Vol 27, No 8 (2024)
- Year: 2024
- Articles: 12
- URL: https://gynecology.orscience.ru/1386-2073/issue/view/10074
Chemistry
Traditional Uses, Phytochemical Constituents and Ethnopharmacological Properties of Mistletoe from Phoradendron and Viscum Species
Abstract
Plants from the genus Phoradendron and Viscum, also known as American and European mistletoe, are a group of hemiparasitic plants traditionally used to treat many diseases. Mistletoes have a rich content of natural compounds like terpenes, alkaloids, proteins, and phenolic compounds associated with their potential medicinal properties. In this sense, mistletoes have shown antiproliferative, antioxidant, anti-inflammatory, and antimicrobial activity, which has been attributed to their phytochemical constituents. The mechanisms in which mistletoe plants act vary and depend on their phytochemical content and distribution, which in part will depend on the mistletoe species. In this sense, recent literature research is needed to visualize state of the art in the ethnopharmacological potential of mistletoe. Thus, this literature review aims to systematically report recent studies (2010-2023) on the phytochemical characterization and bioactive studies of mistletoe plants, mainly the Viscum and Phoradendron genera. We gather recent information of 140 references selected in our research. Here we report that although there are several bioactivity studies of mistletoe species, bioavailability studies are still scarce, and the precise mechanisms of action are not fully known. We encourage that further studies include a systematic strategy to cover these areas of opportunity.
1093-1110
Development and Validation of a Risk Prediction Algorithm for Evaluating the Efficacy of Postoperative Adjuvant TACE Therapy for Hepatocellular Carcinoma
Abstract
Background and Purpose:There is a lack of a reliable outcome prediction model for patients evaluating the feasibility of postoperative adjuvant transarterial chemoembolization (PATACE) therapy. Our goal was to develop an easy-to-use tool specifically for these patients
Methods:From January 2013 to June 2017, patients with hepatocellular carcinoma from the Liver Center of the First Affiliated Hospital of Chongqing Medical University received postoperative adjuvant Transarterial chemoembolization (TACE) therapy after liver cancer resection. A Cox proportional hazards model was established for these patients, followed by internal validation (enhanced bootstrap resampling technique) to further evaluate the predictive performance and discriminanceevaluate the predictive performance and discriminance, and compare it with other predictive models. The prognostic factors considered included tumour number, maximum tumor diameter, Edmondson-Steiner (ES) grade, Microvascular invasion (MVI) grade, Ki67, age, sex, hepatitis B surface antigen, cirrhosis, Alpha-fetoprotein (AFP), Albumin-bilirubin (ALBI) grade, Childpugh grade, body mass index (BMI), Neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR).
Results:The endpoint of the study was overall survival. The median overall survival was 36 (95%CI: 34.0-38.0) months, with 1-year, 2-year and 3-year survival rates being 96.3%, 84.0% and 75.3%, respectively. Tumour number, MVI grade, and BMI was incorporated into the model, which had good differentiation and accuracy. Internal validation (enhanced bootstrap) suggested that Harrells C statistic is 0.72. The model consistently outperforms other currently available models.
Conclusion:This model may be an easy-to-use tool for screening patients suitable for PA-TACE treatment and guiding the selection of clinical protocols. But further research and external validation are required.
1111-1118
DOCK4 is a Novel Prognostic Biomarker and Correlated with Immune Infiltrates in Colon Adenocarcinoma
Abstract
Background:Dedicator for cytokinesis 4 (DOCK4) is a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. However, the functions of DOCK4 concerning the tumor microenvironment (TME) in colon adenocarcinoma (COAD) remain uncertain.
Methods:The TIMER and GEPIA databases were used to analyze the DOCK4 expression between COAD tissues and adjunct normal tissues. The PrognoScan database was used to assess the prognosis of DOCK4 expression in COAD. The co-expression networks of DOCK4 in COAD were constructed by the LinkedOmics website. Furthermore, the correlation between DOCK4 expression and TME of COAD was explored using TIMER and TISIDB databases. Finally, the clone formation assay was used to further verify the function of DOCK4 in COAD. The Western blotting assay was used to confirm the mechanism related to DOCK4 in COAD.
Results:The DOCK4 expression was different significantly in COAD tissues and paracancerous tissues. The DOCK4 was found to play a poor role in the prognosis of patients with COAD. The DOCK4 was found to participate in the TME by promoting immune evasion of COAD. The reduction of DOCK4 expression inhibited the clone formation and Ras-associated protein 1A (Rap1A) expression of HCT116 cells.
