scholarly journals Gonadotropins in Keratoconus: The Unexpected Suspects

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1494
Author(s):  
Dimitrios Karamichos ◽  
Brayden Barrientez ◽  
Sarah Nicholas ◽  
Symon Ma ◽  
Lyly Van ◽  
...  

Keratoconus (KC) is the most common ectatic corneal disease with a significant visual acuity burden. The actual burden is intangible given that KC can disrupt daily activities (reading, driving, and various career paths). Despite decades of research and clinical studies, the etiology, onset, and pathobiology of KC remain a mystery. The purpose of this study was to investigate the role of gonadotropins in KC. We recruited 86 KC patients (63 males, 23 female), and 45 healthy controls (22 male, 23 female). Plasma samples were collected and analyzed using an enzyme-linked immunosorbent assay. Corneal stromal cells from KC and healthy controls, and human epithelial corneal cells, were also investigated for gonadotropin-related markers. Our results show significant alterations of LH/FSH in KCs, compared to healthy controls. Our data also reveals, for the first time, the existence of gonadotropins and their receptors in KC. Our study is the first to demonstrate the role of LH/FSH in KCs, and expand the list of organs known to express gonadotropins, or their receptors, to include the human cornea. Our findings suggest that the human cornea is capable of responding to gonadotropins, and propose an intriguing mechanism for the onset and/or progression of KC.

2019 ◽  
Vol 51 (1) ◽  
pp. 27-41 ◽  
Author(s):  
Hara Levy ◽  
Shuang Jia ◽  
Amy Pan ◽  
Xi Zhang ◽  
Mary Kaldunski ◽  
...  

Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and the development of inflammation and progression of lung disease are not fully understood, which limits our ability to predict an individual patient’s clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status with plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients ( n = 103) and unrelated, healthy controls ( n = 31). Gene expression levels were measured with an Affymetrix microarray (GeneChip Human Genome U133 Plus 2.0). Peripheral blood samples from a subset of the CF patients ( n = 40) were immunophenotyped by flow cytometry, and the data were compared with historical data for age-matched healthy controls ( n = 351). Plasma samples from another subset of CF patients ( n = 56) and healthy controls ( n = 16) were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA) for numerous cytokines and chemokines. Principal component analysis and hierarchical clustering of induced transcriptional data revealed disease-specific plasma-induced PBMC profiles. Among 1,094 differentially expressed probe sets, 51 genes were associated with pancreatic sufficient status, and 224 genes were associated with infection with Pseudomonas aeruginosa. The flow cytometry and ELISA data confirmed that various immune modulators are relevant contributors to the CF molecular signature. This study provides strong evidence for distinct molecular signatures among CF patients. An understanding of these molecular signatures may lead to unique molecular markers that will enable more personalized prognoses, individualized treatment plans, and rapid monitoring of treatment response.


2019 ◽  
Vol 47 (8) ◽  
pp. 3709-3718 ◽  
Author(s):  
Yan Kong ◽  
Cuizhi Geng ◽  
Qian Dong

Objective To investigate the role of promoter and pre-rRNA antisense (PAPAS) long noncoding (Lnc) RNA in cancer biology. Methods Tumour and tumour-adjacent healthy tissue biopsies from patients with triple-negative breast cancer (TNBC), and plasma samples from these patients plus healthy controls, were assessed for PAPAS and microRNA (miR)-34a. Effects of PAPAS and miR-34a overexpression were also investigated in vitro. Results PAPAS was upregulated in tumour tissues of patients with TNBC versus tumour-adjacent healthy tissues. Plasma PAPAS levels were also upregulated in patients with TNBC versus healthy controls. Levels of PAPAS in tumour tissue was significantly positively correlated with PAPAS levels in plasma from patients with TNBC. MiR-34a was downregulated in tumour tissues versus adjacent healthy tissues, and was significantly correlated with PAPAS in tumour tissues. PAPAS overexpression in vitro was associated with miR-34a inhibition, while miR-34a failed to significantly affect PAPAS levels. PAPAS overexpression promoted in vitro migration and invasion of TNBC cells, while miR-34a overexpression was inhibitory. MiR-34a overexpression decreased the enhanced cell migration and invasion associated with PAPAS overexpression. PAPAS overexpression showed no significant effects on cancer-cell proliferation. Conclusion LncRNA PAPAS may promote TNBC by downregulating miR-34a.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
T. Jazedje ◽  
A. L. Ribeiro ◽  
M. Pellati ◽  
H. M. de Siqueira Bueno ◽  
G. Nagata ◽  
...  

