C-reactive Protein Expression Research Articles

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

C-reactive protein is a prognostic biomarker in pancreatic ductal adenocarcinoma patients.

The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes. The non-randomized Phase II study "Gemcitabine and Abraxane for resectable Pancreatic cancer" (GAP) demonstrated the feasibility of perioperative gemcitabine/abraxane. Long-term survival in PDAC requires an effective immune response; hence, we undertook this translational study of the GAP trial cohort to identify immune-oncology biomarkers for clinical use. We combined Nanostring nCounter technology with immunohistochemistry to investigate the correlation between gene expression and overall patient survival. Findings were investigated in samples from the International Cancer Genome Consortium (ICGC, n=88) and the Australian Pancreatic Genome Initiative (APGI, n=227). We confirmed that human equilibrative nucleoside transporter 1 (hENT1) expression was not a prognostic marker in PDAC but patients with high levels of hENT1 were more likely to live longer than 24 months post-surgery. Additionally, CD274 (PD-L1) and two novel biomarkers of survival, cathepsin W (CTSW) and C-reactive protein (CRP), were identified in the GAP cohort (n=19). CRP expression was confirmed in data from the ICGC. Although PD-L1 and CTSW proteins were not significant across all three cohorts, results show that low CRP mRNA and protein expression are associated with longer overall survival in all three patient groups. PDAC patients with long survival have higher hENT1 expression levels. Furthermore, CRP expression is a biomarker of poor prognosis following perioperative chemotherapy and resection in PDAC patients and thus may be useful for identifying patients who could benefit from more aggressive adjuvant strategies.

New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats.

Morus alba L. (Sangzhi) alkaloid (SZ-A) is a new antidiabetic drug approved by the China National Medical Products Administration in 2020. Diabetic nephropathy (DN) is a common diabetic complication and an important cause of morbidity and mortality in patients with diabetes. The effects of SZ-A on DN remain unknown. This study evaluated the effects of SZ-A on DN in Zucker diabetic fatty (ZDF) rats and explored the underlying mechanisms based on nitrosative stress, inflammation, and fibrosis. Diabetic ZDF rats were orally administered 100 and 200 mg/kg of SZ-A once daily for 9 weeks. The glucose metabolism and kidney function were assayed. The pathological injury and fibrosis of the kidneys were separately evaluated using hematoxylin and eosin staining and Masson's staining. The oxidative and nitrosative stress and inflammation were assayed by determining the levels of related indices in the blood and kidneys and quantifying the related gene and protein expression. The expression of transforming growth factor β1 (TGFβ1) gene and protein were assayed by quantitative real-time PCR and immunohistochemistry, respectively. The renal transcriptomics was analyzed using RNA sequencing. Repeated treatment with SZ-A significantly improved glucose metabolism, dose-dependently decreased the levels of blood urea nitrogen, urinary albumin, and β2-microglobulin, and evidently relieved the renal injury in diabetic ZDF rats. As for the mechanisms, SZ-A remarkably ameliorated systemic nitrosative stress through lowering the levels of blood inducible nitric oxide synthase and nitric oxide, and significantly relieved systemic and renal inflammation by reducing the levels of blood interleukin-1β and monocyte chemoattractant protein-1 (MCP-1) and decreasing the levels of renal C-reactive protein content and expression of tumor necrosis factor-α in the kidneys. SZ-A also improved renal fibrosis by lowering the expression of TGFβ1 in the kidneys. Additionally, SZ-A significantly lowered the expression of stimulator of chondrogenesis 1 in the kidneys. Repeated treatments with SZ-A significantly ameliorates DN by regulating systemic nitrosative stress, renal inflammation, and renal fibrosis partially through inhibition of the cytokine-NO and TGF-β1 signaling in ZDF rats, providing evidence for the additional application of SZ-A in clinical use for the treatment of DN.

