Potential Mechanisms of the Impact of Hepatocyte Growth Factor Gene-Modified Tendon Stem Cells on Tendon Healing

The therapeutic impact of stem cells is potentially largely attributable to secretion of exosomes and soluble factors. The present study evaluates the impact of hepatocyte growth factor (HGF)–expressing tendon stem cells (TSCs) on tendon healing in a rat model. Patellar tendon TSCs were isolated and underwent transfection with lentiviral vectors containing HGF or green fluorescent protein (GFP) genes. In vivo, immunohistochemistry of tendons sampled 1 week postsurgery demonstrated that all stem cell–treated groups exhibited higher numbers of CD163+ M2 monocytes and IL-10+ cells (anti-inflammatory), and lower numbers of CCR7+ M1 monocytes and IL-6+ as well as COX-2+ cells (pro-inflammatory). Effects were most pronounced in the HGF-expressing TSCs (TSCs + HGF) treated group. Histology ± immunohistochemistry of tendons sampled 4 and 8 weeks postsurgery demonstrated that all stem cell–treated groups exhibited more ordered collagen fiber arrangement and lower levels of COLIII, α-SMA, TGF-β1, and fibronectin (proteins relevant to fibroscarring). Effects were most pronounced in the TSCs + HGF–treated group. For the in vitro study, isolated tendon fibroblasts pretreated with TGF-β1 to mimic the in vivo microenvironment of tendon injury were indirectly cocultured with TSCs, TSCs + GFP, or TSCs + HGF using a transwell system. Western blotting demonstrated that all stem cell types decreased TGF-β1-induced increases in fibroblast levels of COX-2, COLIII, and α-SMA, concomitant with decreased activation of major TGF-β1 signaling pathways (p38 MAPK, ERK1/2, but not Smad2/3). This effect was most pronounced for TSCs + HGF, which also decreased the TGF-β1-induced increase in activation of the Smad2/3 signaling pathway. The presence of specific inhibitors of these pathways during fibroblast TGF-β1 stimulation also attenuated increases in levels of COX-2, COLIII, and α-SMA. In conclusion, TSCs + HGF, which exhibit HGF overexpression, may promoting tendon healing via decreasing inflammation and fibrosis, perhaps partly via inhibiting TGF-β1-induced signaling. These findings identify a novel potential therapeutic strategy for tendon injuries, warranting additional research

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Metodika zpracování "Směrnice velitele záchranných sil leteckého dne"

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta hornicko-geologická. Institut bezpečnostního inženýrství (547

Current Sample Preparation Methodologies for Determination of Catecholamines and Their Metabolites

Catecholamines (CAs) and their metabolites play significant roles in many physiological processes. Changes in CAs concentration in vivo can serve as potential indicators for the diagnosis of several diseases such as pheochromocytoma and paraganglioma. Thus, the accurate quantification of CAs and their metabolites in biological samples is quite important and has attracted great research interest. However, due to their extremely low concentrations and numerous co-existing biological interferences, direct analysis of these endogenous compounds often suffers from severe difficulties. Employing suitable sample preparation techniques before instrument detection to enrich the target analytes and remove the interferences is a practicable and straightforward approach. To date, many sample preparation techniques such as solid-phase extraction (SPE), and liquid-liquid extraction (LLE) have been utilized to extract CAs and their metabolites from various biological samples. More recently, several modern techniques such as solid-phase microextraction (SPME), liquid–liquid microextraction (LLME), dispersive solid-phase extraction (DSPE), and chemical derivatizations have also been used with certain advanced features of automation and miniaturization. There are no review articles with the emphasis on sample preparations for the determination of catecholamine neurotransmitters in biological samples. Thus, this review aims to summarize recent progress and advances from 2015 to 2021, with emphasis on the sample preparation techniques combined with separation-based detection methods such capillary electrophoresis (CE) or liquid chromatography (LC) with various detectors. The current review manuscript would be helpful for the researchers with their research interests in diagnostic analysis and biological systems to choose suitable sample pretreatment and detection methods

Design of a Subretinal Injection Robot Based on the RCM Mechanism

This study presents an investigation focusing on the advancement of a robot designed for subretinal injections in the context of macular degeneration treatment. The technique of subretinal injection surgery stands as the most efficacious approach for the successful transplantation of stem cells into the retinal pigment epithelium layer. This particular procedure holds immense significance in advancing research and implementing therapeutic strategies involving retinal stem cell transplantation. The execution of artificial subretinal surgery poses considerable challenges which can be effectively addressed through the utilization of subretinal injection surgery robots. The development process involved a comprehensive modeling phase, integrating computer-aided design (CAD) and finite element analysis (FEA) techniques. These simulations facilitated iterative enhancements of the mechanical aspects pertaining to the robotic arm. Furthermore, MATLAB was employed to simulate and visualize the robot’s workspace, and independent verification was conducted to ascertain the range of motion for each degree of freedom

Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3

Abstract Background The use of adipose-derived mesenchymal stromal cell-derived exosomes (ADSC-Exos) may become a new therapeutic method in biomedicine owing to their important role in regenerative medicine. However, the role of ADSC-Exos in tendon repair has not yet been evaluated. Therefore, we aimed to clarify the healing effects of ADSC-Exos on tendon injury. Methods The adipose-derived mesenchymal stromal cells (ADSCs) and tendon stem cells (TSCs) were isolated from the subcutaneous fat and tendon tissues of Sprague-Dawley rats, respectively, and exosomes were isolated from ADSCs. The proliferation and migration of TSCs induced by ADSC-Exos were analyzed by EdU, cell scratch, and transwell assays. We used western blot to analyze the tenogenic differentiation of TSCs and the role of the SMAD signaling pathways. Then, we explored a new treatment method for tendon injury, combining exosome therapy with local targeting using a biohydrogel. Immunofluorescence and immunohistochemistry were used to detect the expression of inflammatory and tenogenic differentiation after tendon injury, respectively. The quality of tendon healing was evaluated by hematoxylin-eosin (H&E) staining and biomechanical testing. Results ADSC-Exos could be absorbed by TSCs and promoted the proliferation, migration, and tenogenic differentiation of these cells. This effect may have depended on the activation of the SMAD2/3 and SMAD1/5/9 pathways. Furthermore, ADSC-Exos inhibited the early inflammatory reaction and promoted tendon healing in vivo. Conclusions Overall, we demonstrated that ADSC-Exos contributed to tendon regeneration and provided proof of concept of a new approach for treating tendon injuries

From crystal structure of α-conotoxin GIC in complex with Ac-AChBP to molecular determinants of its high selectivity for α3β2 nAChR

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking data, we suggest the key residues of GIC in determining its high affinity and selectivity for human α3β2 vs α3β4 nAChRs. These suggestions were checked by radioligand and electrophysiology experiments, which confirmed the functional role of detected contacts for GIC interactions with Ac-AChBP and α3β2 nAChR subtypes. While GIC elements responsible for its high affinity binding with Ac-AChBP and α3β2 nAChR were identified, our study also showed the limitations of computer modelling in extending the data from the X-ray structures of the AChBP complexes to all nAChR subtypes

Additional file 3: Table S3. of Genome-wide identification of lncRNAs associated with chlorantraniliprole resistance in diamondback moth Plutella xylostella (L.)

Differentially expressed lncRNAs between CHS and CHR as well as CHS and ZZ. (XLSX 26 kb

Nursing of two patients with suspected Creutzfeldt-Jakob disease (2例疑似克雅氏病患者的护理)

To summarize the nursing experiences of two patients with suspected Creutzfeldt-Jakob disease (CJD). Because of the complex clinical manifestation and rapid course of CD, nurses caring for patients and families are challenged to understand the nature of CJD, manage the patients’ signs and symptoms, and create a therapeutic experience by integrating the psychological, emotional, spiritual, and social components of nursing care. During the hospitalization, nurses had closely observed the changes of patients’ conditions, maintained the patients’ airway unobstructed, strictly executed the disinfection and isolation rules, and carried out the corresponding protection and nursing. Neither patient had any nursing related complications or cross infection during hospitalization. (本文总结2例疑似克雅氏病患者护理的经验。克雅氏病临床表现复杂, 病程进展快速, 临床护士需要了解克雅氏病的本质, 管理患者的症状和体征, 并通过整合护理的心理、情感、精神和社会组成部分来创造治疗经验。在院期间, 应严密观察病情变化, 保持患者呼吸道通畅; 严格执行消毒隔离制度, 做好相应消毒隔离的防护护理。2例患者住院期间未发生护理相关并发症, 未出现交叉感染。

Do different vegetative organs exhibit a similar temperature sensitivity in growth?

Although phenology and growth traits of leaves or woods have been the focus of research on growth-climate relationships, more is needed regarding whether there is a consistent growth response of different organs to environmental change. However, such work is crucial to accurately assess the impact of climate change on tree growth. Here, the growth timing, duration, rate, and increment of Picea meyeri needles, shoots, and stems were examined, and the corresponding environmental effects were revealed along an altitudinal gradient (2040–2740 m a.s.l.) in North-Central China during 2016 and 2017. The three organs showed a consistent altitudinal variation in growth onset timing, but a different variation in other traits; the growth duration, rate, and increment of needles changed slightly while those of shoots and stems dropped markedly with altitude. The air temperature was the key environmental factor driving the altitudinal variation. For each 1 °C increase in air temperature, the onset timing of needle and shoot elongation and xylem cell production was synchronously advanced by 3.3–3.7 ± 0.2 days; the peak timing was advanced by 3.4 ± 0.2 days, 2.2 ± 0.1 days, and 0 days; and the cessation timing was delayed by −3.8 ± 0.0 days, 2.1 ± 0.3 days, and 2.4 ± 0.1 days. Meanwhile, the duration was lengthened by 0 days, 5.6 ± 0.3 days, and 6.4 ± 0.2 days, respectively; the average rate was improved by 0%, 7.0 ± 1.2%, and 6.5 ± 0.5%, respectively; the increment was increased by 1.3 ± 0.1%, 8.2 ± 0.4%, and 11.0 ± 0.4%, respectively. These findings suggested that the aboveground vegetative growth of P. meyeri exhibits different temperature sensitivities; stem growth will benefit more from future warming than shoot and needle growth. It adds a new clue to conducting growth-climate relationship studies, and the response difference of organ growth to temperature should be considered in revealing future climate warming on tree growth