Notes

To Achieving any Vaccine-Derived Group Defenses Limit with regard to COVID-19 within the U.Ersus.
Region specific brain organoids are brain organoids derived by patterning protocols using extrinsic signals as opposed to cerebral organoids obtained by self-patterning. The main focus of this review is to discuss various region-specific brain organoids developed so far and their application in modeling neurodevelopmental disease. We first discuss the principles of neural axis formation by series of growth factors, such as SHH, WNT, BMP signalings, that are critical to generate various region-specific brain organoids. Then we discuss various neurodevelopmental disorders modeled so far with these region-specific brain organoids, and findings made on mechanism and treatment options for neurodevelopmental disorders (NDD).Glia have been known for its pivotal roles in physiological and pathological conditions in the nervous system. To study glial biology, multiple approaches have been applied to utilize glial cells for research, including stem cell-based technologies. Human glial cells differentiated from pluripotent stem cells are now available, allowing us to study the structural and functional roles of glia in the nervous system, although the efficiency is still low. Direct conversion is an advanced strategy governing fate conversion of diverse cell types directly into the desired lineage. This novel strategy stands as a promising approach for preliminary research and regenerative medicine. Direct conversion employs genetic and environmental cues to change cell fate to that with the required functional cell properties while retaining maturity-related molecular features. As an alternative method, it is now possible to obtain a variety of mature cell populations that could not be obtained using conventional differentiation methods. This review summarizes current achievements in obtaining glia, particularly oligodendrocytes and Schwann cells.The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has completely changed human life for more than two years. Upon the emergence of this new lethal virus, multiple approaches were utilized to gain basic knowledge about its biology. Moreover, modern technologies, such as the organoid model system and next-generation sequencing, enabled us to rapidly establish strategies to tackle the disease, including vaccines and therapeutics. The recently developed organoid technology reflects human physiology more closely than other model systems. Coupled with its rapidness, high efficiency, and outstanding reliability, it has provided an opportunity to develop new drugs and understand the impact of the viral pathogen on the host. Recent findings using organoids have successfully revealed the cellular tropism of the virus in different organs and identified potential drug candidates that impact the disease. This review will summarize current achievements made with organoids in the fight against COVID-19.Oncological scoring systems in surgery are used as evidence-based decision aids to best support management through assessing prognosis, effectiveness and recurrence. Currently, the use of scoring systems in the hepato-pancreato-biliary (HPB) field is limited as concerns over precision and applicability prevent their widespread clinical implementation. The aim of this review was to discuss clinically useful oncological scoring systems for surgical management of HPB patients. A narrative review was conducted to appraise oncological HPB scoring systems. Original research articles of established and novel scoring systems were searched using Google Scholar, PubMed, Cochrane, and Ovid Medline. Selected models were determined by authors. This review discusses nine scoring systems in cancers of the liver (CLIP, BCLC, ALBI Grade, RETREAT, Fong's score), pancreas (Genç's score, mGPS), and biliary tract (TMHSS, MEGNA). Eight models used exclusively objective measurements to compute their scores while one used a mixture of both subjective and objective inputs. Seven models evaluated their scoring performance in external populations, with reported discriminatory c-statistic ranging from 0.58 to 0.82. Selection of model variables was most frequently determined using a combination of univariate and multivariate analysis. Calibration, another determinant of model accuracy, was poorly reported amongst nine scoring systems. A diverse range of HPB surgical scoring systems may facilitate evidence-based decisions on patient management and treatment. Future scoring systems need to be developed using heterogenous patient cohorts with improved stratification, with future trends integrating machine learning and genetics to improve outcome prediction.Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2022. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.
Difficulties often encountered in separating and purifying active muscle satellite cells (MSCs) from skeletal muscle tissues have limited the supply of cells for muscle therapy and artificial meat production. Here, we report an effective isolation protocol to economically and conveniently retrieve active MSCs from skeletal muscle tissues in mice.

We optimized an enzyme-based tissue digestion protocol for isolating skeletal muscle-derived primary cell population having a large number of active MSCs and described a method of differential plating (DP) for improving purity of active MSCs from skeletal muscle-derived primary cell population. Then, the age of the mouse appropriate to the isolation of a large number of active MSCs was elucidated. The best isolation yield of active MSCs from mouse skeletal muscle tissues was induced by the application of DP method to the primary cell population harvested from skeletal muscle tissues of 2-week-old mice digested in 0.2% (w/v) collagenase type II for 30 min at 37℃ and then in 0.1% (w/v) pronase for 5 min at 37℃.

The protocol we developed not only facilitates the isolation of MSCs but also maximizes the retrieval of active MSCs. Our expectation is that this protocol will contribute to the development of original technologies essential for muscle therapy and artificial meat industrialization in the future.
The protocol we developed not only facilitates the isolation of MSCs but also maximizes the retrieval of active MSCs. Our expectation is that this protocol will contribute to the development of original technologies essential for muscle therapy and artificial meat industrialization in the future.
Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously. Thus, the objective of this study was to investigate the immunomodulatory effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD.

To explore the mechanism involved in the therapeutic effect of MSCs for AD, a secretome array was performed using culture medium of hUCB-MSCs. Among the list of genes common for epithelium development and skin diseases, we focused on the function of EGF. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA. These cells were then co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF disrupted immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration. It also significantly reduced levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor (TNF)-α, thymus and activation-regulated chemokine (TARC), and IL-22, as well as IgE levels. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs.

EGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.
EGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.
Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment.

BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively.

CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.
CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.
Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema.

hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were divided into four groups Control, Control＋MSC, SU5416 and SU5416＋MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×10
hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed.
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