Serum and genetic markers related to rapid clinical progression of coronary artery disease

Introduction and objectivesPatients with clinically evident coronary artery disease differ in their rate of progression, which impacts prognosis. We aimed to characterize serum and genetic markers in patients with rapid clinical progression (RCP) of coronary artery disease vs those with long standing stable (LSS) disease. MethodsRetrospective study of cases (RCP) and controls (LSS) (1:2). Patients requiring ≥ 2 revascularizations due to atherosclerotic progression in the 10 years after a first angioplasty were considered to be RCP and those without events during the same period after the first angioplasty were considered to have LSS disease. After patient selection, we analyzed serum values, mRNA expression and genetic polymorphisms of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor (TNF)-a, and atherogenic markers consisted of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, sterol regulatory element binding transcription factor 2, and apolipoprotein-B. ResultsThe study included 180 patients (58 RCP and 122 LSS). Demographic characteristics, classic risk factors and the extent of coronary disease were similar in the 2 groups. Patients with RCP showed higher serum levels of interleukin-6 and PCSK9 and higher TNF mRNA expression. Interleukin-6 rs180075C, TNF rs3093664 non-G and PCSK9 rs2483205 T alleles conferred a risk of RCP (P<.05 in all cases). Among patients with RCP, 51.7% had all 3 risk alleles vs 18% of those with LSS (P<.001). ConclusionsWe suggest the existence of specific phenotypic and genotypic markers associated with RCP of coronary artery disease that could help to individualize the type and intensity of treatment.

Xylopia aethiopica suppresses markers of oxidative stress, inflammation, and cell death in the brain of Wistar rats exposed to glyphosate.

The herbicide "Roundup" is used extensively in agriculture to control weeds. However, by translocation, it can be deposited in plants, their proceeds, and the soil, thus provoking organ toxicities in exposed individuals. Neurotoxicity among others is one of the side effects of roundup which has led to an increasing global concern about the contamination of food by herbicides. Xylopia aethiopica is known to have medicinal properties due to its antioxidative and anti-inflammatory properties, and it is hypothesized to neutralize roundup-induced neurotoxicity. Thirty-six (36) Wistar rats were used for this study. The animals were shared equally into six groups with six rats each. Glyphosate administration to three of the six groups was done orally and for 1 week. Either Xylopia aethiopica or vitamin C was co-administered to two of the three groups and also administered to two other groups and the final group served as the control. Our studies demonstrated that glyphosate administration led to a significant decrease in antioxidants such as catalase, superoxide dismutase, glutathione, and glutathione peroxidase. We also observed a significant increase in inflammatory markers such as tumor necrosis factor-α, interleukin 6, C-reactive protein, and immunohistochemical expression of caspase-3, cox-2, and p53 proteins (p < 0.05). However, Xylopia aethiopica co-administration with glyphosate was able to ameliorate the aforementioned changes when compared to the control (p < 0.05). Degenerative changes were also observed in the cerebellum, hippocampus, and cerebral cortex upon glyphosate administration. These changes were not observed in the groups treated with Xylopia aethiopica and vitamin C. Taken together, Xylopia aethiopica could possess anti-oxidative and anti-inflammatory properties that could be used in combating glyphosate neurotoxicity.

Impact of enteral administration of sodium hypochlorite on the mechanisms of inflammation and hemostasis in cancer patients with enteral insufficiency syndrome after multi-organ surgeries

Background. Enteral insufficiency syndrome is a complicated and multifactorial symptom complex that is accompanied with impaired functions of the gastrointestinal tract and is also one of the main causes of the development of endotoxicosis, systemic inflammatory response syndrome, abdominal sepsis, septic shock, and multi-organ failure. Thrombosis, which is associated with oncological diseases, is another common cause of death among patients with cancer after the progression of the disease. Development and implementation of new methods of detoxification in cancer patients in clinical practice after multi-organ surgeries is a major problem in intensive care. Purpose – to study the effectiveness of the enteral administration of sodium hypochlorite in cancer patients after multi-organ surgeries with systemic inflammatory response syndrome and to monitor the dynamics of certain markers of inflammation. Materials and methods. 53 patients with cancer were observed after having undergone multi-organ surgeries on the abdominal organs. The patients were divided into two groups: the main group (n=27), in which indirect electrochemical detoxification with sodium hypochlorite at a concentration of 0,06% was carried out by the drip infusion method through a gastrointestinal tube, and the comparison group (n=26), in which the treatment was performed according to standard treatment regimens. The examination was carried out at 3 stages – before NaClO infusion, on the 1st and the 7th day after the indirect electrochemical detoxification. Groups were compared according to age and anatomical and functional zones of the surgery (the surgery was performed on the abdominal organs). Results. Patients with stage 2/3 enteral insufficiency syndrome were treated with the method of electrochemical detoxification with sodium hypochlorite, which led to the inflammation reduction and normalization of the hemostatic system parameters. In patients, who were receiving sodium hypochlorite (the main group), the reduction in inflammatory mediators was observed: C-reactive protein (CRP) – from 22.1 to 5.6 mg/l, interleukin-6 (IL-6) – from 14,36 to 1.55 pg/ml, and also hemostatic parameters were improved. A decrease in the international normalized ratio (INR), fibrin, activated partial thromboplastin time (APTT), D-dimer level, blood clotting time, and an increase in prothrombin index were observed. Analyzing the effectiveness, it should be noted that the correction of the hemostatic system and the development of inflammation are significantly faster (on the 1st day after the NaClO infusion) compared with standard treatment methods while also ensuring plasma preservation. Conclusions. The use of the method of electrochemical detoxification with 0,06% NaClO in postoperative intensive therapy in enteral insufficiency syndrome prevents the development of systemic inflammation and hypocoagulation. The inclusion of sodium hypochlorite in the complex postoperative therapy during the day allowed the development of inflammation (a decrease in the expression of IL-6 and CRP) to be halted and procoagulative changes (a decrease in INR, fibrin, APTT, D-dimer level, blood clotting time, and an increase in prothrombin index) to be achieved.

