C-reactive Protein Expression Research Articles

The Effects of Non-Surgical Periodontitis Therapy on the Clinical Features and Serological Parameters of Patients Suffering from Rheumatoid Arthritis as Well as Chronic Periodontitis.

ObjectiveThe present study aims to evaluate the effects of basic periodontal disease therapy on the general condition and serum inflammatory indicators of patients with rheumatoid arthritis (RA) combined with chronic periodontitis (CP).MethodsForty patients with RA were enrolled in the study and, based on the results of an oral examination and in line with the 2018 periodontitis diagnostic criteria, they were divided into a group with CP (the RA + CP group) and a group without CP (the RA group). Twenty-nine patients with CP who attended the periodontal department of our hospital were recruited as a group with only CP (the CP group), and 20 volunteers without any systemic or periodontal disease were recruited as a healthy control group (the H group). The periodontal and joint conditions of the subjects in the four groups were recorded; anti-cyclic citrullinated protein antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and rheumatoid factor levels, which reflect the severity of the RA, were detected, and the differences between the groups were analyzed. The probing depth (PD), clinical attachment loss, and sulcus bleeding index (SBI), which reflect the severity of the periodontitis, were correlated with the factor levels. The RA + CP and CP groups received therapeutic intervention, and the differences in each indicator before and six weeks after the treatment were compared, and their data were compared with those of patients in the RA group and H groups.ResultsCompared with the RA group, the serum expressions of ESR, CRP, and IL-6 were significantly higher in the RA + CP group. There were significant differences in the levels of PD, SBI, IL-6, and CRP in the patients receiving basic periodontal disease therapy before and after the treatment.ConclusionA relatively large proportion of patients with RA have chronic periodontitis, and the local inflammatory state of CP might exacerbate the systemic inflammatory response in RA. Basic periodontal disease therapy may improve the oral condition of patients with RA and reduce the serum levels of the inflammatory factors.

Mitigation of apoptosis-mediated neurotoxicity induced by silver nanoparticles via rutaceae nutraceuticals: P53 activation and Bax/Bcl-2 regulation

Rapid progress in nano-scales and nanostructure extremely altered the way of diagnosing or preventing numerous diseases. One of the most important nano-medicines used in cancer treatment and diagnosis is silver nanoparticles (AgNPs). Regardless of their extensive utilization, their prospective neurotoxicity wasn’t studied yet. Herein, male Swiss Albino mice were intoxicated via two Nano-scales of AgNPs; (20 nm and 100 nm) for one month (100 mg/kg) then treated by leaves extracts of both Casimiroa edulis (C. edulis) and Glycosmis pentaphylla (G. pentaphylla), in addition to, mucilage and protein, the separated compounds from C. edulis fruits and seeds respectively in a dose of (500 mg/kg). Molecular, Biochemical and histopathological examinations were then conducted. Data recorded showed a significant elevation in hydrogen peroxide (H2O2) level and reduction in glutathione peroxidase (GPX) level post AgNPs intoxication. The oxidative stress occurred was modulated upon treatment regimens. Protein expression of C-reactive protein (CRP) showed a significant elevation and Molecular analysis recorded a significant up-regulation in the expression of both Bax and caspace-3 genes upon AgNPs intoxication in both particles size. On the contrary, both Bcl2 and P53 gene expression were shown to be significantly reduced. Treatment by C. edulis, G. pentaphylla, protein and mucilage extracts revealed modulation in apoptotic and pro-apoptotic biomarkers. Histopathological examination confirmed the obtained results. AgNPs exposure could induce neurotoxicity, genetic alternation and oxidative stress; the targeted extracts could be considered as a promising candidate in modulating apoptosis and neurotoxicity induced by AgNPs.

Assessment of mechanisms of infectious pneumonia based on expression of fibrinogen, procalcitonin, high-sensitivity C-reactive protein expression, T helper 17 cells, regulatory T cells interleukin-10, and interleukin-17.

