CCL24 Protects Renal Function by Controlling Inflammation in Podocytes

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1β was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.

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Role of Regulatory B Cells in the Progression of Cervical Cancer

Mediators of Inflammation ◽

10.1155/2019/6519427 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Zhifang Chen ◽

Yuejie Zhu ◽

Rong Du ◽

Nannan Pang ◽

Fengbo Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

T Cells ◽

Cancer Patients ◽

Intraepithelial Neoplasia ◽

Serum Levels ◽

Hpv Infection ◽

Control Group ◽

Cell Percentage

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

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The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder

BMC Neurology ◽

10.1186/s12883-021-02198-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhila Maghbooli ◽

Abdorreza Naser Moghadasi ◽

Nasim Rezaeimanesh ◽

Abolfazl Omidifar ◽

Tarlan Varzandi ◽

...

Keyword(s):

Insulin Sensitivity ◽

Neuromyelitis Optica ◽

Serum Levels ◽

Spectrum Disorder ◽

Control Group ◽

Neuromyelitis Optica Spectrum Disorder ◽

Downstream Signaling ◽

Reduce Insulin Sensitivity ◽

Circulating Levels

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. Methods We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. Results Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. Conclusions Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

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SAT0296 SERUM LEPTIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3390 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1093.1-1093

Author(s):

G. Pellegrino ◽

K. Stefanantoni ◽

F. Facioni ◽

C. Angelelli ◽

A. Gigante ◽

...

Keyword(s):

Systemic Sclerosis ◽

Chronic Diseases ◽

Cardiac Fibrosis ◽

Serum Levels ◽

High Serum ◽

Control Group ◽

Pathologic Finding ◽

Serum Leptin ◽

Ecg Abnormalities

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared

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Role of vitamin D serum levels in prevention of primary and recurrent melanoma

Scientific Reports ◽

10.1038/s41598-021-85294-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

M. Lombardo ◽

A. Vigezzi ◽

G. Ietto ◽

C. Franchi ◽

V. Iori ◽

...

Keyword(s):

Vitamin D ◽

Serum Levels ◽

Mitotic Rate ◽

Control Group ◽

Healthy Population ◽

Histological Subtype ◽

Melanoma Diagnosis ◽

Significant Difference ◽

Tumour Location

AbstractPatients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p < 0.0001). No correlation between VDSL and both Breslow’s depth and Clark’s level was discovered, but the VDSL comparison between thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p < 0007). Nevertheless, no connection was found between VDSL and both ulceration and positive sentinel nodes (p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.

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PapRIV, a BV-2 microglial cell activating quorum sensing peptide

Scientific Reports ◽

10.1038/s41598-021-90030-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yorick Janssens ◽

Nathan Debunne ◽

Anton De Spiegeleer ◽

Evelien Wynendaele ◽

Marta Planas ◽

...

Keyword(s):

Quorum Sensing ◽

Cell Model ◽

Dependent Manner ◽

Communication Signals ◽

Gram Positive Bacteria ◽

A Cell ◽

Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

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The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness

Cancers ◽

10.3390/cancers13061330 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1330

Author(s):

Filipe Pinto ◽

Liliana Santos-Ferreira ◽

Marta T. Pinto ◽

Catarina Gomes ◽

Celso A. Reis

Keyword(s):

Clinical Value ◽

Knock Out ◽

Angiogenic Potential ◽

In Vivo Experiments ◽

Cancer Aggressiveness ◽

Advanced Stages ◽

Oncogenic Gene

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.

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Abstract 172: The Role of Activin A in Maternal Diabetes-Induced Cardiac Malformations

Circulation Research ◽

10.1161/res.111.suppl_1.a172 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Zhiyong Zhao

Keyword(s):

