Acta biochimica Polonica最新文献

Introduction: Liver transplantation (LTx) is the only successful treatment for end-stage liver disease. The results of liver transplantation depend not only on graft survival but may be also affected by superimposed cardiovascular morbidities. The aim of this retrospective study was to assess the prevalence of lipid disorders as one of the important cardiovascular risk factors in patients before and after successful LTx.

Material and methods: One hundred eleven patients who underwent liver transplantation because of liver cirrhosis and survived at least 2 years with functioning graft between November 2005 and May 2014 were included in this retrospective analysis. The mean age of the patients at the time of liver transplantation was 49.7±12.2 years. The prevalence of dyslipidemia was assessed before and two years after liver transplantation. This was analyzed in relation to the etiology of liver disease, including alcohol toxicity, viral or autoimmune diseases.

Results: The prevalence of hypertriglyceridemia before and after LTx was 13.5% and 40.5%, respectively (P<0.001). Similarly, hypercholesterolemia was noted in 17.1% and 51.4% respectively (P<0.001). The annual incidence of hypertriglyceridemia and hypercholesterolemia during the first two years after LTx was 16.2% and 20.7%, respectively. The prevalence of hypertriglyceridemia (18.5% vs 66.7%, P<0.001) and hypercholesterolemia (29.6% vs 70.0%, P=0.002) was significantly lower in patients with the autoimmune cause of liver cirrhosis in comparison to patients with the alcoholic liver disease.

Conclusions: The prevalence of dyslipidemia is increased after liver transplantation. The prevalence of dyslipidemia may be related to the cause of liver injury before LTx.

Diabetic nephropathy (DN), a microvascular complication of diabetes, increases the risk of all-cause diabetes and cardiovascular mortalities. Moreover, oxidative stress and pyroptosis play important roles in the pathogenesis of DN. Rhubarb is widely used in traditional medicine, and chrysophanol (Chr), a free anthraquinone compound abundant in rhubarb, exhibits potent antioxidant properties and ameliorates renal fibrosis. Therefore, this study aimed to investigate the effects of Chr on renal injury, oxidative stress, and pyroptosis in mice with DN. A DN model was established by feeding the mice a high-sugar and fat diet and injecting them with 50 mg/kg streptozotocin as a positive control. The DN mice had significantly impaired renal function, thickened glomerular thylakoids and basement membranes, increased fibrous tissue, and inflammatory cell infiltration. Superoxide dismutase (SOD) levels were reduced, malondialdehyde (MDA) levels were increased, interleukin (IL)-1β and IL-18 increased, and cleaved caspase-1, caspase-1, and gasdermin D (GSDMD) involved in the process of pyroptosis were upregulated in DN. Kelch-like ECH-associated protein 1 (Keap1) expression was upregulated, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was downregulated. Compared to those in the DN group, the Chr-treated mice with DN had improved renal dysfunction, weakened glomerular thylakoid and basement membrane thickening, and reduced fibrous tissue proliferation and inflammatory cell infiltration. Additionally, Chr increased SOD levels, decreased MDA, IL-1β, and IL-18, down-regulated caspase-1, cleaved caspase-1, GSDMD, and Keap1 expression, and upregulated Nrf2 expression, which reversed the DN. Therefore, Chr reduced oxidative stress and pyroptosis in DNmice by activating the Keap1/Nrf2 pathway.

Introduction: Familial Hypercholesterolemia (FH) is a common condition caused by inherited genetic abnormalities. Inadequate clearance of the circulating low-density lipoproteins (LDL) is the primary cause of the excessive concentrations of LDL seen in FH patients. The relation with vitamin D deficiency and vitamin D receptor (VDR) gene is well documented in the Saudi Arabia.

Aim: The aim of this study was to investigate the role of molecular analysis studied between FH patients and fours polymorphisms associated with VDR gene in Saudi Population.

Methods: In this case-control study, 120 patients were selected, and 50 patients were confirmed as FH and 70 subjects were confirmed as healthy controls. Genotyping was performed with polymerase chain reaction followed by restriction fragment length polymorphism analysis using ApaI, BsmI, TaqI and FokI polymorphisms in the VDR gene.

