Current Issues in Molecular Biology最新文献

Despite advances in cancer treatment, breast cancer (BC) remains one of the most common cancers affecting women worldwide. This study aimed to determine serum circFBXW7, circABCB10, and circ0103552 levels and compare BC patients and healthy controls to investigate their roles in the molecular mechanism of BC and the significance of these circRNAs in BC diagnosis. The study group consisted of 92 patients with BC and 31 healthy controls. Total RNA was isolated from serum samples. Following total RNA, complementary DNA was synthesized from this material. Following complementary DNA analysis, the circRNA levels were analyzed by the qRT-PCR method. Expression levels were evaluated in ΔCt values. High ΔCt values of circFBXW7 and circ0103552 and low ΔCt values of circABCB10 were correlated with BC diagnosis (circFBXW7, p = 0.043, r = 0.183, circ0103552, p < 0.001, r = 0.321, circABCB10, p = 0.001, r = -0.291). According to Fold Change (FC) values, circFBXW7 (FC = 0.30) and circ0103552 (FC = 0.26) showed low expression in the patient group compared to the control group, while circABCB10 (FC = 11.09) showed high expression (p < 0.05, for all comparisons). We think that our study is one of the rare studies investigating the relationship between BC and serum circRNA levels. This study concludes that the significant downregulation of circFBXW7 and circ0103552 and the upregulation of circABCB10 are directly related to the diagnosis of BC and can be used for diagnosis, but further studies are needed to elucidate the molecular mechanism of the relationship between circRNAs and BC.

Glioblastoma multiforme (GBM) is one of the most aggressive and difficult-to-treat brain tumors, with a poor prognosis due to its high resistance to conventional therapies. Current treatment options, including surgical resection, radiotherapy, and chemotherapy, have limited effectiveness in improving long-term survival. Despite the emergence of new therapies, monotherapy approaches have not shown significant improvements, highlighting the need for innovative therapeutic strategies. Combination therapies appear to be the most promising solution, as they target multiple molecular pathways involved in GBM progression. One area of growing interest is the incorporation of phytotherapy and micotherapy as complementary treatments, which offer potential benefits due to their anti-tumor, anti-inflammatory, and immunomodulatory properties. This review examines the current challenges in GBM treatment, discusses the potential of combination therapies, and highlights the promising role of phytotherapy and micotherapy as integrative therapeutic options for GBM management.

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Quantitative real-time PCR (qRT-PCR) is an essential tool for analyzing and selecting stable reference genes. In order to screen for suitable reference genes under high-temperature stress conditions in Arabidopsis, this study measured the relative expression levels of 17 candidate reference genes using qRT-PCR. Among these, four are traditional reference genes, while the remaining thirteen are candidate reference genes with no previous reports on their use as reference genes. The expression stability of the candidate reference gene expression was analyzed and evaluated using five methods: ΔCt, geNorm, NormFinder, BestKeeper, and RefFinder. The results indicated that the LHCB4.1 and LHCB5 genes displayed the highest stability in expression under high-temperature stress conditions. To verify the stability of the reference genes, we treated Arabidopsis with high-temperature stress, used the selected LHCB4.1 and LHCB5 as references, and analyzed the expression of the heat-responsive gene HSFA2 using qRT-PCR. The results showed that when LHCB4.1 and LHCB5 were used individually or in combination as reference genes, the relative expression of HSFA2 significantly increased and remained consistent under high-temperature treatment. This indicates that both LHCB4.1 and LHCB5 are suitable reference genes for qRT-PCR analysis in Arabidopsis exposed to high-temperature stress. The novel reference genes identified in this study will serve as a reliable reference standard for gene expression studies in Arabidopsis under high-temperature stress, thereby enhancing the accuracy and comparability of experimental data.

