Tissue Angiogenesis Research Articles

Biomineralized Nanocomposite-Integrated Microneedle Patch for Combined Brachytherapy and Photothermal Therapy in Postoperative Melanoma Recurrence and Infectious Wound Healing.

In the surgical management of malignant melanoma, incomplete tumor resection and large-area cutaneous defects are major contributors to high locoregional recurrence and uncontrolled wound infections, resulting in poor prognosis and prolonged recovery times for patients. Herein, a versatile nanocomposite microneedle patch (referred to as GM-Ag2S/Ca32P) is designed to simultaneously eliminate residual tumor post-surgery and promote the healing of infectious wounds. This microneedle patch effectively penetrates subcutaneous tissues, delivering therapeutic payloads to infiltrating tumor cells and bacteria. The Ag2S/Ca32P nanocomposites encapsulated within the microneedle patch decompose in the acidic microenvironment of tumors and bacterial biofilms, releasing radioactive 32P and Ag2S nanodots, which enhance tumor eradication and bacteria killing through synergistic brachytherapy and photothermal therapy (PTT). Moreover, the nanocomposite microneedle patch promotes scar-free wound healing by reducing inflammation, and promoting granulation tissue formation, collagen deposition, and angiogenesis, thanks to localized hyperthermia, radiation, and the swelling and biodegradation of the microneedle matrices. This microneedle patch-based postoperative adjuvant therapy offers a comprehensive strategy for addressing melanoma recurrence and infectious wound healing, with promising potential for clinical application in postsurgical management.

AP39, a novel mitochondria-targeted hydrogen sulfide donor, promotes cutaneous wound healing in an in vivo murine model of acute frostbite injury.

Frostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role. The present study investigated whether AP39, a novel mitochondria-targeted slow-releasing hydrogen sulfide donor, applied topically in a vehicle cream at 200 nM or 1 µM could mitigate frostbite injury and promote wound healing in mice. Frostbite injury was induced continuously for 3 min on the dorsal skin of C57BL/6 mice (Mus musculus) using magnets frozen on dry ice (-80 °C). AP39, delivered via a vehicle cream, was used daily to treat frostbite injury until animals were euthanized on day 15 after induction of frostbite injury. Wound tissues were stained with hematoxylin and eosin along with immunofluorescence staining with cleaved caspase-3, CD31, KI-67, CD163, fibronectin and cytokeratin. While 200 nM AP39 improved granulation tissue maturation (p < 0.001), angiogenesis (p < 0.01) and cell proliferation (p < 0.001) compared to vehicle control, 1 µM AP39 further increased granulation tissue formation compared to other frostbite groups (p < 0.001). Thus, AP39 promoted frostbite wound healing, and therefore could be considered as a treatment option for patients with frostbite injury.

A Review on Autologous Platelet-Rich Plasma (Prp) Associated with Split Thickness Skin Grafting (Stsg) in the Treatment of Chronic Non-Healing Ulcers

Chronic non-healing ulcers present a significant clinical challenge due to their prolonged healing times and resistance to conventional treatments. Recent advances in regenerative medicine have introduced autologous platelet-rich plasma (PRP) as a promising therapeutic option. PRP, known for its high concentration of growth factors, has been shown to accelerate wound healing by enhancing tissue regeneration and angiogenesis. When combined with split-thickness skin grafting (STSG), PRP offers a synergistic approach to the management of chronic ulcers. This review evaluates the efficacy of PRP in conjunction with STSG in the treatment of chronic non-healing ulcers, drawing on recent clinical studies, case reports, and trials. The review highlights the biological mechanisms of PRP in wound healing, the procedural considerations in integrating PRP with STSG, and the clinical outcomes associated with this combined approach. Findings suggest that the use of autologous PRP alongside STSG significantly improves graft acceptance, reduces healing time, and promotes faster epithelialization, ultimately leading to better wound closure and patient recovery. However, the need for standardized protocols and further large-scale studies is emphasized to establish consistent guidelines for its use in clinical practice. This review aims to provide healthcare professionals with an updated perspective on this evolving treatment modality for chronic non-healing ulcers. KEY WORDS: Chronic ulcers, Platelet-rich plasma, Split-thickness skin grafting, Regenerative medicine, Wound healing, Tissue regeneration.

BSP promotes skin wound healing by regulating the expression level of SCEL.

Burn injuries are complex, life-threatening events involving intricate cellular and molecular processes, including angiogenesis, which is vital for effective wound healing. