Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

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.

Three-dimensional chromatin landscapes in hepatocellular carcinoma associated with hepatitis B virus.

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.

[Phage antibody library technology in tumor therapy: a review].

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.

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

Medicarpin suppresses proliferation and triggeres apoptosis by upregulation of BID, BAX, CASP3, CASP8, and CYCS in glioblastoma.

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.

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells.

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.

The effect of green coffee extract supplementation on obesity indices: critical umbrella review of interventional meta-analyses.

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.

[Advances in predictive biomarkers associated with immune checkpoint inhibitors for tumor therapy].

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.

[Biomarkers for early screening and diagnosis of breast cancer: a review].

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.

[Advances of glioma biomarkers].

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.

A comprehensive review of antitumor properties of Angelica species and their antitumor-responsible constituents and the underlying molecular mechanisms involved in tumor inhibition.

Angelica species have been traditionally used for their medicinal properties. Recent studies have suggested their potential use as anticancer agents, making them an area of interest for further research. The review aims to summarize the current understanding of the potential anticancer effects of Angelica species and to provide insights for further research in this area. We searched for "Angelica" related information on Google Scholar, PubMed, ScienceDirect, Wiley, Science Citation Index Finder, and Springer link by searching keywords such as "Angelica," "Angelica phytochemical," "Angelica antitumor effect," "Angelica molecular mechanisms," and "Angelica clinical application." Included articles focused on the Angelica plant's anticancer properties and clinical studies, while non-cancer-related biological or phytochemical investigations were excluded. We conducted a comprehensive search of books, journals, and databases published between 2001 and 2023, identifying 186 articles for this narrative review. The articles were analyzed for their potential anticancer properties and therapeutic applications. Active compounds in the Angelica genus, such as coumarins, furanocoumarins, phthalides, and polysaccharides, exhibit anticancer properties through various mechanisms. Specific species, like A. archangelica, Angelica sinensis, A. gigas, and A. ksiekie, have the potential as anticancer agents by targeting cellular pathways, generating reactive oxygen species, and inducing apoptotic cell death. Further research into the properties of the Angelica genus is needed for developing new treatments for cancer. Phytochemicals from Angelica species possess potential as anticancer agents, requiring further research for the development of effective, low-cost, and low-toxicity cancer treatments compared to synthetic antitumor drugs.

Ligustilide induces apoptosis and reduces proliferation in human bladder cancer cells by NFκB1 and mitochondria pathway.

Ligustilide (LIG), the bioactive constituent of Angelica sinensis, may exert potential benefits in cancer treatment. However, the potential mechanism of LIG in the suppression of bladder cancer (BC) has not been reported yet. This study uncovered the inhibitory effect of LIG on the proliferation and cell cycle arrest of BC cells (T24 and EJ-1) along with unveiling the underlying molecular mechanism. The IC50 values of LIG-treated T24 for 24 and 48 h are 39.91 µg/mL (209.8 µM) and 40.94 µg/mL (215.2 µM) separately. The same conditions, the IC50 values of EJ-1 are 45.73 µg/mL (240.4 µM) and 43.81 µg/mL (230.3 µM), separately. Additionally, LIG induced apoptosis and cycle arrest of T24 and EJ-1 cells in sub-G1 phase. Further studies showed that LIG induced apoptosis of BC cells by upregulating Caspase-8, truncated BID (tBID) and BAX proteins, and downregulating NFκB1 (p50) protein. In conclusion, LIG significantly inhibits the growth of BC cells in vitro and in vivo by inducing apoptosis and is inexpensive, making it a promising candidate for novel anti-BC drugs.

Glabridin inhibits urothelial bladder carcinoma cell growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest.

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.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Risk Prediction of Coronary Artery Stenosis in Patients with Coronary Heart Disease Based on Logistic Regression and Artificial Neural Network.

