Acta biochimica Polonica最新文献

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.

The phenomenon of growth is a leading factor for aquaculture success. The uneven growth of major Indian carps (Labeo rohita, Catla catla, and Cirrhinus mrigala) is a serious issue in fish culture from an economic point of view. The growth hormone (GH) gene is crucial for selection in commercially cultivated fish species for better growth and production. Indian major carp (L. rohita, C. catla, and C. mrigala) are commonly cultured in Pakistan. The GH expression was examined using qPCR to understand growth in fish species better. Muscle tissue samples (n=480) from 160 individuals of the same age were collected from three species (L. rohita, C. catla, and C. mrigala). Individuals were divided into two groups (high-weight and low-weight groups), cultured under normal conditions. The housekeeping gene β-actin validated GH expression in fast and slow-growing fishes from the same species. Results showed that GH expression varies across species and fish specimens that overweight their counterpart feature have higher GH expression. A selection for overweight fish in the aquaculture breeding systems is preferable as those fish could inherit their genomics to the future cohort, enhancing production, and commercial profit for farmers. Comprehensive research about different growth genes and the environmental aspects that influence fish growth is mandatory. No work has been reported regarding the growth gene analysis of fish from Pakistan. This report was Pakistan's first and baseline study regarding growth analysis of main culturable fish species at the molecular level.

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

Objective: Circular RNAs (circRNAs) are enriched in the brain and involved in various central nervous system diseases. The potential role of circCCDC6 in cerebral ischemia-reperfusion defects was partly elucidated in the work.

Methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation and re-oxygenation (OGD/R)-treated SH-SY5Y cell model were constructed. CircCCDC6 expression in the two models was examined, and circCCDC6-involved mechanisms in neuronal pyroptosis and inflammation were analyzed through loss- and gain-of-function assays.

Results: MCAO/R rat brain tissues and OGD/R-treated SH-SY5Y cells exhibited upregulated circCCDC6. Silencing circCCDC6 attenuated neuronal pyroptosis and inflammation in the brain tissue of MCAO/R rats. Overexpressing circCCDC6 or inhibiting miR-128-3p stimulated OGD/R-induced pyroptosis and inflammation in SH-SY5Y cells, while upregulating miR-128-3p attenuated OGD/R injury. CircCCDC6 silencing-induced effects on SH-SY5Y cells were antagonized by TXNIP overexpression.

Conclusion: Mechanistically, circCCDC6 mediates miR-128-3p and activates TXNIP/NLRP3, thereby promoting OGD/R-induced neuronal pyroptosis and inflammation. CircCCDC6 may provide a new strategy for the treatment of MCAO/R.

Monocyte-chemoattractant protein-induced protein 1 (MCPIP1, or Regnase-1) is an endoribonuclease that degrades translationally active mRNA molecules. MCPIP1 is mostly known for its anti-inflammatory actions, but it is also an important regulator of adipogenesis and lipid metabolism. Its overexpression impairs adipogenesis by reducing mRNA levels of C/EBPβ and PPARγ, key transcription factors regulating this process. Although adipocytes overexpressing MCPIP1 are characterised by impaired glucose uptake, the function of MCPIP1 in hepatocyte metabolism remains unknown. In this study, conditional deletion of Zc3h12a in murine liver epithelial cells was used to characterise the role of Mcpip1 in adaptation to 24-hour food restriction. We found that Mcpip1 deficiency in liver epithelial cells (Mcpip1fl/flAlbCre mice) resulted in higher blood glucose levels in response to fasting in comparison to Mcpip1fl/fl counterparts. Hepatic proteome analysis showed 26 down-regulated and 117 up-regulated proteins in Mcpip1fl/flAlbCre animals that were involved in cellular adhesion, extracellular matrix and metabolic processes. In conclusion, our studies provide new insight into the hepatic function of Mcpip1 and its involvement in metabolic control.

Purpose Ferroptosis and cuproptosis are both metal-dependent regulated cell death that play an important role in cancer. However, the expression patterns and the prognostic values of ferroptosis-related genes (FRGs) associated with cuproptosis in breast cancer (BC) are largely unknown. This study aims to explore the prognostic value of cuproptosis-related FRGs and their relationship with tumor microenvironments in BC. Methods The clinical and RNA sequencing data of BC patients from TCGA, METABRIC and GEO databases were analyzed. The least absolute shrinkage and selection operator regression analysis was used to establish prognostic signatures based on cuproptosis-related FRGs. The overall survival between risk subgroups was assessed by Kaplan-Meier analysis. The changes in risk score during neoadjuvant chemotherapy, and differences in immune cells, immune checkpoints, and drug sensitivity between risk subgroups were also analyzed in this study. Results A successful development of a prognostic signature based on cuproptosis-related FRGs in the TCGA cohort was achieved and it was validated in the METABRIC cohort. Gene set enrichment analysis results revealed the enrichment of steroid biosynthesis and ABC transporters in the high-risk group. Moreover, the signature was also found to be associated with immune cells and immune checkpoints. Lower risk score in patients after neoadjuvant chemotherapy and higher sensitivity of the high-risk group to AKT inhibitor VIII and cisplatin was also observed. Conclusion Cuproptosis-related FRGs can be used as a novel prognostic signature for predicting the overall survival of BC patients. This can provide meaningful insights into the selection of immunotherapy and antitumor drugs for BC.