BackgroundInfectious pneumonia is one of the important causes of neonatal death that can lead to the imbalance of T helper 17 cells (Th17) and T regulatory T cells (Treg) cells. The correlation between plasma fibrinogen (FIB), procalcitonin (PCT), C-reactive protein (CRP) and Th17/Treg-IL-10/IL-17 axis balance and their specific role in the occurrence and development of infectious pneumonia are not completely clear.MethodsThirty specific-pathogen free Sprague Dawley (SD) rats were randomly divided into a control group for comparison and IPN model group. After the establishment of infectious pneumonia model, levels of FIB, PCT, hs-CRP, IL-10, and IL-17 in the serum of the two groups were measured using enzyme linked immunosorbent assay (ELISA), the pathological changes of lung tissue were observed using hematoxylin and eosin (HE) staining, the number of Treg and Th17 cells and the ratio of Th17/Treg in serum were detected using flow cytometry, and the levels of retinoic acid-related orphan receptor γt and forkhead box P3 (FOXP3) in lung tissue were detected using reverse transcription polymerase chain reaction (RT-PCR) and western blot.ResultsThe results showed that the serum levels of FIB, PCT, hs-CRP, Th17 cell number, Th17/Treg ratio, left lung dry and wet weight, lung tissue wet/dry ratio, lung pathology score and IL-17 level in the model group were significantly higher than those in the control group, while the number of Treg cells and the level of IL-10 in the model group were significantly lower than those in the control group. In addition, the expression of Foxp3mRNA and protein in lung tissue of model group decreased significantly, while the expression level of ROR- γ t mRNA and protein increased.ConclusionsIn infectious pneumonia, the expression levels of FIB, PCT and hs-CRP are up-regulated, and Th17 cells are activated, Treg cells are inhibited, proinflammatory cytokine IL-17 expression is up-regulated, anti-inflammatory cytokine IL-10 expression is down-regulated, resulting in increased inflammatory response, thus promoting the occurrence and development of infectious pneumonia.

Application Value of Blood Heparin-Binding Protein in the Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective To investigate the expression and clinical significance of serum heparin-binding protein (HBP), C-reactive protein (CRP), and white blood cell count (WBC) in an acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods A prospective research model was used to select 63 patients with acute exacerbation of chronic obstructive pulmonary disease who were hospitalized in Xuzhou First People's Hospital from January 2020 to June 2020, and among the chronic obstructive pulmonary disease patients who were followed up in our hospital during the same period, 18 patients were in the stable phase, and 43 healthy patients in our hospital during the same period were selected as the healthy control group. 18 patients with stable chronic obstructive pulmonary disease were selected as the observation group, and 43 healthy people who underwent examination at the same time as the control group. For patients with acute COPD recombination, 5 ml of venous blood was collected according to whether the condition of COPD patients with acute exacerbation was stable or not. 5 ml of venous blood was collected for acute exacerbation. According to their clinical symptoms (such as cough, sputum, and asthma), dyspnea score (MRC score), and pulmonary function (FEV1 and FEV1/FVC), it is determined whether the patient's condition is stable. Patients in the stable COPD group will collect 5 ml of venous blood during the outpatient follow-up, and those in the healthy physical examination group will collect veins on the day of the physical examination. In 5 ml of blood, the levels of HBP and CRP in the blood were measured by the enzyme-linked immunosorbent method and the immunoturbidimetric method, respectively, and the peripheral blood WBC was measured by a blood cell analyzer and its supporting reagents. The differences of the three indicators in each group were statistically analyzed. Normally distributed measurement data were compared using t-test, homogeneity of variance of nonnormally distributed measurement data were compared using one-way analysis of variance, uneven variance of nonnormally distributed measurement data were compared using a rank-sum test, and Pearson linear analysis was used for correlation test. Subject working characteristic curve (ROC) was drawn, P < 0.05 means the difference is statistically significant, the receiver working characteristic curve was established, and the area under the curve (AUC) was calculated to analyze blood HBP. The value of blood CRP and peripheral blood WBC counts alone or in combination in the diagnosis of acute exacerbations of chronic obstructive pulmonary disease. Results The level of blood heparin-binding protein in the acute exacerbation phase was significantly higher than that in the stable phase and healthy controls (P < 0.05). In the acute exacerbation stage and stable stage group, the blood heparin binding protein, the percentage of leukocytes, neutrophils, and CRP were detected. There is a correlation between (P < 0.05) and a correlation with lung function (FEV1) (P < 0.05). The predictive value of heparin-binding protein, white blood cells, neutrophil percentage, CRP, etc. for the acute exacerbation of chronic obstructive pulmonary disease, with the area under the heparin-binding protein curve, is the largest, and compared with the stable phase, the comparison of heparin-binding protein, white blood cells, and CRP is statistically significant (P < 0.05). Conclusion Heparin-binding protein increases in the stable phase and acute exacerbation phase and is related to other inflammatory factors. It is one of the important inflammatory factors in chronic obstructive pulmonary disease. Heparin-binding protein, white blood cells, CRP, etc. have diagnostic and predictive value for acute exacerbation of chronic obstructive pulmonary disease. Heparin-binding protein has the best predictive result, and the combined index test has a better diagnostic predictive value, which is better than single index detection.

