Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to ...adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature (Sox9
/Cdh5-Cre
RosaYFP) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature (Rbpj
/Cdh5-CreER RosaYFP) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene (Snail, Slug, Twist1, Twist2, TGF-β) expression. Similarly, increased endothelial hedgehog signaling (Ptch1
/Cdh5-CreER RosaYFP), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9, reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9, highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.
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Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally ...unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone–bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.
Spices are the esoteric food adjuncts that are used for enhancing the sensory quality of the food in Punjabi diets and add many health benefits. Estimating the intake of spices at the individual ...level is a challenging task as they are consumed in very small quantities as compared to other foods. The present study aimed to assess the intake and spices consumption level of spices among urban and rural households. A study was carried out among 100 households each from urban and rural areas from Ludhiana district of Punjab, India to collect the information regarding frequency of spice usage and portion sizes using a questionnaire. The information pertaining to sociodemographic characteristics of female respondents from urban and rural households were also collected. The commonly used 25 spices in Punjabi diets were selected to assess their dietary intake at the individual level among households. Spice consumption frequency was more in urban households in comparison to rural households. The maximum mean consumption frequency score among urban and rural households was observed for red chilli powder (5.00) and turmeric powder (5.00). Maximum percentage (76 and 72%) of urban and rural households preferred to use the unroasted form of spices, respectively. The highest mean intake and range was observed for red chilli powder (3.19 g with range 0.35-5.23 g) among urban women and (2.41 g with range 0.25-3.75 g) for rural women. Spice intake from individual dishes showed the maximum number of portion sizes for red chilli powder that were from vegetabledhal > curry preparations among urban and dhal > vegetablecurry preparation among rural households. Average amount of spices consumed by urban adult women was 10.04 g per day which was higher as compared to spices consumed by rural adult women per day (7.68 g). The study concluded that the urban households showed higher consumption of spices as compared to rural households thus assessing the quantifying intake of spices. Urban adult women consumed more spices per day as compared to rural women. Therefore, more encouragement for increased use of spices is required to reap various health benefits of spices in combating metabolic disorders.
Macrophages regulate cutaneous wound healing by immune surveillance, tissue repair and remodelling. The depletion of dermal macrophages during the early and middle stages of wound healing has a ...detrimental impact on wound closure, characterised by reduced vessel density, fibroblast and myofibroblast proliferation, delayed re-epithelization and abated post-healing fibrosis and scar formation. However, in some animal species, oral mucosa and foetal life, cutaneous wounds can heal normally and remain scarless without any involvement of macrophages. These paradoxical observations have created much controversy on macrophages’ indispensable role in skin wound healing. Advanced knowledge gained by characterising macrophage subsets, their plasticity in switching phenotypes and molecular drivers provides new insights into their functional importance during cutaneous wound healing. In this review, we highlight the recent findings on skin macrophage subsets, their functional role in adult cutaneous wound healing and the potential benefits of targeting them for therapeutic use.
The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine ...femoral fracture model internally fixed using a flexible plate (MouseFix) was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80+ Mac-2+ ) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80+ Mac-2neg ), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.
Gamma ray shielding ability of WO3 borate glasses is analyzed by using the Phy-X/PSD software. Mass attenuation coefficient of glasses gets enhanced with addition of tungsten oxide resulting in ...lowering of the values of MFP, HVL, TVL and EBF at 10 mol % of tungsten as compared to many commercial and radiation shielding glasses/concretes. The higher value of FNRCS (∑R) in studied glasses than concretes shows their neutron shielding ability. The sample with highest value of tungsten is most suitable for making radiation shielding materials. The OPD, OMV, n¯c, nb and dbb values indicate the rigid and stable glass structure due to the formations of stable BO4 groups. Poisson ratio confirms high cross density and stability of prepared glasses as its value decreases from 0.233 to 0.226. The increased values of elastic constants and VHN are also in the favour of higher stability and rigidity of the glasses due to addition of WO3. All of these parameters are in good relation with each other and support the shielding power of the studied glasses.