Expression and prognostic value of C-reactive protein in adult immune thrombocytopenia (ITP) patients.

The aim of this study was to investigate the effect of C-reactive protein (CRP) on the prognosis of adult patients with Immune thrombocytopenia purpura (ITP). A retrospective study of 628 adult ITP patients, as well as 100 healthy and 100 infected patients, attending the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2022 was performed. The ITP patients were grouped according to their CRP levels, and the differences in clinical characteristics of each group and the influencing factors of efficacy in newly diagnosed ITP patients were analyzed. CRP levels were significantly higher in the ITP and infected groups compared with healthy controls (P < 0.001), and platelet counts were significantly lower in the ITP group (P < 0.001). Between the CRP normal and elevated group, their age, white blood cell count, neutrophil count, lymphocyte count, red blood cell count, hemoglobin, platelet count, complement C3 and C4, PAIgG, bleeding score, proportion of severe ITP, and proportion of refractory ITP were significantly different (P < 0.05). Patients of severe ITP (P < 0.001), refractory ITP (P = 0.002), and with active bleeding (P < 0.001) had significantly higher CRP levels. Patients with no response after treatment had significantly higher CRP levels than those who achieved CR or R (P < 0.001). Platelet counts (r = - 0.261, P < 0.001) in newly diagnosed ITP patients and treatment outcomes (r = - 0.221, P < 0.001) were negatively correlated with CRP levels, and bleeding score was positively correlated with CRP levels (r = 0.207, P < 0.001). Treatment outcome was positively correlated with decrease in CRP levels (r = 0.313, P = 0.027). A multifactorial regression analysis of the influencing factors of treatment outcomes on newly diagnosed patients found that CRP was an independent risk factor of the prognosis (P = 0.011). In conclusion, CRP can help assess the severity and predict the prognosis of ITP patients.

Diagnostic value of echocardiography combined with serum C-reactive protein level in chronic heart failure

BackgroundChronic heart failure (CHF) is regarded as common clinical heart disease. This study aims to investigate the clinical diagnostic value of echocardiography (Echo) and serum C-reactive protein (CRP) levels in patients with CHF.MethodsA total of 75 patients with CHF (42 males, 33 females, age 62.72 ± 1.06 years) were enrolled as study subjects, with 70 non-CHF subjects (38 males, 32 females, age 62.44 ± 1.28 years) as controls. The left ventricular ejection fraction (LVEF), fraction shortening rate of the left ventricle (FS), and early to late diastolic filling (E/A) were determined by Echo, followed by an examination of the expression of serum CRP by ELISA. In addition, the Pearson method was used to analyze the correlation between echocardiographic quantitative parameters (EQPs) (LVEF, FS, and E/A) and serum CRP levels. Receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic efficacy of EQPs and serum CRP levels for CHF. The independent risk factors for CHF patients were measured by logistics regression analysis.ResultsThe serum CRP level of CHF patients was elevated, the values of LVEF and FS decreased, and the E/A values increased. ROC curve revealed that the EQPs (LVEF, FS, and E/A) combined with serum CRP had high diagnostic values for CHF patients. Logistic regression analysis showed that the EQPs (LVEF, FS, and E/A) and serum CRP levels were independent risk factors for CHF patients.ConclusionEcho combined with serum CRP level has high clinical diagnostic values for CHF patients.

