scholarly journals Chronic Inflammation in PCOS: The Potential Benefits of Specialized Pro-Resolving Lipid Mediators (SPMs) in the Improvement of the Resolutive Response

2020 ◽  
Vol 22 (1) ◽  
pp. 384
Author(s):  
Pedro-Antonio Regidor ◽  
Anna Mueller ◽  
Manuela Sailer ◽  
Fernando Gonzalez Santos ◽  
Jose Miguel Rizo ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Unsaturated Fatty Acids ◽  
Inflammatory Diseases ◽  
Reproductive Age ◽  
Lipid Mediator ◽  
Female Population ◽  
Tnf Α ◽  
Potential Benefits ◽  
Cardinal Symptoms ◽  
Resolution Processes

PCOS as the most common endocrine disorder of women in their reproductive age affects between 5–15% of the female population. Apart from its cardinal symptoms, like irregular and anovulatory cycles, hyperandrogenemia and a typical ultrasound feature of the ovary, obesity, and insulin resistance are often associated with the disease. Furthermore, PCOS represents a status of chronic inflammation with permanently elevated levels of inflammatory markers including IL-6 and IL-18, TNF-α, and CRP. Inflammation, as discovered only recently, consists of two processes occurring concomitantly: active initiation, involving “classical” mediators including prostaglandins and leukotrienes, and active resolution processes based on the action of so-called specialized pro-resolving mediators (SPMs). These novel lipid mediator molecules derive from the essential ω3-poly-unsaturated fatty acids (PUFAs) DHA and EPA and are synthesized via specific intermediates. The role and benefits of SPMs in chronic inflammatory diseases like obesity, atherosclerosis, and Diabetes mellitus has become a subject of intense research during the last years and since PCOS features several of these pathologies, this review aims at summarizing potential roles of SPMs in this disease and their putative use as novel therapeutics.

scholarly journals PCOS: A Chronic Disease that Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs)

2021 ◽  
Author(s):  
Pedro-Antonio Regidor ◽  
Xavier de la Rosa ◽  
Anna Mueller ◽  
Manuela Sailer ◽  
Fernando Gonzalez Santos ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Initial Response ◽  
Lipid Mediators ◽  
Reproductive Age ◽  
Lipid Mediator ◽  
Low Grade ◽  
Healthy Women ◽  
Inflammatory State ◽  
Inflammatory Molecules ◽  
Resolution Processes

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, a characteristic multi-follicular morphology of the ovary, an elevated ratio of LH/FSH, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. Inflammatory processes consist of the acute inflammatory response and resolution processes initiated concomitantly. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. SPM biosynthesis starts from the essential polyunsaturated fatty acids DHA, DPA, or EPA via certain hydroxylated intermediates (18-HEPE, 17-HDHA, 14-HDHA). The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Blood samples were taken (20 ml), separated into plasma and serum, and analyzed by HPLC/MS-QQQ. Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Ratio [(sum of pro-inflammatory molecules)/sum of SPMs]. Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Hacat Cells ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mapk Signaling Pathways ◽  
Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

scholarly journals Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 17
Author(s):  
Vikrant Rai ◽  
Devendra K. Agrawal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Chronic Inflammation ◽  
Therapeutic Target ◽  
Primary Liver Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Hcc Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target.

scholarly journals Seroprevalence of toxoplasmosis in Vojvodina

2010 ◽  
Vol 138 (5-6) ◽  
pp. 333-336 ◽  
Author(s):  
Snezana Brkic ◽  
Gorana Gajski ◽  
Mirjana Bogavac ◽  
Daniela Maric ◽  
Vesna Turkulov ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
General Population ◽  
Pregnant Women ◽  
Acute Infection ◽  
Clinical Manifestations ◽  
Congenital Toxoplasmosis ◽  
Reproductive Age ◽  
Female Population ◽  
Effective Measure ◽  
Female Patients

