Biomarkers in Systemic Sclerosis: An Overview.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor ß (TGF-ß) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

Analysis of cerebral Interleukin-6 and tumor necrosis factor alpha patterns following different ventilation strategies during cardiac arrest in pigs.

Hypoxia-induced neuroinflammation after cardiac arrest has been shown to be mitigated by different ventilation methods. In this prospective randomized animal trial, 35 landrace pigs were randomly divided into four groups: intermittent positive pressure ventilation (IPPV), synchronized ventilation 20 mbar (SV 20 mbar), chest compression synchronized ventilation 40 mbar (CCSV 40 mbar) and a control group (Sham). After inducing ventricular fibrillation, basic life support (BLS) and advanced life support (ALS) were performed, followed by post-resuscitation monitoring. After 6 hours, the animals were euthanized, and direct postmortem brain tissue samples were taken from the hippocampus (HC) and cortex (Cor) for molecular biological investigation of cytokine mRNA levels of Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα). The data analysis showed that CCSV 40 mbar displayed low TNFα mRNA-levels, especially in the HC, while the highest TNFα mRNA-levels were detected in SV 20 mbar. The results indicate that chest compression synchronized ventilation may have a potential positive impact on the cytokine expression levels post-resuscitation. Further studies are needed to derive potential therapeutic algorithms from these findings.

Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence.

Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1ß. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1ß improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1ß was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1ß, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.

Dactylogyrus extensus and Pseudomonas fluorescens dual infection in farmed common carp (Cyprinuscarpio).

Dactylogyrus extensus and Pseudomonas fluorescens are serious pathogens in Cyprinus carpio aquaculture causing severe impacts and substantial economic losses. During the early spring of 2021, abnormal mortalities were reported among farmed C. carpio. Moribund fish showed anorexia, respiratory distress, dermal ulcers, and septicemia. The water analysis revealed low dissolved oxygen (3.4 mg/L), and high un-ionized ammonia levels (0.65 mg/L). Seventy moribund C. carpio specimens were collected and subjected to parasitological and bacteriological examinations. The monogenetic trematode D. extensus was discovered in wet mounts from the gills of all the examined fish samples (100%). The identity of recovered parasites was confirmed by sequencing and alignment of the 28S rDNA gene. P. fluorescens was concurrently identified in the infested fish samples (58.5%) based on phenotypic characteristics using the API20 E. The identity of bacterial isolates was confirmed further by sequencing and alignment of 16S rRNA gene. The IL-1ß and MHCII were upregulated in infested fish in tandem with the severity of infections. P. fluorescens isolates displayed high resistance to most of the tested antibiotics. The study is one of the earlier reports on D. extensus and P. fluorescens co-infections in farmed C. carpio and highlights the need of effective control programs to protect fish health and minimize losses.

Luffa operculata at a late period of gestation dysregulates melatonin and cytokines interfering with weight of dams and their male offspring.

ETHNOPHARMACOLOGICAL RELEVANCE: The tea made with the fruits of Luffa operculata (L.) Cogn. (Cucurbitaceae; EBN) is popularly used as abortive. AIM OF THE STUDY: The present work aimed at accessing how the exposition of female Wistar rats to 1.0 mg/kg of EBN (experimental group, EG), or distilled water (control group, CG), by gavage, at gestational days (GD) 17-21 interfered with the reproductive performance, and with dams' behavior after weaning. MATERIALS AND METHODS: At post-natal day 2 (PND2), the number of male and female pups was evaluated, as well as their weight. After weaning (PND21), dams were euthanized, and their liver and kidneys were removed for histological and biochemical analyses, while the blood was used in the evaluation of cytokines IL-1α, IL-1ß, IL-6 and TNF-α, corticosterone, adrenocorticotrophic hormone, melatonin, AST, ALT and creatinine levels. RESULTS AND DISCUSSION: Dams that were treated with EBN showed an anxiety-like behavior, weight loss at the end of gestation and weight gain at weaning, accompanied with a significant decrease in pro-inflammatory cytokines and in the melatonin level. No significant histological or biochemical alterations have occurred in the liver or kidneys. The number of female pups was significantly higher in the EG. The male pups showed weight gain at PND60. CONCLUSION: The presence of cucurbitacins is probably involved in the dysregulations that were found, due to their polycyclic steroid triterpene structure.