Results: The current study results confirmed no association between clinical characteristics studied between FH cases and controls (p>0.05). Hardy Weinberg Equilibrium analysis was present in ApaI and FokI polymorphisms (p<0.05). Only ApaI (C vs A: OR-15.1 (95% CI:5.78-39.41); p<0.001; AC+CC vs AA: OR-6.59 (95% CI:2.42-17.95); p=0.0006) and BsmI (G vs A: OR-2.88 (95% CI:1.54-5.38); p=0.0006 and AG+GG vs AA: OR-3.79 (95% CI:1.72-8.35); p=0.0007) polymorphisms showed both allele and genotype association between FH patients and controls. ANOVA analysis confirmed that TG levels were associated (p=0.02) with combination of heterozygous and homozygous genotypes present in all four polymorphisms studied in this population.

Conclusion: ApaI and BsmI polymorphisms in the VDR gene showed association with FH patients in the Saudi Population.

Objective: Necrotizing enterocolitis (NEC) is a devastating inflammatory disease with high morbidity and mortality, mainly affecting premature infants. This study aimed to explore the role of miRNA-301a in the pathogenesis of NEC.

Methods: The differentially expressed miRNAs and mRNAs were screened by collating RNA-Seq data from the GEO database of intestinal tissue samples. The differential miRNA-mRNAs regulatory network was constructed based on functional enrichment analysis. Newborn BALB/c mice were used to establish the NEC model. Haematoxylin and eosin staining was used to assess intestinal damage. The levels of IL-8 and TNF-α in mouse serum were evaluated by ELISA. qRT-PCR was used to detect the expression of miRNA-301a in intestinal tissues.

Results: Bioinformatics analysis showed that miRNA-301a was involved in intestinal lesions. Intestinal tissue damage was reduced and serum levels of the inflammatory cytokines IL-8 and TNF-α were lower in NEC model mice treated with miRNA-301a antagonists. The level of miRNA-301a in intestinal tissues of NEC model mice was significantly higher than in the control group and miRNA-301a antagonists treated group.

Conclusion: miRNA-301a plays an important role in the pathogenesis of NEC by promoting inflammation, and is a potential therapeutic target of NEC.

Previously, the direct interactions of Bβ26-42 fibrin residues with prothrombin were demonstrated. It was also shown that forming prothrombin complexes with E- or DDE-fragments causes non-enzymatic prothrombin activation. The direct measuring of the prothrombin level in the blood plasma of patients with acute myocardial infarction (AMI) allowed us to find a situation where such an activation can occur in vivo. Blood coagulation parameters in the blood plasma of patients with AMI were measured at 2 hours, three days, and seven days after the thrombolysis by streptokinase accompanied with intravenous administration of anticoagulants: unfractionated high molecular weight heparin (HMWH) and low-molecular-weight heparin (LMWH). The prothrombin level in the blood plasma of patients with AMI was normal before thrombolytic therapy and substantially decreased after streptokinase administration. This effect was prominent in the case of concomitant anticoagulant therapy with LMWH and was not observed when HMWH was applied. It can be explained by the fact that LMWH preferentially inhibits factor Xa, while the HMWH is an effective inhibitor of both factor Xa and thrombin. This observation suggested that the prothrombin level decrease was caused by the thrombin-like activity and possible autolysis of prothrombin by thrombin. Also, thrombolytic therapy with streptokinase caused the accumulation of fibrin degradation products (FDPs), some of which were able to bind prothrombin. The dramatic decrease of prothrombin level in the blood plasma of patients with AMI during thrombolysis allowed us to conclude the non-enzymatic prothrombin activation with the following autolysis of prothrombin that contributes to the pathology.

Background and objective: Previous studies have shown that miR-221-3p plays an important role in vascular remodeling, but it is unclear whether it contributes to angiogenesis after burn injury. The purpose of this study was to investigate the effect of miR-221-3p on angiogenesis in HUVECs after burn injury and to reveal its underlying molecular mechanism.

Methods: The burn HUVECs model was established by heat treatment. Plasmid or oligonucleotide transfection altered the expression of miR-221-3p and CDKN1B in HUVECs. MTT, colony formation, Transwell, flow cytometry, and tube formation experiments were applied to assess the proliferation, migration, apoptosis, cell cycle, and tube formation capacity of HUVECs. miR-221-3p, CDKN1B, Ki-67, and PCNA expression was assessed by RT-qPCR or Western blot. The dual-luciferase reporter assay verified the targeting relationship between miR-221-3p and CDKN1B.

Results: miR-221-3p was lowly expressed and CDKN1B was highly expressed in burn HUVECs. Overexpression of miR-221-3p promoted the proliferation, migration, and tube formation ability of burn HUVECs and inhibited apoptosis and the proportion of cells in the G0/G1 phase, whereas overexpression of CDKN1B had the opposite effect. Knockdown of miR-221-3p further inhibited the angiogenic capacity of burn HUVECs, but this effect was reversed by knockdown of CDKN1B. Mechanistically, miR-221-3p targeted CDKN1B.

