Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models.

Background: Recent research suggests a possible role of Notch signaling pathway in development of liver fibrosis, but exact cellular and molecular mechanisms are still not well defined. Methods: We modulated Notch signaling in activated hepatic stellate cells/myofibroblasts using the model of inducible activation or inhibition of Notch signaling selective for αSMA positive cells in murine models of toxic fibrosis induced by CCl4 and cholestatic fibrosis induced by DDC supplemented feeding.

Results: Our results confirm that Notch signaling pathway is activated in both CCL4 and DDC model of liver fibrosis and that αSMA positive myofibroblasts are of activated hepatic stellate cells origin.

Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity.

Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This study evaluated the potential of novel nanoformulation based on poly(lactic--glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX). toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX).

Effects of epidurally administered dexmedetomidine and dexamethasone on postoperative pain, analgesic requirements, inflammation, and oxidative stress in thoracic surgery.

The aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to preoperative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the postoperative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine ( = 18) or dexamethasone ( = 24) group.

Paraoxonase and arylesterase activity of paraoxonase 1 and oxidative stress parameters in cervical intraepithelial neoplasia.

Introduction: Paraoxonase 1 (PON1) is the enzyme that removes carcinogenic radicals from lipids. The aim of the study was to investigate the differences in PON1 activity and oxidation stress parameters between patients with cervical intraepithelial neoplasia (CIN) and healthy controls.

Materials And Methods: The study included 65 women with CIN and 109 healthy women.

Effect of Alpha-Lipoic Acid Supplementation on Low-Grade Squamous Intraepithelial Lesions-Double-Blind, Randomized, Placebo-Controlled Trial.

Low-grade squamous intraepithelial lesion (SIL) is a cytologic diagnosis etiologically related to human papilloma virus (HPV) infection that leads to the release of inflammation mediators, the formation of reactive oxygen species (ROS) and decreased levels of antioxidants in tissues, which is why antioxidants might be considered effective against SIL progression. This randomized double-blind placebo-controlled study aimed to investigate the effectiveness of alpha-lipoic acid (ALA) supplementation (600 mg/day) on the regression of low-grade SIL in 100 patients. Low-grade SIL was determined after the cytological screening, colposcopic examination and targeted biopsy and histological confirmation of cytological−colposcopic diagnosis.

Toxicity of nanomixtures to human macrophages: Joint action of silver and polystyrene nanoparticles.

Increasing use of nano-enabled products provides many benefits in various industrial processes and medical applications, but it also raises concern about release of nanoparticles (NPs) into the environment and subsequent human exposure. While potential toxicity of individual NPs types has been well described in scientific literature, exposure and health-related effects of nanomixtures has been poorly described. This study aimed to evaluate the combined effect of silver (AgNP) and polystyrene NPs (PSNP) on the human macrophages.

Tamoxifen Ameliorates Cholestatic Liver Fibrosis in Mice: Upregulation of TGFβ and IL6 Is a Potential Protective Mechanism.

The available treatments for cholestatic liver fibrosis are limited, and the disease often progresses to liver cirrhosis. Tamoxifen is a selective modulator of estrogen receptors, commonly used in breast cancer therapy. A recent in vitro study showed that tamoxifen deactivates hepatic stellate cells, suggesting its potential as an antifibrotic therapeutic, but its effects in vivo remain poorly investigated.

Cytotoxicity of nanomixture: Combined action of silver and plastic nanoparticles on immortalized human lymphocytes.

Background: Silver nanoparticles (AgNP) are one of the most commercialized types of nanomaterials, with a wide range of applications owing to their antimicrobial activity. They are particularly important in hospitals and other healthcare settings, where they are used to maintain sterility of surfaces, textiles, catheters, medical implants, and more. However, AgNP can not only harm bacteria, but also damage mammalian cells and tissue.

Light and heavy ferritin chain expression in the liver and kidneys of Wistar rats: aging, sex differences, and impact of gonadectomy.

Ferritin is the main intracellular storage of iron. Animal studies show that female liver and kidney express more ferritin and accumulate more iron than male. However, no study so far has investigated sex and age differences in light (FtL) and heavy (FtH) ferritin chain expression.

Two Needle Passes Achieve Similar Diagnostic Yield Compared to Three Passes Regarding Diagnosis of Solid Pancreatic Lesions in Endoscopic Ultrasound-Guided Fine Needle Aspiration.

Current guidelines advocate 3-4 passes with a fine-needle aspiration (FNA) to achieve high rates of diagnostic samples for malignancy when performing endoscopic ultrasound (EUS)-guided sampling of solid pancreatic lesions, in the absence of on-site cytologic evaluation. The aim of this study is to compare 2 vs. 3 needle passes in EUS-FNA for solid pancreatic lesions in terms of incremental diagnostic yield and to identify factors associated with the procedure's outcome.