We probe roles of blackbody friction forces (BBFFs) in slowing down alkali atoms, from Li through Fr, for high-precision measurements. An atom can encounter BBFF caused by the blackbody. We probe ...roles of blackbody friction radiations of the stray electromagnetic fields present in experimental set-up and other metallic shielding during measurements. Strengths of BBFFs on the alkali atoms are estimated by integrating complex parts of dynamic polarizabilities of atoms over a wide range of frequency. Slowdown times of moving atoms due to these friction forces are analysed as a function of temperature. The results are determined by both including and excluding nonresonant contributions in the polarizabilities of atomic states. This shows that inclusion of nonresonant contributions affects the slowdown time of atoms significantly at low temperatures. Our study will be useful in accounting for these slowdown times in the ongoing and future high-precision experiments involving alkali atoms.
Graphic Abstract
Distinct subsets of resident tissue macrophages are important in hematopoietic stem cell niche homeostasis and erythropoiesis. We used a myeloid reporter gene (Csf1r-eGFP) to dissect the persistence ...of bone marrow and splenic macrophage subsets following lethal irradiation and autologous hematopoietic stem cell transplantation in a mouse model. Multiple recipient bone marrow and splenic macrophage subsets survived after autologous hematopoietic stem cell transplantation with organ-specific persistence kinetics. Short-term persistence (5 weeks) of recipient resident macrophages in spleen paralleled the duration of extramedullary hematopoiesis. In bone marrow, radiation-resistant recipient CD169+ resident macrophages and erythroid-island macrophages self-repopulated long-term after transplantation via autonomous cell division. Posttransplant peak expansion of recipient CD169+ resident macrophage number in bone marrow aligned with the persistent engraftment of phenotypic long-term reconstituting hematopoietic stem cells within bone marrow. Selective depletion of recipient CD169+ macrophages significantly compromised the engraftment of phenotypic long-term reconstituting hematopoietic stem cells and consequently impaired hematopoietic reconstitution. Recipient bone marrow resident macrophages are essential for optimal hematopoietic stem cell transplantation outcomes and could be an important consideration in the development of pretransplant conditioning therapies and/or chemoresistance approaches.
•Recipient macrophages persist in hematopoietic tissues and self-repopulate via in situ proliferation after syngeneic transplantation.•Targeted depletion of recipient CD169+ macrophages after transplant impaired long-term bone marrow engraftment of hematopoietic stem cells.
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Wnt signaling controls blood vessel growth, regression and patterning during embryonic and postnatal life. Macrophages are major producers of Wnt ligands and angiogenic growth factors. It regulates ...vascular development and specification during embryogenesis and wound healing. Macrophage dysregulation in wound healing impairs vessel regeneration and delay wound closure. During cutaneous wound healing, the endovascular progenitors (EVPs) proliferate and differentiate into mature endothelial (D) cells in response to signals produced by perivascular cells, including macrophages, governing blood vessels regeneration. However, the role of macrophage’s Wnt production on endothelial cells, especially the EVPs during wound healing is currently unknown. Here we used a cutaneous excisional wound model in mice with conditional deletion of Wnt secretion by myeloid cells (
Wls
fl/fl
LysM-Cre
+
) to assess the kinetics of endothelial subpopulations (including EVP), myeloid infiltration, collagen deposition and wound closure. Deletion of
Wls
expression by myeloid cells did not affect wound closure and collagen deposition, indicating that myeloid
Wls
expression does not promote wound healing and regeneration. Myeloid-specific
Wls
deletion elevated the EVP population during the peak of angiogenesis, yet without affecting blood vessel density. Wounds in
Wls
fl/fl
LysM-Cre
+
animals showed unperturbed myeloid infiltration and differentiation. Overall, our data indicate that macrophage Wnt production shapes EVP kinetics without major relevance to wound healing. These findings extend the knowledge of macrophage and endothelial molecular crosstalk and position myeloid-derived Wnt production as a regulator of endovascular progenitor.
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