Number Of Blood Vessels Research Articles

Stimuli-induced NOergic Molecules and Neuropeptides Mediated Axon Reflexes Contribute to Tracers along Meridian Pathways.

An abundance of studies from different international groups have demonstrated tracers along linear pathways resembling meridians over the body surface of humans. All experiments of the studies have been conducted by injection of a radiotracer solution or tracer dyes in a volume of solution into acupuncture points (acupoints). The solution injected into acupoints produces much stronger mechanical stimuli than acupuncture, which causes axon reflex. Anatomical studies have demonstrated that acupoints/meridians exist higher number of small nerve fibers and blood vessels with rich nitric oxide (NO) and neuropeptides in the cutaneous tissues as structures for the biomolecules mediated axon reflexes. Recent advances have determined that NO and calcitonin generelated peptides play crucial roles in the comprehension of the axon reflex. The stimuli-evoked axon reflex and NOergic biomolecules/neuropeptides increase local blood flow with higher levels in acupoints/meridians, which move radioactive substances or tracer dyes in the skin and subcutaneous tissue under a linear path resembling acupoints and meridians, the important phenomena of meridians induced by the stimuli. The evidence and understanding of the biomolecular processes of the tracers along linear pathways resembling meridians have been summarized with an emphasis on recent developments of NO and neuropeptides mediating stimuli-evoked axon reflexes to increase local blood flow with higher levels in acupoints/meridians, which move radioactive substances or tracer dyes in the skin and subcutaneous tissue contributing to tracers along linear pathways resembling meridians in this mini-review.

Transmembrane stem factor nanodiscs enhanced revascularization in a hind limb ischemia model in diabetic, hyperlipidemic rabbits

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.

Polydioxanone Enhances Bone Regeneration After Resection and Reconstruction of Rat Femur with rhBMP2.

The aim of this study was to assess the bone regeneration potential of a polydioxanone (PDO) scaffold together with recombinant human bone morphogenetic protein-2 (rhBMP-2) for the reconstruction of large bone defect. In total, 24 male rats (6 months old) were subjected to bilateral femoral stabilization using titanium plates to create a 2 mm gap, and reconstruction using rhBMP-2 (Infuse®; 3.25 μg). The bone defects were covered with PDO (PDO group), or with titanium mesh (Ti group). Animals were euthanized on days 14 and 60. Simultaneously, 16 rats received PDO and Ti in their dorsum for the purpose of biocompatibility analysis at 3, 5, 7, and 10 days postoperatively. X-ray densitometry showed a higher density in the PDO group on day 14. On day 60, coverage of the bone defect with PDO showed a larger quantity of newly formed bone than that found for the Ti group, a lower inflammatory infiltrate value, and a more significant number of blood vessels on day 14. By immunohistochemical assessment, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) showed higher labeling on day 14 in the PDO group. On day 60, bone morphogenetic protein-2 (BMP-2) showed higher labeling in the PDO group, whereas Ti showed higher labeling for osteoprotegerin, nuclear factor kappa B ligand-activating receptor, RUNX2, and OCN. Furthermore, biocompatibility analysis showed a higher inflammatory response in the Ti group. The PDO scaffold enhanced bone regeneration when associated with rhBMP-2 in rat femur reconstruction. Impact statement Regeneration of segmental bone defects is a difficult task, and several techniques and materials have been used. Recent advances in the production of synthetic polymers, such as polydioxanone (PDO), produced by three-dimensional printing, have shown distinct characteristics that could improve tissue regeneration even in an important bone defect. The present preclinical study showed that PDO membranes used as scaffolds to carry recombinant human bone morphogenetic protein-2 (rhBMP-2) improved bone tissue regeneration by more than 8-fold when compared with titanium mesh, suggesting that PDO membranes could be a feasible and useful material for use in guided bone regeneration. (In English, viable is only used for living creatures capable of sustaining life.