Commercial albumin solution enhances endotoxin-induced vasoplegia and inflammation.

BACKGROUND: The Gram-negative bacterium Escherichia coli, commonly involved in severe sepsis and septic shock, shed endotoxin that upon detection by the host triggers an inflammatory cascade. Efficiency of albumin solutions to restore hypovolemia during sepsis has been debated. To aid identification of subgroups of sepsis patients that may respond positively or negatively to treatment with albumin we investigated if preparations of albumin for medical use could affect endotoxin-induced inflammatory response. METHODS: Isolated human omental arteries obtained during surgery were incubated with endotoxin in the presence or absence of albumin solution. Isolated human monocytes were incubated with endotoxin in the presence or absence of five different commercially available albumin solutions. Vascular contractile response to noradrenaline and release of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were measured. RESULTS: Incubation with albumin together with endotoxin decreased median maximum contraction and increased release of IL-6 and IL-8 from the arteries compared to incubation with endotoxin alone. All albumin solutions except one significantly increased endotoxin-induced TNF-α release from monocytes. IL-6 and IL-10 were also increased and no concentration dependency of TNF-α release was observed above 2 mg mL-1 . Incubation with albumin alone did not affect contraction or release of cytokines while no potentially endotoxin-enhancing contaminant could be identified. CONCLUSION: We have shown that albumin solution in combination with endotoxin cause vasoplegia in human omental arteries, paralleled by an inflammatory response. This finding could explain the variable efficiency of albumin solutions for sepsis treatment.

Avian model to mitigate gut-derived immune response and oxidative stress during heat.

The tissue injury at the early stages of the heat stress response triggers release of inflammatory and oxidative agents from intestinal content into the milieu of the body. Intestinal homeostasis (i.e., eubiosis) improves the barrier function and mitigates the gut-derived influx of endotoxins. In this study we have analyzed the mitigating role of embryonic stimulation of the gut homeostasis in chickens on immune and oxidative responses to heat. The animal trial was conducted on broiler chickens. The treatment included a single in ovo injection of the galactooligosaccharides (GOS) prebiotic into the air cell of the egg on day 12 of incubation. Control eggs were in ovo injected with the same volume of sterile physiological saline. After hatching, birds were raised in group pens (6 pens/group, 25 birds/pen). Short-term, mild heat stress was induced on day 32 post-hatching by increase in the ambient temperature above the thermal comfort (30 °C for 8.5 h). The spleen was harvested from randomly selected individuals. The relative gene expression study was conducted with RT-qPCR. The two gene panels were analyzed: (1) immune response genes (IL-1ß, IL-2, IL-4, IL-6, IL-12p40 and IL-17) and (2) stress response genes (HSP25, HSP70, HSP90, BAG3, CAT and SOD). Data were evaluated by the analysis of variance in a 2 × 2 factorial design that included in ovo treatment and ambient temperature as factors. We have found that the immune-related and stress-related gene expression signatures were triggered in animals subjected to heat but with unbalanced intestinal flora (i.e., dysbiotic, without in ovo stimulation with GOS). These animals had increased expression of the genes involved in the immune responses (IL-4 and IL17) and stress responses (HSP25, HSP70, HSP90, CAT and SOD) to short-term heat stress that indicated presence of inflammatory and oxidative mediators (P < 0.05). The individuals that were in ovo stimulated with GOS did not mount the anti-inflammatory or antioxidative responses. Heat shock proteins (HSP25 and HSP70) were increased in both groups challenged with heat, which indicated their role in adaptation to heat.

Distinct CCL2, CCL5, CCL11, CCL27, IL-17, IL-6, BDNF serum profiles correlate to different job-stress outcomes.