Pattern of Neuroinflammatory miRNAs, C-reactive Protein and Alanine Aminotransferase in Hospitalization In Recovered or Not-recovered COVID-19 Patients.

Our aim was to investigate the expression of miRNAs, C-reactive protein as a blood inflammation marker, and alanine aminotransferase as a tissue inflammation marker, in recovered and not-recovered COVID-19 patients. This cross-sectional project was conducted at three medical centers in Iran from December to March 2021. In total, 20 confirmed cases of COVID-19 with grade III severity and 20 healthy subjects were enrolled in the study. Subsequently, the neuroinflammatory expression of miRNAs (miR-199, miR-203, and miR-181), C-reactive protein, and alanine aminotransferase was investigated during hospitalization from week 0 to week 2. Among COVID-19 subjects who did not recover, the expression levels of miR-199, miR-203, and miR-181 were decreased, while the levels of C-reactive protein and alanine aminotransferase increased during hospitalization. Conversely, in recovered COVID-19 subjects, the relative expression of miR-199, miR-203, and miR-181 increased and the levels of C-reactive protein and alanine aminotransferase decreased during hospitalization. The expression pattern of neuroinflammatory miRNAs depends on whether the COVID-19 patient is recovering or deteriorating. Their expression is downregulated in COVID-19 patients who do not recover and upregulated in those who do recover.

Clinical Effect of Clarithromycin Combined with Tinidazole on Helicobacter pylori-Related Gastritis and Its Influence on COX-2 Expression.

Studies have shown that COX-2 expression is upregulated in gastric cancer (GC) as well as in precancerous lesions and in Helicobacter pylori-induced inflammation, suggesting that cyclooxygenase-2 (COX-2) may play an important role in gastric carcinogenesis. We attempted to investigate the role of clarithromycin with tinidazole on Helicobacter pylori-related gastritis from the aspects of clinical effect and COX-2 expression. From January 2016 to January 2019, 130 patients with Helicobacter pylori-related chronic gastritis were collected and grouped into the observation group (OG) and the control group (CG). Altogether, 80 patients in the OG were treated with clarithromycin with tinidazole, while 50 patients in the CG were treated with amoxicillin with metronidazole. Clinical symptom improvement time, content of COX-2 and B cell lymphoma-2 (BCL-2), content of inflammatory factors interleukin-1 (IL-1), IL-4, and C-reactive protein (CRP), expression level of nutritional indicators serum albumin (ALB), realbumin (PA), and transferrin (TF), clearance of Helicobacter pylori, total effective rate, and incidence of adverse reactions were detected. Compared with the CG, the OG had shorter clinical symptom improvement time, lower COX-2 and Bcl-2, lower expression of inflammatory factors IL-1, IL-4, and CRP, higher expression of nutritional indicators ALB, TF, and PA, higher clearance rate of Helicobacter pylori, higher total effective rate, and lower incidence of adverse reactions. Clarithromycin combined with tinidazole can effectively improve the clinical effect of Helicobacter pylori-related gastritis and reduce the expression level of COX-2.

Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD.

The incidence of incision infections after lumbar fusion and the significance of dynamically monitoring serum albumin and C-reactive protein levels.

