Turkish journal of biology = Turk biyoloji dergisi最新文献

Background: Compelling evidence has manifested a strong association between aberrant expression of long noncoding RNAs (lncRNAs) and gastric carcinoma (GC) development. Nonetheless, biological impacts of differentially expressed lncRNAs (DElncRNAs) on GC are not scrutinized.

Methods: Bioinformatics methods were employed for differential expression analysis and target gene prediction. MTT, colony formation, and Transwell methods were implemented for GC cell proliferation, migration, and invasion assessment. Western blot was implemented to test the protein level. The binding of genes was tested with dual-luciferase and RNA binding protein immunoprecipitation (RIP) approaches.

Results: Noticeably high level of LINC00460 was observed in GC tissues and cells. LINC00460 silencing constrained proliferation, migration, and invasion of GC cells. FISH and nuclear-cytoplasmic separation assays confirmed the main presentation of LINC00460 in the cytoplasm. Bioinformatics predicted that LINC00460 had binding sites to miRNA-143-5p, which was upregulated in GC. Dual luciferase and RIP experiments also confirmed the binding relationship. Concurrent silencing of LINC00460s and miRNA-133-5p rescued the repressive influence of sh-LINC004600 on GC cell proliferation, migration, and invasion. HMGA2 was predicted to be a target gene downstream of miRNA-143-5p, their binding relationship was validated via dual luciferase assays. Silencing HMGA2 constrained GC cell proliferation, invasion, and migration. LINC00460 modulated HMGA2 expression via binding miRNA-143-5p, thereby affecting proliferation, invasion, and migration of GC cells.

Conclusion: These findings validated that LINC00460 could regulate HMGA2 via sponging miRNA-143-5p to facilitate GC proliferation, invasion, and migration, which provides a deeper understanding of lncRNAs in the development of GC.

Breast and ovarian cancers are women's most commonly diagnosed cancers. Seeking an efficient anticarcinogenic compound is still a top priority regarding the aggressiveness of these cancers and the limited benefit of current therapies. Hydroquinidine (HQ) is a natural alkaloid used in arrhythmia and Brugada syndrome. As an ion channel blocker, HQ exhibits its activity by altering ion gradient and membrane potential. Considering the growing evidence of ion channel blockers' antineoplastic potential, we were prompted to test HQ's effect on breast and ovarian cancers. MCF-7 and SKOV-3 cell lines were used to inspect how HQ acts on survival, clonogenicity, migration, tumorigenicity, proliferation, and apoptosis. The molecular basis for the remarkable antiproliferative and proapoptotic effect of HQ in these cells was dissected by proteomics. CDK1, PSMB5, PSMC2, MCM2, MCM7, YWHAH, YWHAQ, and YWHAB proteins in HQ-treated MCF-7 cells, and RRM2, PSMD2, PSME2, COX2, COX4l1, and CDK6 proteins in HQ-treated SKOV-3 cells were found as low-abundant, which was noteworthy. Based on the in-depth analysis, upon HQ treatment, several cell cycle-related processes were found as suppressed, whereas apoptosis and ferroptosis pathways were found to be activated. The observed proteome alteration in cancer cells may provide mechanistic explanations for the growth-limiting effects of HQ at the cellular level.

Background/aim: Dietary restriction, mainly carbon and/or methionine restriction are among the upcoming supporting interventions along with chemotherapy in various cancers. Although dietary restriction has been proven to be beneficial, the main cellular machineries affected by its administration lacks deeper information considerably, a notable pitfall in its use as a personalized nutritional approach.

Materials and methods: In this study, cellular effects of methionine restriction on a yeast model are explored via systems biology approaches. The methionine biosynthesis network, constructed by integrating interaction data with gene ontology terms, was analysed topologically, and proved to be informative about the intertwined relationship of methionine biosynthesis and cancer. Experimentally, effects of methionine restriction on the yeast model were explored in vivo, with transcriptome analyses.

Results: The integrative analysis of the transcriptional data together with the reconstructed network gave insight into cellular machineries such as TOR, MAPK, and sphingolipid-mediated signaling cascades as the mostly responsive cellular pathways in the methionine-restricted cases with Sch9p (functional orthologue of mammalian S6 kinase) being placed at the intersection of these signaling routes.

Background: Osteonecrosis of the femoral head (ONFH) is an ischemic disease characterized by the impairment of angiogenesis. We have previously elucidated the role of tsRNAs and BMSC exosomes in ONFH, but whether tsRNA-modified BMSC exosomes promote angiogenesis in ONFH remains unclear.