Conclusion: miR-221-3p improves the angiogenesis of burn HUVECs by targeting CDKN1B expression, and the miR-221-3p/CDKN1B axis may serve as a potential molecular target for future burn therapy.

Diabetes mellitus is one of the important independent risk factors for the development of neurological disorders such as ischemic stroke, transient ischemic attacks, vascular dementia and neurodegenerative processes. Hyperglycemia plays a crucial role as a trigger in the pathogenesis of these disorders. In this review, we summarize the existing data on the molecular mechanisms of diabetic encephalopathy development, consider the features of oxidative and nitrosative stresses, changes in the thiol-disulfide system, as well as mitochondrial and endothelial dysfunction in diabetes. We focus on the role of HSP 70 in cellular responses in diabetic encephalopathy. HSP70 protein is an important component of the endogenous system of neuroprotection. It acts as an intracellular chaperone, providing the folding, retention, and transport of synthesized proteins, as well as their degradation under both normoxic and stress-induced denaturation conditions. HSP70 can be considered a molecular marker and a promising therapeutic target in the treatment of diabetes mellitus.

Imiquimod-induced psoriasis is widely-employed to study disease pathogenesis and to screen drugs. While the original protocol was published more than a decade ago and has been rigorously used in research since then, a modified protocol was described recently with several advantages including milder systemic manifestations although the disease morphology is highly conserved. Being a toll-like receptor 7 and 8 agonist, IL-23/IL-17 axis predominates in imiquimod-induced psoriasis. In addition, different immunocytes were described to aggravate or supress the disease. This article aims to review the currently available protocols of imiquimod-induced psoriasis in vivo, to characterize the model as described in literature and to define the five important independent factors adversely influencing the model which researchers should pay attention to.

Purpose: Due to its crucial cancer regulatory role, microRNA-508-3p has been reported as a potential therapeutic anticancer molecular target. The present work encompassed the molecular characterization of microRNA-508-3p in lung cancer emphasizing on understanding the possible mechanism of its regulatory action.

Methods: qRT-PCR was performed to estimate the relative gene expression of microRNA-508-p in the tissue samples. The proliferation of cancer cells was determined by cell counting kit-8. The colony formation from cancer cells was analyzed by clonogenic assay. Mitotic phase distribution was understood by employing the flow cytometric technique. Edu-Hoechst staining was used for the assessment of cell viability. In silico analysis and dual-luciferase assay were used for target identification of microRNA-508-3p in lung cancer. Immunofluorescence and western blotting studies were carried out for relative protein expression. The rat models were used for performing the in vivo experimental procedures.

Results: The study showed the significant down-regulation of microRNA-508-3p in lung cancer. The lower expression levels of microRNA-508-3p were shown to be associated with poor survival of lung cancer patients. The over-expression of microRNA-508-3p was found to decline the proliferation and viability of cancer cells together with the induction of mitotic cell cycle arrest at G1 by targeting G1 to S phase transition 1 (GSPT1) protein. MicroRNA-508-3p up-regulation inhibited the in vivo tumor growth in rat models.

Conclusion: Our study identifies miR-508-3p as a pivotal regulator of lung cancer cell proliferation by targeting the GSPT1 protein. This highlights its potential as a tumor suppressor and a therapeutic target for lung cancer. Our findings offer mechanistic insights into miRNA-mediated cancer progression, prompting further research in this intricate regulatory network.

Pets are inhabiting more and more human homes every year. In 2020, the cat population in Europe was 110 million, including 6.8 million in Poland. Dry food is the most popular dietary model for cats because of its easy storage and efficient satisfaction of pet needs. The high processing temperature of dry food reduces the chance of microbial contamination, but this can occur later, during post-production or storage in the pet's caregiver's home or, in the case of weighed foods, in the store. The purpose of this study was to investigate the microbiological safety of dry feed sold in the original manufacturer's packaging and the same feed from the same manufacturers sold in a retail store by weight. Six discriminants, presence of Salmonella spp., number of coliforms, number of coagulase-positive staphylococci, determination of yeast and mould counts, Enterobacteriaceae count, Listeria monocytogenes and determination of total aerobic microbial count were used for the analysis. Then, cat food was then stored for 45 days according to the manufacturer's recommendations. Based on the samples tested both after opening and after storage, it was concluded that the dry cat food analyzed posed a law microbiological risk to animals and humans.