Innate Immune Zonation in the Liver: NF-κB (p50) Activation and C-Reactive Protein Expression in Response to Endotoxemia Are Zone Specific.

Hepatic innate immune function plays an important role in the pathogenesis of many diseases. Importantly, a growing body of literature has firmly established the spatial heterogeneity of hepatocyte metabolic function; however, whether innate immune function is zonated remains unknown. To test this question, we exposed adult C57BL/6 mice to endotoxemia, and hepatic tissue was assessed for the acute phase response (APR). The zone-specific APR was evaluated in periportal and pericentral/centrilobular hepatocytes isolated using digitonin perfusion and on hepatic tissue using RNAscope and immunohistochemistry. Western blot, EMSA, chromatin immunoprecipitation, and immunohistochemistry were used to determine the role of the transcription factor NF-κB in mediating hepatic C-reactive protein (CRP) expression. Finally, the ability of mice lacking the NF-κB subunit p50 (p50-/-) to raise a hepatic APR was evaluated. We found that endotoxemia induces a hepatocyte transcriptional APR in both male and female mice, with Crp, Apcs, Fga, Hp, and Lbp expression being enriched in pericentral/centrilobular hepatocytes. Focusing our work on CRP expression, we determined that NF-κB transcription factor subunit p50 binds to consensus sequence elements present in the murine CRP promoter. Furthermore, pericentral/centrilobular hepatocyte p50 nuclear translocation is temporally associated with zone-specific APR during endotoxemia. Lastly, the APR and CRP expression is blunted in endotoxemic p50-/- mice. These results demonstrate that the murine hepatocyte innate immune response to endotoxemia includes zone-specific activation of transcription factors and target gene expression. These results support further study of zone-specific hepatocyte innate immunity and its role in the development of various disease states.

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring.

Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Effects of sericin and egg white on the inflammation of damaged skin in mice

Sericin and egg white (EW) have shown the ability to promote wound healing. However, there have been insufficient studies regarding the effects of sericin and EW mixtures on wound healing. This study aimed to investigate the effects of a hybrid sericin and EW solution on wound repair and inflammation-related indicators in mouse skin. In this work, sericin with a low molecular weight was first mixed with homogeneous EW to prepare a hybrid wound dressing. Histology evaluation, the expression of C-reactive protein (CRP) and inflammatory cytokines in mice were tested to determine the effects of this dressing on skin injuries in mice. The results showed that sericin and the hybrid solution of sericin and EW effectively promoted wound healing in mouse skin. The wound recovery rates of mice 12 days after treatment with a medium dose of sericin (0.2 g ml−1) and the same dosage of sericin with added EW were 1.32 and 1.65 times that of mice treated with phosphate buffer saline as a control, respectively. In addition, the mixture solution was more effective in wound healing than sericin alone. Sericin with EW significantly reduced the expression of CRP and inflammatory cytokines in mice during wound healing. A sericin and EW hybrid solution can effectively shorten the time needed for wound healing and reduce inflammation-related indicators in mice, making it a promising candidate for wound dressing.

Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: The case of lysine.

The relationship between non-communicable diseases (NCDs) and eating behaviour has long been attributed to a surplus of food and energy. However, the increase in the prevalence of NCDs and their underlying low-grade inflammatory milieu among people of low socioeconomic status (SES) has highlighted the existence of a confounding factor. In this work, we aim to study the effect of lysine deficiency on some inflammatory markers in the absence or presence of an inflammatory insult [lipopolysaccharide (LPS)]. For this purpose, thirty-two five-week-old male Sprague Dawley rats were randomly distributed into four groups: 1) control diet, 2) control diet+LPS, 3) lysine-deficient diet, and 4) lysine-deficient diet+LPS. Groups were only allowed their experimental diets for four weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that lysine deficiency blunted growth and body compartments development, decreased albumin production and elevated liver c-reactive protein (CRP) expression, independently of interleukins 6 and 1β, the main precursors of CRP. Also, the insufficient levels of lysine in the diet increased hyperactivity and triggered an anxiety-like behaviour, exacerbated with LPS. This work presents evidence that various physiological changes are associated with the absence of a sufficient amount of lysine in the diet and can potentially increase the risk factor for diseases. Thus, the increment in NCDs among the low SES populations, who heavily rely on cereals as a main source of protein, can be, at least partially, blamed on low lysine availability in diets.

