Cell and Tissue Research最新文献

Diabetic foot ulcers (DFU) are a type of chronic wound that constitute one of the most serious and debilitating complications associated with diabetes. The lack of clinically efficacious treatments to treat these recalcitrant wounds can lead to amputations for those worst affected. Biomaterial-based approaches offer great hope in this regard, as they provide a template for cell infiltration and tissue repair. However, there is an additional need to treat the underlying pathophysiology of DFUs, in particular insufficient vascularization of the wound which significantly hampers healing. Thus, the addition of pro-angiogenic moieties to biomaterials is a promising strategy to promote the healing of DFUs and other chronic wounds. In this review, we discuss the potential of biomaterials as treatments for DFU and the approaches that can be taken to functionalise these biomaterials such that they promote vascularisation and wound healing in pre-clinical models.

The promising field of regenerative medicine is thrilling as it can repair and restore organs for various debilitating diseases. Mesenchymal stem cells are one of the main components in regenerative medicine that work through the release of secretomes. By adopting the use of the secretome in cell-free-based therapy, we may be able to address the challenges faced in cell-based therapy. As one of the components of cell-free-based therapy, secretome has the advantage of a better safety and efficacy profile than mesenchymal stem cells. However, secretome has its challenges that need to be addressed, such as its bioprocessing methods that may impact the secretome content and its mechanisms of action in clinical settings. Effective and standardization of bioprocessing protocols are important to ensure the supply and sustainability of secretomes for clinical applications. This may eventually impact its commercialization and marketability. In this review, the bioprocessing methods and their impacts on the secretome profile and treatment are discussed. This improves understanding of its fundamental aspects leading to potential clinical applications.

PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein and is associated with the malignant pathological features of several tumors. However, the prognostic value of PDLIM1 and the molecular mechanisms by which it is involved in the metabolism and progression in gastric cancer (GC) are still unclear. The GEPIA database was used to predict the expression and prognosis of PDLIM1 in GC. qRT-PCR and western blot assays were applied to detect the mRNA and protein expression in GC tissues and cells. Loss- and gain-of-function experiments were performed to evaluate the biological role of PDLIM1 in GC cells. The Warburg effect was detected by a battery of glycolytic indicators. The interaction of PDLIM1 and hexokinase 2 (HK2) was determined by a co-immunoprecipitation assay. Furthermore, the modulatory effects of PDLIM1 and HK2 on Wnt/β-catenin signaling were assessed. The results showed that PDLIM1 expression was upregulated in GC tissues and cells and was associated with a poor prognosis for GC patients. PDLIM1 inhibition reduced GC cell proliferation, migration and invasion and promoted cell apoptosis. In the glucose deprivation (GLU-D) condition, the PDLIM1 level was reduced and PDLIM1 overexpression led to an increase in glycolysis. Besides, mechanistic investigation showed that PDLIM1 interacted with HK2 to mediate biological behaviors and the glycolysis of GC through Wnt/β-catenin signaling under glucose deprivation. In conclusion, PDLIM1 interacts with HK2 to promote gastric cancer progression by enhancing the Warburg effect via Wnt/β-catenin signaling.

To investigate the effect and mechanism of Huogu injection (HG) on steroid-induced osteonecrosis of the femoral head (SONFH), we established a SONFH model in rabbits using horse serum and dexamethasone (DEX) and applied HG locally at the hip joint. We evaluated the therapeutic efficacy at 4 weeks using scanning electron microscopy (SEM), micro-CT, and qualitative histology including H&E, Masson's trichrome, ALP, and TUNEL staining. In vitro, we induced osteogenic differentiation of bone marrow stromal cells (BMSCs) and performed analysis on days 14 and 21 of cell differentiation. The findings, in vivo, including SEM, micro-CT, and H&E staining, showed that HG significantly maintained bone quality and trabecular number. ALP staining indicated that HG promoted the proliferation of bone cells. Moreover, the results of Masson's trichrome staining demonstrated the essential role of HG in collagen synthesis. Additionally, TUNEL staining revealed that HG reduced apoptosis. ALP and ARS staining in vitro confirmed that HG enhanced osteogenic differentiation and mineralization, consistent with the WB and qRT-PCR analysis. Furthermore, Annexin V-FITC/PI staining verified that HG inhibited osteoblast apoptosis, in agreement with the WB and qRT-PCR analyses. Furthermore, combined with the UPLC analysis, we found that naringin enhanced the osteogenic differentiation and accelerated the deposition of calcium phosphate. Salvianolic acid B protected osteoblasts derived from BMSCs against GCs-mediated apoptosis. Thus, this study not only reveals the mechanism of HG in promoting osteogenesis and anti-apoptosis of osteoblasts but also identifies the active-related components in HG, by which we provide the evidence for the application of HG in SONFH.