The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.


Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 1996-2005 ◽  
Author(s):  
Julien Tirard ◽  
Johann Gout ◽  
Anne Marie Lefrançois-Martinez ◽  
Antoine Martinez ◽  
Martine Begeot ◽  
...  

The aldo-keto reductase 1B7 (AKR1B7) encodes an aldose-reductase that has been reported as a detoxification enzyme until now. We have demonstrated that AKR1B7 is differently expressed in various mouse white adipose tissues depending on their location. Its expression is associated with a higher ratio of preadipocytes vs. adipocytes. The cells that express AKR1B7 did not contain lipid droplets, and the expression level of akr1b7 was very low in mature adipocytes. We have defined the role of AKR1B7 in adipogenesis using either primary cultures of adipose stromal cells (containing adipocyte precursors) or the 3T3-L1 cell line. Under the same differentiation conditions, adipose stromal cells from tissues that expressed AKR1B7 had a decreased capacity to accumulate lipids compared with those that did not express it. Moreover, the overexpression of sense or antisense AKR1B7 in 3T3-L1 preadipocytes inhibited or accelerated, respectively, their rate of differentiation into adipocytes. In vivo experiments demonstrated that AKR1B7-encoding mRNA expression decreased in adipose tissues from mice where obesity was induced by a high-fat diet. All these results attributed for the first time a novel role to AKR1B7, which is the inhibition of adipogenesis in some adipose tissues.


Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.


2011 ◽  
Vol 31 (6) ◽  
pp. 343-352 ◽  
Author(s):  
Sema Becerik ◽  
Beral Afacan ◽  
Veli Özgen Öztürk ◽  
Harika Atmaca ◽  
Gülnur Emingil

Aim:The aim of the present study was to investigate gingival crevicular fluid (GCF) calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx) levels in health along with different periodontal diseases.Material and methods:Twenty chronic periodontitis (CP), 20 generalized aggressive periodontitis (G-AgP), 20 gingivitis and 20 healthy subjects were included. Probing depth, clinical attachment level, plaque index and papillary bleeding index was recorded. GCF calprotectin, osteocalcin and NTx levels were analyzed by enzyme-linked immunosorbent assay (ELISA).Results:CP, G-AgP and gingivitis groups had higher GCF calprotectin total amount compared to healthy subjects (p< 0.008). CP and G-AgP groups had similar, but higher levels compared to gingivitis groups (p< 0.008). CP and G-AgP groups had lower GCF osteocalcin total amount compared to gingivitis and healthy groups (p< 0.008). CP group had higher GCF NTx but lower osteocalcin total amount and osteocalcin/NTx ratio than the G-AgP group (p< 0.008)Conclusions:Our results suggest that elevated GCF calprotectin levels play a role as a reliable inflammatory marker in the pathogenesis of periodontal disease. Fluctuating GCF levels of osteocalcin and NTx might point out to the abnormal bone turnover in periodontitis. Our data document for the first time the role of NTx in the pathogenesis of different periodontal diseases.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jennifer M. Kishimori ◽  
Akihiro Takemura ◽  
Jo-Ann C. Leong

Neobenedenia melleniis a significant monogenean pathogen of fish in aquaculture facilities and public aquaria. Immunity after exposure to liveN. melleniis well established, but the mechanisms of immunity remain unclear. In this study, tilapia (Oreochromis mossambicus) were continuously exposed toN. melleniover a four-month period and assessed for immunity as determined by a reduction in the number of parasites dislodged from the experimental animals during freshwater immersion. Specific mucosal and systemic antibody levels were by determined via enzyme-linked immunosorbent assay. At 45 days postexposure (DPE), fish displayed high parasite loads and baseline levels of mucosal antibodies. At 102 and 120 DPE parasite loads were significantly decreased, and antibody levels were significantly increased for mucus and plasma samples. The correlation between immunity (reduction in parasite load) and an increased humoral antibody response suggests a key role of antibody in the immune response. This is the first report of immunity againstN. mellenithat is associated with specific mucosal or systemic antibodies.