Effect of Combination of Purple Sweet Potato (Ipomoea batatas L.) Ethanolic Extract and Ramipril Administration on Myocardial C-Reactive Protein Expression and Aortic Intima-Media Thickness in Hypertensive Rat Model

Purposes: To determine the effect of giving a combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril in a rat model of hypertension. Methods: This is an experimental study with a post-test-only control group design and is a collaborative study of the effect of giving a combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril in a rat model of hypertension. Thirty male Wistar rats were given 2 mL/day of a 4% NaCl diet to induce hypertension. The rats were divided into three treatment groups, consists of NaCl 4% 2 mL/day + combination therapy with purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day and ramipril 1 mg/day (P1), NaCl 4% 2 mL/day + purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) and NaCl 4% 2 mL/day + ramipril 1 mg/day (P3). At week 5, the rat was executed to examine myocardial CRP expression and measure aortic IMT. All the data obtained were analyzed statistically. Results: There was a significant difference in myocardial CRP expression between the three treatment groups (p value&lt;0.05). The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day (P1) showed a better effect on reducing myocardial CRP expression than administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) (mean difference 216.44 ng/ml; 95% CI 133.56 – 299.32; p value&lt;0.001) or Ramipril 1 mg/day (P3) (mean difference 144.44 ng/ml; 95% CI 29 .40 – 199.47; p value=0.010). Administration of Ramipril 1 mg/day (P3) showed a better effect on reducing myocardial CRP expression than the group given purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day (P2) (mean difference 102.00 ng/ml; CI 95% 19 .11 – 184.88; p value=0.018). There was a significant difference in aortic IMT between the three treatment groups (p value&lt;0.05). The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day (P1) showed a better effect on reducing aortic IMT than administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) (mean difference 10,16 μm; 95% CI 6,63 – 13,69; p value&lt;0.001) or Ramipril 1 mg/day (P3) (mean difference 5,10 μm; 95% CI 1,40 – 8,70; p value=0.008). Administration of Ramipril 1 mg/day (P3) showed a better effect on reducing aortic IMT than the group given purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day (P2) (mean difference 5,05 μm; CI 95% 1,50 – 8,50; p value=0.007). Combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril showed a higher potential effect on reducing myocardial CRP expression and aortic IMT compared to single therapy. Conclusion: The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day can provide the best decrease in the expression of myocardial CRP and aortic IMT compared to the administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day or ramipril 1 mg/day.

Effects of customized CAD/CAM abutments on cytokine levels in peri-implant crevicular fluid during early implant healing: a pilot study

ObjectivesThis study aimed to assess levels of biomarkers associated with inflammation and tissue destruction in peri-implant crevicular fluid (PICF) of implants provided with customized or standard healing abutments during early implant healing.Materials and methodsThirty implants were placed in 22 patients with partial posterior edentulism. Subsequently, test group implants (n=15) received one-piece titanium abutments that were fabricated using computer-aided design/computer-aided manufacturing (CAD/CAM). Control group implants (n=15) were provided with standard abutments. PICF collection and standardized periapical radiographs were carried out at suture removal one week later, following crown delivery after 3 months and at 6 months. Expression of C-reactive protein (CRP), interferon-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12A, IL-17A, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase (MMP)-13, osteopontin, osteoactivin, Receptor Activator of NF-κB (RANK), and TGF-β were analyzed using a multiplex ELISA kit.ResultsBoth groups showed a significant decrease in protein expression of CRP, IL-1β, IL-6, IL-8, MIP-1α, osteopontin, osteoactivin, and TGF-β, while MMP-13 levels increased during the observation period. A rise in OPG and RANK levels was detected among customized abutments. Expression of CRP was higher, whereas IL-1β, IL-1α, and MIP-1α were decreased in control compared to test group implants after 6 months. Marginal bone loss did not depend on abutment modality.ConclusionsBoth abutment types showed distinctive temporal expression of inflammatory biomarkers during 6 months following implant placement.Trial registrationISRCTN98477184, registration date 18/05/2022Clinical relevanceCustomized healing abutments exert similar effects on inflammation during early implant healing compared to standard healing abutments.

