Over the past few decades, advances in immunological knowledge have led to the identification of novel immune checkpoints, reinvigorating cancer immunotherapy. Immunotherapy, represented by immune ...checkpoint inhibitors, has become the leader in the precision treatment of cancer, bringing a new dawn to the treatment of most cancer patients. Galectin-9 (LGALS9), a member of the galectin family, is a widely expressed protein involved in immune regulation and tumor pathogenesis, and affects the prognosis of various types of cancer. Galectin-9 regulates immune homeostasis and tumor cell survival through its interaction with its receptor Tim-3. In the review, based on a brief description of the signaling mechanisms and immunomodulatory activities of galectin-9 and Tim-3, we summarize the targeted expression patterns of galectin-9 in a variety of malignancies and the promising mechanisms of anti-galectin-9 therapy in stimulating anti-tumor immune responses.
Cerebrovascular diseases such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage provoke cardiac complications such as heart failure, neurogenic stress-related cardiomyopathy and ...Takotsubo cardiomyopathy. With regards to the pathophysiology of stroke-induced heart injury, several mechanisms have been postulated to contribute to this complex interaction between brain and heart, including damage from gut dysbiosis, immune and systematic inflammatory responses, microvesicle- and microRNA-mediated vascular injury and damage from a surge of catecholamines. All these cerebrovascular diseases may trigger pronounced catecholamine surges through diverse ways, including stimulation of hypothalamic-pituitary adrenal axis, dysregulation of autonomic system, and secretion of adrenocorticotropic hormone. Primary catecholamines involved in this pathophysiological response include norepinephrine (NE) and epinephrine. Both are important neurotransmitters that connect the nervous system with the heart, leading to cardiac damage via myocardial ischemia, calcium (Ca2+) overload, oxidative stress, and mitochondrial dysfunction. In this review, we will aim to summarize the molecular mechanisms behind catecholamine-induced cardiotoxicity including Ca2+ overload, oxidative stress, apoptosis, cardiac hypertrophy, interstitial fibrosis, and inflammation. In addition, we will focus on how synchronization among these pathways evokes cardiotoxicity.
Display omitted
Drug discovery is important in cancer therapy and precision medicines. Traditional approaches of drug discovery are mainly based on in vivo animal experiments and in vitro drug screening, but these ...methods are usually expensive and laborious. In the last decade, omics data explosion provides an opportunity for computational prediction of anti-cancer drugs, improving the efficiency of drug discovery. High-throughput transcriptome data were widely used in biomarkers' identification and drug prediction by integrating with drug-response data. Moreover, biological network theory and methodology were also successfully applied to the anti-cancer drug discovery, such as studies based on protein-protein interaction network, drug-target network and disease-gene network. In this review, we summarized and discussed the bioinformatics approaches for predicting anti-cancer drugs and drug combinations based on the multi-omic data, including transcriptomics, toxicogenomics, functional genomics and biological network. We believe that the general overview of available databases and current computational methods will be helpful for the development of novel cancer therapy strategies.
Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use is greatly limited by the life-threatening cardiotoxicity. N6-methyladenosine (m6A) RNA modification participates in varieties of ...cellular processes. Nonetheless, it remains elusive whether m6A modification and its methyltransferase METTL3 are involved in the progression of DOX-induced cardiotoxicity (DIC).
Mice were administrated with DOX (accumulative dosage of 20 mg/kg) repeatedly to establish a chronic DIC model. Cardiomyocyte-specific conditional METTL3 knockout mice were employed to evaluate the effects of altered m6A RNA modification on DIC. The effects of METTL3 on cardiomyocyte ferroptosis were also examined in response to DOX stimulation.
DOX led to increased levels in m6A modification and METTL3 expression in cardiomyocytes in a c-Jun-dependent manner. METTL3-knockout mice exhibited improved cardiac function, remodeling and injury following DOX insult. Besides, inhibition of METTL3 alleviated DOX-induced iron accumulation and ferroptosis in cardiomyocytes, whereas METTL3 overexpression exerted the opposite effects. Mechanistically, METTL3 promoted m6A modification of TFRC mRNA, a critical gene governing iron uptake, and enhanced its stability through recognition of the m6A reader protein, IGF2BP2. Moreover, pharmacological administration of a highly selective METTL3 inhibitor STM2457 effectively ameliorated DIC in mice.
METTL3 plays a cardinal role in the etiology of DIC by regulating cardiac iron metabolism and ferroptosis through TFRC m6A modification. Inhibition of METTL3 might be a potential therapeutic avenue for DIC.
