Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.

Background and Objectives: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. Materials and Methods: After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. Results: A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older (p = 0.007) and have a higher prevalence of diabetes (p < 0.001) and hypertension (p = 0.030), higher systolic blood pressure (p = 0.011), and higher endocan levels (p < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, p < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, p = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, p = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, p < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (ß = 0.405, adjusted R2 change = 0.152; p < 0.001). Conclusions: The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.

Resistin: A Potential Indicator of Aortic Stiffness in Non-Dialysis Chronic Kidney Disease Patients.

Background and Objectives: In the progression and development of atherosclerosis, resistin plays a significant role. Chronic kidney disease (CKD), frequently associated with atherosclerosis, exhibits a marked increase in morbidity and mortality rates. This study set out to explore the association between aortic stiffness and serum levels of resistin in non-dialysis-dependent CKD patients ranging from stages 3 to 5. Materials and Methods: We collected fasting blood samples from 240 CKD patients across stages 3 to 5. The concentration of resistin in serum was determined using a commercially available enzyme immunoassay kit. Those patients who exhibited a carotid-femoral pulse wave velocity (cfPWV) greater than 10 m/s were identified as the aortic stiffness group. Results: Out of the 240 CKD patients, 88 (36.7%) were classified within the aortic stiffness group. This group demonstrated higher incidences of diabetes, advanced age, increased body weight, body mass index, body fat mass, systolic and diastolic blood pressure, fasting glucose, and serum resistin levels. Multivariate logistic regression analysis highlighted resistin, diabetes, and body weight as independent predictors of aortic stiffness. Additionally, body fat mass, logarithmically transformed cfPWV (log-cfPWV) values and log-triglyceride levels were independent predictors of log-resistin levels by multivariate stepwise linear regression analysis. Conclusions: In CKD patients from stages 3 to 5, a positive correlation exists between elevated serum resistin levels and cfPWV values, identifying resistin as a potential predictor of aortic stiffness.

Positive correlation of serum indoxyl sulfate level with peripheral arterial disease in hemodialysis patients.

OBJECTIVES: Indoxyl sulfate, known for its cardiovascular toxicity, is associated with vascular and coronary artery diseases and increased mortality. Peripheral arterial disease, defined by low ankle-brachial index, is associated with increased mortality in patients on hemodialysis. The present study aimed to determine the relationship between the serum indoxyl sulfate level and peripheral arterial disease in patients on maintenance hemodialysis. METHODS: The present cross-sectional, single-center study included 75 patients on maintenance hemodialysis. Serum indoxyl sulfate levels were determined by high-performance liquid chromatography-mass spectrometry. Ankle-brachial index values were measured using an automated oscillometric device. Patients with ankle-brachial indexes of < 0.9 were categorized into the low ankle-brachial index group. RESULTS: In the study cohort, 12 of the 75 patients (16.0%) had low ankle-brachial indexes. The rates of diabetes mellitus (p = 0.010) as well as the serum levels of C-reactive protein (p < 0.001) and indoxyl sulfate (p < 0.001) were higher in the low ankle-brachial index group than the normal ankle-brachial index group. The multivariable logistic regression analysis revealed that serum levels of indoxyl sulfate (odds ratio = 1.123, 95% confidence interval 1.011-1.249, p = 0.031) and C-reactive protein (each 0.1 mg/dL increase, odds ratio = 1.169, 95% confidence interval 1.018-1.343, p = 0.027) were independently associated with peripheral arterial disease in patients on maintenance hemodialysis. CONCLUSIONS: Serum indoxyl sulfate levels were associated with peripheral arterial disease in patients on maintenance hemodialysis.

Association between serum indoxyl sulfate levels with carotid-femoral pulse wave velocity in patients with chronic kidney disease.

BACKGROUND: The role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear. MATERIALS AND METHODS: We investigated the association between serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography-mass spectrometry analysis. RESULTS: Of these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio [aOR] 1.436, 95% confidence interval [CI] 1.085-1.901, p = 0.011), age (aOR 1.058, 95% CI 1.021-1.097, p = 0.002), and SBP (aOR 1.019, 95%CI 1.000-1.038, p = 0.049) were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677 (95%CI 0.598-0.750, p = 0.0001) to predict the development of AS in patients with CKD. CONCLUSION: These finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD.