To explore the incidence of incision infections and dynamically monitor albumin (ALB) and C-reactive protein (CRP) levels after lumbar fusion. A total of 1,773 patients undergoing lumbar fusion in our hospital from March 2011 to March 2021 were selected and divided into the infection group and the non-infection group according to whether incision infections occurred postoperatively. The incidence of postoperative incision infections, the pathogenic characteristics and drug resistance of the pathogenic bacteria in patients in the infection group were analyzed. The general clinical data, serum ALB and CRP levels at different time points were compared between the two groups of patients, and the correlation between ALB and CRP levels was analyzed. ROC curve was used to evaluate the predictive value of serum ALB and CRP levels on the incidence of postoperative incision infections. Of the 1,773 patients, 41 (2.31%) experienced postoperative incision infections. A total of 57 pathogens were detected, including 36 gram-negative bacteria (63.16%), 18 gram-positive bacteria (31.58%), and 3 fungi (5.26%). Among gram-negative bacteria, Pseudomonas aeruginosa had the highest resistance to ampicillin. Among gram-positive bacteria, Staphylococcus aureus had the highest resistance to penicillin and erythromycin. The age, BMI, the number of diabetes patients, levels of serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and procalcitonin (PCT) IL-8 at 1 d after operation in the infection group were significantly higher than those in the non-infection group (P<0.05). The serum ALB and CRP levels of the two groups differed over time, and the differences were statistically significant in terms of time, inter-group, time and inter-group interaction factors (P<0.05). Correlation analysis showed that ALB was significantly negatively correlated with CRP expression. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of combined ALB and CRP detection was 0.856, which was significantly higher than that of single detection with ALB or CRP (P<0.05). Gram-negative bacterial infection was the main type of incision infection in patients after lumbar fusion. The changes in ALB and CRP levels were related to the incidence of postoperative incision infections.

Effect of Psychological Care Combined with Traditional Chinese Medicine on Postoperative Psychological Stress Response in Patients with Advanced Cervical Cancer.

Objective To study the effects of psychological care combined with traditional Chinese medicine treatment on the postoperative psychological stress response and the expression levels of serum C-reactive protein (CRP) and interferon-γ (IFN-γ) in patients with advanced cervical cancer. Method 232 postoperative advanced cervical cancer patients treated in our hospital from December 2015 to December 2018 were selected as study objects and divided into the control group and study group using the random number table method. The control group was given basic care combined with traditional Chinese medicine treatment, while the study group was given psychological care treatment on the basis of the control group to compare the treatment effect, psychological stress response, pain level, quality of life, and long-term efficacy of the two groups. The serum CRP and IFN-γ levels and their correlation with different psychological stress responses were compared between the two groups before and after treatment. Result Comparing the clinical efficacy of the two groups, the total effective rate of the study group was higher than that of the control group. VAS scores in the study group were significantly lower than those in the control group 30 and 60 days after treatment. The SCL-90 scores of the study group after treatment were lower than those of the control group. After treatment, the differences between the two groups were statistically significant in the scores of emotional function, social function, and role function. The two-year cumulative survival rate in the study group (82.76%) was significantly increased compared to that in the control group (55.17%). The serum CRP and IFN-γ expression levels in the two groups were significantly decreased after treatment compared to those before treatment, and the serum CRP and IFN-γ expression levels in the study group were significantly decreased compared to those in the control group. Conclusion Psychological care combined with traditional Chinese medicine in the treatment of advanced cervical cancer patients after surgery was effective in improving patients' psychological status, reducing their pain level, relieving postoperative negative emotions, increasing compliance, improving the quality of life, helping to prolong survival time, and controlling serum indexes back to normal, which was worth promoting in clinical practice.

Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats.

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.

C-Reactive Protein Protects Against Acetaminophen-Induced Liver Injury by Preventing Complement Overactivation.

Background and aimsC-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI).MethodsThe effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice.ResultsCRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine.ConclusionOur results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

The role of targeted regulation of COX11 by miR-10a-3p in the development and progression of paediatric mycoplasma pneumoniae pneumonia.