Microbiota derived d-malate inhibits skeletal muscle growth and angiogenesis during aging via acetylation of Cyclin A

Metabolites derived from the intestinal microbiota play an important role in maintaining skeletal muscle growth, function, and metabolism. Here, we found that D-malate (DMA) is produced by mouse intestinal microorganisms and its levels increase during aging. Moreover, we observed that dietary supplementation of 2% DMA inhibits metabolism in mice, resulting in reduced muscle mass, strength, and the number of blood vessels, as well as the skeletal muscle fiber type I/IIb ratio. In vitro assays demonstrate that DMA decreases the proliferation of vascular endothelial cells and suppresses the formation of blood vessels. In vivo, we further demonstrated that boosting angiogenesis by muscular VEGFB injection rescues the inhibitory effects of d-malate on muscle mass and fiber area. By transcriptomics analysis, we identified that the mechanism underlying the effects of DMA depends on the elevated intracellular acetyl-CoA content and increased Cyclin A acetylation rather than redox balance. This study reveals a novel mechanism by which gut microbes impair muscle angiogenesis and may provide a therapeutic target for skeletal muscle dysfunction in cancer or aging.

Preparation and characterization of a jelly fig (Ficus awkeotsang Makino) polysaccharide-based bioactive 3D scaffold for improved vascularization and skin tissue engineering applications

Jelly fig polysaccharides (JFP) were extracted from Ficus awkeotsang Makino achenes. The yield of JFP was approximately 10–15 %. FT-IR spectrum of the extracted JFP confirmed that it was made of low methoxyl pectin (LMP). 3D scaffolds of JFP (JFP scaffold) were fabricated using ionic crosslinking of 2 % (w/v) JFP solution with Ca2+ ions and freeze-drying. The JFP scaffold showed 73.46 ± 1.97 % porosity and a 12-fold swelling capacity. The porous morphology was also observed in SEM micrographs. JFP scaffolds were completely degraded in 14 days when incubated in 1 mg/mL lysozyme solution, compared to the 50 % degradation observed in PBS alone. The antioxidant activity of the JFP and JFP scaffold was approximately 40 %. The hemolytic assay of the JFP scaffold showed <5 % (3.0 ± 0.4) RBC lysis. The cytocompatibility of the JFP scaffold was evaluated using L929 mouse fibroblasts and human dermal fibroblasts (HDF). The in vitro studies using L929 cells showed that the JFP scaffold is cytocompatible. HDF cells cultured in the presence of JFP scaffolds show a higher fold cell viability, proliferation, and migration. Collagen expression and deposition were also studied, and no significant changes occurred with JFP scaffold treatment. In vivo CAM assay showed an increase in the number and thickness of blood vessels by 1.185-fold and 1.19-fold, respectively. These results confirm the angiogenic property of the JFP scaffold. These biocompatible and bioactive properties of the JFP scaffold could be beneficial for tissue engineering and regenerative medicine applications.

Distribution of neurovascular structures within the prostate gland and their relationship to complications after radical prostatectomy.

Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy. Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired ttests were applied to establish statistically significant differences across the measured variables. Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer. We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes.

Bioactive additives from the dorsal dermis of mice for enhanced vascularization in 3D bioprinting.

Effective angiogenesis is essential for creating complex vascular networks in tissue engineering; however, there is a scarcity of safe and potent pro-angiogenic factors. Although a decellularized extracellular matrix (dECM) offers excellent biocompatibility and is widely used in tissue engineering as a pro-angiogenic additive, its conventional extraction technique resulting in significant loss of bioactivity limits clinical potential. The dorsal dermal tissue has rich blood perfusion and its dECM is rich in angiogenic factors. In this study, the dECM components from the dorsal dermis of mice (DD) were produced to enhance in vitro and in vivo pro-angiogenic abilities using a novel physical method. Morphological studies showed no significant difference between DD-wild-type (DD-wt) and DD-wild-type-newborn (DD-wtn), and there was also no difference in DNA or RNA concentration. In addition, DD-wtn outperformed DD-wt in maintaining the stemness of MSCs, promoting inflammatory response and facilitating endothelial cell differentiation. It is of greater significance to note that the dermal combined fibrous capsule thickness is greater in the DD-wt treated group than in the DD-wtn group. Furthermore, the number of blood vessels in the subcutaneously implanted scaffold with DD-wtn increased by 233%. Consequently, our current finding provides a promising strategy to produce a novel pro-angiogenic bioink additive for enhancing vascularization in 3D bioprinting.

