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Abstract Background Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is a common, yet highly efficient, cellular immunotherapy for lymphoma. However, many recent studies have reported on its cardiovascular (CV) toxicity. This study analyzes the cardiotoxicity of CD19 CAR T cell therapy in the treatment of lymphoma for providing a more valuable reference for clinicians. Methods The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The Cochrane Collaboration tool and the Newcastle–Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale. Results A risk analysis of two randomized controlled trials and nine cohort studies, totaling 1379 patients with lymphoma receiving CD19 CAR-T, is conducted. The incidences for all-cause mortality, CV events, and hypotension were found to be 17.8%, 17.8%, and 52.8%, respectively. Additionally, the incidences of heart failure (HF), cardiomyopathy, cardiac arrest, and other CV events are 3%, 0.6%, 1.3%, and 2.5%, respectively. In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as adverse events, patients treated with CD19 CAR T cells are also at risk of CV events. The most common CV events are arrhythmia and HF. Our further analysis showed that the incidence of CV events was 28.7% in the elderly and 13.5% in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant. Furthermore, the incidence of CV events and hypotension is strongly associated with patients with CRS. Conclusion Therefore, clinicians should pay close attention to the occurrence of such CV events and take timely prevention and intervention measures to further improve the safety of CD19 CAR T cell therapy.

BackgroundClinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.MethodsWe retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsWe incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%–96.9%], 50.5% (95% CI, 38.0%–62.9%), 78.8% (95% CI, 53.0%–100%), and 26.0% (95% CI, 7.4%–44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%–84.7%), the CRR was 34.3% (95% CI, 25.9%–42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%–90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%–66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3–5 CRS and ICANS was only 5.4% (95% CI, 2.0%–10.4%) and 3.3% (95% CI, 0.6%–8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3–5 CRS and ICANS was only 1.6% (95% CI, 0.0%–6.5%) and 2.7% (95% CI, 0.7%–6.2%), respectively.ConclusionGPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment.

Abstract Background The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. Methods The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. Results A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups. Conclusions Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Abstract Background 3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs). Methods CCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model. Results Our data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self‐renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability. Conclusions Microserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method.

PurposeTo investigate the efficacy of the application of microecological agents in patients with perioperative colorectal cancer.MethodsThe seven electronic databases including PubMed, Cochrane Library, Excerpt Medica Database (Embase), Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang Database were systematically searched for eligible studies from 2000 to February 2023.ResultsA total of 38 randomized controlled clinical trials were included in this study, with a total of 1765 patients in the microecological preparation group and 1769 patients in the control group. All data were analyzed using Review Manager 5.4 and R 4.2.2 software. Meta-analysis showed that in the perioperative period of colorectal cancer, the microecological agents group reduced patients’ adverse drug reactions, improved intestinal flora with Lactobacillus (SMD, 3.0858, [2.0197; 4.1520], p< 0. 0001), Bifidobacterium (SMD, 2.1551, [1.6145; 2.6956], p< 0.0001) and Escherichia coli (SMD, -1.1393, [-1.6247; -0.6538], p< 0.0001); protection of intestinal mucosal barrier function, endotoxin (SMD, -2.6850 [-4.1399; -1.2301], p=0.0003), DAO (SMD, -2.5916, [-3.4694; -1.7137], p

IntroductionFluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF–TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments.MethodsThis study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting.ResultsAll rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities.DiscussionCurrently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.

IntroductionUltrasound (US) has gained popularity in the evaluation of haemophilic joint diseases because it enables the imaging of soft-tissue lesions in the joints and bone-cartilage lesions. We aimed to determine the correlation between US evaluations and clinical assessments performed using HJHS 2.1 and to evaluate their respective characteristics in assessing early haemophilic arthropathy.MethodsA total of 178 joints (32 knees, 85 elbows, and 61 ankles) in 45 haemophilia A patients (median age, 10 years; range, 6–15) were assessed using US and HJHS 2.1. Ultrasonographic scoring was performed in consensus assessments by one imager by using the US scores.ResultsThe total HJHS 2.1 and US scores showed a strong correlation (rS=0.651, P=0.000, CI: 0.553–0.763), with an excellent correlation for the elbows (rS=0.867, P=0.000, CI: 0.709–0.941) and a substantial correlation for the knees (rS=0.681, P=0.000, CI: 0.527–0.797). The correlation for the ankles was relatively moderate (rS=0.518, P=0.000, CI: 0.308–0.705). Nine subjects (15.5%) without abnormalities, as indicated by HJHS 2.1, showed haemophilic arthropathy in US scoring. All nine joints showed moderate (1/9) to severe (8/9) synovial thickening in the ankle (5/9) and elbow joints (4/9). In contrast, 50 joints (50.5%) showed normal US scores and abnormal changes as indicated by HJHS 2.1. S scores correlated well with HJHS 2.1 for overall and individual joints.DiscussionUS could identify some early pathological changes in joints showing normal clinical findings, but still cannot replace the HJHS; however, it can serve as an imaging examination complementing HJHS 2.

Abstract Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification.Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein–protein interaction (PPI) networks and further screening of core targets.Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that “steroid receptor activity” and the “PI3K/AKT signaling pathway” were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase.Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.

IntroductionAcupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression.MethodsWe searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis.ResultsEleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p < 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43).DiscussionThis study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients’ quality of life.

