Activity

CPS had a positive effect on reducing potassium, and could especially maintain the serum potassium concentration in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Patiromer might reduce all-cause mortality in CKD patients with hyperkalemia and have a positive effect on potassium-lowering, though it had significant gastrointestinal adverse effects. GPCR agonist SZC had a potassium-lowering effect in both the short-term and long-term, and can be a promising long-term treatment for the hyperkalemia in CKD patients, especially in combination with RAASi.

These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.

These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.Chronic wounds are associated with inflammation, infections, and hypoxic environment. Macrophages play a crucial role in wound healing removing bacteria and secreting signal molecules to coordinate tissue repair. Recently, dextran-shelled Oxygen-Loaded NanoDroplets (OLNDs) have been proposed as new tools to counteract hypoxia in chronic wounds. Here we investigated the effects of OLNDs on Enterococcus faecalis (E. faecalis) killing and the secretion of inflammatory and angiogenic factors by murine (BMDM) and human (dTHP-1, differentiated THP-1) macrophages, in normoxia and hypoxia. Both OLNDs and Oxygen-Free NanoDroplets (OFNDs) significantly increased reactive oxygen species production by BMDM in normoxia (4.1 and 4 fold increase by 10% OLNDs and OFNDs, respectively, after 120 min) and hypoxia (3.8 and 4 fold increase by 10% OLNDs and OFNDs respectively) but not by dTHP-1. Moreover, only OLNDs induced nitric oxide secretion by BMDM in normoxia. Consequently, both nanodroplets improved E. faecalis killing by BMDM in normoxia (% of killing OLNDs = 44.2%; p less then 0.01; OFNDs = 41.4%; p less then 0.05) and hypoxia (% of killing OLNDs = 43.1%; p less then 0.01; OFNDs = 37.7%; p less then 0.05), while dTHP-1-mediated killing was not affected. The secretion of the inflammatory cytokines (TNFα, IL-6, IL-1β) induced by E. faecalis infection in dTHP-1 was reduced by both types of nanodroplets, suggesting a novel anti-inflammatory activity of the dextran shell. Instead, the increase of VEGF induced by hypoxia was reduced only by OLNDs. These data provide new knowledge on the effects of OLNDs as innovative adjuvant in chronic wounds healing promoting bacterial killing and reducing inflammation.Curcumin nicotinate (Curtn) is a synthesized ester derivative of curcumin and niacin. Our previous study has shown that Curtn lowers serum low-density lipoprotein cholesterol (LDL-C) levels in apoE-/- mice and promotes LDL-C uptake into HepG2 cells in vitro. The present study was to test the hypothesis that Curtn decreases serum LDL-C levels through decreased expression of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and subsequent increase in LDL receptor expression. Male Wistar rats on high-fat diet (HFD) were treated with Curtn or rosuvastatin. Curtn or rosuvastatin treatment significantly decreased serum levels of total cholesterol (TC) and LDL-C in rats on HFD with increased liver LDL receptor expression. LDL-C-lowering effect of Curtn was not observed in LDL receptor deficient (LDLR-/-) mice on HFD, while rosuvastatin still decreased serum lipid levels in LDLR-/- mice, indicating that the reduction of serum LDL-C levels by Curtn treatment was LDL receptor-dependent. Curtn treatment also significantly decreased the protein expression of PCSK9 in Wistar rats and LDLR-/- mice. In HepG2 cells with overexpression of human PCSK9, Curtn treatment significantly increased LDL-C uptakes into hepatocytes, and increased LDL receptor distribution on cell surface in association with decreased PCSK9 protein expression. RNAi-LDLR significantly attenuated the effect of Curtn on LDLR distribution on cell surface. These data indicates that Curtn would decrease serum LDL-C level at least partially through inhibition of PCSK9 expression, and subsequent increase in LDL receptor expression and distribution in hepatocytes, serving as a potential novel compound to treat hyperlipidemia.Current treatments for Parkinson’s Disease (PD) only provide symptomatic relief; however, they don’t delay the disease progression, hence new treatment options should be considered. Carvedilol is a nonselective β & α1 blocker with additional effects as an antioxidant, anti-inflammatory and neuro protective properties. In this research, an insilico study was conducted to primarily evaluate carvedilol as an anti-parkinsonian and anti-tau protein target. PASS prediction was performed followed by a docking study of carvedilol. Carvedilol yielded promising results and forward guided this study onto its in vivo evaluation. The in vivo study aimed to assess the neuro-protective effects of carvedilol in rotenone-induced rat model of PD and investigate the potential underlying mechanisms. The effects of carvedilol (2.5, 5, and 10 mg/kg) on the measured parameters of open field, catalepsy, Y-maze tests as well as brain histology, and tyrosine hydroxylase (TH) were evaluated. The effective doses (5 and 10 mg/kg) were further tested for their potential anti-tau protein effects. Carvedilol (5 and 10 mg/kg) prevented rotenone-induced motor deficits, spatial memory dysfunction, and histological damage. Additionally, carvedilol significantly inhibited rotenone-induced decrease in TH expression in the striata of the rats. These effects were associated with reduction of rotenone-induced neuro-inflammation, microglial activation and release of glial fibrillary acidic protein (GFAP), along with reduction in N-methyl-D-aspartate receptors activation, alpha-synculein and phospho-Tau (P-Tau) protein expression. Carvedilol also reduced tau protein hyper-phosphosrylation by Glycogen synthase 3β (GSK 3β) inhibition and Phosphoinositide 3-kinase (PI3K) stimulation. Collectively, these results suggest that carvedilol might be a possible candidate for management of PD.

