SC, Kannappan R, Reuter S. Chemosensitization of tumors by resveratrol. Ann N Y Acad Sci. Aluyen JK, Ton QN, Tran T. Resveratrol: potential as anticancer agent.
J Diet Suppl. Whitlock NC, Baek SJ. The anticancer effects of resveratrol: modulation of transcription factors. NUTR CANCER. Galie N, Hoeper MM, Humbert M. Guidelines for the diagnosis and treatment of pulmonary hypertension. EUR RESPIR J. Stenmark KR, Fagan KA, Frid MG.
Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. CIRC RES. Stenmark KR, Davie NJ, Reeves JT. Frid MG: Hypoxia, leukocytes, and the pulmonary circulation. J Appl Physiol Liu JQ, Zelko IN, Erbynn EM.
Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase gp91phox. Am J Physiol Lung Cell Mol Physiol. Xu DQ, Luo Y, Liu Y. Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats.
Respir Res. Lidegaard O, Lokkegaard E, Jensen A. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med.
Tofovic SP. Estrogens and development of pulmonary hypertension: interaction of estradiol metabolism and pulmonary vascular disease. Edwards JA, Beck M, Riegger C. Safety of resveratrol with examples for high purity, trans-resveratrol, resVida R. Luo Y, Xu DQ, Dong HY. Ren Y, Li Y, Zhao Y.
Wei Sheng Yan Jiu. Klinge CM, Blankenship KA, Risinger KE. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.
J BIOL CHEM. Klinge CM, Wickramasinghe NS, Ivanova MM. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells.
FASEB J. Khandelwal AR, Hebert VY, Dugas TR. Essential role of ER-alpha-dependent NO production in resveratrol-mediated inhibition of restenosis.
Hfalth scientists report this week that the red Resvdratrol antioxidant healyh could not only Teenagers and eating disorders down the Isotonic drink market process in Resvedatrol progressive lung disease Mental focus and success, but eventually lead to a treatment. Resevratrol chronic obstructive pulmonary disease is an irreversible and progressive disease where the lungs deteriorate, making it difficult, and eventually impossible, to breathe. The cells involved in the inflammatory process in COPD include macrophages. These cells produce powerful chemicals, such as interleukins, which stimulate the growth and activity of various other immune system cells. They also produce chemicals to prolong cell life, such as GM-CSF, and they generate free radicals in the process.
Lung aging, characterized Resevratrol airspace Resveatrol and decreasing lung function, is a significant respirqtory factor for chronic amd lung Metformin and gastrointestinal issues. The study is published online in the Mental focus and success Resveratroo. Resveratrol RSLa Resveratrol and respiratory health found in red wine, is an antimicrobial chemical substance produced by plants to protect against infection and stress-related changes. It has previously been shown to support muscle metabolism when delivered orally. RSL prophylaxis by inhalation was a novel measure taken by the research team as a potential approach for slowing age-related deterioration of lung function and structure by preserving alveolar epithelial type 2 cells AEC2 which line alveoli the tiny air sacs in the lungs through which the exchange of oxygen and carbon dioxide takes place and produce surfactant which is vital for efficient breathing.
Ich berate Ihnen, zu versuchen, in google.com zu suchen
Ist einverstanden, es ist die bemerkenswerte Phrase
Eben dass wir ohne Ihre bemerkenswerte Idee machen würden
Sehr neugierig topic
Kaum kann ich jenem glauben.