Abstract Background This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM). Methods We systematically searched PubMed, ScienceDirect, Google Scholar, CNKI, EMBASE, Web of Science, MEDLINE, and the Cochrane Library for studies published from the establishment of the databases to November 2020. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed- or random-effects models. Results We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239 participants) to examine the efficacy of mesenchymal stem cells (MSCs) therapy in the treatment of diabetes mellitus. According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated group was significantly lower than it was at baseline (mean difference (MD) = −1.51, 95% CI −2.42 to −0.60, P = 0.001). The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the control group (SMD = 0.89, 95% CI 0.36 to 1.42, P = 0.001), and their insulin requirement was significantly lower than it was at baseline (SMD = −1.14, 95% CI −1.52 to −0.77, P < 0.00001). Conclusion Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially T1DM, and no obvious adverse reactions.

Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

Abstract Background Colorectal adenocarcinoma (CRA) is one of the leading causes of cancer-related deaths in the world. Long non-coding RNAs (lncRNAs) have been implicated to be effective regulators in the disease course of human cancers, including CRA. Small nucleolar RNA host gene 17 (SNHG17) belongs to lncRNAs, and it has been reported in breast cancer and gastric cancer. However, the function of SNHG17 and its mechanism in CRA progression remain largely unknown. In this study, we attended to shedding some light on the role of SNHG17 in CRA. Methods RT-qPCR was used to assess SNHG17 expression in CRA cells. CCK-8 assay, colony formation and transwell assay were carried out to detect the regulatory effect of SNHG17 silencing on CRA cell proliferation and migration. The angiogenesis of SNHG7-downregulated CRA cells was analyzed by tube formation assay. Mechanism experiments were conducted to identify the interaction between miR-23a-3p and SNHG17 or C-X-C motif chemokine ligand 12 (CXCL12). Results SNHG17 possessed with high expression in CRA cells. Knockdown of SNHG17 caused the inhibition on CRA cell proliferation and migration. SNHG17 promoted CRA cell proliferation and migration by sponging miR-23a-3p to upregulate CXCL12. Conclusion SNHG17 promotes the proliferation and migration of CRA cells by inhibiting miR-23a-3p to modulate CXCL12-mediated angiogenesis.

Background/Aims: Nasopharyngeal carcinoma is a common head and neck cancer in South China and Southeast Asia. Radiotherapy is the standard treatment for nasopharyngeal carcinoma. Accumulating evidence showed that the expression of miR-34a was abnormal in nasopharyngeal carcinoma. Here, this study investigates the effect of miR-34a on radiosensitivity of nasopharyngeal carcinoma cells and explored the underlying mechanisms. Methods: Reverse transcription quantitative polymerase chain reaction was used to analyze the expression of miR-34a in nasopharyngeal carcinoma cell lines and NP69 cells. The effect of miR-34a on radiosensitivity of nasopharyngeal carcinoma (CNE-1 cells) was evaluated by Cell Counting Kit-8, flow cytometry, and Transwell migration assays following transfection with miR-34a mimic. Luciferase reporter assay was used to assess the target genes of miR-34a. Results: In this study, it revealed that miR-34a was downregulated, while silent information regulator 1 was upregulated in nasopharyngeal carcinoma cell lines. The overexpression of miR-34a enhanced radiation-induced proliferation and migration inhibition and apoptosis in CNE-1 cells. Bioinformatics, Luciferase reporter, reverse transcription quantitative polymerase chain reaction, and Western blotting assays indicated that silent information regulator 1 is a direct target of miR-34a in nasopharyngeal carcinoma cells. Knockdown of silent information regulator 1 enhanced radiosensitivity of nasopharyngeal carcinoma cells as evidenced by increasing proliferation and migration inhibition and apoptosis after radiation exposure. Conclusion: In summary, our results indicated that the overexpression of miR-34a enhanced radiosensitivity of nasopharyngeal carcinoma cells by targeting silent information regulator 1. Further studies are warranted to investigate the potential use of miR-34a in the clinical management and treatment prediction of patients with nasopharyngeal carcinoma.

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune systemenhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification. Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein--protein interaction (PPI) networks and further screening of core targets. Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that "steroid receptor activity" and the "PI3K/AKT signaling pathway" were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase. Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) plays a key regulatory role in the pathogenesis of colorectal cancer (CRC). In the present study, the specific regulatory role of lncRNA ezrin antisense RNA 1 (EZR-AS1) on CRC was investigated. The expression of lncRNA EZR-AS1 was significantly up-regulated in CRC cell lines (HCT8, HCT116, HT29, and SW620 cells), which was significantly different from that of normal human fetal colonic mucosa cells (FHC cells) (P<0.01). HCT116 and HT29 cells were then transfected with EZR-AS1 shRNA (sh-EZR-AS1) to silence lncRNA EZR-AS1 (P<0.01). When compared with the Control, after transfection of SH-EZR-AS1, E-cadherin was up-regulated, Vimentin was down-regulated, the apoptosis rate was increased, the cell viability, wound healing rate, and the number of invasive cells were decreased in HCT116 and HT29 cells (P<0.05). Silencing of lncRNA EZR-AS also significantly reduced the tumor volume and weight in mice injected with sh-EZR-AS1-transfected HCT116 and HT29 cells (P<0.05). The regulatory relationship between lncRNA EZR-AS1 and transforming growth factor β (TGF-β) signaling was further identified in CRC cells. Silencing of lncRNA EZR-AS1 significantly down-regulated TGF-β, Smad2, and a-SMA expression in HCT116 and HT29 cells at the protein level (P<0.05). The intervention of SB431542 (a TGF-β receptor blocker) and silencing of Smad2 both significantly down-regulated lncRNA EZR-AS1 expression in HCT116 and HT29 cells (P<0.01). In conclusion, silencing of lncRNA EZR-AS1 inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transition, and promoted the apoptosis of CRC cells through blocking TGF-β signaling. [ABSTRACT FROM AUTHOR]