PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVD) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Per- and polyfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry (LC-MS-MS), supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, while PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of cardiovascular diseases in this population.

The evaluation of salivary leucine-rich alpha-2 glycoprotein (LRG) and C-reactive protein (CRP) in humans with periodontal health or periodontal disease.

OBJECTIVE: The purpose of the present research is to evaluate the salivary levels of leucine-rich alpha-2 glycoprotein (LRG) and C-reactive protein (CRP) in periodontal health and disease (gingivitis and stage III periodontitis) and also to compare the discriminative efficiencies of both biomarkers in periodontal disease. BACKGROUND: LRG is a new acute-phase protein whose functions are still being investigated. LRG and CRP are both biomarkers that are increased by inflammation. No clinical study has yet investigated the comparison of the level of LRG and CRP in periodontal health, gingivitis and periodontitis in saliva samples. METHODS: A total of 60 individuals, including 20 periodontally healthy (control group/group C), 20 with gingivitis (group G), and 20 with Stage III periodontitis (group P), who were systemically healthy and non-smokers, participated in this study. Periodontal charts were used for recording clinical periodontal parameters and saliva LRG and CRP levels were measured by ELISA. Analyzing the area under the curve (AUC) was performed by the receiver-operating characteristics curve. RESULTS: Salivary levels of LRG and CRP were significantly higher in disease groups than in group C (p < .05). Positive statistically significant correlations were observed between both biomarkers and clinical parameters (p < .05). There was also a strong positive correlation between two biomarkers (p < .05). In distinguishing periodontal disease from periodontal health, LRG (AUC = 0.833) and CRP (AUC = 0.826) were found to have similar accuracy (p = .923). CONCLUSION: LRG and CRP may be useful and similarly effective biomarkers in the diagnosis of periodontal diseases based on the findings of this study.

Different application procedures of Nd:YAG laser as an adjunct to scaling and root planning in smokers with stage III grade C periodontitis: a single-blind, randomized controlled trial.

BACKGROUND: The aim of the present study was to evaluate whether different Nd:YAG laser applications as an adjunct to scaling and root planning (SRP) improve the healing response to periodontal therapy in smokers with periodontitis. METHODS: This clinical trial included eighty systemically healthy smokers with periodontitis. Patients were randomly allocated to a treatment group: SRP alone (group 1), SRP+low-level laser therapy (LLLT) with Nd:YAG laser (group 2), SRP+pocket debridement with ND:YAG laser (group 3), and SRP+combined pocket debridement and LLLT with Nd:YAG laser (group 4). Gingival index (GI), plaque index (PI), bleeding on probing (%), probing depth (PD), and clinical attachment level (CAL) were recorded, and gingival crevicular fluid (GCF) samples for metalloproteinase-8 (MMP-8) levels were collected at baseline, 1 month and 3 months after treatment. RESULTS: There were no significant differences between the treatment groups for the GI, PI, and BOP (%) parameters and MMP-8 levels at any time points (p > 0.05). For moderately deep pockets, PD and CAL reductions were significantly greater in all test groups compared to group 1 (p ˂ 0.05). For deep pockets, these reductions were significantly greater in group 2 and group 4 compared to group 1 (p ˂ 0.05). PD and CAL reductions were generally similar between test groups (p > 0.05) except PD reduction between baseline and 3 months in deep pockets (p ˂ 0.05). CONCLUSIONS: The findings of this clinical trial suggest that Nd:YAG laser applications may be beneficial on the healing response of smokers to non-surgical therapy compared to SRP alone.

The relationship between sarcopenia detected in newly diagnosed colorectal cancer patients and FGF21, irisin and CRP levels.

