Abstract:According to the classification presented by Lehmann BD (2016), triple-negative breast cancer (TNBC) is a heterogeneous group of malignant tumors with four specific subtypes: basal-like (subtype 1 and subtype 2), mesenchymal, and luminal androgen receptor (LAR) subtypes. The basal-like subtypes of carcinomas predominate in this group, accounting for up to 80% of all cases. Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile, such tumors are characterized by aggressive biological behavior. To this end, the LAR subtype is of particular interest, since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis. This review is devoted to the analysis of the relevant literature, reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.
Keywords:Luminal androgen receptor (LAR) subtype;Triple-negative breast cancer (TNBC);Androgen receptor (AR);Prognosis
Abstract:Stroke has a high incidence and disability rate, and rehabilitation is an effective means to reduce the disability rate of patients. To systematize rehabilitation assessment, which is the foundation for rehabilitation therapy, we summarize the assessment methods commonly used in research and clinical applications, including the various types of stroke rehabilitation scales and their applicability, and related biomedical detection technologies, including surface electromyography (sEMG), motion analysis systems, transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), and combinations of different techniques. We also introduce some assessment techniques that are still in the experimental phase, such as the prospective application of artificial intelligence (AI) with optical correlation tomography (OCT) in stroke rehabilitation. This review provides a useful bibliography for the assessment of not only the severity of stroke injury, but also the therapeutic effects of stroke rehabilitation, and establishes a solid base for the future development of stroke rehabilitation skills.
Abstract:Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system (UPS), heat shock protein 27 (Hsp27), and chaperone-mediated autophagy (CMA). Its structure contains three α-helices and eleven β-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B (MsrB) and mammalian suppressor of Sec4 (Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor (GEF) activity on small guanosine triphosphatase (GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain (Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog (Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament (MF) and microtubule (MT) proteins and inducing the epithelial-mesenchymal transition (EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival; meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.
Keywords:Translationally controlled tumor protein (TCTP);Invasion;Migration;Cancer;Clinical drugs
Abstract:The global outbreak of the coronavirus disease 2019 (COVID-19) led to the suspension of most treatments with assisted reproductive technique (ART). However, with the recent successful control of the pandemic in China, there is an urgent public need to resume full reproductive care. To determine whether the COVID-19 pandemic had any adverse effects on female fertility and the pregnancy outcomes of women undergoing ART, a systematic review and meta-analysis was conducted using the electronic Chinese and English databases. Dichotomous outcomes were summarized as prevalence, and odds ratios (ORs) and continuous outcomes as standardized mean difference (SMD) with 95% confidence interval (CI). The risk of bias and subgroup analyses were assessed using Stata/SE 15.1 and R 4.1.2. The results showed that compared with women treated by ART in the pre-COVID-19 time frame, women undergoing ART after the COVID-19 pandemic exhibited no significant difference in the clinical pregnancy rate (OR 1.07, 95% CI 0.97 to 1.19; I2=0.0%), miscarriage rate (OR 0.95, 95% CI 0.79 to 1.14; I2=38.4%), embryo cryopreservation rate (OR 2.90, 95% CI 0.17 to 48.13; I2=85.4%), and oocyte cryopreservation rate (OR 0.30, 95% CI 0.03 to 3.65; I2=81.6%). This review provided additional evidence for gynecologists to guide the management of women undergoing ART treatment during the COVID-19 pandemic timeframe.
Abstract:Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%‒15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2 (BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL; however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase (HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.
Keywords:Diffuse large B-cell lymphoma (DLBCL);Histone deacetylase (HDAC) inhibitor;Venetoclax;MYC;BCL2;TP53
Abstract:ObjectiveTo determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.MethodsThe predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-α (PFT-α) and GSK690693 for further investigation.ResultsThe 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.ConclusionsCurcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
Keywords:Curcumin;Network pharmacology;p53;Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK);Apoptosis;Autophagy