Search

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

Despite a multitude of investigations assessing the impact of green coffee extract supplementation on obesity indices, there is still a great deal of heated debate regarding the benefits of this intervention in obesity management. Therefore, in order to clarify the effect of green coffee extract on waist circumference (WC), body mass index (BMI) and body weight (BW), we conducted an umbrella review of interventional meta-analyses. The Web of Science, Scopus, PubMed/Medline, and Embase databases were searched using specific keywords and word combinations. The umbrella meta-analysis was performed using the Stata software version 17 (Stata Corp. College Station, Texas, USA). We pooled effect sizes (ES) and confidence intervals (CI) for the outcomes using the random effects model (the DerSimonian and Laird method). In total, 5 eligible meta-analyses were included in the final quantitative assessment. Data pooled from 5 eligible papers revealed that green coffee extract can reduce BW (WMD: −1.22 kg, 95% CI: −1.53 to −0.92, p < 0.001), BMI (WMD: −0.48 kg/m2, 95% CI: −0.67 to −0.29, p < 0.001) and WC (WMD: −0.55 cm, 95% CI: −0.80 to −0.31, p < 0.001). Subgroup analyses highlighted that green coffee extract supplementation in dosages ≤600 mg/day and interventions lasting >7 wk are more likely to decrease BW. The present umbrella meta-analysis confirms the beneficial effects of green coffee extract in reducing WC, BMI, and BW. Thus, we may infer that green coffee extract can be used as a complementary therapy in the management of obesity. [ABSTRACT FROM AUTHOR]

Peimenine (PEI) is a steroid alkaloid substance isolated from Fritillaria thunbergii bulbs. It has various pharmacological activities, such as relief from coughs and asthma, expectorant properties, antibacterial effects, sedative qualities, and anti‐inflammatory properties. Notably, PEI can effectively inhibit the proliferation and tumor formation of liver cancer and osteosarcoma cells by inducing autophagic cell death. However, the precise effect and mechanisms of PEI on urothelial bladder cancer (UBC) cells remain uncertain. Thus, this study aims to investigate the impact of PEI on UBC cells both in vivo and in vitro. The IC50 values of BIU‐87 and EJ‐1 cells after 48 h were 710.3 and 651.1 μg/mL, respectively. Additionally, PEI blocked the cell cycle in BIU‐87 and EJ‐1 cells during the G1 phase. Furthermore, it hindered the migration of BIU‐87 and EJ‐1 cells substantially. PEI significantly inhibited the tumor development of EJ‐1 cells within the xenograft tumor model in vivo. Mechanically, PEI augmented the protein and mRNA expression of BIM, BAK1, and Cytochrome C (CYCS) in UBC cells. Taken together, PEI suppressed the proliferation of UBC cells both in vitro and in vivo by inducing cell death and cell cycle arrest, suggesting that PEI could be applied in the treatment of UBC. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. Methods: Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. Results: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4–chr10, chr13–chr21, chr15–chr22, and chr16–chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A–B or B–A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000–6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. Conclusion: This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most malignant brain tumor and incurable. Medicarpin (MED), a flavonoid compound from the legume family, has multiple targets and anticancer properties. However, the role of MED in GBM remains unclear. The objective of this study was to explore the effects of MED on the apoptosis of GBM and to explain the potential molecular mechanisms. We found that the IC50 values of U251 and U‐87 MG cells treated with MED for 24 h were 271 μg/mL and 175 μg/mL, and the IC50 values for 48 h were 154 μg/mL and 161 μg/mL, respectively. Additionally, the cell cycle of U251 and U‐87 MG cells were arrested at the G2/M phase. Furthermore, the apoptosis rate of U251 and U‐87 MG cells increased from 6.26% to 18.36% and 12.46% to 31.33% for 48 h, respectively. The migration rate of U251 and U‐87 MG decreased from 20% to 5% and 25% to 15% for 12 h and these of U251 and U‐87 MG decreased from 50% to 28% and 60% to 25% for 24 h. MED suppressed GBM tumorigenesis, and improved survival rate of tumor‐bearing mice. Taken together, MED triggered GBM apoptosis through upregulation of pro‐apoptotic proteins (BID, BAX, CASP3, CASP8, and CYCS), showed strong inhibitory effects on cell proliferation and cell migration, and displayed anti‐tumor activity in nude mice. [ABSTRACT FROM AUTHOR]