BackgroundMiR-10a-3p is associated with the pathogenesis of many immune inflammatory diseases including Mycoplasma pneumoniae pneumonia (MPP), and cytochrome coxidase assembly homologue 11 (COX11) is one of its direct target proteins. This study investigates the function and mechanism of miR-10a-3p targeting with COX11 in the development and progression of paediatric MPP.MethodsNinty-seven paediatric MPP patients and 100 age- and sex-matched healthy children were enrolled. Clinical and laboratory indicators of paediatric MPP patients were collected. The mRNA levels of the COX11 gene and miR-10a-3p were detected by qRT-PCR. THP-1 mononuclear macrophages were stimulated using MPP lipid-associated membrane proteins (Mp-LAMPs). The relative expression level of miR-10a-3p was detected after 12, 24, and 48 h. THP-1 cells were transfected to overexpress or inhibit the expression of miR-10a-3p, miR-10a-3p, COX11 mRNA, NF-κB signalling pathway-related proteins, and C-reactive protein (CRP) were detected after 48 h by Western blot.ResultsThe relative expression level of miR-10a-3p in the MPP group was 2.38±0.52, compared with 1.76±0.38 in control group (t=4.584, P<0.001) whileCOX11 in MPP group was 3.70±1.12, compared to 5.78±1.84 in control group (t=4.876, P<0.001). Pearson correlation analysis showed that miR-10a-3p and COX11 in MPP group presented a negative correlation (r=-0.679, P<0.001). By searching in the prediction website of TargetScan database, it was found that miR-10a-3p and Cox11 genes had targeted regulatory binding sites, and the targeting relationship between miR-10a-3p and Cox11 genes was confirmed by dual luciferase reporting assay in 293T cells. Among paediatric MPP patients, miR-10a-3p expression had a positive correlation with the white blood cells count, erythrocyte sedimentation rate (ESR), and CRP expression, while COX11 mRNA expression had a positive correlation with ESR and CRP. After LAMP stimulation, the miR-10a-3p expression level in THP-1 cells significantly increased (P<0.05). After THP-1 cells were transfected with the miR-10a-3p mimic or inhibitor, the relative expression level of miR-10a-3p significantly increased or decreased, respectively. COX11 expression in the mimic group significantly decreased, whereas COX11 in the inhibitor group significantly increased (both P<0.05). In addition, after transfection, IκBα expression significantly decreased and that of p-IKKα/β, p-p65, and CRP significantly increased in the mimic group, and the opposite was true in the inhibitor group.ConclusionsIn paediatric MPP, increased miR-10a-3p downregulated COX11, activating NF-κB signalling pathway to promote disease development and progression.

Serum levels of SIRT3 and other inflammatory factors are associated with clinical outcomes and prognosis in severe community-acquired pneumonia in adults: A prospective study.

The aim of this study was to investigate clinical significance of SIRT3 in severe community-acquired pneumonia (CAP) patients.This prospective observational research enrolled a total of 114 severe CAP patients who went to our hospital during January 2018 to December 2019. Serum SIRT3 and IL-1β, IL-6, and tumor necrosis factor (TNF)-α levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. Demographic data, including age, sex, and body mass index (BMI), as well as clinical symptoms, SOFA and SMART-COP scores were collected. The routine blood test was conducted for all patients and white blood cell (WBC) amount, as well as serum levels of C-reactive protein (CRP), D-Dimer, and procalcitonin (PCT).Among all patients, 55 cases died during the study period. The serum levels of CRP, PCT, IL-1β, and IL-6, as well as SOFA and SMART-COP scores were markedly higher in deceased patients than in the survival patients. The expression of SIRT3 was significantly decreased in severe CAP patients compared with the healthy, especially in the deceased patients. SIRT3 levels were negatively correlated with levels of CRP, PCT, IL-1β, and IL-6. Patients with SIRT3 low expression showed remarkably higher expression of CRP, PCT, IL-1β, and IL-6, as well as high SMART-COP scores, higher 1-month mortality rate, and shorter survival. Only SIRT3 and IL-1β were independent risk factors for 1-month mortality in severe CAP patients.Lower serum SIRT3 level predicts poor clinical outcomes and prognosis in severe CAP patients.