Chronic psychosocial stress at workplace is an important factor in the development of physical and mental illness. Objective biological measures of chronic stress are still lacking, but inflammatory response and growth factors are increasingly considered as potential stress biomarkers. Therefore, we investigated the relationship between psychophysical strain and serum levels of 48 chemokines, cytokines and growth factors measured using a multiplex immunoassay, and serum brain-derived neurotrophic factor (BDNF) measured by ELISA. Severity of psychophysical strain was scored in 115 healthy hospital workers using specific scales for anxiety, depression-like emotion, gastrointestinal or cardiac disturbances, and ergonomic dysfunction. Multivariate analysis revealed that higher anxiety scale scores were correlated with lower serum chemokine C-C motif ligand-2 (CCL2/MCP-1), chemokine C-C motif ligand-5 (CCL5/RANTES), chemokine C-C motif ligand-27 (CCL27/CTACK), chemokine C-C motif ligand-11 (CCL11/Eotaxin) and interleukin-6 (IL-6); gastrointestinal disturbances correlated with increased levels of interleukin-17 (IL-17) and reduced CCL11/Eotaxin, CCL27/CTACK and CCL2/MCP-1; while cardiac dysfunctions associate only to reduced CCL27/CTACK, and ergonomic dysfunction correlated with increased BDNF and reduced CCL11/Eotaxin and CCL5/RANTES. Thus, these 7 serum factors may provide a distinct signature for each different stress-related psychophysical outcome giving indications on individual vulnerabilities.

Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats.

The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 107 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.

Evaluation of IL-1ß, IL-1ra, and IL-10 levels and outcome of periodontal therapy in chronic periodontitis with familial Mediterranean fever.

OBJECTIVES: This study aimed to examine the IL-1ß, IL-1ra, and IL-10 cytokine levels in gingival crevicular fluid (GCF) and serum of familial Mediterranean fever (FMF) and chronic periodontitis (CP) patients, and their response to nonsurgical periodontal therapy. MATERIALS AND METHODS: A total of 50 patients, 15 FMF patients with generalized chronic periodontitis (FMF-CP), 15 systemically healthy patients with generalized chronic periodontitis (CP), ten systemically and periodontal healthy controls (HC), and ten periodontally healthy FMF patients (FMF-HC) were enrolled in the study. The cytokine levels in GCF and serum were determined by ELISA. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks were recorded. RESULTS: The study indicated statistically significant healing of the clinical parameters in both FMF-CP and CP groups after periodontal treatment. GCF IL-1ß levels at 6 weeks in FMF-CP group were significantly lower than the CP group (p < 0.05), and GCF IL-1ra levels were significantly decreased at 6 week in the FMF-CP group (p < 0.05). GCF IL-10 levels were significantly higher in the FMF-CP group than in the other groups at baseline and 6 weeks (p < 0.05). There were no significant differences in serum-IL-1ß, IL-1ra, and IL-10 levels either FMF-CP or CP groups at baseline or 6 weeks (p > 0.05). CONCLUSIONS: The results of our study suggested that there was a positive correlation between gingival inflammation and serum cytokine levels in FMF patients and also colchicine treatment showed protective effects on GCF cytokine levels in FMF-CP group. CLINICAL RELEVANCE: Following treatment, GCF IL-1ß and GCF IL-1ra levels were decreased in FMF-CP group. GCF IL-10 levels were increased in FMF-CP group compared to other groups. Also, the serum cytokine levels associated with periodontal inflammation in FMF patients.

Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

In this article second trimester amniotic fluid biomarkers are measured for correlation with preterm delivery. One additional milliliter of amniotic fluid is collected during amniocentesis for dosages of IL-6, MMP-9, CRP and glucose levels, along with maternal serum CRP and glucose. MMP-9 and Il-6 levels were measured with the corresponding Human Quantikine(R) ELISA Kit (R&D systems) according to the instructions provided by the manufacturer. Cut-off values for AF MMP-9 and IL-6 were fixed by the kit sensitivity thresholds. Data includes ROC curves for glucose (Fig. 1), IL-6 (Fig. 2) and MMP-9 (Fig. 3), aiming to search for sensitivity and specificity in the prediction of premature delivery. Statistical analyses are performed with SPSS v20.0 software. Statistical significance is determined using the Mann-Whitney and one way ANOVA test. The association with preterm delivery is performed using a two proportions test. Correlations are measured using the Pearson׳'s coefficient. A p value<0.05 is considered statistically significant. The data is presented in the figures provided. Data relied on a previous publication "Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid" (A. Kesrouani, E. Chalhoub, E. El Rassy, M. Germanos, A. Khazzaka, J. Rizkallah, E. Attieh, N. Aouad, 2016) [1].