Glabridin (GLA) has a variety of biological activities and therapeutic effects in cancers. Whereas the effect of GLA on urothelial bladder carcinoma (UBC) cells and its underlying mechanisms remain unknown. The study revealed the effect of GLA on UBC and the potential mechanism of inducing cell apoptosis in vivo and in vitro. After treated with different concentrations of GLA, the cell activity decreased in a time‐ and dose‐dependent manner. The IC50 values of BIU‐87 and EJ cells at 48 h were 6.02 μg/ml (18.6 μm) and 4.36 μg/ml (13.4 μm), respectively. Additionally, GLA‐induced apoptosis and cycle arrest of BIU‐87 and EJ cells in G2 phase. Furthermore, wound healing experiments showed that GLA significantly reduced the migration activities of BIU‐87 and EJ cells. Mechanically, GLA obviously increased the expression of BIM, BAK1, and CYCS in both mRNA and protein levels, which led to the activation of the endogenous apoptotic pathway. Finally, GLA remarkably inhibited the growth of UBC tumors in vivo. In summary, GLA inhibited UBC cells growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest, highlighting that GLA could be utilized as a component to design a novel anti‐UBC drug. [ABSTRACT FROM AUTHOR]

H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive. Here, a genome-wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)-induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP-Seq and RNA-Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1-promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF-κB pathway to promote macrophages M1 polarization, representing a crucial event in MASLD progression. A bovine serum albumin nanoparticle is fabricated to provide sustained release of Allopurinol (NPs-Allo) for TDO2 inhibition, possessing excellent biocompatibility and desired targeting capacity. Venous injection of NPs-Allo robustly alleviates HFD-induced metabolic disorders. This study reveals the pivotal role of TDO2 and its underlying mechanisms in pathogenesis of MASLD epigenetically and genetically. Targeting H3K27ac-TDO2-NF-κB axis may provide new insights into the pathogenesis of abnormal lipid accumulation and pave the way for developing novel strategies for MASLD prevention and treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p  < 0.001; I 2 =79.0%, p  < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p  < 0.001; I 2 = 48.8%, p  < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p  < 0.001; I 2 =44.4%, p  = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p  < 0.001; I 2 =31.3%, p  = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p  < 0.001; I 2 =95.5%, p  < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72  p  < 0.001; I 2 =22.1%, p  = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p  < 0.001; I 2 =90.7%, p  < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p  < 0.001; I 2 =0.00%, p  = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.

Glioma is the most common primary brain tumor, accounting for 81% of intracranial tumors. The diagnosis and prognosis assessment of glioma are mainly based on imaging. However, imaging cannot be fully used as the basis for diagnosis and prognosis assessment due to the infiltrative growth characteristics of glioma. Therefore, the discovery and identification of novel biomarkers is particularly important for the diagnosis, treatment and prognosis assessment of glioma. The latest findings suggest that a variety of biomarkers in the tissues and blood of glioma patients can be used for the auxiliary diagnosis and prognosis assessment of glioma. Among them, IDH1 / 2 gene mutation, BRAF gene mutation and fusion, p53 gene mutation, increased telomerase activity, circulating tumor cells and non-coding RNA can be used as diagnostic markers. Prognostic markers include 1p/19p codeletion, MGMT gene promoter methylation, upregulation of matrix metalloproteinase-28, insulin-like growth factor-binding protein-2 and CD26, and downregulation of Smad4. This review highlights the latest advances of biomarkers in the diagnosis and prognosis assessment of glioma.

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.