Advances in Acute Myeloid Leukemia Stem Cells

As a common hematological malignant tumor, acute leukemia is believed to originate from a subpopulation of special cancer cells, named cancer stem cells. Cancer stem cells are recognized to be the main source of tumor origin, multidrug resistance, metastasis, and recurrence. Leukemic stem cells (LSCs) were first identified and confirmed to play an important role in the occurrence and development of leukemia. In this article, we summarize the following content: special markers and sorting methods for acute myeloid leukemia stem cells and the role of cancer stem cells in treatment resistance, metastasis and invasion, recurrence, and target treatment of acute leukemia

Short-term association of CO and NO2 with hospital visits for glomerulonephritis in Hefei, China: a time series study

ObjectiveRecent studies suggest air pollution as an underlying factor to kidney disease. However, there is still limited knowledge about the short-term correlation between glomerulonephritis (GN) and air pollution. Thus, we aim to fill this research gap by investigating the short-term correlation between GN clinical visits and air pollution exposure.MethodsBetween 2015 and 2019, daily GN visit data from two grade A tertiary hospitals in Hefei City were collected, along with corresponding air pollution and meteorological data. A generalized linear model integrated with a distributed lag nonlinear model was employed to analyze the relationship between GN visits and air pollutants. Moreover, we incorporated a dual pollutant model to account for the combined effects of multiple pollutants. Furthermore, subgroup analyses were performed to identify vulnerable populations based on gender, age, and season.ResultsThe association between 23,475 GN visits and air pollutants was assessed, and significant positive associations were found between CO and NO2 exposure and GN visit risk. The single-day lagged effect model for CO showed increased risks for GN visits from lag0 (RR: 1.129, 95% CI: 1.031–1.236) to lag2 (RR: 1.034, 95% CI: 1.011–1.022), with the highest risk at lag0. In contrast, NO2 displayed a more persistent impact (lag1–lag4) on GN visit risk, peaking at lag2 (RR: 1.017, 95% CI: 1.011–1.022). Within the dual-pollutant model, the significance persisted for both CO and NO2 after adjusting for each other. Subgroup analyses showed that the cumulative harm of CO was greater in the cold-season and older adult groups. Meanwhile, the female group was more vulnerable to the harmful effects of cumulative exposure to NO2.ConclusionOur study indicated that CO and NO2 exposure can raise the risk of GN visits, and female and older adult populations exhibited greater susceptibility

Regulation of Matrix Metalloproteinase-2 Secretion from Scleral Fibroblasts and Retinal Pigment Epithelial Cells by miR-29a

. Purpose. To identify an effective method to prevent myopia progression by characterizing the regulation of matrix metalloproteinase-(MMP-) 2 expression and its secretion from scleral fibroblasts and retinal pigment epithelium (RPE) cells by miR-29a. Methods. The effects of miR-29a on the growth of scleral fibroblasts and RPE cells were assessed using the cell counting kit-8. The changes in MMP-2 mRNA levels in scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor were measured by quantitative PCR. Enzyme-linked immunosorbent assays were used to determine the changes in MMP-2 secretion from scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor. Results. The miR-29a mimics or inhibitor did not significantly alter the growth of scleral fibroblasts or RPE cells at 24, 48, or 72 hours after transfection. MMP-2 mRNA levels were significantly decreased in scleral fibroblasts and RPE cells transfected with the miR-29a mimics. The secretion of MMP-2 by scleral fibroblasts and RPE cells was significantly decreased in cells transfected with the miR-29a mimics. Conclusions. Suppression of scleral fibroblast and RPE cell expression and secretion of MMP-2 by miR-29a can be used as a therapeutic target for the prevention and treatment of myopia

Greedy search method for separable nonlinear models using stage Aitken gradient descent and least squares algorithms

Aitken gradient descent (AGD) algorithm takes some advantages over the standard gradient descent (SGD) and Newton methods: (1) can achieve at least quadratic convergence in general; (2) does not require the Hessian matrix inversion; (3) has less computational efforts. When using the AGD method for a considered model, the iterative function should be unchanging during all the iterations. This paper proposes a hierarchical AGD algorithm for separable nonlinear models based on stage greedy method. The linear parameters are estimated using the least squares algorithm, and the nonlinear parameters are updated based on the AGD algorithm. Since the iterative function is changing at each iteration, a stage AGD algorithm is introduced. The convergence properties and simulation examples show effectiveness of the proposed algorithm