Exploring the role of monocyte chemoattractant protein-1 in fibroblast-like synovial cells in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease with persistent synovitis. In the present study, the impact of monocyte chemoattractant protein-1 (MCP-1) was explored to determine methods for the diagnosis and treatment of RA.MethodsFirst, fibroblast-like synoviocytes (FLSs) were obtained from a collagen-induced rat RA model. Next, MCP-1-overexpression plasmid and small interfering RNA were transfected into human and rat FLSs. Cell Counting Kit-8 (CCK-8), Transwell migration and flow cytometry assays were used to analyze cell proliferation, migration and apoptosis of FLSs following MCP-1 transfections, respectively. Furthermore, western blotting was used to analyze the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β in FLSs following MCP-1 transfection. In addition, reverse transcription-quantitative PCR and ELISAs were used to analyze the expression levels of C-reactive protein (CRP), estrogen receptor, MCP-1 and pentraxin-3 in patients with clinical RA, followed by correlation analysis of clinical data. Finally, expression validation, diagnostic and protein-protein interaction (PPI) network analysis of MCP-1 were performed.ResultsMCP-1 promoted FLS proliferation and migration, and affected the apoptosis of FLSs. In addition, the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β were also affected by MCP-1. In patients with clinical RA, the expression level of MCP-1 was increased. Moreover, CRP expression level was significantly up-regulated in RA. Clinically, MCP-1 was strongly correlated with tender joint count, swollen joint count, visual analog scale for general health and disease activity score 28 (DAS28)-MCP-1, and was moderately correlated with DAS28 and DAS28-CRP. PPI analysis showed that MCP-1 mainly interacted with other inflammatory cytokines.ConclusionIn conclusion, MCP-1 may play a significant regulatory role in RA, and could be used as a measurement index of clinical RA activity.

Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient.

PurposeNesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM).MethodsDemographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples.ResultsThe results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1.ConclusionThese findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.

DIAGNOSTICS AND TREATMENT OF ANEMIC SYNDROME IN PATIENTS WITH BREAST CANCER ON THE BACKGROUND OF NEOADJUVANT CHEMOTHERAPY

Introduction. In recent years, a separate publications have appeared indicating that interleukin 6 (IL-6) and the protein hepcidin 25 (GP25) play a significant role for the development of functional iron deficiency (FID) in oncological patients with a widespread tumor process. It is important to differentiate between FID and iron deficiency anemia (IDA), since they have the same morphological characteristics, but their treatment is fundamentally different.The aim of this study was to study the main metabolites of ferrokinetics, IL-6 and C-reactive protein (CRP) expression parameters in patients with breast cancer on the background of neoadjuvant chemotherapy to develop individual approaches to the diagnosis and treatment of anemic syndrome (AS), prediction, early detection of anemia and its adequate correction.Materials and methods. The study was conducted in 31 breast cancer patients, during of 6 cycles of chemotherapy. The main metabolites of ferrokinetics were studied: GP25, ferritin, soluble transferrin receptors, transferrin, iron, erythropoietin, IL-6 and CRP indices. The control group consisted of 29 apparently healthy women.Results. AS was detected in 14 (45.1 %) of breast cancer patients. IDA prevailed with microcytic, hypochromic characteristics of erythrocytes, a low concentration of ferritin, iron, GP25, IL-6, CRP, and a high level of transferrin and soluble transferrin receptors. A some patients were diagnosed with FID, mainly with the III and IV stages of the disease. Unlike IDA, they had a high concentration of ferritin, CRP and significant production of GP25, IL-6. Erythropoietin level was not optimal for the majority of patients with AS. A few patients on the background of treatment with recombinant erythropoietins revealed a deficiency of vitamins B12 (cyanocobalamin) and folic acid.Conclusion. Early diagnosis, a personalized approach to the prescription of iron preparations, recombinant erythropoietins, vitamins B12 and folic acid in patients with AS allowed for 6 cycles neoadjuvant chemotherapy without a significant decrease in erythrocytes, hemoglobin and hematocrit in most of them. The data obtained on IL-6, GP25, and CRP indicate relationship between them in the development of FID in breast cancer patients with a widespread tumor process and require further study.