High Glucose ◽

Heart Defects ◽

Maternal Diabetes ◽

Activin A ◽

Brdu Incorporation ◽

Control Group ◽

Endocardial Cushions ◽

Diabetic Embryopathy ◽

Cardiac Malformations

Diabetes mellitus in pregnancy causes heart defects, especially atrioventricular septal defects (AVSDs), in infants. Manifestation of AVSDs results from dysmorphogenesis of the endocardial cushions in the embryo, which is regulated by members of the transforming growth factor (TGF) β family. Among the TGFβs, we have previously observed that the inhibin βA gene, which encodes a protein to form homodimers as activin A, is markedly downregulated by maternal diabetes. To further determine the involvement of inhibin βA and its signaling in diabetic embryopathy, the levels of inhibin βA protein and activation of its downstream transcription factors, Smad2 and Smad3, were examined using immunohistochemical, proximity ligation, and immunoblot assays, and shown to be decreased in the embryonic hearts of diabetic mice induced via intravenous injection of streptozotocin. To investigate the role of activin A in hyperglycemia-induced cardiac malformations, mouse embryos at embryonic day 9.5 (E9.5) cultured in high glucose (22 mM) were treated with activin A (50 ng/ml) for 24 hours. The treatment rescued the development of the endocardial cushions and cell proliferation (BrdU-incorporation assay) in the myocardium, similar to those in normal glucose control (8.3 mM). The role of activin A in endocardial cell migration, an important process for cellularization of the cardiac jelly, was investigated by treating E10.5 endocardial cushion explants cultured in high glucose with activin A (50 ng/ml) in a collagen matrix-based assay system. The treatment significantly increased the number of migrating cells, compared with that in high glucose-treated group, to the level in the control group. These effects were associated with restoration of the activation of Smad2/3. The results demonstrate that the activin-Smad2/3 signaling system plays an important role in cardiac malformation in diabetic embryopathy.

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Shortened platelet half-life in multiple myeloma

Blood ◽

10.1182/blood.v68.2.514.bloodjournal682514 ◽

1986 ◽

Vol 68 (2) ◽

pp. 514-520

Author(s):

E Fritz ◽

H Ludwig ◽

W Scheithauer ◽

H Sinzinger

Keyword(s):

Multiple Myeloma ◽

Half Life ◽

Serum Levels ◽

Statistical Correlation ◽

Control Group ◽

Healthy Controls ◽

Platelet Factor ◽

Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

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IN VITRO FERTILITY TEST OF HUMAN SPERMATOZOA MEMBRANE PROTEIN FERTILIN BETA ANTIBODY IN MICE (Mus musculus Balb/c) AS IMMUNOCONTRACEPTIVE CANDIDATE

Folia Medica Indonesiana ◽

10.20473/fmi.v52i3.5453 ◽

2017 ◽

Vol 52 (3) ◽

pp. 209

Author(s):

Reny I’tishom ◽

Doddy M Soebadi ◽

Aucky Hinting ◽

Hamdani Lunardhi ◽

Rina Yudiwati

Keyword(s):

In Vitro Fertilization ◽

Membrane Protein ◽

Mus Musculus ◽

Human Spermatozoa ◽

Control Group ◽

Reproductive Process ◽

Vitro Fertilization ◽

Antibody Induction

One of the materials as potential candidates immunocontraception material is spermatozoa. Fertilin beta is spermatozoa membrane protein and is found only in mature spermatozoa and ejaculate, which serves as an adhesion molecule. Spermatozoa membrane protein that is used as an ingredient immunocontraception candidate, must have specific criteria that the specificity of spermatozoa, the role of antigen in the fertilization process, which includes the formation of immunogenicity sufficient antibody response has the potential to block fertilization. Antibodies against spermatozoa affect the stages before fertilization of the reproductive process and can hinder the development of the embryo after fertilization. Until now very little research data spermatozoa membrane protein as an ingredient immunocontraception are up to the test of experimental animals. The research objective is to prove the role of the resulting antibody induction of antibodies fertilin beta protein in the membrane of human spermatozoa induce agglutination and reduce motility thus reducing the number of in vitro fertilization. Research conducted at the IVF Laboratory, Department of Biology of Medicine, Faculty of Medicine, University of Airlangga. This research includes: Test the potential of antibody protein beta fertilin membrane of human spermatozoa and inhibit the role of antibodies in vitro fertilization in mice (Mus musculus Balb/c). In vitro studies have resulted in fertilization figure of 25% is smaller than the number that is equal to control fertilization of 58.7%, whereas previously the spermatozoa were incubated first with a beta membrane protein antibody fertilin human spermatozoa. While the percentage of inhibition of sperm to fertilize an oocyte by 33.75%. Potential imunokontraseptif considered effective if it decreased significantly (P <0.05) than the numbers fertilization in the treatment group compared with the control group. This shows fertilin beta membrane protein antibody has the ability to inhibit human spermatozoa to fertilize oocytes that reduce the number of fertilization.

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proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

Translational Psychiatry ◽

10.1038/s41398-021-01667-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bangkun Yang ◽

Lesheng Wang ◽

Ying Nie ◽

Wei Wei ◽

Wenping Xiong

Keyword(s):

Neural Plasticity ◽

Cell Model ◽

Neurotrophin Receptor ◽

Control Group ◽

P75 Neurotrophin Receptor ◽

Post Stroke ◽

Post Stroke Depression ◽

Cellular Apoptosis ◽

Related Proteins

AbstractBrain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.

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