Conclusions:DOCK4 potentially plays an important role in the regulation of TME in COAD. DOCK4 facilitates the development through the Rap1A pathway, thus becoming a novel prognostic biomarker in COAD.
1119-1130
MiR-301b-3p can be used as a Potential Marker for the Diagnosis of Lung Adenocarcinoma
Abstract
Background:The involvement of aberrantly expressed miR-301b-3p has been discovered in diverse human tumors. Our study was primarily centered around the role of miR-301b-3p in diagnosing lung adenocarcinoma (LUAD).
Method:We used the TCGA database to download the TCGA-LUAD dataset and selected miR- 301b-3p as the object of our study by differential expression analysis of miRNAs combined with previous studies. The LUAD diagnostic model was constructed utilizing machine learning based on miR-301b-3p expression. The predictive performance of the diagnostic model was found to be excellent by ROC curves combined with the clinical information of the dataset samples. GSEA, GO, and KEGG enrichment analyses demonstrated that miR-301b-3p may mediate the cell cycle by regulating the expression of hormones. Subsequently, combined with tumor immunity and mutation analysis, it was found that patients in the low-expression group had better immune infiltration, indicating that their response rate to immunotherapy may be relatively high. Finally, a mouse xenograft model was constructed to verify how miR-301b-3p affected LUAD progression in mice.
Result:The results illustrated that overexpressed miR-301b-3p could cause faster tumor growth in mice. On the contrary, the growth of LUAD could be impeded by the downregulated miR-301b-3p expression. It was suggested that miR-301b-3p had a crucial part in LUAD progression.
Conclusion:Overall, the diagnostic performance of the LUAD diagnostic model constructed based on miR-301b-3p is great, and the model can be used as a potential diagnostic marker for LUAD to provide new ideas for clinical diagnosis.
1131-1139
Downregulation of miR-4284 can Inhibit the Apoptosis of Human Arterial Smooth Muscle Cells (HASMCs) in Arteriosclerosis Obliterans (ASO)
Abstract
Introduction:The disease arteriosclerosis obliterans (ASO) affects the lower extremities. ASO's mechanism involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The miR-4284 is involved in several biological processes of the cardiovascular system, including VSMC proliferation, migration, and death. However, it is unknown if the miR-4284 gene is involved in the control of ASO. Furthermore, the molecular processes behind the contribution of human arterial smooth muscle cells (HASMCs), one of the most significant components of the arterial wall, to arteriosclerosis obliterans (ASO) pathogenesis remain unknown. Previously, we explored the alterations of miRNAs in the blood of ASO patients, and now we wanted to test further whether these changes also take place in the HASMCs that are responsible for the pathogenesis of ASO.
Methods:The expression levels of miR-29a in arterial walls were analyzed via a real-time polymerase chain reaction. An ASO cell model was established to investigate the expression of miR- 4284 on HASMCs. The Transwell system and CCK-8 detection were used to assess the migration and proliferation of HASMCs. The proportion of apoptotic cells as well as the concentrations of apoptotic signal protein production were assessed using flow cytometry. A Western blot technique was used to identify B cell lymphoma-2 (Bcl2), Bcl2-associated X protein (BAX), as well as Xlinked inhibitors of apoptosis protein (XIAP).
Results:The results showed that PCR confirmed that the qualified production or expression of miR-4284 was significantly reduced in HASMCs after they were cultured without FBS and in an atmosphere of 1% O2 + 5% CO2 + 94% N2 and that glucose had no effect on its expression. MiR- 4284 has no effect on migration and proliferation, but downregulation of miR-4284 can decrease the apoptotic rate of HASMCs, as revealed by flow cytometry. Furthermore, western blot experiments showed that the expression of BAX was low, while the expression of the other two proteins, viz., Bcl2 and XIAP, was over-expressed.
Conclusion:We found that miR-4284 downregulation enhanced Bcl2, as well as XIAP, and decreased Bax. This shows that downregulated miR-4284 regulates apoptosis-related protein expression in HASMCs. The mechanism is not clear, and we need further study to confirm it.
1140-1148
Clinical Analysis of Bacterial Infection Characteristics in Lymphoma Patients with High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation-A Single-Centered Retrospective Study
Abstract
Background:High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.
Objective:To characterise pathogenic bacterial infections in HDT/AHSCT-treated lymphoma patients. The prevalence of pathogenic microorganisms and the timing of foci after transplantation, along with bloodstream infection (BSI) risk factors, can help determine the need for empirical antibiotics after AHSCT.