Preparation of Double-Layer Nanoparticles for Inhibitory Efficiency in Vascular Restenosis via Balloon Infusion

ABSTRACTThe effect of double-layer nanoparticles (DNPs) on vascular restenosis was investigated in this study, which were prepared by combining vascular endothelial growth factor (VEGF) and paclitaxel (PTX). Different blank NPs (Blank), VEGF NPs, PTX-NPs single-layer NPs (PTX-NPs), and DNPs were prepared with VEGF, PTX, polylactic-polyglycolic acid (PLGA), and polyvinyl alcohol (PVA), so as to analyze the cytotoxicity of NPs. Besides, different NPs were compared in terms of the characterization, encapsulation efficiency (EE), in vitro release (IVR), and cell proliferation inhibition ability. 30 adult New Zealand white rabbits were selected to construct a balloon injury model (BIM). Then, they were divided into 5 groups according to different treatment NPs, including a model group (BIM), a Blank group (BIM + Blank NPs); a PTX-NP group (BIM + PTX-NPs), a VEGF-NPs group (BIM + VEGF-NPs), and DNPs group (BIM + DNPs), with 6 rabbits in each group. There was a comparison on the histology, arterial stenosis, hyperplasia index (HI), and intimal thickness (IT) of arterial vessels from different groups, and immunohistochemistry was employed to analyze the changes of VEGF and C-reactive protein (CRP) protein expression levels in arterial tissues of different groups. The results showed that the cell survival rate (SR) was 88.69 ±3.17% and 90.64 ± 1.86% in turn when PLGA and PVA were both 100 ¿tg/mL. The polydispersity index (PDI), minimal Zeta potential (ZP), and average particle size (APS) of DNPs were 0.16 ±0.02, -8.45 ±0.07, and 242.26 ±2.58 nm, respectively. The drug loading (DL) of PTX and plasmid VEGF 165 in DNPs were 29.33% and 4.93%, respectively. The release of PTX from DNPs on the 30th day was close to 50%, and the cumulative release of deoxyribonucleic acid (DNA) was close to 75%. There was no obvious difference in the cell SR within 7 days after DNPs were added into Chinese Hamster ovary (CHO) cells and vascular smooth muscle cells (VSMC) compared with the control group (P &gt; 0.05). The arterial stenosis, HI, and IT of the DNPs group were greatly lower than those of the model group (P &lt; 0.05). The expression of VEGF protein in arterial tissues of DNPs group was higher in contrast to the model group (P &lt; 0.01), while the expression of CRP protein was lower than that of the model group (P &lt; 0.05). It showed that the DNPs combined with VEGF and paclitaxel administered by balloon infusion could obviously inhibit the vascular restenosis by increasing the expression of VEGF and reducing the expression of CRP, which provided a reference for the clinical prevention and treatment of postoperative vascular restenosis.

Efficacy and safety of Tripterygium glycosides in Sjögren's syndrome treatment: evidence from 12 randomized controlled trials.

Tripterygium glycosides (TGs) has been widely used in the treatment of Sjögren's syndrome (SS). Seven databases, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Medical Database, China Science and Technology Journal Database, and the Chinese Biomedicine database, were selected to collect randomized controlled trials (RCTs) related to the treatment of SS with TGs alone or in combination. The participants, intervention, comparison, outcome, and study design principle were adopted for the inclusion of related studies. The risk of bias was assessed using the Cochrane Collaboration's tool. Meta-analysis was conducted using RevMan 5.3, with risk ratios (RRs) or standard mean differences (SMDs) and 95% confidence intervals (CIs). Overall, 12 trials involving 668 patients were analyzed. The results of the meta-analysis showed that TGs in combination with total glucosides of paeony (TGP) had significantly lower symptom scores than TGs alone on dry eyes (SMD =-0.61, 95% CI: -1.12 to -0.10, P=0.02) or dry mouth (SMD =-1.29, 95% CI: -1.84 to -0.74, P<0.00001). The efficacy rates of TG + TGP vs. TGs (P<0.00001) and TG + HM vs. TGs (P=0.01) were significantly different. In addition, compared to hydroxychloroquine (HCQ), TGs could induce expression of C-reactive protein (P=0.007), globulin (P<0.00001), and immunoglobulin A (IgA) (P=0.006), whereas the TG + TGP group had lower levels of immunoglobulin G (IgG) (P<0.00001), immunoglobulin M (IgM) (P=0.02), and IgA (P<0.00001), as well as saliva flow rate (P<0.00001) and lacrimal gland function (P<0.00001). The adverse events between TGs and HCQ were not evident, and there was no increase in the risk of adverse reactions when combined with other drugs. TGs are potentially effective for treating SS without increasing the risk of adverse events. High-quality, multi-center, and large-scale RCTs are required.

