Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit.
...This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer.
Although combination chemotherapy regimens are shown to be superior to gemcitabine monotherapy for both metastatic pancreatic cancer and adjuvant chemotherapy after surgical resection, it should be recognized that all combination chemotherapy regimens offer only limited benefits. In addition, there is a paucity of clinical trials that directly compare the various combination chemotherapy regimens.
With the advancement of systemic cancer treatment beyond chemotherapy, it is important to devote more investigation into better understanding the biology of these chemotherapy regimens, such that we combine them with targeted therapeutics and immunotherapeutics in a rational and scientific manner. For the current treatment of pancreatic cancer, the available chemotherapy regimens have shown modest but statistically significant improvements in survival. However, it is important to avoid cross-comparisons of trials and choose regimens based on patient characteristics and the side-effect profiles of the regimen.
•Surface browning, the contents of MDA and H2O2 were reduced by melatonin treatment.•Melatonin inhibited the growth of microorganism and delayed the ascorbic acid loss.•Melatonin increased total ...phenolic content and antioxidant capacity.•Melatonin increased PAL and CHS activities and decreased the PPO activity.•Melatonin down-regulated the expression of genes participating in enzymatic browning.
The effects of exogenous melatonin treatment on the enzymatic browning and nutritional quality of fresh-cut pear fruit were investigated. Fresh-cut fruit soaked with 0, 0.05, 0.1 and 0.5 mM melatonin were stored at 4 °C. Our results showed that 0.1 mM melatonin treatment was optimal for reducing the surface browning and maintaining the titratable acidity of the fresh-cut fruit, which significantly decreased MDA and H2O2 contents and the growth of microorganism, enhanced total phenolic content and antioxidant capacity, and delayed the reduction of ascorbic acid. Furthermore, melatonin treatment at 0.1 mM decreased the expression of genes involving in enzymatic browning pathway including POD, PPO1, PPO5 and LOX1, and reduced PPO activity. Moreover, this treatment increased the expression of PAL and CHS, and enhanced PAL and CHS activities. These results showed that melatonin treatment might be a promising strategy to alleviate browning and improve the nutritional quality of fresh-cut pear fruit.
The problem of blind noise level estimation arises in many image processing applications, such as denoising, compression, and segmentation. In this paper, we propose a new noise level estimation ...method on the basis of principal component analysis of image blocks. We show that the noise variance can be estimated as the smallest eigenvalue of the image block covariance matrix. Compared with 13 existing methods, the proposed approach shows a good compromise between speed and accuracy. It is at least 15 times faster than methods with similar accuracy, and it is at least two times more accurate than other methods. Our method does not assume the existence of homogeneous areas in the input image and, hence, can successfully process images containing only textures.
Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an ...enzyme‐free, high‐efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single‐stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in‐depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000‐fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.
Catalytic hairpin assembly (CHA), a robust, versatile, and enzyme‐free nucleic acid isothermal amplification method, has attracted broad attention. Herein, the mechanisms of several extended CHA systems, hairpin designs, and reaction conditions are introduced in detail. Various analytical platforms are applied for signal output of CHA. Biosensors based on CHA are presented. Finally, challenges and the outlook of CHA developments are considered.
Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer ...types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with cancer immunotherapy has been tested both in preclinical settings and in multiple clinical trials. In this review, we highlight the basic biological mechanisms underlying the synergy between epigenetic therapy and immunotherapy and discuss current efforts to translate this knowledge into clinical benefits for patients.
Pyroptosis is a pro-inflammatory form of regulated cell death and is dependent on the enzymatic activity of inflammatory proteases that belong to the family of cysteine-dependent aspartate-specific ...proteases (caspases). Pyroptosis is morphologically, mechanistically, and pathophysiologically distinct from other forms of cell death, including apoptosis and necrosis. Pyroptosis is characterized by rapid plasma membrane rupture, with the consequent release of intracellular contents and pro-inflammatory mediators, including interleukin (IL)-1β, IL-18, and the alarmin HMGB-1.Recent studies have shown that pyroptosis may be involved in atherosclerosis and play an important role in atherosclerotic lesion instability. Here, we review the progress made in understanding the morphological, molecular, and pathophysiological mechanisms of pyroptosis and its potential role in atherosclerosis.
Summary
Ligand‐receptor pairs play important roles in cell–cell communication for multicellular organisms in response to environmental cues. Recently, the emergence of single‐cell RNA‐sequencing ...(scRNA‐seq) provides unprecedented opportunities to investigate cellular communication based on ligand‐receptor expression. However, so far, no reliable ligand‐receptor interaction database is available for plant species. In this study, we developed PlantPhoneDB (https://jasonxu.shinyapps.io/PlantPhoneDB/), a pan‐plant database comprising a large number of high‐confidence ligand‐receptor pairs manually curated from seven resources. Also, we developed a PlantPhoneDB R package, which not only provided optional four scoring approaches that calculate interaction scores of ligand‐receptor pairs between cell types but also provided visualization functions to present analysis results. At the PlantPhoneDB web interface, the processed datasets and results can be searched, browsed, and downloaded. To uncover novel cell–cell communication events in plants, we applied the PlantPhoneDB R package on GSE121619 dataset to infer significant cell–cell interactions of heat‐shocked root cells in Arabidopsis thaliana. As a result, the PlantPhoneDB predicted the actively communicating AT1G28290‐AT2G14890 ligand‐receptor pair in atrichoblast–cortex cell pair in Arabidopsis thaliana. Importantly, the downstream target genes of this ligand‐receptor pair were significantly enriched in the ribosome pathway, which facilitated plants adapting to environmental changes. In conclusion, PlantPhoneDB provided researchers with integrated resources to infer cell–cell communication from scRNA‐seq datasets.
PDF