Hepatitis, a significant medical concern owing to its potential to cause acute and chronic liver disease, necessitates early intervention. In this study, we aimed to elucidate the histopathological features of lipopolysaccharide-induced hepatitis in mice, focusing on tissue alterations. The results demonstrated that hepatocytes exhibited decreased eosin staining, indicating cellular shrinkage, whereas sinusoids were swollen with blood cells. Detailed electron microscope analysis identified these blood cells as leukocytes and erythrocytes, which confirmed a thrombus formation within the liver. Pre-treatment with aspirin significantly attenuated these pathological changes, including reductions in inflammatory markers such as C-reactive protein, interleukin-1β, and tumor necrosis factor-alpha. These findings highlight aspirin's anti-inflammatory and antiplatelet effects in mitigating liver inflammation and thrombus formation. In this study, we highlighted the potential of aspirin as a therapeutic agent for liver inflammation, in addition to providing insights into hepatocyte alterations and sinusoidal blood cell aggregation in liver inflammation. Aspirin, through the protection of endothelial cells and reduction of cytokine levels, may have broader applications in managing liver disease and other systemic inflammatory conditions. This emphasizes its value in prevention and therapy.

The kidney plays an essential role in the proper homeostasis of glucose. In the kidney, glucose transport is carried out across cell membranes by two families of glucose transporters-facilitated diffusion glucose transporters (GLUTs) and Na(+)-dependent glucose co-transporters (SGLT family). Among the transporters, sodium-dependent glucose co-transporters play a major role in the kidney's ability to reabsorb glucose. Although the localization of glucose transporters has been extensively studied in mammals, there are still knowledge gaps regarding the localization of SGLTs in birds. The aim of this research was to conduct a comparative study of the immunolocalization of the sodium-dependent glucose co-transporters SGLT1 and SGLT2 in the kidneys of healthy and T-2-mycotoxicated chickens. Immunohistochemical staining was carried out using the polyclonal primary antibodies SGLT1 and SGLT2 (Abcam, UK) in kidney tissue derived from seven healthy and seven T-2-mycotoxicated 7-day-old female layer-type Ross chickens (Gallus gallus domesticus). The sections were stained using an immunohistochemistry kit (Abcam, UK). In the kidneys of the healthy birds, strong staining of SGLT1 and SGLT2 was observed in the cytoplasm of the epithelial cells of the proximal straight and convoluted tubules. In the kidneys of the birds of the T-2 toxin group, weak expression of SGLT1 and SGLT2 with morphological changes occurred, indicating reduced glucose transport in the urinary system during T-2 mycotoxicosis.

Dendrobium devonianum is an important medicinal plant, rich in flavonoid, with various pharmacological activities such as stomachic and antioxidant properties. In this study, we integrated metabolome and transcriptome analyses to reveal metabolite and gene expression profiles of D. devonianum, both green (GDd) and purple-red (RDd) of semi-annual and annual stems. A total of 244 flavonoid metabolites, mainly flavones and flavonols, were identified and annotated. Cyanidin and delphinidin were the major anthocyanidins, with cyanidin-3-O-(6″-O-p-Coumaroyl) glucoside and delphinidin-3-O-(6″-O-p-coumaroyl) glucoside being the highest relative content in the RDd. Differential metabolites were significantly enriched, mainly in flavonoid biosynthesis, anthocyanin biosynthesis, and flavone and flavonol biosynthesis pathways. Transcriptomic analysis revealed that high expression levels of structural genes for flavonoid and anthocyanin biosynthesis were the main reasons for color changes in D. devonianum stems. Based on correlation analysis and weighted gene co-expression network analysis (WGCNA) analysis, CHS2 (chalcone synthase) and UGT77B2 (anthocyanidin 3-O-glucosyltransferase) were identified as important candidate genes involved in stem pigmentation. In addition, key transcription factors (TFs), including three bHLH (bHLH3, bHLH4, bHLH5) and two MYB (MYB1, MYB2), which may be involved in the regulation of flavonoid biosynthesis, were identified. This study provides new perspectives on D. devonianum efficacy components and the Dendrobium flavonoids and stem color regulation.