A rapid and reliable method for the determination of Lactiplantibacillus plantarum during wine fermentation based on PMA-CELL-qPCR

Real-time monitoring of microbial dynamics during fermentation is essential for wine quality control. This study developed a method that combines the fluorescent dye propidium monoazide (PMA) with CELL-qPCR, which can distinguish between dead and live microbes for Lactiplantibacillus plantarum. This method could detect the quantity of microbes efficiently and rapidly without DNA extraction during wine fermentation. The results showed that (1) the PMA-CELL-qPCR enumeration method developed for L. plantarum was optimized for PMA treatment concentration, PMA detection sensitivity and multiple conditions of sample pretreatment in wine environment, and the optimized method can accurately quantify 104–108 CFU/mL of the target strain (L. plantarum) in multiple matrices; (2) when the concentration of dead bacteria in the system is 104 times higher than the concentration of live bacteria, there is an error of 0.5–1 lg CFU/mL in the detection results. The optimized sample pretreatment method in wine can effectively reduce the inhibitory components in the qPCR reaction system; (3) the optimized PMA-CELL-qPCR method was used to monitor the dynamic changes of L. plantarum during the fermentation of Cabernet Sauvignon wine, and the results were consistent with the plate counting method. In conclusion, the live bacteria quantification method developed in this study for PMA-CELL-qPCR in L. plantarum wines is accurate in quantification and simple in operation, and can be used as a means to accurately monitor microbial dynamics in wine and other fruit wines

Advance in Pancreatic Cancer Diagnosis and Therapy

Pancreatic carcinoma is the fourth leading cause of cancer death in the word wild. Although the advance in treatment this disease, the 5-years survival rate is still rather low. In the recent year, many new therapy and treatment avenues have been developed for pancreatic cancer. In this chapter, we mainly focus on the following aspect: 1) the treatment modality in pancreatic cancer, including chemotherapy, radiotherapy, and immunotherapy; 2) the mechanism of pancreatic cancer treatment resistance, especially in cancer stem cells and tumor microenvironment; 3) the diagnosis tools in pancreatic cancer, including serum markers, imaging methods and endoscopic ultrasonography. Novel molecular probes based on the nanotechnology in the diagnosis of pancreatic cancer are also discussed

Programmable and Multifunctional DNA-Based Materials for Biomedical Applications

DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson–Crick base‐pairing interactions between only four types of nucleotides, well‐designed DNA self‐assembly can be programmable and predictable. Stem‐loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA‐based structures. The oligonucleotides experience thermal annealing in a near‐neutral buffer containing a divalent cation (usually Mg2+) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA‐based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA‐based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA‐based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost. </p

Toll-like receptor 2 and Toll-like receptor 4 exhibit distinct regulation of cancer cell stemness mediated by cell death-induced high-mobility group box 1

Background: High-mobility group box 1 (HMGB1), a common extracellular damage associated molecular pattern molecule, is overexpressed in several solid tumors including pancreatic carcinoma. We previously observed that radiotherapy induced dying cells secrete HMGB1 and accelerate pancreatic carcinoma progression through an unclear mechanism.Methods: Using the Millicell system as an in vitro co-culture model, we performed quantitative reverse transcriptase-polymerase chain reaction, western blot and sphere forming ability analyses to access the effect of dying-cell-derived HMGB1 on CD133(+) cancer cell stemness in vitro and in vivo. Interactions between HMGB1 and Toll-like receptor 2(TLR2)/TLR4 were studied by co-immunoprecipitation. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect HMGB1 and TLR2/TLR4 signaling activity.Findings: Radiation-associated, dying-cell-derived HMGB1 maintained stemness and contributed to CD133(+) cancer stemcell self-renewal in vitro and in vivo. In overexpressing and silencing experiments, we demonstrated that the process was activated by TLR2 receptor, whereas TLR4 antagonized HMGB1-TLR2 signaling. Wnt/beta-catenin signaling supported the HMGB1-TLR2 mediated stemness of CD133(+) cancer cells.Interpretation: Our results show how irradiation-induced cell death might enhance the stemness of resident cancer cells, and indicate HMGB1-TLR2 signaling as a potential therapeutic target for preventing pancreatic cancer recurrence. (c) 2018 Haitao Zhu. Published by Elsevier B.V