Mesenchymal stem cells from human umbilical cord decrease inflammation and increase vascularization of induced apical periodontitis model in diabetes mellitus rats.

to evaluate inflammation and vascularization in a model of apical periodontitis in diabetic Wistar rats through histopathological examination of blood vessels and immunohistochemical examination of interleukin 1b (IL-1b) and tumor necrosis factor-a (TNF-a). Diabetes was induced in 20 Wistar rats using multiple low-dose injections of streptozotocin (STZ) until blood glucose levels stabilized above 300 mg/dL, confirmed by glucometer. Under anesthesia, apical periodontitis was induced in the right mandibular first molars. After preparing the access cavity and extirpating pulp and canal, the teeth were left open. Apical periodontitis was projected seven days afterwards and the Wistar rats were assigned in random into four groups, each group consisting of five rats. The first group (C14) was euthanized 14 days post-induction, while the second group (C28) was euthanized 28 days later, serving as controls. The third group (T14) received mesenchymal stem cells from human umbilical cords and was euthanized after 14 days, while the fourth group (T28) received mesenchymal stem cells from human umbilical cord and was euthanized after 28 days. The number of blood vessels and the expressions of IL-1b and TNF-a were analyzed. Data were evaluated with ANOVA and by Tukey's HSD test, with significance at p<0.05. Both control and treatment groups showed a significant increase in vascularization in the apical periodontal area of apical periodontitis in the control and treatment groups at 14 and 28 days (p<0.05). A significant reduction of IL-1b and TNF-a levels was found in the mesenchymal stem cells treatment groups when compared to control groups (p<0.05). Our findings support the use of mesenchymal stem cells from human umbilical cords to decrease inflammation and increase vascularization in an induced apical periodontitis model in diabetes mellitus Wistar rats.

Organisms-on-a-chip

The progression of fibrosis is frequently related to a failed healing process, and it may affect many tissues and organs causing severe consequences including post-infarct heart insufficiency, post-injury limb paralysis, cirrhosis, nephropathy, retinopathy, failure of implanted devices and even resistance to chemotherapy in solid tumours. Experimental models, both in vitro and in vivo, are widely used for studies of basic pathophysiology, and for pre-clinical testing of pharmacological therapies counteracting fibrosis. However, conventional models are not able to realistically reproduce the revascularization aspect of the inflammatory reaction that leads to the generation of fibrotic tissue. In this talk, I will present the most advanced frontier in this sector, represented by the new concept of an “organism-on-a-chip”. This is a hybrid model, in which an organ-on-a-chip is implanted sub-cute in a living organism, such as a mouse or an embryonated avian egg, thus eliciting a foreign-body reaction with the formation of a fibrotic microenvironment. In an organism-on-a-chip, the fibrotic reaction can be guided using microscopic scaffolds incorporated in the implanted chip. The fibrotic microenvironment can then be imaged longitudinally, in high resolution, in single and multiphoton optical microscopy, with the added advantage of significantly reducing animal sacrifice. The optical measurements performed in the platform address parameters of the extra-cellular matrix (stiffness, collagen density, collagen orientation, coefficient of diffusion) and vascularity (number of blood vessels, length, blood velocity and vessel permeability).

Regenerative role of mast cells and mesenchymal stem cells in histopathology of the sciatic nerve and tibialis cranialis muscle, following denervation in rats.

Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells. Ninety adult male Wistar rats were divided into six main groups (n=15) and three subgroups (2, 4, and 8 weeks). Groups: control; without surgery, Tr; sciatic nerve transected in silicone tube, S; collagen gel put inside the silicone tube, MC; placed 3×104 mast cells mixed with scaffold, MSC; placed 3×104 mesenchymal stem cells mixed with scaffold, and MC+MSC; 3×104 of each of the mast cell and mesenchymal stem cells along with scaffold. Animals were euthanized and sampled for muscle and nerve histological and nerve immunohistochemical evaluations. Diameter of muscle fibers, ratio of the muscle fiber's nuclei to the fibrocyte nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fiber's number (mn/mf), and ratio of the blood vessels number to the number of muscle fibers (v/mf) in all treatment groups, especially the MC + MSC group, increased compared to the Tr group but the number of mast cells, the percentage of sarcoplasmolysis, and necrosis fibers decreased. Histomorphometric results of the nerve in its various parts and immunohistochemistry results also showed improved nerve conduction, especially in the MC + MSC group. In this study, nerve improvement happened mainly for two reasons: cells and time. So, the most obvious improvement occurred in the group with mast and mesenchymal cells in the 8th week.