Food (Matrix) Effects on Bioaccessibility and Intestinal Permeability of Major Olive Antioxidants.

Background: olive pomace extract (OPE) is a rich source of health promoting polyphenols (hydroxytyrosol (HTS) and tyrosol (TS)) and can be used as a nutraceutical ingredient of dietary supplements and functional foods. Its adequate bioavailability is a prerequisite for excreting biological activity and can be significantly and specifically affected by different food matrices.

Methods: in order to investigate food effects on polyphenol bioaccessibility, OPE was co-digested with different foods according to internationally harmonized in vitro digestibility method.

Forgotten partners and function regulators of inducible metallothioneins.

Metallothioneins are peculiar cysteine rich, heat resistant, small cellular plasma proteins expressed through almost all life forms. The currently established biological functions of metallothioneins are the homeostasis of essential metals and protection against toxic transitional metals (TM) alongside defence from oxidative stress by direct scavenging of reactive oxygen and nitrogen species (ROS and RNS). In mammals, among the four main evolutionary conserved forms, only the ubiquitously expressed metallothionein 1 and 2 (here abbreviated as MT) are inducible by TM, oxidative stress, glucocorticoids and starvation among various other stimuli.

Synergistic effects of parabens and plastic nanoparticles on proliferation of human breast cancer cells.

Many personal care products on the market contain endocrine disrupting chemicals, including parabens. Parabens are well known chemical additives used as preservatives. They have been found in mammary glands and breast cancer tissues.

Importance of genetic polymorphisms in liver transplantation outcomes.

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach.

Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma.

Background: Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers.

LPS-induced inflammation desensitizes hepatocytes to Fas-induced apoptosis through Stat3 activation-The effect can be reversed by ruxolitinib.

Recent studies have established a concept of tumour necrosis factor-α (TNF-α)/Fas signalling crosstalk, highlighting TNF-α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF-α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome.

Optimization of a fast screening method for the assessment of low molecular weight thiols in human blood and plasma suitable for biomonitoring studies.

An adequate level of low molecular weight thiols (LMW-SH, especially glutathione (GSH)) protects cellular macromolecules against toxic agents, and is used as a sensitive biomarker of exposure to toxic compounds. During sample collection, storage and preparation, non-enzymatic and enzymatic oxidation of LMW-SH can occur leading to analytical inaccuracy. The aim of this study was to optimize a fast and reliable screening method for the determination of LMW-SH, mainly GSH, in blood and plasma samples as well as to investigate the impact of storage conditions on the LMW-SH stability.

A modern approach to the treatment of plaque psoriasis.

Psoriasis is a common chronic inflammatory skin disease which affects 0.5-1 % of children and 2-3 % of the adult population. In Croatia, 1.

Targeting Tumor Markers with Antisense Peptides: An Example of Human Prostate Specific Antigen.

The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2.

Higher Post-Operative Serum Vitamin D Level is Associated with Better Survival Outcome in Colorectal Cancer Patients.

25-Hydroxyvitamin D (25-OHD) may have a prognostic value in colorectal cancer (CRC) patients. However, as 25-OHD concentration is strongly impacted by surgery, it is uncertain what is the most reliable time-point for 25-OHD assessment, pre- or post-operative. Therefore, we examined 515 CRC patients (AJCC I-III) who underwent surgery.

Impact of pharmacotherapeutic education on medication adherence and adverse outcomes in patients with type 2 diabetes mellitus: a prospective, randomized study.

Aim: To evaluate the impact of pharmacotherapeutic education on 30-day post-discharge medication adherence and adverse outcomes in patients with type 2 diabetes mellitus (T2DM).

Methods: The prospective, randomized, single-center study was conducted at the Medical Department of University Hospital Dubrava, Zagreb, between April and June 2018. One hundred and thirty adult patients with T2DM who were discharged to the community were randomly assigned to either the intervention or the control group.

Genetic coding algorithm for sense and antisense peptide interactions.

Sense and antisense peptides, i.e. peptides specified by complementary DNA and RNA sequences, interact with increased probability.

[Pharmacoeconomics - Challenges for Health Professionals].

Over the last 30 years, medical expenditure has increased throughout the world. The main reasons estimated to lay behind it include aging, ever more chronic diseases and new emerging diseases, new drugs, expanded indications of current drugs, and development of pharmaceutical industry. A challenge for healthcare professionals is to sustain current quality of care and enable medical innovations while attempting to contain costs.

Modulation of γ2-MSH hepatoprotection by antisense peptides and melanocortin subtype 3 and 4 receptor antagonists.

Melanocortins, i.e., melanocyte stimulating hormones (MSH) are peptides with strong antiinflammatory effects.

Hepatoprotective effects of Met-enkephalin on acetaminophen-induced liver lesions in male CBA mice.

Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.