Methods: The expression of angiogenesis-related tsRNA in plasma exosomes from ONFH patients was examined by q-PCR. The function of tsRNA in HUVECs was identified by CCK-8 and angiogenesis assay. Exosomes purified from tsRNA-15797 overexpressed BMSCs were cocultured with HUVECs to examine their role in angiogenesis. The molecule mechanism of tsRNA-15797-modified exosomes was explored by RNA sequencing, dual-luciferase assay, and immunofluorescence.

Results: A tRNA-derived small RNA tsRNA-15797 was down-regulated in plasma exosomes of ONFH patients. We found the effects of BMSCs-derived exosomes on accelerating HUVECs angiogenesis and migration, which were further enhanced after overexpressing tsRNA-15797. Besides, overexpression of tsRNA-15797 would lead to down-regulation of LFNG correlated with angiogenesis. tsRNA-15797 could directly interact with LFNG. We demonstrated that LNFG overexpression weakened the pro angiogenic and migratory effects of tsRNA-15797-modified BMSCs-derived exosomes.

Conclusion: We successfully constructed tsRNA-15797-modified BMSC-derived exosomes and demonstrated that it induced the angiogenesis of HUVECs by targeting the down-regulation of LFNG. Thus, tsRNA-15797-loaded BMSCs-derived exosomes may be a potential target therapy drug for ONFH.

Seeds, by-products derived from various plants such as mango, quince, and apples, are considered waste, though they have emerging commercial potential, and have been used in biological, industrial, and physiological research. Seed-derived natural macromolecules- mainly polysaccharides, mucilage, gums, and cellulose-have physicochemical and structural diversification, giving the potential for forming gels, texturing, thickening, and providing interfacial adsorption. Seed-derived natural macromolecules have been widely used during the last few years in cell research and tissue engineering applications. Their widespread approachability and safety, high rate of biodegradability, biocompatibility, supporting cell proliferation, and extracellular matrix synthesis are the main properties making plant seed derivatives appropriate for use. The gel-forming ability of these derivatives gives them the capability of creating natural polymer-based scaffolds with the aptitude to resemble extracellular matrices (ECM). These ECM exhibit the high potential in scaffolds for tissue renewal. A deeper knowledge of the physicochemical characteristics of seed-derived mucilage and gum has been indicated as a key ingredient in several pharmaceutical preparations, but it has been remarkably utilized in nanomedicine for the last few years as a drug carrier for drug delivery, in gene therapy, and as scaffold components for tissue engineering purposes. Here, we afford up-to-date data about the different extracts from plant seeds-mainly mucilage and gum, we summarize the extraction techniques used to isolate these macromolecules, and we focus on their application in scaffold fabrication for tissue engineering purposes and regenerative medicine applications.

Since obesity causes at least 2.8 million death each year and is a major risk factor for many diseases, it is critical to evaluate alternative treatment approaches. In this context, studies on the research of natural product-based therapeutics in the fight against obesity are increasing. In this study, it was aimed to evaluate the antiadipogenic and antiobesogenic efficacy of pterostilbene a natural phenolic compound in 3T3-L1 cells. The mature 3T3-L1 adipocytes were exposed to pterostilbene at different concentrations and half-maximum inhibitory concentrations (IC₅₀) were determined by MTT assay. Oil-Red-O staining was applied to determine lipid accumulation. Phase contrast microscopy, Giemsa, F-actin and DAPI staining were applied to examine the efficacy of pterostilbene on the morphology of 3T3-L1 adipocyte cells. Moreover, expressions of adinopectin and glucose transporter-4 (Glut-4) in relation to insulin resistance were evaluated using immunofluorescent staining and qRT-PCR. Pterostilbene caused no significant cytotoxicity towards preadipocytes at concentrations ≤7.5 -M and the percentage of viable cells remained above about 86% for 24 h, 48 h and 72 h (p > 0.05). Therefore, pterostilbene treatment at 5 and 7.5 -M was used in the subsequent experiments as safe dosages. In addition, it was observed that pterostilbene treatment reduced lipid accumulation in adipocyte differentiation. Adipocytes treated with a dose of 7.5 -M for 14 days showed less intense lipid deposition and a more spindle-like morphology compared to the adipocytes treated with a dose of 5 -M. Especially on the 14th day, actin filaments were filamentous in adipocytes treated with pterostilbene 7.5 -M compared to the adipocytes treated with a dose of 5 -M; the filaments were similarly oriented as in preadipocytes, and chromatin condensation was observed to be quite high. Our data suggests that the pterostilbene supplementation may help weight control and the antiadipogenic and that antiobesogenic activity is mediated in part by reduction of lipid accumulation and induction of Glut-4 and Adiponectin levels.