Peroxisome proliferator-activated receptors (PPAR) downregulate the expression of pro-inflammatory molecules in an experimental model of myocardial infarction.

Myocardial infarction (MI) has been associated with an inflammatory response and a rise in TNF-α, interleukin (IL)-1ß, and IL-6. Peroxisome proliferator-activated receptors (PPARs) promote a decreased expression of inflammatory molecules. We aimed to study whether PPAR stimulation by clofibrate decreases inflammation and reduces infarct size in rats with MI. Male Wistar rats were randomized into 3 groups: control, MI + vehicle, and MI + clofibrate (100 mg/kg). Treatment was administered for 3 consecutive days, previous to 2 h of MI. MI induced an increase in protein expression, mRNA content, and enzymatic activity of inducible nitric oxide synthase (iNOS). Additionally, MI incited an increased expression of matrix metalloproteinase (MMP)-2 and MMP-9, intercellular adhesion molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear factor-κB (NF-κB) and decreased IκB, both in myocyte nuclei and cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and MMP-9, ICAM-1, IL-6, NF-κB, and IκB. Infarct size was smaller in clofibrate-treated rats compared to MI-vehicle animals. In silico analysis exhibited 3 motifs shared by genes from renin-angiotensin system, PPARα, iNOS, MMP-2 and MMP-9, ICAM-1, and VCAM-1, suggesting a cross regulation. In conclusion, PPARα-stimulation prevents overexpression of pro-inflammatory molecules and preserves viability in an experimental model of acute MI.

New developments in the treatment of osteoarthritis - focus on biologic agents.

Osteoarthritis (OA) is one of the most common diseases around the world. Medical, social, and financial consequences oblige clinicians, surgeons, and researchers to focus on finding the best treatment option, to eradicate and stop this degenerative joint disease, in order to avoid surgical options which in many instances are over-indicated. Noninvasive treatments, such as anti-inflammatory drugs, physiotherapy, orthotic devices, dietary supplements, have demonstrated lack of effectiveness. The possibility to perform intra-articular injections with hyaluronic acid, corticosteroids, or the newest but criticized treatment based on platelet-rich plasma (PRP) has changed the management of OA disease. The use of PRP has led to many differences in treatment since there is a lack of consensus about protocols, indications, number of doses, cost-effectiveness, and duration of the treatment. Many publications have suggested efficacy in tendon injuries, but when PRP has been indicated to treat cartilage injuries, things are more inconsistent. Some authors have reported their experience treating OA with PRP, and it seems that, if well indicated, it is an option as a supplementary therapy. Therefore, we need to understand that OA is a mechanical disease which not only produces changes in radiographs, but also affects the quality of life. Pathogenesis of OA has been well explained, providing us new knowledge and future possibilities to improve the clinical approach. From basic science to surgery, there is a great field we all need to contribute to, because the general population is aging and total joint replacements should not be the only solution for OA. So herein is an actual review of the developments for treating OA with biologics, intended to be useful for the population inside orthopedics who could be called bio-orthopedists, since OA is a molecular homeostasis disbalance between catabolism and anabolism triggered by mechanical stress.

The role of miR-29 in pulmonary fibrosis.