AIM: Sarcopenia is a progressive and generalized syndrome that can be linked to many causes such as cancers, and is caused by a quantitative and qualitative disorder (loss of muscle strength and/or physical performance) of skeletal muscle mass. Although sarcopenia has some hypothetical explanation in clinical practice, the mechanisms underlying this condition have not been clearly differentiated in patients with cancer. We aimed to investigate the relationship between irisin, FGF21 and CRP in detecting sarcopenia in colorectal cancer patients. MATERIAL AND METHODS: Current prospectively study included non-metastatic newly diagnosed colorectal cancer patients. Patients were divided into 2 groups of 25 people, those with and without sarcopenia. Body composition measurements by examined by BIA. To measure the level of iris and FGF21 from patients, blood samples were taken into the biochemistry tube and their levels were measured. RESULTS: The median age of the patients included in the study was 60 years (range: 21-81), 68% were men. It was found that there was a significant relationship between sarcopenia and gender and BMI measurement. When Spearman correlation analysis was performed between skeletal muscle mass index and FGF21, irisin and CRP, there was a positive correlation between skeletal muscle mass index and irisin and FGF21, while there was a negative correlation between skeletal muscle mass index and CRP. [respectively: (r: 0.282, p: 0.048), (r: 0.564, p: < 0.001) and (r: - 0.360, p: 0.010)]. Similar results were found between hand-grip strength and FGF21, irisin and CRP. [respectively: (r: 0.342, p: 0.015), (r: 0.290, p: 0.041) and (r: - 0.476, p < 0.001)]. When sarcopenia was treated as the dependent variable in the logistic regression analysis, and FGF21, irisin, CRP, gender and BMI were treated as the independent variables, irisin and CRP levels were determined as independent predictors. CONCLUSION: This study was revealed that there is a negative relationship between sarcopenia and irisin and FGF-21 in operated non-metastatic colorectal cancer patients and there may be a relationship between sarcopenia and inflammation. It suggests that these biomarkers may play a role in the pathophysiology of sarcopenia. However, our results need to be validated in different types of cancer and with more patients.

Evaluation of galectin-3, peptidylarginine deiminase-4, and tumor necrosis factor-α levels in gingival crevicular fluid for periodontal health, gingivitis, and Stage III Grade C periodontitis: A pilot study.

BACKGROUND: Comparing the gingival crevicular fluid (GCF) levels of galectin-3, peptidylarginine deiminase 4 (PAD4) and tumor necrosis factor-alpha (TNF-α) in individuals with stage III grade C periodontitis and gingivitis and with healthy periodontium was the purpose of this clinical research. METHODS: Sixty systemically healthy and non-smoker individuals consisting of stage III grade C periodontitis (group S3P/n = 20), gingivitis (group G/n = 20), and periodontally healthy (group HP/n = 20) were recruited for this research. Clinical parameters such as probing depth, clinical attachment level, gingival index, plaque index, and bleeding on probing were recorded in periodontal charts. Enzyme-linked immunosorbent assay method was used in evaluating the GCF levels of galectin-3, PAD4, and TNF-α for study groups. RESULTS: The GCF galectin-3 total amount was highest in group S3P compared with group G and group HP (P <0.05). Its total amount was also higher in group G compared with group HP (P <0.05). The GCF PAD4 total amount was higher in group S3P compared with group HP (P <0.05) but was similar with group G (P >0.05). Its total amounts were also similar in group G and group HP (P >0.05). The GCF TNF-α total amounts were similar in group S3P and group G (P >0.05) but significantly greater than the group HP (P ˂0.05). The GCF galectin-3, PAD4, and TNF-α concentrations were lower in the group S3P and group G compared with the group HP (P <0.05). There were significant positive correlations between GCF galectin-3 total amount and all clinical parameters (P ˂0.01) and also between GCF galectin-3 and TNF-α total amounts (P ˂0.01). There was no correlation between PAD4 and clinical parameters, or between PAD4 and TNF-α (P >0.05). CONCLUSIONS: Galectin-3 and PAD4 may be involved in the periodontal disease pathogenesis considering the elevated levels of these molecules in periodontal disease. These biomarkers may be used in the diagnosis of periodontal diseases.

Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer.

Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b-/- mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and α-amylase. Interestingly, either NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers.NEW & NOTEWORTHY We reported tissues expressing FAM134B-2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and α-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers.

The role of inflammation in adjuvant chemotherapy-induced sarcopenia (Izmir Oncology Group (IZOG) study).