Introduction Toxoplasmosis is an acute infectious anthropozoonotic disease with mild asymptomatic clinical manifestations in immunocompetent persons and more severe in immunocompromised patients. Acute infection in pregnancy can result in severe congenital toxoplasmosis with severe sequels. Objective Aims of study were to detect Toxoplasma gondii seroprevalence in general population of Vojvodina, Serbia, differences between genders and determination of seroprevalence in women of reproductive age and pregnant women. Methods Our retrospective study was conducted from 2006 to 2008 including 625 immunocompetent patients, hospitalized or observed as outpatients at the Clinical Centre of Vojvodina, Novi Sad. We performed commercial ELISA kits SERION - ELISA classic test by VIRION for the presence of specific IgG and IgM antibodies. According to seroepidemiological aim of the study, our results were presented only in qualitative values. Results We observed 173 male and 452 female patients. Seroprevalence in general population of Vojvodina was 38.1%. In male population seroprevalence was 45.7%, and in female population it was 35.2%, the difference which was statistically significant (p<0.05). Seroprevalence increased with age and seroconversion was detected to occur in persons aged about 20 years. In all female patients, 353 (78.1%) were in reproductive age with seroprevalence of 30%. In 161 pregnant women seroprevalence was 31.7%. Conclusion In this study we screened actual seroepidemiological situation to Toxoplasma gondii in Vojvodina, thus giving a contribution to the continuous epidemiological screening done in this region and in the country. According to our results, almost 70% of women in reproductive age were sensitive to primary acute infection during further pregnancies, which is highly important for the prevention of congenital toxoplasmosis. Although not routinely conducted in many countries, routine serological testing to Toxoplasma gondii in pregnant women and their education about preventive measures against this infection could be an effective measure in the future.

CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

2004 ◽  
Vol 92 (08) ◽  
pp. 419-424 ◽  
Author(s):  
Stefan Blankenberg ◽  
Christine Espinola-Klein ◽  
Joern Dopheide ◽  
Christoph Bickel ◽  
Karl Lackner ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Animal Studies ◽  
Inflammatory Diseases ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Hs Crp ◽  
Artery Disease ◽  
Fourth Quartile

SummaryMonocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p<0.001). Logistic regression analysis including quartiles of CD14+CD16+ monocytes showed that CD14+CD16+ monocytes were associated with prevalence of CAD (OR 4.9, 95% CI 2.5–19.1, for subjects in the fourth quartile in comparison to subjects in the first quartile). The association between CD14+CD16+ monocytes and CAD remained independently significant after adjustment for most potential confounders (OR 5.0, 95% CI 1.2-20.0). Serum concentrations of TNF-α were elevated in subjects within the highest quartiles of CD14+CD16+ monocytes (p=0.018). Our study showed that increased numbers of CD14+CD16+ monocytes are associated with coronary atherosclerosis and TNF-α. In accordance, recent animal studies suggest a possibly important role of these monocytes in the development of atherosclerosis.

scholarly journals An Ayurvedic Approach in Management of Poly Cystic Ovarian Syndrome

2020 ◽  
Vol 11 (4) ◽  
pp. 644-649
Author(s):  
Saroj Kumari ◽  
Sarvesh Kumar Singh ◽  
Kshipra Rajoria ◽  
Avadhesh Kumar
Keyword(s):  
Polycystic Ovarian Syndrome ◽  
Dietary Habits ◽  
Reproductive Age ◽  
Herbal Drugs ◽  
Polycystic Ovaries ◽  
Female Population ◽  
Hormonal Imbalance ◽  
Hormonal Dysfunction ◽  
Cardinal Feature ◽  
Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a probably fastest growing endocrinological disorder in females of reproductive age. In PCOS, follicular growth is influenced by hormonal imbalance during the ovarian cycle, leads to affected follicles remain in the ovary. The prevalence of PCOS is estimated 6-10% globally and 3.7% - 22.5% in Indian female population, which is relatively high. It is characterised by hyperandrogenism, anovulation and polycystic ovaries which clinically manifests in the terms of amenorrhea or oligomenorrhea, hirsutism, acne, infertility etc. In present scenario, incidence of this disease increasing exponentially due to sedentary lifestyle and faulty dietary habits. This particular disease is not described word to word in Ayurveda. Associated features of PCOS are closely resembling with Bandhya Yonivyapada, Artavavahasrotasa-Vidhha Lakshana, Nastartava and Ksheenaartava described by Acharya Sushruta and Pushpghani Jatharini and Vikuta Jatharini mentioned by Acharya Kashyap. Maximum congruence of PCOS can be established with Bandhya Yonivyapada. The purpose of this study is to understand Nastartava which is the cardinal feature of Bandhya. Word Artava has been used exclusively in Samhita in context of menstrual blood, ovum and ovarian hormones. Therefore Amenorrhea, anovulation, hormonal dysfunction is considered exposed manifestations of Nastartava. Possible line of treatment is stipulated with Nidanaparivarjan, herbal drugs and Panchakarma procedures. Keywords- Ayurveda, Artava, Nastartava, PCOS, Herbal drugs, Panchakarma

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