Methods:We retrospectively analyzed 133 lymphoma patients treated by HDT/AHSCT from April 2017 to October 2021 at Peking University International Hospital, Beijing, China. We analyzed their clinical characteristics, microbiological distribution characteristics, and BSI risk factors in detail.
Results:In order, intestinal infection (56 cases), BSI (17 cases), pulmonary (12 cases), upper respiratory tract (5 cases), and perianal (4 cases) were the most common locations of infection after HDT/AHSCT. The infection sites yielded 92 putative pathogenic pathogens, with bacteria predominating (61.96%), fungi (28.26%), viruses (5.43%), and mycoplasma (4.35%). Gram-negative bacteria (GNB) strains outnumbered gram-positive bacteria (GPB) strains (73.68%). Two strains of Escherichia coli produced extended-spectrum β-lactamase (ESBL) and one strain of carbapenem-resistant enterobacteriaceae (CRE). Methicillin-resistant Staphylococcus epidermidis (MRSE) had one strain. BSI was caused by Escherichia coli (82.35%), Intestinal mucositis (23.52%), and catheter-associated infections (11.76%). Age, CD34, pretreatment regimen, antibiotic regimen, and past chemotherapeutic agent lung damage were BSI risk variables in univariate analysis. CD34 and past chemotherapeutic drug lung damage were the primary causes of BSI after HDT/AHSCT for lymphoma.
Conclusion:High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.
1149-1160
Machine Learning-derived Multi-omics Prognostic Signature of Pyroptosis-related lncRNA with Regard to ZKSCAN2-DT and Tumor Immune Infiltration in Colorectal Cancer
Abstract
Background:Colorectal cancer (CRC) has become the most prevalent gastrointestinal malignant tumor, ranking third (10.2%) in incidence and second (9.2%) in death among all malignancies globally. The most common histological subtype of CRC is colon adenocarcinoma (COAD), although the cause of CRC remains unknown, as there are no valid biomarkers.
Methods:A thorough investigation was used to build a credible biomolecular risk model based on the pyroptosis-associated lncRNAs discovered for COAD prediction. Furthermore, Cibersort and Tumor Immune Dysfunction and Exclusion (TIDE), the methods of exploring tumor immune infiltration, were adopted in our paper to detect the effects of differential lncRNAs on the tumor microenvironment. Finally, quantitative real-time polymerase chain reaction (qPCR), as the approach of exploring expressions, was utilized on four different cell lines.
Results:Seven pyroptosis-related lncRNAs have been identified as COAD predictive risk factors. Cox analysis, both univariate and multivariate, revealed that the established signature might serve as a novel independent factor with prognostic meaning in COAD patients. ZKSCAN2-DT was shown to be considerably overexpressed in the COAD cell line when compared to normal human colonic epithelial cells. Furthermore, ssGSEA analysis results revealed that the immune infiltration percentage of most immune cells dropped considerably as ZKSCAN2-DT expression increased, implying that ZKSCAN2-DT may play an important role in COAD immunotherapy.
Conclusion:Our research is the first to identify pyroptosis-related lncRNAs connected with COAD patient prognosis and to construct a predictive prognosis signature, directing COAD patient prognosis in therapeutic interventions.
1161-1174
Screening of Immune-related lncRNAs in Lung Adenocarcinoma and Establishing a Survival Prognostic Risk Prediction Model
Abstract
Objective:This study aimed to improve lung adenocarcinoma (LUAD) prognosis prediction based on a signature of immune-related long non-coding RNAs (lncRNAs).
Methods:LUAD samples from the TCGA database were divided into the immunity_H group and the immunity_L group. Differentially expressed RNAs (DERs) between the two groups were identified. Optimized immune-related lncRNAs combination was obtained using LASSO Cox regression. A prognostic risk prediction (RS) model was built and further validated in the training and validation datasets. A network among lncRNAs in the RS model, their co-expressed DERs, and the related KEGG pathways were established. Critical lncRNAs were validated in LUAD tissue samples.
Results:In total, 255 DERs were obtained, and 11 immune-related lncRNAs were significantly related to prognosis. Six lncRNAs were demonstrated as an optimal combination for building the RS model, including LINC00944, LINC00930, LINC00607, LINC00582, LINC00543, and LINC00319. The KM curve and ROC curve revealed the RS model to be a reliable indicator for LUAD prognosis. LINC00944 and LINC00582 showed a co-expression relationship with the MS4A1. LINC00944, LINC00582, and MS4A1 were successfully validated in LUAD samples.
Conclusion:We have established a promising LUAD patient survival prediction model based on six immune-related lncRNAs. For LUAD patients, this prognostic model could guide personalized treatment.