Serum homocysteine is a valuable marker for predicting aggravation of infection in intestinal obstruction patients.

The aim of this study was to investigate the expression of serum homocysteine (HCY), procalcitonin (PCT), and C-reactive protein (CRP) in abdominal infectious disease and analyze their relationship with the degree of abdominal infection. We conducted a retrospective study involving 157 patients with abdominal infections at Xuzhou Central Hospital between January 2016 and October 2019. The patients were composed of intestinal obstruction (73 cases), appendicitis (45 cases), perforation of the digestive tract (25 cases), and cholecystitis (14 cases). The HCY, PCT, and CRP levels of patients with abdominal infections were detected using enzyme-linked immunosorbent assay (ELISA), and correlation analysis between the HCY, PCT, and CRP levels and abdominal infection was performed using Pearson's correlation analysis. Compared with before treatment, the HCY, PCT, and CRP levels in the four groups decreased significantly after treatment. The levels in the patients in the intestinal obstruction group decreased more markedly than in those in the other groups. There were positive correlations among the HCY level, PCT, and CRP before treatment only in patients with intestinal obstruction (P < 0.001). The difference was statistically significant in the HCY level between the non-operation and the operation groups in patients with intestinal obstruction (P < 0.001). Serum HCY may be a valuable marker for predicting aggravation of infection in patients with intestinal obstruction.

Sleep quality traits correlate with inflammatory markers in the breast tissue of women.

Several mechanisms have been posited to play a role in the sleep and breast cancer association, including alterations in immune function, but evidence remains inconclusive. A closer look at how sleep quality traits affect the breast microenvironment may provide clues for molecular mechanisms underlying the link between sleep and breast cancer. We examined the association between sleep quality traits (sleep duration, sleep aids, and insomnia) and tissue-based protein levels and gene expression of several inflammatory markers associated with breast cancer. Breast tissues (normal n=165 and adipose n=74) were surgically obtained from women diagnosed with breast cancer. Protein levels by immunohistochemistry were determined using the quickscore method for 11 inflammatory markers in the normal epithelial breast tissue (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), cyclooxygenase-2 (COX-2), leptin, serum amyloid A1 (SAA1), lactoferrin, transforming growth factor-beta (TGF-β), and signal transducer and activator of transcription 3 markers (STAT3). Relative quantification of 4 genes (COX-2, IL-6, TNF-α and LEP) in the adipose breast tissue was carried out using qPCR. Patient characteristics and sleep traits (average sleep duration per night, taking sleeping aids in the past year, and the average number of insomnia episodes per month) were determined by telephone interview. Associations were tested using Spearman's rank correlation (rs) coefficients adjusted (ars) for age at surgery, menopausal status and PCR batch when applicable. Sleep duration categories (<7, 7-9, >9h) and root- or log-transformed biomarker levels were examined with adjusted linear mixed models. TGF-β and CRP levels in normal epithelial breast tissue were positively correlated with sleep aids (ars=0.28, p=0.013), and insomnia (ars=0.23, p=0.044) in postmenopausal women, respectively. IL-6 in the adipose breast tissue was inversely correlated with sleep aids (ars=-0.26, p=0.029) in all women. None of the sleep traits significantly correlated with inflammatory markers in premenopausal women. Several markers tended to correlate at 0.05≥p≤0.10. Adjusted mean levels of inflammatory markers were significantly different across sleep duration categories (<7, 7-9, >9h). Higher mean levels of IL-6, CRP, IL-10, and IL-6 and COX-2 expression were noted in the breast tissues of women sleeping<7, and particularly, >9h per night (p<0.05). Our findings indicate that sleep duration, sleep aids, and insomnia may differently affect women's breast tissues depending on menopausal status. From a public health perspective, these results warrant further validation in larger studies. Since sleep is a modifiable factor, it may be an interesting approach for breast cancer prevention.

Early and Effective Diagnosis of Sepsis Using Flow Cytometry.