Prostate cancer (PCa) is one of the most common malignancies in older men. The study of tissue markers of PCa can provide information about the state of proliferation and apoptosis in tumors, the susceptibility of tumor cells to metastasis and the mechanisms of resistance to therapy, which, in turn, can help predict the course of the disease and develop personalized treatment. Polyamines (PAs) spermine, spermidine, putrescine are of particular interest in terms of PCa tissue markers.

To investigate the levels of basic and acetylated forms of PAs in the postoperative samples of malignant and benign tumors of the human prostate and evaluate the possibility of their use for differential diagnosis and assessment of the PCa aggressiveness.

57postoperative tumor samples from patients with prostate adenocarcinoma of different Gleason score (GS) and clinical stage (T1-T4) and 20samples of tumors from patients with benign prostate hyperplasia (BPH) were studied. The content of PAs was determined by high performa The obtained results indicate an association of Spm levels in tumors with the GS. This may indicate Spm involvement in the formation of the aggressiveness of PCa. The results of the study can be further used for differential diagnosis of prostate tumors and for assessing the aggressiveness of PCa.

To assess the inducible NO-synthase activity and the total RNase activity in tissue samples and blood neutrophils of the patients with prostateintraepithelial neoplasia (PIN) and prostate cancer (PCa) of different stages.

NO level was measured in tumor tissue and neutrophils of patients with PIN and PCa of different stages by electron paramagnetic resonance using the spin traps technology. RNase activity in tumor tissue of patients with PIN and PCa was measured by the method of zymography.

We have found that NO levels in prostate tumor tissue were significantly higher than in the PIN and increased along with the disease progression. Analysis of NO level in neutrophils of the PCa patients demonstrated that the values were not dispersed and did not depend on the stage of disease. NO level in neutrophils of the PCa patients increased manifold as compared with that in healthy donors. At the same time, the RNase activity in the prostate tumor tissue gradually decreased with PCa progression.

Activities of inducible NO-synthase and RNases change significantly with progression of PCa.

Activities of inducible NO-synthase and RNases change significantly with progression of PCa.

In spite of significant advances in diagnosis of prostate cancer (PCa), thedetection and differential diagnosis of metastatic lymph node involvement remains an important clinical dilemma in a large number of cases. Contrast-enhanced abdominal computed tomography and magnetic resonance imaging (MRI), in part when using T1-weighed images (T1-WI and T2-WI), allow evaluating indirectly thepresence of invasion in regional lymph nodes by assessing their diameter and morphology. Nonetheless, these techniques do not appear to be sufficiently sensitive for direct identification of lymph nodes with metastatic lesions.

To study thesignificance of theapparent diffusion coefficient (ADC) of diffusion-weighted MRI in detection of metastatic lymph node involvement in PCa patients.

Thestudy involved 35patients with histologically verified PCa. Based on multiparametric prostatic MRI findings and pathomorphological reports, we have performed ADC measurements for pelvic lymph nodes either with (n = 15, mean size 1.78±0.59cm) or without metastases (n = 20, mean size 0.94±0.06cm) in PCa patients who underwent radical prostatectomy with lymph node dissection.

No significant diffe-rences were observed when comparing mean sizes of N+ and N- pelvic lymph nodes. At thesame time, when comparing mean ADC values for N+ and N- pelvic lymph nodes, we observed a statistically significant difference 0.74±0.09 · 10-3mm2/s in metastatic lymph node vs 1.05±0.23 · 10-3mm2/s in lymph nodes without metastatic involvement (p<0.001).

Theuse of ADC for diffusion-weighted MRI may provide valuable information for detection of metastatic lymph node involvement in patients with PCa.

The use of ADC for diffusion-weighted MRI may provide valuable information for detection of metastatic lymph node involvement in patients with PCa.

Thelevel of heat shock protein 60 (Hsp60) is elevated in tumor cells compared with normal prostate epithelium. Hsp60is involved in tumor growth, invasion, and metastasis and is considered as a biomarker for cancer diagnosis and prognosis.

To study thelevel of antibodies against prokaryotic homolog of human Hsp60 (GroEL) in prostate cancer (PCa) patients as an additional risk marker for theprediction of biochemical recurrence after radical prostatectomy (RP).

A total of 55patients with localized and locally advanced PCa, who had undergone RP between July 2013and May 2014were enrolled. Level of antibodies to GroEL and human Hsp60was determined by enzyme-linked immunosorbent assay before surgery. Serum samples of blood donors with low reactivity to GroEL and human Hsp60were used as controls. Therelationship between IgG antibodies against bacterial Hsp60and human Hsp60and clinicopathological features were analyzed. Thebiochemical recurrence (BCR) free survival rate was estimated by theKaplan – Meier method.