Display omitted
Zinc is a necessary trace element and an important constituent of proteins and other biological molecules. It has many biological functions, including antioxidant, skin and mucous membrane integrity ...maintenance, and the promotion of various enzymatic and transcriptional responses. The skin contains the third most zinc in the organism. Zinc deficiency can lead to a range of skin diseases. Except for acrodermatitis enteropathic, a rare genetic zinc deficiency, it has also been reported in other diseases. In recent years, zinc supplementation has been widely used for various skin conditions, including infectious diseases (viral warts, genital herpes, cutaneous leishmaniasis, leprosy), inflammatory diseases (hidradenitis suppurativa, acne vulgaris, rosacea, eczematous dermatitis, seborrheic dermatitis, psoriasis, Behcet's disease, oral lichen planus), pigmentary diseases (vitiligo, melasma), tumor-associated diseases (basal cell carcinoma), endocrine and metabolic diseases (necrolytic migratory erythema, necrolytic acral erythema), hair diseases (alopecia), and so on. We reviewed the literature on zinc application in dermatology to provide references for better use.
Aggressive B-cell non-Hodgkin's lymphoma (B-NHL) patients often develop drug resistance and tumor recurrence after conventional immunochemotherapy, for which new treatments are needed.
We ...investigated the antitumor effects of CBL0137. In vitro, cell proliferation was assessed by CCK-8 and colony formation assay. Flow cytometry was performed to analyze cell cycle progression, apoptosis, mitochondrial depolarization, and reactive oxygen species (ROS) production. Autophagy was detected by transmission electron microscopy and mGFP-RFP-LC3 assay, while western blotting was employed to detect proteins involved in apoptosis and autophagy. RNA-sequencing was conducted to analyze the transcription perturbation after CBL0137 treatment in B-NHL cell lines. Finally, the efficacy and safety of CBL0137, rituximab, and their combination were tested in vivo.
CBL0137, a small molecule anticancer agent that has significant antitumor effects in B-NHL. CBL0137 sequesters the FACT (facilitates chromatin transcription) complex from chromatin to produce cytotoxic effects in B-NHL cells. In addition, we discovered novel anticancer mechanisms of CBL0137. CBL0137 inhibited human B-NHL cell proliferation by inducing cell cycle arrest in S phase via the c-MYC/p53/p21 pathway. Furthermore, CBL0137 triggers ROS generation and induces apoptosis and autophagy in B-NHL cells through the ROS-mediated PI3K/Akt/mTOR and MAPK signaling pathways. Notably, a combination of CBL0137 and rituximab significantly suppressed B-NHL tumor growth in subcutaneous models, consistent with results at the cellular level in vitro.
CBL0137 has potential as a novel approach for aggressive B-NHL, and its combination with rituximab can provide new therapeutic options for patients with aggressive B-NHL. Video Abstract.
The recognition of new diagnostic and prognostic biological markers for lung cancer, the most severe malignant tumor, is an essential and eager study. In a microenvironment, superoxide dismutase 3 ...(SOD3) can adjust active oxygen, and it refers to a secreted antioxidant enzyme. It was also found to be cancer-related, and in lung cancer, it was remarkably down-regulated. More and more new cancer research focuses on the function of SOD3. Despite this, there is no good description of SOD3 function in the LC progression.
Through bioinformatics analysis, we found that SOD3 was a possible novel lung cancer gene in this study. We analyzed data sets from Gene Expression Comprehensive Database (GEO) and the Cancer Genome Atlas (TCGA), and SOD3 expression was studied in lung cancer. This study estimated the SOD3 diagnosis and prognosis through gene expression differential display, gene set enrichment analysis (GSEA), enrichment and genomes (KEGG) analysis, and gene ontology (GO). Then in order to investigate the SOD3 presentation in lung cancer cells, we used Western Blot and also applied Flow cytometry to detect the impact of anti-tumor medicine on tumor cell apoptosis.
We found that the expression level of SOD3 in lung cancer was low (P = 4.218E-29), while the survival of lung cancer patients with high SOD3 expression was shorter (LUSC p =0.00086, LUAD p=0.00038). According to the result of western blot, the expression of SOD3 in tumor cells was higher than that in normal cells. The ratio of early apoptosis induced by anti-cancer drugs was 10.5% in normal cells, 35.1% in squamous cell carcinoma and 36.9% in adenocarcinoma.The SOD3 high expression was associated with poor survival probability by multivariate analysis (HR: 1.006, 95% CI 1.002-1.011, p=0.006). Moreover, SOD3 high expression group had higher ESTIMATE scores, and larger amount of immune infiltrating cells. SOD3 expression is correlated with PDCD1 and CTLA4 expression.