Projecting from most cell surfaces, cilia serve as important hubs for sensory and signaling processes and have been linked to a variety of human disorders, including Bardet-Biedl Syndrome (BBS), Meckel-Gruber Syndrome (MKS), Nephronophthisis (NPHP), and Joubert Syndrome, and these diseases are collectively known as a ciliopathy. DCDC2 is a ciliopathy protein that localizes to cilia; nevertheless, our understanding of the role of DCDC2 in cilia is still limited. We employed C. elegans to investigate the function of C. elegans RPI-1, a Caenorhabditis elegans ortholog of human DCDC2, in cilia and found that C. elegans RPI-1 localizes to the entire ciliary axoneme, but is not present in the transition zone and basal body. We generated a null mutant of C. elegans rpi-1, and our analysis with a range of fluorescence-based ciliary markers revealed that DCDC2 and nephronophthisis 4 (NPHP-4/NPHP4) display functional redundant roles in regulating cilia length and cilia positions. Taken together, our analysis discovered a novel genetic interaction between two ciliopathy disease genes (RPI-1/DCDC2 and NPHP-4/NPHP4) in C. elegans.

From Astragalus membranaceus (Fisch.) Bge.var. mongholicus (Bge.) Hsiao, astragaloside IV (AS-IV), a saponin can be purified and is considered traditional Chinese medicine. The purpose of this study was to evaluate the AS-IV-mediated mechanism on chronic glomerulonephritis (CGN). A cationic bovine serum albumin-induced CGN rat model was established and 10, 15, or 20 mg/kg of AS-IV was administered to measure renal function and inflammatory infiltration. Influences of AS-IV on proliferation, cell cycle, and inflammation of LPS-induced rat mesangial cells (RMCs) were determined. The results demonstrated that AS-IV alleviated renal dysfunction, renal lesions, and inflammation in CGN rats. AS-IV prolonged the G0-G1 phase, shortened the S phase, and inhibited cell proliferation and inflammation in RMCs. AS-IV can promote miR-181d-5p expression to inhibit CSF1. miR-181d-5p promotion or CSF1 suppression could further enhance the therapeutic role of AS-IV in CGN rats, while miR-181d-5p silencing or CSF1 overexpression abolished the effect of AS-IV. In conclusion, AS-IV by mediating the miR-181d-5p/CSF1 axis protects against CGN.

Human SARS coronavirus 2 (SARS-CoV-2) causes the current global COVID-19 pandemic. The production of an efficient vaccine against COVID-19 is under heavy investigation. In this study, we have designed a novel multiepitope DNA vaccine against SARS-CoV-2 using reverse vaccinology and DNA vaccine approaches. Applying these strategies led to reduce the time and costs of vaccine development and also improve the immune protective characteristics of the vaccine. For this purpose, epitopes of nucleocapsid, membrane glycoprotein, and ORF8 proteins of SARS-CoV-2 chose as targets for B and T-cell receptors. Accordingly, DNA sequences of selected epitopes have optimized for protein expression in the eukaryotic system. To this end, the Kozak and tissue plasminogen activator sequences were added into the epitope sequences for proper protein expression and secretion, respectively. Furthermore, interleukin-2 and beta-defensin 1 preproprotein sequences were incorporated to the designed DNA vaccine as an adjuvant. Modeling and refinement of fused protein composed of SARS-CoV-2 multiepitope antigens (fuspMA) have performed based on homology modeling of orthologous peptides, then constructed 3D model of fuspMA was more investigated during 50 ns of molecular dynamics simulation. Further bioinformatics predictions demonstrated that fuspMA is a stable protein with acceptable antigenic features and no allergenicity or toxicity characteristics. Finally, the affinity of fuspMA to the MHC I and II and TLRs molecules validated by the molecular docking procedure. In conclusion, it seems the designed multiepitope DNA vaccine could have a chance to be introduced as an efficient vaccine against COVID-19 after more in vivo evaluations.

The working mechanism of the chemotherapeutic drug doxorubicin, which is frequently used in cancer treatment, its effects on cell metabolism, and pathways activated solely by doxorubicin are not fully known. Understanding these principles is important both in improving existing therapies and in finding new drug targets. Here, I describe a systems-biology approach to find a generalizable working principle for doxorubicin by superimposition of human interactome over gene datasets commonly expressed among various cancer types. The common -in at least two different diseases-transcriptional response of distinctive cancer cell lines to doxorubicin was reflected via 199 significantly and differentially expressed genes, mostly related to the regulation of transcription. Then, by integrating with interactome data, an active network was constructed allowing detection of clusters. Since each cluster defines densely connected regions, another level of understanding of functional principles is provided. Significant clusters were associated with the linked transcription factors and transcriptional factor enrichment analysis within these regulatory networks led to the proposition of Pou5f1b, Znf428, Prmt3, Znf12, Erg, Tfdp1, Foxm1, and Cenpa as new drug targets in drug development that can be applied in different cancer types.