Association of Serum Indoxyl Sulfate Levels with Skeletal Muscle Mass and Strength in Chronic Hemodialysis Patients: A 2-year Longitudinal Analysis.

Sarcopenia is highly prevalent in patients undergoing chronic hemodialysis (HD). This study investigated the relationship among serum indoxyl sulfate (IS) levels, muscle mass, and strength in HD patients. A total of 108 HD patients were enrolled. Skeletal muscle mass and handgrip strength (HGS) were assessed, using bioimpedance analysis and a hand-held dynamometer, respectively. Skeletal muscle index (SMI) was defined as skeletal muscle mass/height2 (kg/m2). Serum IS, p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO) levels were determined using liquid chromatography-mass spectrometry. Patients were classified into two groups based on median serum IS values. HGS measurement was repeated after 2 years. Patients in the high IS group had longer HD duration and higher serum TMAO levels than those in the low IS group. Log-normalized IS level was negatively correlated with SMI (r = - 0.227; p = 0.018), but PCS and TMAO levels were not. Among 78 patients who completed 2-year follow-up, those in the high IS group (n = 41) showed greater absolute (- 2.48 kg versus - 0.25 kg, p = 0.035) and relative HGS loss (- 9.1% versus 1.4%, p = 0.036) than those in the low IS group, after adjustment for potential confounders. Indoxyl sulfate (IS) may play a significant role in uremic sarcopenia. Further large-scale studies are needed to confirm our preliminary findings.

Serum indoxyl sulfate as a potential biomarker of aortic arterial stiffness in coronary artery disease.

BACKGROUND AND AIMS: Indoxyl sulfate (IS), a dietary tryptophan metabolite, acts as a cardiotoxin and uremic toxin. High IS levels are associated with chronic kidney disease and cardiovascular diseases. This study investigated the association between serum IS levels and aortic arterial stiffness (AAS) in coronary artery disease (CAD) patients. METHODS AND RESULTS: The carotid-femoral pulse wave velocity (cfPWV) was measured by the SphygmoCor system and patients with values of >10 m/s were classified in the AAS group. The baseline characteristics were recorded and measured (including biochemical and clinical data). Serum IS levels were determined using liquid chromatography-mass spectrometry. AAS occurred in 50 (34.7%) of 144 patients with CAD. They were older, had higher IS levels and percentages of diabetes, systolic blood pressure, blood urea nitrogen, and creatinine but lower estimated glomerular filtration rates. The IS level and older age significantly correlated with AAS [odds ratio (OR) = 3.834, p = 0.031; OR = 1.095, p = 0.002, respectively]. Furthermore, the serum IS level (ß = 0.167, adjusted R2 change: 0.026, p = 0.027) had a significant positive correlation with cfPWV. CONCLUSIONS: Taken together, higher serum IS levels are potential independent biomarkers for AAS in patients with CAD. Therefore, early checking of serum IS levels may help prevent CAD progression and have clinical implications in the near future.

Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis.

Osteoprotegerin (OPG) is a potential biomarker of cardiovascular disease complications and severity. Peripheral arterial disease (PAD) is associated with an increased risk of death in patients on peritoneal dialysis (PD). Therefore, this study aimed to evaluate the relationship between serum OPG levels and PAD by measuring the ankle-brachial index (ABI) of patients on PD. A commercial enzyme-linked immunosorbent assay kit was used to measure OPG values. Left or right ABI values of <0.9 were categorized as the low ABI group. Among 70 patients on PD, 13 (18.6%) were categorized in the low ABI group. Patients in the low ABI group had higher prevalence of diabetes mellitus (p = .044) and higher serum C-reactive protein (CRP) (p < .001) and OPG levels (p < .001) but lower creatinine (p = .013) and peritoneal Kt/V (p = .048) levels than those in the normal ABI group. Results of multivariable logistic regression analysis revealed that OPG [adjusted odds ratio (aOR) 1.027, 95% confidence interval (CI) 1.010-1.045, p = .002] and CRP (aOR 1.102, 95% CI 1.006-1.207, p = .037) levels were independent predictors of PAD in patients on PD. OPG can also be used to predict PAD development with the area under the receiver operating characteristic curve of 0.823 (95% CI: 0.714-0.904, p < .001) in patients on PD. Therefore, serum OPG and CRP levels can be considered as risk factors for PAD development in patients on PD.

Impact of sarcopenia and its diagnostic criteria on hospitalization and mortality in chronic hemodialysis patients: A 3-year longitudinal study.

