Despite great progress in clinical treatment, cancer remains a serious health problem contributing to significant morbidity and mortality worldwide. Although chemotherapy is a common therapeutic ...measure, multidrug resistance (MDR) presents a major challenge that often leads to poor prognosis. The abnormal expression of glycosyltransferases (GTs) leading to aberrant glycosylation patterns are considered a marker of cancer. Furthermore, the biosynthesis of these glycoconjugates has been associated with tumor proliferation, invasion and metastasis. Recently, studies have found that GTs are involved in mediating MDR in cancer cells through complex mechanisms and can influence therapeutic effect. In this review, we focus on several types of cancers and summarize previous studies on the correlation between GTs and MDR.
•Descripted the glycosylation process.•Summarized the main glycosyltransferases.•Summarized the researches about the glycosyltransferases and multidrug resistance in cancer.•Provided the theoretical basis for clinical cancer chemotherapy.
Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using ...individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same time-scale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
Poly(ADP-ribose)polymerase (PARP) is a significant therapeutic target for the treatment of numerous human diseases. Olaparib has been approved as a PARP inhibitor. In this paper, a series of new ...compounds were designed and synthesized with Olaparib as the lead compound. In order to evaluate the inhibitory activities against PARP1 of the synthesized compounds, in vitro PARP1 inhibition assay and intracellular PARylation assay were conducted. The results showed that the inhibitory activities of the derivatives were related to the type of substituent and the length of alkyl chain connecting the aromatic ring. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)-based assay also proved that these compounds demonstrating strong inhibition to PARP1 also have high anti-proliferative activities against BRCA2-deficient cell line (Capan-1). Analysis of the entire results suggest that compound 23 with desirable inhibitory efficiency may hold promise for further in vivo exploration of PARP inhibition.
Recently, the matrix information geometry (MIG) detector, which characterizes sample data as a Hermitian positive definite (HPD) matrix located on the HPD manifold, was rapidly developed and ...demonstrated extraordinary performance in numerous applications, especially in heterogeneous clutter backgrounds. In this article, the geodesic normal coordinate (GNC)-based manifold filter is proposed to improve the detection performance of the MIG detector in strong clutter backgrounds. Using the GNC system, the distribution of target echoes and clutter on the high-dimensional manifold can be visualized and analyzed. Moreover, by exploiting the information concerning the distribution of matrices, the manifold filter is proposed to enhance target echoes and suppress strong clutter. Then, the manifold-filter-based MIG detector is designed, and its superiority is theoretically analyzed. The actual clutter data are utilized to verify the effectiveness of the proposed method. The results show that the proposed manifold filter achieves a signal-to-clutter ratio improvement of more than 5 dB over the existing MIG detectors.
Clutter suppression in heterogeneous environments is a serious challenge for airborne radar. To address this problem, a matrix-manifold-based clutter suppression method is proposed. First, the ...distributions of training data in heterogeneous environments are analyzed, while the received data are characterized on a Riemannian manifold of Hermitian positive definite matrices. It is indicated that the training data with different distributions with the same power are separated, whereas data with the same distribution are closer together. This implies that the underlying geometry of the data can be better revealed by manifolds than by Euclidean space. Based on these properties, homogeneous training data are selected by establishing a binary hypothesis test such that the negative effects of the use of heterogeneous samples are alleviated. Moreover, as exploiting a geometric metric on manifolds to reveal the underlying information of data, experimental results on both simulated and real data validate that the proposed method has a superior performance with small sample support.
Abstract Background Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. ...While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. Methods In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. Results Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1 , a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. Conclusions Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.
Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of ...patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles.
This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy.
Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline.
T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Copy number alteration (CNA) is a major contributor to genome instability, a hallmark of cancer. Here, we studied genomic alterations in single primary tumor cells and circulating tumor cells (CTCs) ...from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the
gene and the
gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions. Integrative CNA analyses of 97 CTCs from 23 patients confirmed the convergence of CNAs and revealed single, concurrent, and mutually exclusive CNAs that could be the driving events in cancer metastasis.
Aim
Pre‐eclampsia (PE) is the usual complication during pregnancy. Long noncoding RNAs are essential regulatory factors in many diseases. Nevertheless, the role of LINC00511 in the development of PE ...has not been fully elucidated.
Methods
The expression of LINC00511, homeobox protein A7 (HOXA7) and miR‐31‐5p was determined by quantitative real‐time polymerase chain reaction. The levels of HOXA7 protein and autophagy‐related proteins were measured by western blot analysis. Besides, cell proliferation was evaluated using cell counting kit 8 and colony formation assays. The apoptosis and invasion of cells were detected via flow cytometry and transwell assay, respectively. Further, the interaction between miR‐31‐5p and LINC00511 or HOXA7 was confirmed by dual‐luciferase reporter assay.
Results
The LINC00511 and HOXA7 expression levels were decreased in placental tissues of PE patients, and the expression levels of both were positively correlated. LINC00511 knockdown suppressed proliferation, invasion and autophagy, while enhanced apoptosis in trophoblast cells. Meanwhile, the elevated HOXA7 expression promoted proliferation, invasion, autophagy, and inhibited the apoptosis of trophoblast cells. Besides, overexpression of HOXA7 also could reverse the effect of LINC00511 knockdown on the biological function of trophoblast cells. Further experiments confirmed that miR‐31‐5p could be sponged by LINC00511 and could target HOXA7. Also, miR‐31‐5p mimic could invert the promoting effect of LINC00511 overexpression on the biological function of trophoblast cells.
Conclusion
LINC00511 expression was crucial for maintaining the normal function of trophoblast cells, and the decreased its expression might promote the progress of PE, which might provide some theoretical strategies for reducing the development of PE.
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