Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a ...self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose ...transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.
Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel ...anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.
Recently, the dysregulation of circular RNA (circRNA) have been shown to have important regulatory roles in cancer development and progression, including hepatocellular carcinoma (HCC). However, the ...roles of most circRNAs in HCC are still unknown.
The expression of circular tripartite motif containing 33-12 (circTRIM33-12) in HCC tissues and cell lines was detected by qRT-PCR. The role of circTRIM33-12 in HCC progression was assessed by western blotting, CCK-8, flow cytometry, transwell and a subcutaneous tumor mouse assays both in vitro and in vivo. In vivo circRNA precipitation, RNA immunoprecipitation, luciferase reporter assays were performed to evaluate the interaction between circTRIM33-12 and miR-191.
Here, we found that circTRIM33-12, is downregulated in HCC tissues and cell lines. The downregulation of circTRIM33-12 in HCC was significantly correlated with malignant characteristics and served as an independent risk factor for the overall survival (OS) and recurrence-free survival (RFS) of patients with HCC after surgery. The reduced expression of circTRIM33-12 in HCC cells increases tumor proliferation, migration, invasion and immune evasion. Mechanistically, we demonstrated that circTRIM33-12 upregulated TET1 expression by sponging miR-191, resulting in significantly reduced 5-hydroxymethylcytosine (5hmC) levels in HCC cells.
These results reveal the important role of circTRIM33-12 in the proliferation, migration, invasion and immune evasion abilities of HCC cells and provide a new perspective on circRNAs in HCC progression.
A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural ...products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid‐derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF‐κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.
This review aims to summarize the integrated research progress of natural products (e.g. curcumin) on the tumor immunotherapy and key intracellular pathways.
As an attractive candidate for dark matter, the primordial black holes (PBHs) in the mass range (8×1014 ∼ 1016) g could be detected via their Hawking radiation, including neutrinos and antineutrinos ...of three flavors. In this paper, we investigate the possibility to constrain the PBHs as dark matter by measuring (anti)neutrino signals at the large liquid-scintillator detector of Jiangmen Underground Neutrino Observatory (JUNO). Among six available detection channels, the inverse beta decay νe + p → e+ + n is shown to be most sensitive to the fraction fPBH of PBHs contributing to the dark matter abundance. Given the PBH mass MPBH = 1015g, we find that JUNO will be able to place an upper bound fPBH ≲ 3×10−5, which is 20 times better than the current best limit fPBH ≲ 6×10−4 from Super-Kamiokande. For heavier PBHs with a lower Hawking temperature, the (anti)neutrinos become less energetic, leading to a relatively weaker bound.
According to guidelines, endoscopic resection should only be performed for patients whose early gastric cancer invasion depth is within the mucosa or submucosa of the stomach regardless of lymph node ...involvement. The accurate prediction of invasion depth based on endoscopic images is crucial for screening patients for endoscopic resection. We constructed a convolutional neural network computer-aided detection (CNN-CAD) system based on endoscopic images to determine invasion depth and screen patients for endoscopic resection.
Endoscopic images of gastric cancer tumors were obtained from the Endoscopy Center of Zhongshan Hospital. An artificial intelligence–based CNN-CAD system was developed through transfer learning leveraging a state-of-the-art pretrained CNN architecture, ResNet50. A total of 790 images served as a development dataset and another 203 images as a test dataset. We used the CNN-CAD system to determine the invasion depth of gastric cancer and evaluated the system’s classification accuracy by calculating its sensitivity, specificity, and area under the receiver operating characteristic curve.
The area under the receiver operating characteristic curve for the CNN-CAD system was .94 (95% confidence interval CI, .90-.97). At a threshold value of .5, sensitivity was 76.47%, and specificity 95.56%. Overall accuracy was 89.16%. Positive and negative predictive values were 89.66% and 88.97%, respectively. The CNN-CAD system achieved significantly higher accuracy (by 17.25%; 95% CI, 11.63-22.59) and specificity (by 32.21%; 95% CI, 26.78-37.44) than human endoscopists.
We constructed a CNN-CAD system to determine the invasion depth of gastric cancer with high accuracy and specificity. This system distinguished early gastric cancer from deeper submucosal invasion and minimized overestimation of invasion depth, which could reduce unnecessary gastrectomy.
High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to ...be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.
Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.
We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.
Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
Background Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be ...one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. Methods A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. Results RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). Conclusion RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.
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