1175-1190
Identifying Oxidative Stress-Related Genes (OSRGs) as Potential Target for Treating Periodontitis Based on Bioinformatics Analysis
Abstract
Background:Periodontitis (PD) is a multifactorial inflammatory disease that is closely associated with periodontopathic bacteria. Numerous studies have demonstrated oxidative stress (OS) contributes to inflammation and is a prime factor in the development of PD. It is imperative to explore the function of newly discovered hub genes associated with OS in the advancement of PD, thereby identifying potential targets for therapeutic intervention.
Objectives:The goal of the current study was to identify the oxidative-stress-related genes (OSRGs) associated with periodontitis (PD) development using an integrated bioinformatics method.
Methods:DEGs from GEO gene-expression data were identified using the \"limma\" package. We obtained OSRGs from GeneCards and utilized a Venn diagram to uncover differentially expressed OSRGs (DEOSRGs). After receiving the DEOSRGs, we employed Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analytical tools to examine their possible functions and pathways in PD. Receiver operating characteristic (ROC) curves screened for hub genes of PD. RT-qPCR and western blot analysis were used to detect DEOSRG expression in mouse ligature-induced periodontitis gingival tissues.
Results:The investigation identified 273 OSRGs. Based on PPI analysis, we recognized 20 OSRGs as hub genes. GO and KEGG enrichment analysis indicated that these hub genes were predominantly enriched in leukocyte migration, lymphocyte proliferation, and humoral immune response, and associated with leukocyte trans-endothelial migration, cytokine-cytokine receptor interaction, and NF-κB signaling pathway. Following ROC analysis, VCAM1, ITGAM, FCGR3A, IL1A, PECAM1, and VCAM1were identified as PD prognostic gene. RT-qPCR and western blot analyses confirmed that the expression ITGAM, FCGR3A, and PECAM1 were significantly elevated in the gingival tissues obtained from mice.
Conclusion:This investigation revealed that ITGAM, FCGR3A, and PECAM1 may have a crucial function in the advancement of PD.
1191-1204
A Novel Natural Killer Cell-related Gene Signature for Improving the Prediction of Prognosis and Immunotherapy Response in Bladder Cancer
Abstract
Background:Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA.
Methods:We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment.
Results:We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells.
Conclusion:To sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.
1205-1221
Lncrna CASC15 Activated By TCF12 Promote Colorectal Cancer Progression via EMT
Abstract
Background:Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors.
Objective:Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC.
Methods:Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT).
Results:We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression.
Conclusion:Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.
1222-1230
LncRNA LINC00847 Accelerates Melanoma Progression by Regulating MiR-133a-3p/TGFBR1 Axis
Abstract
Aims:Growing evidence has suggested that lncRNAs play a regulatory role in tumorigenesis. Dysregulation of a newly identified lncRNA (LINC00847) has been involved in several tumors. Nevertheless, the expression and roles of lncRNAs in skin melanoma remain unclear. Therefore, we attempted to investigate the expressions and roles of lncRNAs in this study.
Materials and Methods:Expression levels of LINC00847 were quantified in tissue samples from the TCGA database and clinically recruited participants. LINC00847 was inhibited in cells by transfecting with si-LINC00847 or si-NC. Expressions of LINC00847 and miR-133a-3p were determined using RT-qPCR, and the TGFBR1 level was determined using Western blotting. Targeting sites of LINC00847 with miR-133a-3p and miR-133a-3p with TGFBR1 were predicted by bioinformatic tools and proved by dual-luciferase reporter system and RNA immunoprecipitation. Cell proliferation, invasion, and migration abilities were assessed using CCK8, cell colony formation, cell wound scratch, and transwell assay, respectively.
Results:In both TCGA and clinical cohorts, the expression of LINC00847 was abnormally upregulated in skin melanoma tissues than that of benign nevus. Besides, LINC00847 expression increased more markedly in A375 and SK-MEL-28 cells than in normal epidermal melanocytes (HEMa-LP cells). LINC00847 knockdown remarkably restrained skin melanoma cell proliferation, metastasis, and wound healing rate. Furthermore, miR-133a-3p/TGFBR1 was the downstream target for LINC00847. LINC00847 negatively regulated miR-133a-3p expression in skin melanoma cells. Both miR-133a-3p inhibitors and TGFBR1 vector transfection reversed the effect of LINC00847 silence in skin melanoma cells.
Conclusion:LINC00847 was highly expressed in skin melanoma, and its overexpression accelerated the malignant tumor behavior of skin melanoma cells. The miR-133a-3p /TGFBR1 axis was involved in the roles of LINC00847 in skin melanoma.
1231-1241