Pulmonary fibrosis is a pathological condition in which lungs become scarred due to the excess extracellular matrix (ECM) deposition and structural alterations in the interstitium of lung parenchyma. Many patients with interstitial lung diseases (ILDs) caused by long-term exposure to toxic substances, chronic infections, or autoimmune responses develop fibrosis. Etiologies for many ILDs are unknown, such as idiopathic pulmonary fibrosis (IPF), a devastating, relentless form of pulmonary fibrosis with a median survival of 2-3 years. Despite several decades of research, factors that initiate and sustain the fibrotic response in lungs remain unclear and there is no effective treatment to block progression of fibrosis. Here we summarize recent findings on the antifibrotic activity of miR-29, a small noncoding regulatory RNA, in the pathogenesis of fibrosis by regulating ECM production and deposition, and epithelial-mesenchymal transition (EMT). We also describe interactions of miR-29 with multiple profibrotic and inflammatory pathways. Finally, we review the antifibrotic activity of miR-29 in animal models of fibrosis and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis.

Novel bisabolane derivative from "arnica-da-serra" (Vernonieae: Asteraceae) reduces pro-nociceptive cytokines levels in LPS-stimulated rat macrophages.

ETHNOPHARMACOLOGY RELEVANCE: Hydro alcoholic leaves extracts (HALE) of Lychnophora ericoides Mart. ("false arnica" or "arnica-da-serra") had been popularly used against pain and inflammatory process. AIM: The present work aimed to look for possible active volatile compounds that could be found in HALE of Lychnophora ericoides among the non volatile anti-inflammatory and analgesic compounds previously reported. METHODS: Harvests were performed during the end of the wet summer season (April) when scented branches were instantly collected and frozen. HALE's were simulated at the lab by following the procedures lectured by the locals. Mass Spectrometry experiments suggested structural information when using both EI-MS and ESI-MS/MS. After isolation through classical thin layer chromatography (TLC) procedures, the NMR experiments and signals assignments were carried out. The effects on the cytokines or nitric oxide (NO) production were assessed at in vitro assays that had monitored the levels of these substances on the supernatant of LPS-stimulated macrophage primary cell culture. RESULTS: The major metabolite from HALE was isolated from the essential oil and the major compound had its molecular formulae established by Mass Spectrometry (High Resolution) and its structure by NMR. Literature-based investigation enables us to define the structure of the new metabolite as 6-methyl-2-(4-methylcyclohex-4-enyl-2-acetyloxy) hept-5-en-2-ol and its name as orto-acetoxy-bisabolol. In vitro assay of interleukins release inhibition was carried out using rat peritoneal macrophages cultures. IL-1ß and TNF-α levels were significantly reduced when cells were previously treated with low doses of orto-acetoxy-bisabolol, but neither IL-6 nor NO levels have their levels reduced. Results suggest that ethnical knowledge of anti-inflammatory and analgesic effects of the "arnica-da-serra" HALE may be associated to the orto-acetoxy-bisabolol ability on synthesis inhibition of the key inflammatory/hypernociceptive mediators. CONCLUSIONS: Phytochemical investigation of the volatile active compounds in Lychnophora ericoides HALE allows us to isolate a new bisabolane derivative (orto-acetoxy-bisabolol) and to infer that this compound inhibits the synthesis of TNF-α and IL-1ß, two important inflammatory mediators in the hypernociception. Our present data, in addition to literature's data, furnish scientific support to folk's use of Lychnophora ericoides as an endemic wound healer.

Can IgA, C3, IL-6 and TNF-α act as predictors for reoccurrence of breast cancer among Iraqi women?

Blood samples were collected from 30 women with age ranged from 27-70 years after 3 cycles of chemotherapy. Sera were used for IgA, IgG, IgM, C3, C4, IL-6 and TNF-α estimation. After 3 cycles of chemotherapy, all the immunological parameters reduced except TNF-α. Patients who developed disease reoccurrence after chemotherapy exhibit a significantly higher IgA, C3, IL-6 and TNF-α levels after 3 cycles of chemotherapy than patients who did not (p < 0.05). Therefore, serum IgA, C3, IL-6 and TNF-α can be used as predictors for breast cancer reoccurrence.

Comparison of maternal serum levels of interleukin-10, interleukin-12, and interleukin-2 in normal and preeclamptic pregnancies.