BACKGROUND/PURPOSE: Sarcopenia is prevalent in chronic hemodialysis patients. This prospective cohort study evaluated the impact of sarcopenia and its diagnostic criteria on hospitalization and mortality in 126 chronic hemodialysis patients. METHODS: Skeletal muscle mass, handgrip strength (HGS), gait speed, and blood parameters were assessed. Sarcopenia was evaluated using the criteria of the European Working Group on Sarcopenia in Older People and the Taiwanese criteria for Sarcopenia. Muscle quality was defined as HGS divided by mid-arm muscle circumference. RESULTS: Prevalences of uremic sarcopenia were 8.7% and 13.5% according to Taiwanese and European criteria, respectively. Low HGS and gait speed were much more prevalent than low muscle mass. Within 3 years, 79 (62.7%) patients were hospitalized and 26 (20.6%) died. Low HGS and slow gait speed were associated with hospitalization and mortality, while sarcopenia was associated with mortality but not with hospitalization. Notably, in our patients without sarcopenia, close associations between increased hospitalization and mortality risk with low HGS and slow gait speed remained unchanged. In Cox proportional hazard analysis, muscle quality [hazard ratio (HR) = 0.42, 95% confidence interval (CI) = 0.19-0.93, p = 0.032] and serum creatinine (HR = 0.82, 95% CI = 0.71-0.95, p = 0.009) were independently associated with composite outcome of hospitalization or death. CONCLUSION: Muscle functionality and quality can predict hospitalization and overall survival in chronic hemodialysis patients, better than muscle mass.

Serum osteoprotegerin is an independent marker of central arterial stiffness as assessed using carotid-femoral pulse wave velocity in hemodialysis patients: a cross sectional study.

BACKGROUND: Cardiovascular morbidity and mortality are highly prevalent in patients with end-stage renal disease, and osteoprotegerin (OPG) may be an important link between bone loss and vascular calcification. This study was conducted to evaluate the relationship between central arterial stiffness and serum OPG levels in hemodialysis (HD) patients. METHODS: Blood samples were collected from 120 HD patients, and the carotid-femoral pulse wave velocity (cfPWV) value was measured using a validated tonometry system. The cfPWV value of > 10 m/s was used to define the high artery stiffness group. Serum OPG levels were analyzed categorically into tertiles. RESULTS: Of the 120 HD patients, 53 (44.2%) were defined as the high arterial stiffness group, who had higher values of systolic blood pressure (p = 0.038), serum calcium (p = 0.007), and OPG (p <  0.001) levels and a higher prevalence of diabetes mellitus (DM, p = 0.001). Increasing tertiles of serum OPG levels were significantly associated with greater height (p = 0.011), male gender (p = 0.008), higher cfPWV values (p = 0.020), and lower intact parathyroid hormone (iPTH, p = 0.049) levels. Multivariable linear regression analysis showed that cfPWV value was independently associated with DM (ß = 1.83, p = 0.008) and increasing tertiles of serum OPG levels (ß = 0.89 and 1.63 for tertile 2 and tertile 3, respectively, p for trend = 0.035) in HD patients. Multivariable logistic regression analysis revealed that, in addition to age, DM, low iPTH levels, and high serum calcium levels, increasing tertiles of serum OPG levels (OR = 5.34 for tertile 2; OR = 7.06 for tertile 3; p for trend = 0.002) were an independent predictor of high arterial stiffness in HD patients. Serum calcium levels positively correlated with cfPWV value only in the highest OPG tertile group (r = 0.408, p = 0.009). CONCLUSION: A positive association was detected between serum OPG levels and central arterial stiffness in HD patients, and patients with high serum OPG levels may have greater influence of calcium load on central arterial stiffening.

Angiotensin II receptor blockade is associated with preserved muscle strength in chronic hemodialysis patients.