Bialorastins A–F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283

Six new highly oxygenated and polycyclic andrastin-type meroterpenoids, namely, bialorastins A–F (1–6), were discovered from the culture of Penicillium bialowiezense CS-283, a fungus isolated from the deep-sea cold seep squat lobster Shinkaia crosnieri. The planar structures and absolute configurations of these compounds were determined by detailed analysis of spectroscopic data, single crystal X-ray diffraction, and TDDFT-ECD calculations. Structurally, bialorastin A (1) represents a rare 17-nor-andrastin that possesses an unusual 2-oxaspiro[4.5]decane-1,4-dione moiety with a unique 6/6/6/6/5 polycyclic system, while bialorastin B (2) is also a 17-nor-andrastin featuring a gem-propane-1,2-dione moiety. Additionally, bialorastins C–E (3–5) possess a 6/6/6/6/5/5 fused hexacyclic skeleton, characterized by distinctive 3,23-acetal/lactone-bridged functionalities. All isolated compounds were evaluated for their proangiogenic activities in transgenic zebrafish. Compound 3 exhibited significant proangiogenic activity, which notably increased the number and length of intersegmental blood vessels in model zebrafish in a dose-dependent manner at concentrations of 20 and 40 μM. On a molecular scale, the tested compounds were modeled through molecular docking to have insight into the interactions with the possible target VEGFR2. Mechanistically, RT-qPCR results revealed that compound 3 could promote angiogenesis via activating VEGFR2 and subsequently activating the downstream PI3K/AKT and MAPK signaling pathways. These findings indicate that 3 could be a potential lead compound for developing angiogenesis agents.

Hollow CuS immobilized in polysaccharide hydrogel promotes photothermally-driven vascularization

Overcoming drastic warming or preventing excessive Cu2+ aggregation is essential for the application of photoresponsive copper sulfide in tissue repair. Here, we prepared a photothermal hydrogel (HG@HCuS) dressing with hollow copper sulfide (HCuS) nanoparticle as the crosslinked core, along with mercapto gelatin and dopamine-coupled hyaluronan as the polymer substrates, which presented stable mechanical strength and controlled Cu2+ release. The HG@HCuS achieved mild photothermal conversion to prevent thermal damage, the temperature dropped to 42 ℃ in comparison with 55 ℃ in solid CuS under the irradiation of 1064 nm laser. The HG@HCuS enhanced the proliferation and migration of vascular endothelial cells, and promoted VEGF protein expression in vitro. Meanwhile, it acquired satisfactory repair capability in a 2 cm diameter wound by significantly inhibiting the inflammatory factors secretion, increasing the collagen deposition and blood vessel number of regenerative dermis. These results demonstrated that photothermally-driven HG@HCuS provide a new strategy for skin regeneration.

Effects of Intramuscular Epinephrine Injection and Systemic Sildenafil Citrate on Rat Transverse Rectus Abdominis Musculocutaneous Flap Survival

Background and Objectives Flaps are commonly employed for reconstruction, and many studies have sought to improve flap survival. In this study, we determined whether sildenafil and epinephrine synergistically improve the survival rate of transverse rectus abdominis musculocutaneous (TRAM) flaps.Materials and Method Twenty-four Sprague-Dawley rats were divided into four groups of six rats each: a control group, an epinephrine group, a sildenafil group, and an epinephrineplus- sildenafil group. TRAM flaps were elevated on the upper abdomen.Results The average flap survival area and number of blood vessels differed significantly between the control and experimental groups; however, the various experimental groups did not differ significantly. The level of vascular epithelial growth factor was higher in the experimental groups than in the control group.Conclusion Both epinephrine and sildenafil citrate significantly improve TRAM flap survival in rats. However, whether effects are better when the drugs are combined rather than when used alone remains unclear. Further research is required.

Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice.

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm2). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-β1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future.

Superparamagnetic Iron Oxide Nanoparticles Activate Mitogen-Activated Protein Kinase Pathway and Promote Bone Marrow Derived Mesenchymal Stem Cells Homing to Repair Bone Defects in Rats with Osteosarcoma