The digestive system structure in pre-zoea and zoea I larvae of the red king crab Paralithodes camtschaticus has been examined. During this development period, the digestive system consists of an esophagus, a stomach, a midgut (where the hepatopancreas ducts open), and a hindgut. The esophagus begins from the oral slit on the animal's ventral side and extends vertically up to the junction with the cardiac stomach. The latter is followed by the pyloric stomach. At the stages under study, crabs have a cardiac-pyloric valve and a pyloric filter in the stomach already developed. The midgut begins with an expansion in the cephalothorax, enters the pleon, grows narrower there, and extends to somite 3 of pleon. The hepatopancreas is represented by a symmetrical paired gland which occupies almost the entire cephalothorax space and opens with its ducts at the junction of the pyloric stomach with the midgut. The hepatopancreas is divided into the anterior and posterior lobes. At the pre-zoea stage, the anterior lobes are large and filled with yolk. At the zoea I stage, the anterior lobes are smaller relative to the entire hepatopancreas, and the posterior lobes increase and form tubular outgrowths. It has been shown that during the transition from pre-zoea to zoea I, the number of mitochondria in enterocytes increases and a peritrophic membrane forms in the midgut. These changes are probably associated with the transition to independent living and feeding.

Nothobranchius furzeri is emerging as an exciting vertebrate organism in the field of biomedicine, developmental biology and ecotoxicology research. Its short generation time, compressed lifespan and accelerated ageing make it a versatile model for longitudinal studies with high traceability. Although in recent years the use of this model has increased enormously, there is still little information on the anatomy, morphology and histology of its main organs. In this paper, we present a description of the digestive system of N. furzeri, with emphasis on the intestine. We note that the general architecture of the intestinal tissue is shared with other vertebrates, and includes a folding mucosa, an outer muscle layer and a myenteric plexus. By immunohistochemical analysis, we reveal that the mucosa harbours the same type of epithelial cells observed in mammals, including enterocytes, goblet cells and enteroendocrine cells, and that the myenteric neurons express neurotransmitters common to other species, such as serotonin, substance P and tyrosine hydroxylase. In addition, we detect the presence of a proliferative compartment at the base of the intestinal folds. The description of the normal intestinal morphology provided here constitutes a baseline information to contrast with tissue alterations in future lines of research assessing pathologies, ageing-related diseases or damage caused by toxic agents.

The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm² in the AC, 166/mm² in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P < 0.001-0.0001). HuCD/SP/ChAT-IR neurons (up to 23%) were overall more abundant than HuCD/SP/nNOS-IR neurons (< 10%). Most SP-IR neurons contained ChAT-IR (62-85%), whereas 18-38% contained nNOS-IR with the highest peak in the OSP. A subpopulation of SP-IR neurons contains both ChAT- and nNOS-IR with the highest peak in the OSP and ISP of DC (33-36%) and the lowest in the ISP of AC (< 10%, P < 0.001). SP-IR varicose fibers were abundant in the ganglia. This study shows that SP-IR neurons are functionally distinct with variable proportions in different plexuses in the AC and DC reflecting diverse functions of specific colonic regions.

Endothelial cells of mammalian blood vessels have multiple levels of heterogeneity along the vascular tree and among different organs. Further heterogeneity results from blood flow turbulence and variations in shear stress. In the aorta, vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates tyrosine kinase receptor Tie2 in the plasma membrane, undergoes downstream polarization and endocytosis in endothelial cells exposed to laminar flow and high shear stress. VE-PTP sequestration promotes Tie2 phosphorylation at tyrosine992 and endothelial barrier tightening. The present study characterized the heterogeneity of VE-PTP polarization, Tie2-pY992 and total Tie2, and claudin-5 in anatomically defined regions of endothelial cells in the mouse descending thoracic aorta, where laminar flow is variable and IgG extravasation is patchy. We discovered that VE-PTP and Tie2-pY992 had mosaic patterns, unlike the uniform distribution of total Tie2. Claudin-5 at tight junctions also had a mosaic pattern, whereas VE-cadherin at adherens junctions bordered all endothelial cells. Importantly, the amounts of Tie2-pY992 and claudin-5 in aortic endothelial cells correlated with downstream polarization of VE-PTP. VE-PTP and Tie2-pY992 also had mosaic patterns in the vena cava, but claudin-5 was nearly absent and extravasated IgG was ubiquitous. Correlation of Tie2-pY992 and claudin-5 with VE-PTP polarization supports their collective interaction in the regulation of endothelial barrier function in the aorta, yet differences between the aorta and vena cava indicate additional flow-related determinants of permeability. Together, the results highlight new levels of endothelial cell functional mosaicism in the aorta and vena cava, where blood flow dynamics are well known to be heterogeneous.