Pelargonic acid vanillylamide and rosuvastatin protect against oxidized low-density lipoprotein-induced endothelial dysfunction by inhibiting the NF-κB/NLRP3 pathway and improving cell-cell junctions

Oxidized low-density lipoprotein (ox-LDL) not only causes hyperlipidemia and contributes to atherosclerosis but also induces the endothelial dysfunction that leads to cardiovascular diseases. The nuclear factor-kappa B (NF-κB) pathway plays a key role in many chronic disorders and is a transcriptional factor in various inflammatory responses. The present study aimed to investigate the synergistic effects of pelargonic acid vanillylamide (PAVA) and rosuvastatin (RSV) on ox-LDL-induced inflammatory responses in human vascular endothelial cells (HUV-EC-C). HUV-EC-C were pretreated with PAVA or RSV and their combination for 2 h followed by ox-LDL for 24 h. The MTT assay was used to measure mitochondrial function. The DCFH-DA assay was used to evaluate oxidative phosphorylation, and western blotting was used to measured NF-κB/NLRP3 and related signaling pathways in HUV-EC-C. Ox-LDL induced lectin-type oxidized LDL receptor 1 (LOX-1) expression, NADPH oxidase 4 activation, and the overexpression of reactive oxygen species, which were inhibited by pretreatment with the combination of PAVA and RSV. Moreover, PAVA and RSV inhibited ox-LDL-induced NF-κBp65 activation. Ox-LDL induced NF-κB/NLRP3 pathway activation by inducing C-reactive protein expression, NLRP3 activation, caspase-1 activation, and IL-1β secretion, which were inhibited by pretreatment with the combination of PAVA and RSV. The combination of PAVA and RSV reduced ox-LDL-induced recruitment of monocytes to the site of inflammation, inhibited activation of the NLRP3 inflammasome, and ameliorated the impairment of cell-cell junctions through the NF-κB pathway. Our results suggest that the synergistic effects of PAVA and RSV provide a novel mechanism for the treatment of cardiovascular diseases.

Baicalin relieves Mycoplasmapneumoniae infection‑induced lung injury through regulating microRNA‑221 to inhibit the TLR4/NF‑κB signaling pathway.

Mycoplasma pneumoniae (MP) is a common pathogen that can cause respiratory infections. MP pneumonia (MPP) leads to numerous complications, including lung injury and even death. The present study aimed to investigate the protective effects of Baicalin treatment on MP infection-induced lung injury and the molecular mechanism underlying these effects. Briefly, after mice were infected intranasally by MP and treated with Baicalin (80 mg/kg), serum levels of MP-immunoglobulin M (IgM) were detected by ELISA. The expression levels of C-reactive protein (CRP) in lung tissue were detected by immunohistochemistry and the bronchoalveolar lavage fluid (BALF) was examined by ELISA. Inflammatory factors and inflammatory cells in the BALF were assessed. The expression levels of microRNA (miR)-221 in lung tissue were examined by reverse transcription-quantitative PCR and pathological changes in lung tissue were detected by H&E staining. Cell apoptosis was evaluated by TUNEL assay and the protein expression levels of TLR4, MyD88 and NF-κB were detected by western blotting. Baicalin treatment significantly reduced serum levels of MP-IgM and CRP expression in lung tissue during MP infection. In addition, Baicalin decreased the levels of IL-1β, IL-6, IL-18 and TNF-α in the BALF, and the number of inflammatory cells. Baicalin also reduced the inflammatory infiltration in lung tissue induced by MP infection, improved the pathological changes detected in lung tissue, reduced apoptosis, and downregulated the protein expression levels of TLR4, MyD88 and NF-κB. Furthermore, Baicalin treatment downregulated the expression of miR-221 and the protective effects of Baicalin were attenuated by miR-221 overexpression. In conclusion, Baicalin has a therapeutic effect on mice with MP infection-induced lung injury, which may be related to inhibition of miR-221 expression and regulation of the TLR4/NF-κB signaling pathway.