Superparamagnetic iron oxide nanoparticles exert its action on repairing bone defects. Whether they have the same repair effect on osteosarcoma bone defects and the mechanism is worth studying. The bone defect model of osteosarcoma rats was constructed and divided into bone defect group, positive control group, low-dose nano-group, medium-dose nano-group, high-dose nano-group, and blocker group followed by analysis of new bone formation, bone marrow derived mesenchymal stem cells (BMSC) homing, bone morphogenetic protein-2 (BMP-2), Collagen I, and Phosphorylated 44/42 mitogen-activated protein kinase (p44/42) protein expression. The proportion of new bone formation in positive control group and different dose groups was higher than bone defect group and blocker group (P &lt;0.05). The positive control group had rich collagen fibers at repair site, which were more cellulose and neatly arranged. Low-dose group was more collagenous than positive control group. There was no new bone formation in the bone defect group and the blocking agent group and no Y chromosome positive cells were found in the blood vessel wall. New bone formation was seen in the positive control group and the nano-group and the number of blood vessels was abundant and rich in Y chromosome positive cells. Compared with the other two groups, positive control group and nano-group had higher BMP-2, Collagen I expression (P &lt;0.05), and lower p44/42 expression (P &lt;0.05). The p-mitogen-activated protein kinase (MAPK) levels were the lowest in bone defect group, blocker group, and positive control group, while nano-group was opposite. Superparamagnetic iron oxide nanoparticles can repair bone defects in osteosarcoma rats, and the mechanism of action is mainly related to the activation of the MAPK pathway.

Application of Recombinant Human Bone Morphogenetic Protein-2 (RhBMP-2) in the Reconstruction of Edentulous Posterior Maxilla: Clinical Protocol, Histological Analysis, and Long-Term Implant Success and Survival Rates

Background: This study evaluated the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in inducing de novo bone formation during the augmentation of the severely resorbed posterior maxilla for dental implant placement. Methods: Composite grafts consisting of rhBMP-2/absorbable collagen sponge (ACS) mixed with deproteinized bovine bone mineral (DBBM) Bio-Oss in a 1:1 ratio were used to reconstruct severely resorbed posterior maxillae in 13 patients (five men, eight women; age range: 50 to 66 years). Three patients were treated with sinus floor augmentation alone, and 10 patients with a combination of sinus floor augmentation and guided bone regeneration. A total of 71 dental implants were used in this study. The residual bone height below the maxillary sinus ranged from 0.5 to 3.0 mm. Clinical, radiological, and histomorphometric analyses were performed to assess the outcomes of bone augmentation. Results: The healing period was uneventful in all patients. The mean alveolar ridge height increased by 14 mm (range, 10–18 mm) and the mean alveolar width increased by 6 mm (range, 4–7 mm). Histopathological analysis revealed that newly formed bone was detectable throughout the implantation sites of sinus biopsies. The analysis of vascularization of the implant bed revealed large numbers of high-lumen vessels, in addition to moderate numbers of smaller blood vessels within the connective tissue. The histomorphometrical analysis of the tissue distribution showed that the amount of newly formed bone was 20.39 ± 4.95%, the amount of the remaining bone substitute was 41.85 ± 11.97%, and connective tissue was 37.76 ± 8.82%. The overall dental implant success and survival rates were 100% and remained unchanged at a follow-up period of 3 to 12 years. Conclusions: The results of this study demonstrated that a composite graft of rhBMP-2/ACS and DBBM can result in predictable reconstruction of a large bone volume of the maxilla for dental implant placement and functional loading.

Evaluation of the antitumoral effects of the mesoionic compound MI-D: Implications for endothelial cells viability and angiogenesis inhibition

Angiogenesis is considered one of the hallmarks of cancer, assisting tumor progression and metastasis. The mesoionic compound, MI-D, can induce cell death and provoke cytoskeletal and metabolic changes in cancer cells. Using in vitro and in vivo models, this study aimed to evaluate the effects of MI-D on the viability of human endothelial cells (EC) and its ability to inhibit tumor-induced angiogenesis induced by tumoral cells. For in vitro analysis, colon carcinoma (HT29) and endothelial (EA.hy926) cells were used as the tumoral and angiogenesis models, respectively. To evaluate cytotoxicity, methylene blue viability stain and annexin-V/7AAD tests were performed with both cell types. For the angiogenesis experiments, scratch wound healing and capillary tube-like formation assays were performed with the EC. The in vivo tests were performed with the chorioallantoic membrane (HET-CAM) methodology, wherein gelatin sponge implants containing MI-D (5, 25, and 50 μM), HT29 cells, or both were grafted in the CAM. Our data showed that MI-D induced apoptosis in both endothelial and colon carcinoma cells, with a strong cytotoxic effect on the tumoral lineage. The drug inhibited the EC's migration and capillary-like structure formation in vitro. In the HET-CAM assays, MI-D reduced the number of blood vessels in the membrane when grafted alone and accompanied by tumor cells. In this study, MI-D interfered in important steps of angiogenesis, such as maintenance of endothelial cell viability, migration, formation of capillary-like structures, as well tumor-induced neovascularization, reinforcing the hypothesis that MI-D might act as an inhibitor of angiogenesis, and a potential antitumor agent.