Objective: Coronary heart disease (CHD) is considered an inflammatory relative disease. This study is aimed at analyzing the health information of serum interferon in CHD based on logistic regression and artificial neural network (ANN) model. Method: A total of 155 CHD patients diagnosed by coronary angiography in our department from January 2017 to March 2020 were included. All patients were randomly divided into a training set (n = 108) and a test set (n = 47). Logistic regression and ANN models were constructed using the training set data. The predictive factors of coronary artery stenosis were screened, and the predictive effect of the model was evaluated by using the test set data. All the health information of participants was collected. Expressions of serum IFN-γ, MIG, and IP-10 were detected by double antibody sandwich ELISA. Spearman linear correlation analysis determined the relationship between the interferon and degree of stenosis. The logistic regression model was used to evaluate independent risk factors of CHD. Result: The Spearman correlation analysis showed that the degree of stenosis was positively correlated with serum IFN-γ, MIG, and IP-10 levels. The logistic regression analysis and ANN model showed that the MIG and IP-10 were independent predictors of Gensini score: MIG (95% CI: 0.876~0.934, P < 0.001) and IP-10 (95% CI: 1.009~1.039, P < 0.001). There was no statistically significant difference between the logistic regression and the ANN model (P > 0.05). Conclusion: The logistic regression model and ANN model have similar predictive performance for coronary artery stenosis risk factors in patients with CHD. In patients with CHD, the expression levels of IFN-γ, IP-10, and MIG are positively correlated with the degree of stenosis. The IP-10 and MIG are independent risk factors for coronary artery stenosis.

A rare case of Pseudomonas aeruginosa bacteremia in a newborn with 58 perforations in the small intestine.

BACKGROUND: Community-acquired infections of Pseudomonas aeruginosa (P. aeruginosa) occur very rarely. CASE PRESENTATION: P. aeruginos was detected in cultures of venous blood and peritoneal exudate of a newborn with 58 perforations in the small intestine. Intravenous administration of imipenem cilastratin sodium and emergency abdominal surgery were performed. The patient fully recovered and was discharged 17 days after the operation. CONCLUSIONS: Mild symptoms of systemic infections in newborns may delay the diagnosis. Early detection and timely treatment are the key to improved prognosis.

Serum Monokine Induced by Gamma Interferon Is Associated With Severity of Coronary Artery Disease.

The immune system may play important roles in the pathogenesis of cardiovascular disease. T-cell mediated immune responses in human progression of atherosclerotic disease and hypertension have recently been revealed, but the significance of T-cell specific chemokines in coronary artery heart disease has not been confirmed. In our study, we sought to examine the association between serum levels of the monokine induced by gamma interferon (MIG)/CXCL9 and the severity of coronary artery disease. We studied 117 patients with coronary heart disease and 80 patients with no coronary heart disease. The severity of coronary artery disease was assessed via coronary artery angiography and the Gensini score was calculated. Clinical and biochemical indices, including serum levels of MIG, CD40L, and IFN-γ were analyzed in all subjects. Finally, we found there was a significant correlation between serum MIG levels and the severity of coronary artery disease, quantified by the Gensini score (r = 0.122, P = 0.009). Furthermore, multivariate regression analysis revealed that serum MIG levels were independently associated with the severity of coronary artery disease, quantified by the Gensini score (ß = 0.100, P = 0.021). Our findings could indicate the potential clinical implication of MIG with respect to early coronary artery atherosclerosis in humans.

Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI.

OBJECTIVE: Both atorvastatin and cell-based therapy were reportedly beneficial to ventricular function after acute myocardial infarction (AMI). In this study, we sought to study the synergistic effects of marrow-derived mesenchymal stromal cells (MSCs) and atorvastatin in a rat model of AMI. METHODS: To create a rat model of AMI, left anterior descending artery (LAD) ligations were performed on 40 Sprague-Dawley (SD) rats. After the establishment of AMI, animals were randomly divided into 4 groups to receive variant treatments: control, MSCs only, atorvastatin only, and MSCs plus atorvastatin, with 10 animals in each group. RESULTS: Four weeks following the treatments, the hemodynamic testing showed significant functional improvement in animals that received MSCs plus atorvastatin compared with controls, MSCs or atorvastatin only treated animals. Histological analysis showed more MSCs were present in animals receiving combination therapy than in animals which received MSCs alone. Vessel density was higher in animals receiving combination therapy than in other groups. DISCUSSION: These results suggest that either atorvastatin or MSCs cannot individually improve ventricular function significantly. However, atorvastatin synergistically enhanced the beneficial effects of MSCs in the treatment of AMI.