Stem cell-based therapy for human diseases Hoang, Duc M.; Pham, Phuong T.; Bach, Trung Q. ...
Signal transduction and targeted therapy,
08/2022, Letnik:
7, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human ...pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
Hypomagnesemia: a clinical perspective Pham, Phuong-Chi T; Pham, Phuong-Anh T; Pham, Son V ...
International journal of nephrology and renovascular disease,
01/2014, Letnik:
7, Številka:
default
Journal Article
Recenzirano
Odprti dostop
Although magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and ...underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.
Background
Osmotic demyelination syndrome (ODS) is a complication generally associated with overly rapid correction of hyponatremia. Traditionally, nephrologists have been trained to focus solely on ...limiting the correction rate. However, there is accumulating evidence to suggest that the prevention of ODS is beyond achieving slow correction rates.
Methods
We (1) reviewed the literature for glial intracellular protective alterations during hyperosmolar stress, a state presumed equivalent to the rapid correction of hyponatremia, and (2) analyzed all available hyponatremia-associated ODS cases from PubMed for possible contributing factors including correction rates and concurrent metabolic disturbances involving hypokalemia, hypophosphatemia, hypomagnesemia, and/or hypoglycemia.
Results
In response to acute hyperosmolar stress, glial cells undergo immediate extracellular free water shift, followed by active intracellular Na
+
, K
+
and amino acid uptake, and eventual idiogenic osmoles synthesis. At minimum, protective mechanisms require K
+
, Mg
2+
, phosphate, amino acids, and glucose. There were 158 cases of hyponatremia-associated ODS where both correction rates and other metabolic factors were documented. Compared with the rapid correction group (>0.5 mmol/L/h), the slow correction group (≤0.5 mmol/L/h) had a greater number of cases with concurrent hypokalemia (49.4 vs. 33.3 %,
p
= 0.04), and a greater number of cases with any concurrent metabolic derangements (55.8 vs. 38.3 %,
p
= 0.03).
Conclusion
Glial cell minimizes volume changes and injury in response to hyperosmolar stress via mobilization and/or utilization of various electrolytes and metabolic factors. The prevention of ODS likely requires both minimization of correction rate and optimization of intracellular response during the correction phase when a sufficient supply of various factors is necessary.
Alpha-mangostin (MGS) is a natural xanthone compound extracted from mangosteen pericarps. It has great potential as an excellent anticancer agent. However, the extremely low solubility of MGS in ...water seriously impedes its medical application. Previously, we found that cyclodextrin (CD)-based hyperbranched polymer nanoparticles (CDNPs) solubilize MGS by encapsulating it in the CD cavity and that their binding constants are 100 times higher than those of native CDs. Our findings suggested that CDNPs could be good carriers of MGS. Here, we prepared three types of CDNP from α-, β-, and ɣCDs and compared them in terms of MGS release and in vitro and in vivo anticancer efficacy. βCDNP/MGS demonstrated the greatest anticancer efficacy, while no efficacy was observed for the other CDNPs. MGS release from CDNPs/MGS can be explained by a model in which the slow and rapid modes are connected in series; before release, MGS must shift from the slow to the rapid mode. We assumed that the slow and rapid modes are related to the interior and surface CDs of CDNPs. βCDNP/MGS showed the slowest release in the slow mode. We assume that slow release in the slow mode is essential for MGS retention until the cancerous region is reached.We examined drug release behavior and anticancer efficacy of cyclodextrin-based nanoparticles (CDNPs) containing alpha-mangostin (MGS) in three different type of CDs (α-, β-, and γ-CD). βCDNP containing MGS demonstrated the best anticancer efficacy, while no efficacy was observed for the other CDNPs. Our findings suggested the anticancer efficacy might depend on the drug retention capability in which the interior and surface CDs in the CDNPs relate to the slow and rapid release modes, respectively. We assume the drug retention capability of slow release mode is important for performing the anticancer efficacy.
The CT supply room is a critical resource in the imaging workflow. However, the supply room for the two CT scanners at our cancer center, one of which is used for our busy interventional service, was ...disorganized, and the time spent searching for the appropriate equipment could potentially lead to delays in service and contribute to patient safety risks. The purpose of this project was to reduce the time to find supplies and to increase the satisfaction of CT technologists and medical providers by reorganizing and clearly labeling supplies using "lean" principles. A multidisciplinary team was assembled to reorganize the CT storage using lean 5S methodology (sort, set in order, shine, standardize, and sustain). Baseline and postintervention analysis of the impact of supply reorganization and labeling was performed using three methods:
the time recorded for a supply retrieval scavenger hunt,
a spaghetti diagram of participant movement during the scavenger hunt, and
satisfaction surveys of radiologists and staff. Seven radiology residents participated in the timed supply retrieval scavenger hunt before and after the intervention. Spaghetti diagrams demonstrated a reduction in redundant foot traffic for supply retrieval after the intervention. There was a 61.7% decrease in the average time to retrieve the 10 items in the scavenger hunt (
< .01). Satisfaction surveys after the intervention had statistically significant positive responses compared with those before the intervention.
RSNA, 2024.
Abstract
Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning ...algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set.
Although renal transplantation ameliorates cardiovascular risk factors by restoring renal function, it introduces new cardiovascular risks including impaired glucose tolerance or diabetes mellitus, ...hypertension, and dyslipidemia that are derived, in part, from immunosuppressive medications such as calcineurin inhibitors, corticosteroids, or mammalian target of rapamycin inhibitors. New onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported to occur in 2% to 53% of all solid organ transplants. Kidney transplant recipients who develop NODAT have variably been reported to be at increased risk of fatal and nonfatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Identification of high-risk patients and implementation of measures to reduce the development of NODAT may improve long-term patient and graft outcome. The following article presents an overview of the literature on the current diagnostic criteria for NODAT, its incidence after solid organ transplantation, suggested risk factors and potential pathogenic mechanisms. The impact of NODAT on patient and allograft outcomes and suggested guidelines for early identification and management of NODAT will also be discussed.
Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract ...infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes.
Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients.
The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections.
Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, we report the design, synthesis and evaluation of novel (E)‐3‐(3‐oxo‐4‐substituted‐3,4‐dihydro‐2H‐benzob1,4oxazin‐6‐yl)‐N‐hydroxypropenamides (4 a–i, 7 a–g) targeting histone deacetylases. ...Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC‐3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a–i bearing the alkyl substituents seemed to be less potent than the benzyl‐containing compounds 7 a–g in all biological assays. Compounds 7 e–f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.
Arsenic (As) in rice has been known as a worldwide human health threat that results originally from the accumulation of As in soil in many rice cultivation regions. This study aims to evaluate As ...levels in the soil-rice system in the Mekong River delta (MRD) with special focuses on the geographical distribution and the relation to soil physio-chemical properties. It was found that soil As contents varied from 0.3 to 15.9 mg kg
−1
(
= 7.22 ± 0.3 mg kg
−1
), whereas straw As content was about one order of magnitude lower (
= 0.92 ± 0.1 mg kg
−1
). The content of As in grain varied from "not detectable" to 1115 µg kg
−1
(
= 73 ± 19 µg kg
−1
). Relatively similar geographical distribution patterns were observed for soil As and straw As, meanwhile grain As did not reveal a clear association with straw As and soil As. The accumulation of As in rice (straw and grain) were likely affected by various factors, but the mutual effects of soil As pool and soil properties were the most obvious. The East coastal area of the MRD has been identified as a vulnerable area to As threat. This finding suggests that in addition to the action plans to preserve coastal paddy soils from the threats of sea level rise and salt intrusion, contamination of As should also be considered.
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