BACKGROUND: Sarcopenia, defined as low muscle mass and strength, is highly prevalent in patients undergoing chronic hemodialysis (HD). However, muscle function and muscle mass do not share the same clinical relevance. In fact, muscle strength was more closely associated with the risk of mortality in chronic HD patients than was muscle mass. Therefore, to identify the risk factors of muscle weakness is vital. Angiotensin II overexpression had been recognized to impair skeletal muscle strength. Accordingly, angiotensin II receptor blockers (ARBs) potentially possess a muscle protective effect. This cross-sectional study aimed to identify the factors associated with low muscle strength and to explore the relationship between ARB use and muscle strength in chronic HD patients. METHODS: A total of 120 chronic HD patients, aged 63.3 ± 13.2 years, were included in this study. Basic characteristics, handgrip strength (HGS), body composition, and nutritional status were assessed, and blood samples for biochemical tests were obtained. We divided these participants into normal- and low HGS groups according to the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: We observed that 78 (65.0%) patients had low HGS. In our cohort, we found that height (r = 0.653; P <  0.001), weight (r = 0.496; P <  0.001), body mass index (r = 0.215; P = 0.020), skeletal muscle index (r = 0.562; P <  0.001), albumin (r = 0.197; P = 0.032), and serum creatinine (r = 0.544; P <  0.001) were positively and age (r = - 0.506; P <  0.001), subjective global assessment (SGA) score (r = - 0.392; P <  0.001), fractional clearance index for urea (Kt/V) (r = - 0.404; P <  0.001) and urea reduction ratio (URR) (r = - 0.459; P <  0.001) were negatively correlated with HGS. According to our analysis, age (Odds ratio, OR = 1.11, 95% confidence interval, 95% CI = 1.05-1.17, P <  0.001), HD duration (OR = 1.01, 95% CI = 1.00-1.02, P = 0.010), diabetes (OR = 13.33, 95% CI = 3.45-51.53, P <  0.001), Kt/V (OR = 1.61, 95% CI = 1.06-2.46, P = 0.027), and SGA score (OR = 1.19, 95% CI = 1.03-1.38, P = 0.017) were regarded as independent predictors of low HGS. In contrast, ARB use (OR = 0.25, 95% CI = 0.07-0.93, P = 0.039) was independently associated with preserved HGS in chronic HD patients, after adjustment for multiple confounding factors. CONCLUSIONS: Our study is the first report in chronic HD patients to indicate a potentially protective effect of ARB on muscle strength. However, further longitudinal follow-up and intervention studies are needed to confirm this finding.

Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease.

BACKGROUND: Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. METHODS: This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0 ± 11.8 years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. RESULTS: Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 ± 0.16 vs. 1.08 ± 0.15, P = 0.028 for the right ABI; 1.01 ± 0.16 vs. 1.06 ± 0.16, P = 0.002 for the left ABI) and VRI (0.83 ± 0.57 vs. 1.08 ± 0.56, P < 0.001) and had higher serum levels of ICAM-1 (P < 0.001), VCAM-1 (P = 0.003) and ET-1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. CONCLUSIONS: Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.

Novel equations incorporating the sarcopenia index based on serum creatinine and cystatin C to predict appendicular skeletal muscle mass in patients with nondialysis CKD.

BACKGROUND & AIMS: Skeletal muscle mass measurements are important for customizing nutritional strategies for patients with chronic kidney disease (CKD). The serum creatinine-to-cystatin C ratio (Cr/CysC) is a potential indicator of sarcopenia. We developed simple equations to predict the appendicular skeletal muscle mass (ASM) of patients with CKD using readily available parameters and Cr/CysC. METHODS: Overall, 573 patients with nondialysis CKD stages 3-5 were included for developing and validating the equations. The participants were randomly divided into development and validation groups in a 2:1 ratio. ASM was measured using the Body Composition Monitor (BCM), a multifrequency bioelectrical impedance spectroscopy device. The height, weight, anthropometric data, and handgrip strength (HGS) of the participants were obtained. Equations were generated using stepwise multiple linear regression models. The prognostic significance of the predicted ASM was evaluated in a CKD registry comprising 1043 patients. RESULTS: The optimal equation without anthropometric data and HGS (Equation 1) was as follows: ASM (kg) = -7.949 - 0.049 × Age (years) - 2.213 × Woman + 0.090 × Height (cm) + 0.210 × Weight (kg) + 1.141 × Cr/CysC. The modified equation (Equation 2) with anthropometric data and HGS was as follows: ASM (kg) = -4.468 - 0.050 × Age (years) - 2.285 × Woman+ 0.079 × Height (cm) + 0.228 × Weight (kg) - 0.127 × Mid-arm muscular circumference (cm) + 1.127 × Cr/CysC. Both equations exhibited strong correlations with the ASM measured via BCM in the validation cohort (r = 0.944 and 0.943 for Equations 1 and 2, respectively) with minimal bias. When Equation 1 was applied to the CKD registry, the estimated ASM index (ASM/Height2) significantly predicted overall mortality over a median of 54 months. CONCLUSIONS: Novel ASM equations offer a simple method for predicting skeletal muscle mass and can provide valuable prognostic information regarding patients with nondialysis CKD.

High-temperature, high-pressure hydrothermal synthesis, crystal structures, and spectroscopic studies of a uranium(IV) phosphate (Na10U2P6O24) and the isotypic cerium(IV) phosphate (Na10Ce2P6O24).

A uranium(IV) phosphate, Na10U2P6O24, was synthesized under hydrothermal conditions at 570 °C and 160 MPa and structurally characterized by single-crystal X-ray diffraction. The valence state of uranium was established by UV-vis and U 4f X-ray photoelectron spectroscopy. The powder sample has a second-harmonic-generation signal, confirming the absence of a center of symmetry in the structure. The structure contains UO8 snub-disphenoidal polyhedra that are linked to monophosphate tetrahedra by vertex and edge sharing such that a three-dimensional framework with intersecting 12-sided circular and rectangular channels is formed. All 10 sodium sites are situated inside the channels and are fully occupied. This is the first uranium(IV) phosphate synthesized under high-temperature, high-pressure hydrothermal conditions. The isotypic cerium(IV) phosphate, Na10Ce2P6O24, was also synthesized under the same hydrothermal conditions. It is the first structurally characterized Ce(IV) phosphate with a P/Ce ratio of 3. Crystal data of Na10U2P6O24: orthorhombic, P212121 (No. 19), a = 6.9289(3) Å, b = 16.1850(7) Å, c = 18.7285(7) Å, V = 2100.3(2) Å(3), Z = 4, R1 = 0.0304, and wR2 = 0.0522. Crystal data of Na10Ce2P6O24: orthorhombic, P2(1)2(1)2(1) (No. 19), a = 6.9375(14) Å, b = 16.215(3) Å, c = 18.765(4) Å, V = 2111.0(7) Å(3), Z = 4, R1 = 0.0202, and wR2 = 0.0529.

Topical histone deacetylase 1 inhibitor Entinostat ameliorates psoriasiform dermatitis through suppression of IL-17A response.

BACKGROUND: Biologics against IL-17A, IL-23 and TNF-α achieve a great success in treating psoriasis. However, the majority of patients still have some residual lesions left and require combination therapy to reach complete clearance. Topical medicine is an optional choice but only has limited categories. Besides, drug resistance is very often. Thus, topical medicine targeting new signaling pathway is still in an urgent need in the biologics era. OBJECTIVE: To investigate the role of topical Entinostat, a selective inhibitor of histone deacetylases 1 (HDAC1) that has been tested in clinic trials to treat solid tumors and hematological malignancies, in psoriasis therapy. METHODS: Efficacious Entinostat were tested in a mouse imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) model. An in vitro model consisting of human CD4 + T cell, murine T cells and NHEKs were used to screen Entinostat for inhibition of cutaneous inflammatory genes. RESULTS: Topical application of Entinostat significantly improved psoriasiform inflammation in imiquimod-induced mice model with great reduction of IL-17A+ Î³Î´T cell infiltration in skin. Entinostat is powerful agent in inhibition of Th17 cell generation and the expression of psoriasis-related inflammatory mediators by primary keratinocytes upon CD4+ T cells stimulation. CONCLUSION: Our findings suggest Entinostat is a promising topical medicine for psoriasis treatment.

Impact of Gut Bacterial Metabolites on Psoriasis and Psoriatic Arthritis: Current Status and Future Perspectives.

There is growing evidence that supports a role of gut dysbiosis in the pathogenesis of psoriasis (Pso). Thus, probiotic supplementation and fecal microbiota transplantation may serve as promising preventive and therapeutic strategies for patients with Pso. One of the basic mechanisms through which the gut microbiota interacts with the host is through bacteria-derived metabolites, usually intermediate or end products produced by microbial metabolism. In this study, we provide an up-to-date review of the most recent literature on microbial-derived metabolites and highlight their roles in the immune system, with a special focus on Pso and one of its most common comorbidities, psoriatic arthritis.

Serum Trimethylamine N-Oxide Level Is Positively Associated with Aortic Stiffness Measured by Carotid-Femoral Pulse Wave Velocity in Patients Undergoing Maintenance Hemodialysis.

Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association between serum TMAO levels and carotid-femoral pulse wave velocity (cfPWV) in patients receiving hemodialysis (HD) therapy. In total, 115 patients with HD were enrolled in this study. The AS group included patients whose cfPWV was >10 m/s. Using high-performance liquid chromatography and mass spectrometry, the levels of serum TMAO were measured. The AS group included 42 (36.5%) patients, and compared with the non-AS group, the rates of diabetes, hypertension, older age, systolic blood pressure, serum glucose, and TMAO levels were high. In the multivariate logistic regression analysis, serum TMAO and age were independently linked with AS after correcting for the factors significantly associated with AS. Following multivariate stepwise linear regression analysis, serum TMAO in these individuals was found to be strongly correlated with cfPWV values (p < 0.001). In patients on chronic HD, serum TMAO level is an independent measure of AS and strongly correlated with cfPWV.

Serum P-Cresyl Sulfate Level Is an Independent Marker of Peripheral Arterial Stiffness as Assessed Using Brachial-Ankle Pulse Wave Velocity in Patients with Non-Dialysis Chronic Kidney Disease Stage 3 to 5.

p-Cresyl sulfate (PCS) is a uremic toxin that causes cardiovascular injury and progression in patients with chronic kidney disease (CKD). Peripheral arterial stiffness (PAS) as measured using the brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3−5 CKD. Liquid chromatography−mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium−phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 (95% confidence interval = 1.029−1.171, p = 0.005). These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3−5 CKD.

Serum adipocyte fatty acid-binding protein level is positively associated with aortic stiffness in nondialysis chronic kidney disease patients: A cross-sectional study.

Aortic stiffness (AS) is a major predictor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD) and adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine that is positively correlated with AS in the general population. Therefore, we investigated the correlation between serum A-FABP levels and AS in nondialysis CKD patients. Fasting blood samples and baseline characteristics were obtained in 270 patients with nondialysis CKD. Serum A-FABP concentrations were determined by enzyme immunoassay and carotid-femoral pulse wave velocity (cfPWV) measurements were acquired using a validated tonometry system. Patients with cfPWV >10 m/s formed the AS group, while those with values ≤10 m/s comprised the comparison group. Among 270 CKD patients, 92 patients (34.1%) were in the AS group. Compared to those in the comparison group, patients in the AS group were older (P < .001), had a higher prevalence of diabetes, along with higher serum A-FABP level (P < .001), larger waist circumference (P = .004), and lower estimated glomerular filtration rate (P = .001) but higher levels of body fat mass (P = .010), systolic blood pressure (P < .001), fasting glucose (P = .014), blood urea nitrogen (P = .009), and serum creatinine (P = .004). The serum log-A-FABP level was positively associated with log-cfPWV (ß = 0.178, P = .001) in nondialysis CKD patients and multivariable logistic regression analysis identified serum A-FABP (P = .006), age (P = .001), and systolic blood pressure (P = .015) as independent predictors of AS in nondialysis-dependent CKD patients. Elevated A-FABP levels may be a significant predictor of AS in nondialysis CKD patients.

Serum Trimethylamine N-Oxide Level Is Associated with Peripheral Arterial Stiffness in Advanced Non-Dialysis Chronic Kidney Disease Patients.

Trimethylamine N-oxide (TMAO) is a gut-derived uremic toxin involved in cardiovascular diseases (CVD). Peripheral arterial stiffness (PAS), measured by the brachial-ankle pulse wave velocity (baPWV) is a valuable indicator of the existence of CVD alongside other diseases. The study recruited 157 patients with chronic kidney disease (CKD) stages 3 to 5, and aimed to determine the correlation between serum TMAO and PAS, defined as a baPWV of >18.0 m/s. Patients with CKD who were diagnosed with PAS (68 patients, 43.3%) were older, had a higher percentage of hypertension or diabetes mellitus, higher systolic blood pressure, and higher fasting glucose, C-reactive protein, and TMAO levels. Furthermore, besides old age and SBP, patients with CKD who had higher serum TMAO were more likely to have PAS, with an odds ratio of 1.016 (95% confidence interval = 1.002−1.029, p = 0.021) by multivariate logistic regression analysis. Correlation analysis demonstrated that serum TMAO was positively correlated with C-reactive protein level and either left or right baPWV. Thus, we supposed that serum TMAO levels were associated with PAS in patients with advanced non-dialysis CKD.