INTRODUCTION: Although the chemotherapy-induced sarcopenia has some explanatory presence in clinical practice, the mechanisms underlying this phenomenon have not been clearly distinguished in patients with cancer. Therefore, we aimed with this study to investigate the role of inflammation by examining the inflammatory markers in the physiopathology of adjuvant chemotherapy-induced sarcopenia in patients with gastrointestinal tract cancer. MATERIAL AND METHOD: To detect the presence of sarcopenia, patients' body composition measurements were assessed using the BIA, and their muscular strength was assessed with a handgrip dynamometer in both pre- and post-adjuvant chemotherapy. At the same time, we examined the baseline and post-adjuvant chemotherapy anthropometric measurements and inflammatory markers in serum (Hs-CRP, IL8, and TNF-α). Patients were divided in three groups. Group 1 consisted of patients who presented post-treatment sarcopenia although they did not have it prior to the treatment, group 2 included the patients who had no pre- or post-treatment sarcopenia, and group 3 was comprised of patients who presented pre-treatment sarcopenia. Each group included 30 patients. RESULTS: A total of 90 patients were included in the study. Fifty-one of them were female patients. Median age was 60.5 (range 27-83). The patients consisted of cases with colorectal and gastric cancers. In group 1, Wilcoxon signed-rank test revealed a significant difference between scores of IL-8 (pg/mL), TNF-α (pg/mL) and Hs-CRP (mg/dL) given for the post-chemotherapy compared with the pre-chemotherapy ((Z 3.61, p < 0.001), (Z 3.254, p = 0.001), (Z 3.319, p = 0.001)). The post-chemotherapy median scores of IL-8 (pg/mL), TNF-α (pg/mL), and Hs-CRP were 76.31, 7.34, and 1.55, respectively, which remained on the levels of 12.25, 1.6, and 0.51 for the pre-chemotherapy. For group 2, a Wilcoxon signed-rank test indicated no significant difference between scores of the same markers given for the post-chemotherapy compared with the pre-chemotherapy. In all patients (including groups 1, 2, and 3), a comparison of the patients with pre-treatment sarcopenia (n = 30) and non-sarcopenic patients (n = 60) in terms of baseline IL-8, TNF-α, and Hs-CRP mean levels, IL-8 and Hs-CRP were found to be statistically different (146.02 (SD 311.96) vs. 47.24 (SD 66.3) (p = 0.009), 3.91 (SD 4.26) vs. 0.75 (SD 1.08) (p < 0.001), respectively). CONCLUSIONS: The present prospective observational study suggested an association of chemotherapy-induced sarcopenia with inflammatory markers Hs-CRP, IL8, and TNF-α. Inflammation may play a role in chemotherapy-induced sarcopenia in newly diagnosed non-metastatic patients.

Gingival crevicular fluid semaphorin 4D and peptidylarginine deiminase-2 levels in periodontal health and disease.

BACKGROUND: The aim of this study was to compare the levels of semaphorin 4D (SEMA4D), peptidylarginine deiminase 2 (PAD2) and matrix metalloproteinase-8 (MMP-8) in gingival crevicular fluid (GCF) in patients with periodontal disease and patients with healthy periodontium and investigate the effects of periodontal treatment on the levels of these molecules. METHODS: GCF samples were collected from periodontally healthy controls (C group, n = 20), patients with gingivitis (G group, n = 20), and patients with chronic periodontitis (CP group, n = 20). Sampling sites were also divided into bleeding (BP) and non-bleeding (NBP) periodontal pocket groups in CP group. Full-mouth clinical periodontal parameters were also recorded. GCF samplings and clinical records were also repeated at 1 and 3 months after treatment for the CP group. SEMA4D, PAD2, and MMP-8 levels were determined by enzyme-linked immunosorbent assay. RESULTS: The GCF SEMA4D, PAD2, and MMP-8 total amounts were similar in CP and G groups (P Ëƒ 0.05) but significantly greater than the C group (P Ë‚ 0.05). The GCF SEMA4D and PAD2 total amounts in the BP group were significantly greater than the NBP group (P Ë‚ 0.05). GCF MMP-8 total amounts were similar in BP and NBP groups (P Ëƒ 0.05). The GCF SEMA4D, PAD2, and MMP-8 total amounts were significantly reduced at first month after treatment (P Ë‚ 0.05). There were positive correlations between GCF total amount of SEMA4D and all clinical parameters (P Ë‚ 0.01) and also between PAD2 and clinical parameters (P Ë‚ 0.05) except clinical attachment level. There was a positive correlation between GCF total amount of SEMA4D and GCF total amount of MMP-8 (P Ë‚ 0.05). CONCLUSIONS: It may be suggested that SEMA4D and PAD2 are related to periodontal disease. Their GCF total amounts may have a diagnostic potential. Additional studies would better clarify their role in periodontal diseases.