Author(s):  
Jie Xiang ◽  
Mingzhe Yan ◽  
Hongze Li ◽  
Ting Liu ◽  
Chenyao Lin ◽  
...  

AbstractBACKGROUNDIn December 2019, a novel coronavirus (SARS-CoV-2)–infected pneumonia (COVID-19) occurred in Wuhan, China. Travel-associated cases have also been reported in other countries. The number of cases has increased rapidly but laboratory diagnosis is limited.METHODSWe collect two groups of cases diagnosed with COVID-19 for experiments. One group collected 63 samples for Enzyme-linked immunosorbent assay (ELISA) IgG and IgM antibodies. The other group collected 91 plasma samples for colloidal gold-immunochromatographic assay (GICA).RESULTSThe sensitivity of the combined ELISA IgM and ELISA IgG detection was 55/63 ( 87.3%), The sensitivity of the combined GICA IgM and GICA IgG detection was 75/91 ( 82.4%), Both methods are negative for healthy controls, specificity of 100%. There is no significant difference between the sensitivity of between ELISA and GICA (IgM+ IgG).CONCLUSIONSELISA and GICA for specific IgM and IgG antibodies are conventional serological assays, they are simple, fast, and safe, the results can be used for clinical reference, and the huge clinical diagnosis and treatment pressure can be greatly relieved.


2018 ◽  
Vol 6 (1) ◽  
pp. 33-43
Author(s):  
Mark Turler ◽  
Shel Thoma

Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis, the direct protective effect of Dopamine on myocardial is still not clear. Here, we aimed to study whether Dopamine can directly protect myocardial from endotoxemia. To test that, we used adult C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Clozapine was administered as D2 antagonist, (intraperitoneal administration shortly before the model of sepsis). Electron microscopy, TUNEL staining, caspase-3 expression, and the Bcl-2/Bax ratio were used to measure myocardial apoptosis. Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining. In conclusion, our results for the first time showed the role of Dopamine to directly protect myocardial from endotoxemia through attenuated proinflammatory cytokines and partly through inhibiting apoptosis.


2017 ◽  
Vol 6 (8) ◽  
pp. 659-666 ◽  
Author(s):  
Yongping Liu ◽  
Shuo Wang ◽  
Qingling Guo ◽  
Yongze Li ◽  
Jing Qin ◽  
...  

Objective Hashimoto’s thyroiditis (HT) is characterized by elevated specific auto-antibodies, including TgAb and TPOAb. Increasing evidence has demonstrated the essential role of Th17 cells in HT. However, the underlying mechanism is still unclear. Semaphorin 5A (Sema 5A) is involved in several autoimmune diseases through the regulation of immune cells. The aim of the present study was to explore the role of Sema 5A in HT. Methods We measured serum Sema 5A levels in HT (n = 92) and healthy controls (n = 111) by enzyme-linked immunosorbent assay (ELISA). RNA levels of Sema 5A and their receptors (plexin-A1 and plexin-B3), as well as several cytokines (IFN-γ, IL-4 and IL-17), were detected by real-time polymerase chain reaction in peripheral blood mononuclear cells from 23 patients with HT and 31 controls. In addition, we investigated the relationship between serum Sema 5A and HT. Results Serum Sema 5A in HT increased significantly compared with healthy controls (P < 0.001). Moreover, serum Sema 5A levels were positively correlated with TgAb (r = 0.511, P < 0.001), TPOAb (r = 0.423, P < 0.001), TSH (r = 0.349, P < 0.001) and IL-17 mRNA expression (r = 0.442, P < 0.001). Increased Sema 5A RNA expression was observed (P = 0.041) in HT compared with controls. In receiver-operating characteristic (ROC) analysis, serum Sema 5A predicted HT with a sensitivity of 79.35% and specificity of 96.40%, and the area under the curve of the ROC curve was 0.836 (95% CI: 0.778–0.884, P < 0.001). Conclusions These data demonstrated elevated serum Sema 5A in HT patients for the first time. Serum Sema 5A levels were correlated with thyroid auto-antibodies and IL-17 mRNA expression. Sema 5A may be involved in immune response of HT patients.


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