Objective Sepsis is a major global health issue due to its high death and morbidity rates. To avoid the negative effects of sepsis and decrease mortality, it is vital to diagnose and treat it as soon as possible. Blood cultures can take up to 2 days to give result, and they are not always reliable. According to recent studies, neutrophil CD64 expression might be a sensitive and specific option for assessing sepsis. This study aimed to evaluate the diagnostic performance of a flow cytometry analysis for the expression of neutrophil CD64 in sepsis and its comparison with other standard tests in a tertiary care center. Materials and Methods Prospective analysis on 40 blood samples from suspected sepsis patients admitted to intensive care units with criteria for the systemic inflammatory response syndrome on presentation was performed for expression of neutrophil CD64, C-reactive protein, procalcitonin, and complete blood count. Ten healthy volunteers were also enrolled in this prospective study. The laboratory results were compared in different groups. Results The neutrophil CD64 had the highest diagnostic value to differentiate between patients of sepsis and nonsepsis groups with a sensitivity of 100% (95% confidence interval [CI]: 77.19-100%) and 100% (95% CI: 55.32-86.83%); specificity of 90.00% (95% CI: 59.58-99.49%) and 87.24% (95% CI: 66.69-99.61%); and likelihood ratio of 10.00 and 7.84, respectively. Conclusion The neutrophil CD64 expression provides a more sensitive, specific, and novel marker for the early detection of sepsis in critically ill patients.

Correlations between Cytokine Levels, Liver Function Markers, and Neuropilin-1 Expression in Patients with COVID-19.

Aim: The study evaluated the correlations between cytokine levels, liver function markers, and neuropilin-1 (NRP-1) expression in patients with COVID-19 in Egypt. The study also aimed to evaluate the accuracy sensitivity, specificity, and area under the curve (AUC) of the tested laboratory parameters in identifying COVID-19 infection and its severity. Patients and Methods: Fifty healthy subjects and 100 confirmed patients with COVID-19 were included in this study. COVID-19 patients were separated into two groups based on the severity of their symptoms. Serum ALT, AST, albumin, C-reactive protein (CRP), interleukin (IL)-1β, IL-4, IL-6, IL-18, IL-35, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) were estimated. We measured the gene expression for nuclear factor-kappa B p50 (NF-κB p50) and nuclear factor-kappa B p65 (NF-κB p65) and NRP-1 in blood samples using quantitative real-time polymerase chain reaction (qRT-PCR). AUC and sensitivity and specificity for cytokine levels and NF-κB p50 and NF-κB p65 and NRP-1 in identifying COVID-19 infection were also determined in both moderate and severe patient groups using receiver-operating characteristic curve (ROC) analysis. Results: All patients with COVID-19 showed higher serum activities of liver enzymes, levels of CRP, IL-1β, IL-4, IL-6, IL-18, IL-35 PGE2, and TXA2, and mRNA expression of NF-κB p50, NF-κB p65, and NRP-1 than healthy subjects. The severe group exhibited a significant increase in serum ALT, AST and IL-6 and a significant decrease in albumin, IL-1β, TXA2, and NF-κB p65 levels compared to the moderate group. In all patients (moderate and severe), all cytokines were positively correlated with NF-κB p50, NF-κB p65 and NRP-1 expression levels. Serum ALT and AST were positively correlated with CRP, cytokines (IL-4, IL-6, IL-18, IL-35 and TXA2), and NF-κB p50 and NF-κB p65 expression levels in both moderate and severe groups. They were also positively correlated with serum IL-1β level in the severe COVID-19 patient group and with NRP-1 expression in the moderate group. Using the logistic regression analysis, the most important four statistically significant predictors associated with COVID-19 infection in the study were found to be IL-6, TAX2, NF-κB p50 and NF-κB p65. ROC analysis of these variables revealed that three of them had AUC > 0.8. In moderate cases, AUC of the serum TXA2 level and NF-κB p65 expression were 0.843 (95% CI 0.517–0.742, p < 0.001) and 0.806 (95% CI 0.739–0.874, p < 0.001), respectively. In the severe group, AUC of serum IL-6 level was 0.844 (95% CI 0.783–0.904, p < 0.001). Moreover, Il-6 had a sensitivity of 100% in both moderate and severe groups. Conclusions: This study concluded that liver injury in patients with COVID-19 may be strongly attributed to the cytokines storm, especially IL-6, which was positively correlated to NF-κB p50, NF-κB p65 and NRP-1 mRNA expression levels. Moreover, ROC analysis revealed that IL-6, TXA2, and NF-κB p65 could be useful in predicting the possibility of infection with COVID-19, and IL-6 could be of possible significance as a good predictor of the severity and disease progress. However, RT-qPCR for SARS-CoV-2 detection is essential to confirm infection and further clinical studies are required to confirm this elucidation.