Serum Resolvin E1 Levels and Its Relationship with Disease Activity in Ulcerative Colitis.

BACKGROUND: Resolvins originate from ω-3 PUFA (polyunsaturated fatty acid) precursors and play a role in the resolution of inflammation. The aim of this study was to determine the serum Resolvin E1 levels in patients with ulcerative colitis (UC) and to evaluate the relationship between the serum Resolvin E1 levels and ulcerative colitis disease activity. METHODS: In this observational study, serum samples were collected from 51 patients with UC and 30 healthy controls for the determination of Resolvin E1 levels. Firstly, we compared the serum Resolvin E1 levels between the UC patients and the control group. Subsequently, Resolvin E1 levels were analyzed in patients with active UC and UC in remission. Finally, the correlation between Resolvin E1 and C-reactive protein (CRP) and partial Mayo score (p-MS) was analyzed to determine the efficacy of Resolvin E1 in predicting disease activity. RESULTS: Serum Resolvin E1 level was determined in the UC group (3126 ± 1413 ng/ml) and in the control group (2758 ± 1065 ng/ml) (p = 0.187). Serum Resolvin E1 levels were determined in patients with active UC (3114 ± 1166 ng/ml) and patients in remission (3132 ± 1520 ng/ml) (p = 0.749). In the UC group, a low-grade positive significant association was found between Resolvin E1 and CRP (r = 0.303, p = 0.031). There was no significant association between Resolvin E1 and partial Mayo score (r = -0.207, p = 0.146). CONCLUSIONS: There was no sufficient evidence that Resolvin E1 was an appropriate inflammatory marker to determine disease activity in UC.

Infection markers as predictors of Bacteremia in an Intensive Care Unit: A prospective study.

OBJECTIVE: Although several biomarkers have been evaluated for the diagnosis and prognosis of sepsis, the gold standard biomarker has not yet been found. We aimed to evaluate the diagnostic value of neutrophil-to-lymphocyte count ratio (NLCR), neopterin, pro-adrenomedullin (pro-ADM) and the other infection markers to predict bacteremia in patients with SIRS, sepsis and severe sepsis/septic shock. METHODS: A prospective cohort study was conducted on septic patients in a tertiary referral hospital between December 2014- July 2015. A total of 156 patients diagnosed with SIRS, sepsis and severe sepsis/septic shock in Anesthesia intensive care unit (ICU) were included in the study. RESULTS: A total of 156 patients who had been diagnosed as SIRS(10.9%), sepsis (44.2%) and severe sepsis/septic shock (44.9%) were included. Positive blood cultures were obtained in 64 patients. NLCR, neopterin and pro-ADM levels were insignificant in predicting bacteremia (p>0.05). The mortality rate was significantly higher in bacteremic sepsis (43.9%) compared to non-bacteremic patients (20.8%) (p=0.001). Only procalcitonin levels were significant predictor of mortality (p<0.001). CONCLUSION: NLCR, CRP, procalcitonin, neopterin and pro-ADM levels were insignificant in diagnosis of bacteremia in critically ill patients. The gold standard method in predicting bacteremia is still blood culture positivity.

Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn's Disease.

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn's disease (CD). Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn's disease activity index (CDAI). Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL) (p = 0.03). SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL) (p < 0.001). A significant positive correlation was found between SDC-1 and CRP (r = 0.687, p < 0.001) and between SDC-1 and CDAI (r = 0.747, p < 0.001). Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.