OBJECTIVE: The aim of this study was 2 fold: (1) to compare the maternal serum levels of IL-10, IL-12, and IL-2 in preeclamptic and normal pregnant women, and (2) to study the serum levels of these cytokines in preeclamptic pregnancies with and without intrauterine growth retardation. STUDY DESIGN: Forty women with singleton pregnancies complicated by preeclampsia (32 severe and 8 mild) and 29 normotensive healthy pregnant women were included in the study. Preeclamptic patients were further divided into 2 groups according to the presence or absence of intrauterine growth retardation. Maternal serum levels of IL-10, IL 12, and IL-2 were compared between these groups using enzyme-linked immunosorbent assays. RESULTS: Maternal serum levels of IL-10 were significantly higher in the preeclampsia group than in controls (p<0.001). There were no statistically significant differences in maternal serum concentrations of IL-2 and IL-10 between the study and control groups (p>0.05). Serum levels of IL-2 and IL-10 in the patients with preeclampsia complicated by IUGR were elevated in comparison with the uncomplicated preeclampsia group. These differences were statistically significant (p<0.05 for both). CONCLUSIONS: IL-10 may be involved in the pathologic process of preeclampsia. Increased serum levels of IL-10 and IL-2 in preeclampsia complicated with IUGR suggests a possible role of these cytokines in IUGR.

Action of Staphylococcal Exfoliative Toxin A on Pemphigus Antigens Expressed on Human Keratinocytes / 中华皮肤科杂志

Objective To study the action and mechanism of staphylococcal exfoliative toxin A(E-TA)on pemphigus foliaceus antigen(PFA)and pemphigus vulgaris antigen(PVA)expressed on cultured human keratinocytes.Methods Stratified human keratinocytes were incubated with ETA and then stained with sera from patients with pemphigus foliaceus or pemphigus vulgaris as the first antibodies and FITC-la-beled sheep anti-human IgG as the second antibody.Total protein was harvested from the cells pretreated with ETA and run on SDS-PAGE for Western blot with the same antibodies.Simultaneously,supernatants of the keratinocytes before and after ETA treatment were collected for detection of the levels of IL-1?,IL-6with ELISA kits.The caseinolytic activities of the supernatants were tested by spectrometry in which casein was used as a non-specific substrate.Results Down-expression of PFA was shown after ETA treatment while no change of PVA expression was found.The high intensity and continuous linear appearance of fluo-rescent staining before ETA treatment became weak and discontinuous after ETA treatment,which were re-covered gradually in24hours.The degradation of proteins recognized by PF sera after ETV treatment was revealed by Western blot.The decreasing tendency of IL-1?concentration was found in the supernatants of cell culture after ETA treatment,but IL-6level was too low to be detected.Increased caseinolytic activities were found in the supernatants,and declined36hours after ETA treatment.Conclusions ETA acts on PFA expressed on keratinocytes in vitro,which is reversible along with withdrawal of ETA.The mechanism of E-TA act on PFA may be related to proteolytic action instead of promoting cytokine secretion.

Interleukine 1 receptor antigonist inhibits proinflammatory factor production by human retinal pigment epithelial cells in vitro / 中华眼底病杂志

Objective To investigate production of interleukine 6 (IL 6) and interleukine 8 (IL 8) by retinal pigment epithelial (RPE) cells and its inhibition by interleukine 1 receptor antigonist(IL 1ra). Methods Cultured human RPE cells was treated with interleukine 1 ? (IL 1?, 10 ng/ml) and/or IL 1ra ( IL 1ra, 1、10、100 ng/ml). IL 6 and IL 8 mRNA and protein expression were detected by ELISA, immunohistochemistry and in situ hybridization (ISH) assay. Results IL 6 and IL 8 in conditioned media of RPE cells in controls was 2 000 pg/ml and 5 000 pg/ml respectively after stimulation of IL 1? for 8 h. IL 1ra (100 ng/ml) significantly inhibited IL 6 (300 pg/ml, t=8.011, P