Role of C-reactive protein in the bone marrow of Modic type 1 changes.

Modic type 1 changes (MC1) are vertebral bone marrow lesions and associate with low back pain. Increased serum C-reactive protein (CRP) has inconsistently been associated with MC1. We aimed to provide evidence for the role of CRP in the tissue pathophysiology of MC1 bone marrow. From 13 MC1 patients undergoing spinal fusion at MC1 levels, vertebral bone marrow aspirates from MC1 and intrapatient control bone marrow were taken. Bone marrow CRP, interleukin (IL)-1, and IL-6 were measured with enzyme-linked immunosorbent assays; lactate dehydrogenase (LDH) was measured with a colorimetric assay. CRP, IL-1, and IL-6 were compared between MC1 and control bone marrow. Bone marrow CRP was correlated with blood CRP and with bone marrow IL-1, IL-6, and LDH. CRP expression by marrow cells was measured with apolymerase chain reaction. Increased CRP in MC1 bone marrow (mean difference: +0.22 mg CRP/g, 95% confidence interval[CI] [-0.04, 0.47], p = 0.088) correlated with blood CRP (r = 0.69, p = 0.018), with bone marrow IL-1β (ρ = 0.52, p = 0.029) and IL-6 (ρ = 0.51, p = 0.031). Marrow cells did not express CRP. Increased LDH in MC1 bone marrow (143.1%, 95% CI [110.7%, 175.4%], p = 0.014) indicated necrosis. A blood CRP threshold of 3.2 mg/L detected with 100% accuracy increased CRP in MC1 bone marrow. In conclusion, the association of CRP with inflammatory and necrotic changes in MC1 bone marrow provides evidence for a pathophysiological role of CRP in MC1 bone marrow.

Expression and prognostic relevance of CRP, PCT, and ll-15 in patients with postoperative infection due to spinal injury.

C-reactive protein (CRP), procalcitonin (PCT), interleukin-15 (ll-15) expression and prognostic relevance were analyzed in patients with postoperative infection due to spinal injury. For this purpose, a total of 169 cases of spinal injury patients who underwent surgical treatment from July 2021 to July 2022 were selected, and the patients were divided into the uninfected group (148 cases), infected group (21 cases) according to the presence or absence of infection after surgery. Looking at the site of infection in both groups, the levels of CRP, PCT, and ll-15 in the two groups were detected using an enzyme-linked immunosorbent assay, and the expression of the three in postoperative infection of spinal injury and the correlation with prognosis were analyzed. Results showed that compared with the uninfected group, the infected group had higher levels of CRP, PCT, and ll-15, which were different (P < 0.05). There were no significant differences in the CRP levels between the superficial infection of the incision and the deep infection of the incision as well as other systemic infection populations at 1 d after surgery (P >0.05). CRP levels were higher in the group with deep infection of the incision as well as other systemic infections compared to the group with superficial infection at 3D and 7d after surgery (P < 0.05). There were no significant differences in the level of PCT between patients with superficial infection of the incision and those with deep infection of the incision as well as other systemic infections at 1 d after surgery (P > 0.05). The level of PCT was higher in the population with deep infection of incision as well as other systemic infections compared to the population with superficial infection at 3D and 7d after the operation (P<0.05). There were no statistically significant differences in the levels of ll-15 between patients with superficial infection of the incision and those with deep infection of the incision as well as other systemic infections at 1 D postoperatively (P>0.05). At 3D and 7d postoperatively, compared to the population with superficial incisions, the population with deep incisions as well as other systemic infections had higher levels of ll-15 with statistical significance (P < 0.05). CRP and PCT showed a positive correlation (r=7.192, P=0.001). CRP, ll-15 showed a positive correlation (r = 5.231, P = 0.001). PCT, ll-15 showed a positive correlation (r=9.029, P=0.001). CRP, PCT, ll-15 levels are closely related to postoperative infection in spinal injury. CRP, PCT, ll-15 showed high expression in postoperative infection of spinal injury and compared with the infection of the superficial part of the incision, the infection of the deep part of the incision, other systems have higher levels of CRP, PCT, ll-15. Moreover, CRP, PCT, and ll-15 were significantly associated with prognosis.