Review on tissue repair and M1‐like to M2a‐like macrophages, exhibiting important differences from in vitro phenotypes.
Mp are crucial for tissue repair and regeneration but can also contribute to ...tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best‐characterized in vitro phenotypes are a proinflammatory “M1” phenotype, produced by exposure to IFN‐γ and TNF‐α, and an anti‐inflammatory “M2a” phenotype, produced by IL‐4 or IL‐13. M2a Mp are frequently termed “wound healing” Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro‐defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a‐associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1‐ and M2‐associated markers may be expressed simultaneously by actual tissue‐repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
Mounting evidence suggests that therapeutic cell and drug delivery strategies designed to actively harness the regenerative potential of the inflammatory response have great potential in regenerative ...medicine. In particular, macrophages have emerged as a primary target because of their critical roles in regulating multiple phases of tissue repair through their unique ability to rapidly shift phenotypes. Herein, we review macrophage-based therapies, focusing on the translational potential for cell delivery of ex vivo-activated macrophages and delivery of molecules and biomaterials to modulate accumulation and phenotype of endogenous macrophages. We also review current obstacles to progress in translating basic findings to therapeutic applications, including the need for improved understanding of context-dependent macrophage functions and the myriad factors that regulate macrophage phenotype; potential species-specific differences (e.g. humans versus mice); quality control issues; and the lack of standardized procedures and nomenclature for characterizing macrophages. Looking forward, the inherent plasticity of macrophages represents a daunting challenge for harnessing these cells in regenerative medicine therapies but also great opportunity for improving patient outcomes in a variety of pathological conditions.
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Polylactic acid (PLA) and Starch are both bio-based biodegradable polymers that have properties that are complementary to each other. PLA/starch blend exploits the good mechanical property of PLA and ...the low cost of Starch. However, PLA/Starch blend is intrinsically brittle. This paper reviews the current state of arts in toughening of PLA/Starch blend, which are categorized as: Additive Plasticization, Mixture Softening, Elastomer Toughening and Interphase Compatibilization. These strategies are not mutually exclusive and can be applied jointly in a single blend, opening up a wide range of toughening techniques that can be employed in PLA/Starch blend. Even though significant progress has been made in this area, there is still much room for research, in order to achieve easy to process, fully bio-based and completely biodegradable PLA/Starch blends that have mechanical properties suitable for a wide range of applications.
The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have many functions in wounds, including host defence, the promotion ...and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound and that the influence of these cells on each stage of repair varies with the specific phenotype. Although the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation or fibrosis under certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds. As a result of advances in the understanding of this multifunctional cell, the macrophage continues to be an attractive therapeutic target, both to reduce fibrosis and scarring, and to improve healing of chronic wounds.
The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during ...the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p<0.05). Thailand had all the highest scores of IES-R, DASS-21 stress, anxiety, and depression scores whereas Vietnam had all the lowest scores. The risk factors for adverse mental health during the COVID-19 pandemic include age <30 years, high education background, single and separated status, discrimination by other countries and contact with people with COVID-19 (p<0.05). The protective factors for mental health include male gender, staying with children or more than 6 people in the same household, employment, confidence in doctors, high perceived likelihood of survival, and spending less time on health information (p<0.05). This comparative study among 7 MICs enhanced the understanding of metal health in the general population during the COVID-19 pandemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Macrophages are essential for the efficient healing of numerous tissues, and they contribute to impaired healing and fibrosis. Tissue repair proceeds through overlapping phases of inflammation, ...proliferation, and remodeling, and macrophages are present throughout this progression. Macrophages exhibit transitions in phenotype and function as tissue repair progresses, although the precise factors regulating these transitions remain poorly defined. In efficiently healing injuries, macrophages present during a given stage of repair appear to orchestrate transition into the next phase and, in turn, can promote debridement of the injury site, cell proliferation and angiogenesis, collagen deposition, and matrix remodeling. However, dysregulated macrophage function can contribute to failure to heal or fibrosis in several pathological situations. This review will address current knowledge of the origins and functions of macrophages during the progression of tissue repair, with emphasis on skin and skeletal muscle. Dysregulation of macrophages in disease states and therapies targeting macrophage activation to promote tissue repair are also discussed.
Water and energy are intimately intertwined, and it is high time to put forth integrated approaches to address the challenges and opportunities of the water-energy nexus. Herein, a novel fluidic ...photothermal structure integrated with a brine-drenching induced electricity generator is reported for simultaneous clean water and power production. The fluidic photothermal structure is capable of sustaining solar-thermal distillation systems (
e.g.
interfacial and multi-stage configurations) at high energy conversion efficiency while completely preventing salt formation from occurring in the long-term desalination process, by taking advantage of unidirectional brine fluid transportation. The brine-drenching induced electricity allows immediate power generation with a piece of wet fabric only. Furthermore, the fabric-based energy generator exhibits remarkable programmable properties, and we have also demonstrated that power generation is also achievable with different water sources such as human sweat, groundwater and rainwater, which opens up exciting applications in various fields of energy harvesting and water detection systems, and provides a promising solution for sustainable powering of wearable devices and electronics.
A fluidic photothermal structure is demonstrated for completely salt-rejecting solar water extraction and simultaneous brine-drenching induced energy generation.