SOD3 gene can be used as a prognostic gene in lung cancer patients, and lung cancer patients with high expression of this gene can reap worse prognostic outcome. It can be used as a new clinical method and prognosticator for lung cancer patients.
The realization of intelligent mining is the only method for realizing high-quality development in the coal industry. As the forefront working link in mine production, achieving automatic roadway ...tunneling control is key to improving production efficiency, enhancing intelligence, and reducing accident rates at fully mechanized tunneling working faces. Among various detection techniques, machine vision technology stands out with advantages of non-contact measurement, rich information acquisition, and high detection accuracy. The detection and control of tunneling equipment groups based on machine vision has become a research hotspot in the intelligence process of coal mines. This study first introduces the key technologies of a visual detection system, including camera calibration, image preprocessing, feature extraction, visual matching, target segmentation and recognition, visual measurement, and 3D reconstruction. It then elaborates on detection principles, workflows, limitations, precautions, and development status of various vision detection systems in practical application scenarios at tunneling faces, such as tunneling equipments, anchoring systems, transportation systems, and safety auxiliary systems, which significantly improve production safety and efficiency. Finally, considering challenging work conditions and strong interference in mines, the successful adaptation of machine vision to excavation sites relies on addressing technical challenges related to poor environment adaptability, limited imaging field of view, and low intelligence level. Furthermore, according to existing research results and the current technical status, this paper forecasts key technologies that need to be developed in the future for coal mine intelligent equipment systems based on machine vision, including multi-sensor information fusion, equipment group collaborative control, and digital twin-driven remote monitoring.
This paper reports the design, fabrication, and test of a 3-D integrated uncooled focal plane array (FPA) using monocrystalline silicon diodes as thermosensitive devices. The diode array is ...fabricated from the silicon device layer of a silicon-on-insulator wafer, and the readout integrated circuits (ROICs) are fabricated on a bulk wafer using the CMOS technology. The silicon diode array is vertically integrated with the ROIC using the 3-D integration technology. Electroless nickel (Ni) plating is developed for fabricating substantial Ni posts to mechanically support the diode pixels to suspension and electrically connect the diode pixels to the ROIC. It allows the integration of monocrystalline device arrays with CMOS circuits fabricated using separate technologies and wafers in vertically suspended configuration. It also improves the filling factors of the FPA chips, shortens the wires between the diodes and the ROIC, and facilitates the releasing process to suspend the diode array. A 160×120 small-scale FPA has been developed as a test vehicle for concept verification. The test results and successful thermal imaging demonstrate the feasibility of the 3-D integration technology and verify the application of 3-D integration in the development of integrated FPAs using monocrystalline thermosensitive devices.
To determine the incidence of acute cardiac injury (ACI), the factors associated with ACI and the in-hospital mortality in patients with COVID-19, especially in severe patients. All consecutive ...in-patients with laboratory-confirmed COVID-19 from Tongji Hospital in Wuhan during February 1 and March 29, 2020 were included. The demographic, clinical characteristics, laboratory, radiological and treatment data were collected. Univariate and Firth logistic regression analyses were used to identify factors associated with ACI and in-hospital mortality, and Kaplan-Meier method was used to estimate cumulative in-hospital mortality. Among 1031 patients included, 215 (20.7%) had ACI and 501 (48.6%) were severe cases. Overall, 165 patients died; all were from the severe group, and 131 (79.39%) had ACI. ACI (OR = 2.34, P = 0.009), male gender (OR = 2.58, P = 0.001), oximeter oxygen saturation (OR = 0.90, P < 0.001), lactate dehydrogenase (OR = 3.26, P < 0.001), interleukin-6 (IL-6) (OR = 8.59, P < 0.001), high sensitivity C-reactive protein (hs-CRP) (OR = 3.29, P = 0.016), N-terminal pro brain natriuretic peptide (NT-proBNP) (OR = 2.94, P = 0.001) were independent risk factors for the in-hospital mortality in severe patients. The mortality was significantly increased among severe patients with elevated hs-CRP, IL-6, hs-cTnI, and/or NT-proBNP. Moreover, the mortality was significantly higher in patients with elevation of both hs-cTnI and NT proBNP than in those with elevation of either of them. ACI develops in a substantial proportion of patients with COVID-19, and is associated with the disease severity and in-hospital mortality. A combination of hs-cTnI and NT-proBNP is valuable in predicting the mortality.
PDF