Efficacy of wearable vibration dressings on full-thickness wound healing in a hyperglycemic rat model.

Local low-frequency vibration promotes blood flow and wound healing in hard-to-heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self-care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low-frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post-wounding days (PWDs) 4-7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post-wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+ /iNOS+ )/(CD163+ ) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self-care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs.

Wnt/β-catenin signaling pathway promotes abnormal activation of fibroblast-like synoviocytes and angiogenesis in rheumatoid arthritis and the intervention of Er Miao San.

Er Miao San (EMS) is an important herbal formula and a representative prescription for the treatment of the downwards flow of damp-heat syndrome. Clinical practice has proven that EMS can effectively treat rheumatoid arthritis (RA). Previous studies have demonstrated that EMS regulates the functions of T cells and dendritic cells and affects the polarization of macrophages. However, it is not clear whether the inhibitory effect of EMS on RA is related to the regulation of abnormal synovial activation and angiogenesis. The aim of this study was to elucidate the effect and potential mechanisms of EMS on the abnormal activation and angiogenesis of fibroblast-like synoviocytes (FLSs) in RA. The effect of EMS on rats with adjuvant arthritis (AA) and MH7A cells was examined by X-ray, haematoxylin-eosin (HE) staining, immunohistochemistry (IHC), ELISA and western blotting. Angiogenesis in AA rats was measured by a small animal ultrasound imaging system, immunofluorescence (IF) analysis and ELISA. An exchange between MH7A cells and HUVECs was induced using conditioned media that mimicked the microenvironment in vivo. CCK-8, western blotting, and scratch healing and Transwell migration assays were used to evaluate the effect of EMS on the Wnt/β-catenin signaling pathway and angiogenesis in the inflammatory microenvironment of RA. Our results showed that EMS had a protective effect on AA rats. On the one hand, there was a decrease in paw swelling, the arthritis index, organ indices and proinflammatory factor levels, as well as relief of joint damage. On the other hand, blood flow, the number of immature blood vessels and proangiogenic factors were decreased. Furthermore, EMS reduced the expression of the Wnt/β-catenin signaling pathway in the synovial tissue of AA rats and MH7A cells. In the inflammatory microenvonrment of RA, the results were consistent. This study demonstrated that EMS could protect against RA by inhibiting the abnormal activation and angiogenesis of FLSs, and the mechanism may be related to inhibiting the activation of the Wnt/β-catenin signaling pathway.

The effect of long exposure to uvb rays on histological features of wistar rats (Rattus norvegicus) in photoaging model

Introduction: Indonesia is a tropical country with exposure to UV rays from the sun throughout the year, so the Indonesian population is very vulnerable to skin aging, especially extrinsic skin aging due to prolonged exposure to UV rays. This study aimed to determine the effect of long exposure to UVB rays on the thickness of the epidermis, the thickness of the dermis, and the number of blood vessels and sunburn cells in (Rattus norvegicus) Wistar strain. Methods: This research was a post-test-only control group design using 27 rats which were divided into 3 groups, namely: control group K was untreated rats, and treatment groups P1 and P2 were rats exposed to UVB radiation for 3 weeks and 6 respectively exposure weeks. Test the effect on the study using the One-Way ANOVA test and Tukey’s Post Hoc Test. Results: The results indicated an increase in epidermal thickness of groups P1 (44.87 μm) and P2 (56.90 μm) (significant p&lt;0.05). A decrease in dermis thickness occurred in groups P1 (726.91 μm) and P2 (559.40 μm) (significant p&lt;0.05). In the photoaging area, there was an increased amount of sunburn cells in group P1 (6.40) and P2 (11.40) (significant p&lt;0.05). There was a difference in the number of blood vessels between groups K and P2 and groups P1 and P2 (p&lt;0.05). Conclusion: There was an effect of long exposure to UVB rays on histology in rats (Rattus norvegicus) of the photoaging model including the thickness of the epidermis layer and dermis layer, the number of blood vessels, and sunburn cells.