Objectives: Dental bone formation involves various cellular and molecular mechanisms, and phytoestrogens such as formononetin (FORM) are promising because of their estrogenic, anti-inflammatory, and antioxidant effects. This study investigated the effect of FORM on osteoblast proliferation, differentiation, and mineralization in combination with spongiosa granulates (BO) in vitro.

Materials and methods: Human fetal osteoblast cells (hFOB1.19) were treated with increasing concentrations of FORM (1, 10, and 100 µg/mL), BO, or their combination. Cell proliferation was assessed using a MTT assay. Alkaline phosphatase (ALP) activity, intracellular Ca²⁺, and Pi levels were measured using ELISA. Vascular endothelial growth factor (VEGF) and osteocalcin expression levels were analyzed by western blotting.

Results: Cell proliferation increased with FORM, with or without BO, after 6 days (p < 0.001). FORM and BO had a synergistic effect on ALP activity (p < 0.001). Intracellular Ca²⁺ and Pi levels were highest in the BO-FORM group, suggesting superior mineralization (p < 0.05). VEGF and osteocalcin expression was significantly upregulated with FORM, alone and with BO (p < 0.05), indicating improved angiogenesis and bone maturation over 9 days.

Conclusions: FORM enhances osteoblast proliferation, differentiation, and mineralization potential, particularly in BO spongiosa granulates. These data support the in vitro potential of formononetin-phytoestrogen in promoting osteoblast differentiation and mineralization potential with BO. These findings suggest that FORM, combined with BO, could improve bone augmentation in clinical applications such as maxillofacial surgery. FORM shows valuable potential for clinical applications, such as maxillofacial surgery, by promoting faster and more effective healing.

Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC). The distinction is essential for offering to patients a conservative treatment compared to the radical management required for endometrial cancer, a critical issue for the significant physical and psychological consequences that one procedure or another can have on women's health. We performed a meta-analysis of the immunohistochemical markers used for the histological diagnosis of APA, comparing it with our case study. The evaluated markers were beta-catenin, h-caldesmon, desmin, vimentin, smooth muscle alpha-actin, CD10, Ki67, estrogen receptor (ER), progesterone receptor (PR), pan-cytokeratin, PTEN, PMS2, MSH2, MSH6, p53, MLH1, and p16. Discrepancies were observed in the expression of CD10, h- caldesmon, and p16 when comparing APA with EC. The results of the case evaluated by our team showed beta-catenin nuclear expression and positive immunostaining for pan-cytokeratin, ER, and PR in the glands; smooth muscle actin and desmin positive expression in stromal muscle; and p16 positive immunostaining in squamous morules. Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology.

The development of anticancer diagnostic and therapeutic strategies is of crucial importance to improve efficacy and therapeutic specificity. Here, we describe the synthesis and characterization of fluorescent self-assembling nanomicelles (NMs) based on a biocompatible polysaccharide (cellulose, CE) functionalized with a tetraphenyl ethylene derivative (TPEHy) and loaded with Doxorubicin (DOX) with aggregation-induced emission (AIE) properties and pH-dependent drug release. We obtained CE-TPEHy-NMs with an average diameter of 60 ± 17 nm for unloaded NMs and 86 ± 25 nm for NMs loaded with DOX, respectively. Upon testing different conditions, we obtained an encapsulation efficiency of 86% and a loading capacity of 90%. A controlled dialysis experiment showed that the release of DOX after 48 h is minimal at pH 7.4 (11%), increasing at pH 6.5 (50%) and at its maximum at pH 4.5 (80%). The cytotoxicity of blank and loaded CE-TPEHy-NMs at increasing concentrations and different pH conditions was tested on a MG-63 human osteosarcoma cell line. Based on viability assays at pH 7.4, neither unloaded nor loaded CE-TPEHy-NMs exerted any inhibition on cell proliferation. At pH 6.5, proliferation inhibition significantly increased, confirming the pH-dependent release. We characterized and studied the performance of CE-based amphiphilic, biocompatible NMs for controlled drug release in acidic conditions, such as tumor microenvironments. Further studies are required to optimize their synthesis process and to validate their antitumoral properties in vivo.