► Diabetic wounds exhibit impaired healing and a persistent inflammatory response. ► Macrophages were isolated from excisional wounds of diabetic and non-diabetic mice. ► Macrophages in non-diabetic ...mice exhibit phenotypes associated with healing. ► Macrophages in diabetic mice exhibit a persistent pro-inflammatory phenotype. ► The persistent pro-inflammatory phenotype in diabetic mice may impede healing.
The hypothesis of this study was that cells of the monocyte/macrophage lineage (Mo/Mp) exhibit an impaired transition from pro-inflammatory to pro-healing phenotypes in wounds of diabetic mice, which contributes to deficient healing. Mo/Mp isolated from excisional wounds in non-diabetic db/+ mice exhibited a pro-inflammatory phenotype on day 5 post-injury, with high level expression of the pro-inflammatory molecules interleukin-1β, matrix metalloprotease-9 and inducible nitric oxide synthase. Wound Mo/Mp exhibited a less inflammatory phenotype on day 10 post-injury, with decreased expression of the pro-inflammatory molecules and increased expression of the alternative activation markers CD206 and CD36. In contrast, in db/db mice, the pro-inflammatory phenotype persisted through day 10 post-injury and was associated with reduced expression of insulin-like growth factor-1, transforming growth factor-β1 and vascular endothelial growth factor. Reduced levels of these growth factors in wounds of db/db mice may have contributed to impaired wound closure, reduced granulation tissue formation, angiogenesis and collagen deposition. The persistent pro-inflammatory wound Mo/Mp phenotype in db/db mice may have resulted from elevated levels of pro-inflammatory interleukin-1β and interferon-γ and reduced levels of anti-inflammatory interleukin-10 in the wound environment. Our findings are consistent with the hypothesis that dysregulation of Mo/Mp phenotypes contributes to impaired healing of diabetic wounds.
Macrophages are thought to play important roles during wound healing, but definition of these roles has been hampered by our technical inability to specifically eliminate macrophages during wound ...repair. The purpose of this study was to test the hypothesis that specific depletion of macrophages after excisional skin wounding would detrimentally affect healing by reducing the production of growth factors important in the repair process. We used transgenic mice that express the human diphtheria toxin (DT) receptor under the control of the CD11b promoter (DTR mice) to specifically ablate macrophages during wound healing. Mice without the transgene are relatively insensitive to DT, and administration of DT to wild-type mice does not alter macrophage or other inflammatory cell accumulation after injury and does not influence wound healing. In contrast, treatment of DTR mice with DT prevented macrophage accumulation in healing wounds but did not affect the accumulation of neutrophils or monocytes. Such macrophage depletion resulted in delayed re-epithelialization, reduced collagen deposition, impaired angiogenesis, and decreased cell proliferation in the healing wounds. These adverse changes were associated with increased levels of tumor necrosis factor-α and reduced levels of transforming growth factor-β1 and vascular endothelial growth factor in the wound. In summary, macrophages seem to promote both wound closure and dermal healing, in part by regulating the cytokine environment of the healing wound.
Information about the frequency and intensity of extreme precipitation is generally derived from fitting extreme value models using point‐observations, but the regionalization of these models is ...challenging. Here we propose using high‐resolution convection‐permitting climate model output as covariates for the estimation of observation‐based spatial rainfall return levels. We apply the Weather and Forecasting Research (WRF) model at a 1.5 km resolution driven by ERA5 reanalysis data over southern Germany, where 1,132 rain gauges provide observations of daily rainfall. For this complex topography, we build three different smooth spatial Generalized Extreme Value (GEV) models: (a) a reference model using latitude, longitude and elevation as covariates; (b) a model adding mean annual precipitation from the WRF; (c) a model adding extreme value statistical model estimates using WRF output. We show that the additional information provided by the WRF model can improve the representation of 10‐year and 100‐year return levels of daily rainfall by lowering the percentage bias, mean absolute error, and root‐mean‐square error. Furthermore, we conduct an extensive cross‐validation, where only 5%, 10%, 20%, 50%, 80%, 90%, and 95% of all rain gauges are considered when building spatial GEV models. Again, the additional information provided by the WRF model can improve results here. This cross‐validation study also highlights the robustness of our approach, showing great potential for use in data‐scarce regions.
Plain Language Summary
Heavy rainfall can trigger floods or landslides. In order to estimate the occurrence probability of these events, statistical models can be built using rainfall observations. However, these measurements are mostly point measurements and hence, one needs to interpolate in space when performing regional analyses. Often, topographical features such as elevation, latitude, and longitude are chosen as auxiliary variables to facilitate this interpolation. Here, we propose to add high‐resolution climate simulations as covariates. We compare three different setups which use data over southern Germany, where a dense rain gauge coverage is available: (a) a reference model using latitude, longitude, and elevation as covariates; (b) a model adding mean annual precipitation from the climate simulation; (c) a model adding extreme value statistical model estimates using data from the climate simulation. We show that the additional information provided by the climate model can improve the spatial representation of extreme daily rainfall. In most parts of the world, the rain gauge density is less than in the study area. Therefore, we test our three approaches with smaller subsets of the observational data. Our approach shows robustness under these conditions, highlighting potential for regions where observational coverage is scarcer but high‐resolution climate simulations are available.
Key Points
We utilize high‐resolution climate model data as covariates in spatial Generalized Extreme Value models to assess extreme precipitation
Compared to using only topographical information, adding climate model data can improve the representation of 10‐ and 100‐year return levels
An extensive cross‐validation study shows great potential of our approach for data‐scarce regions
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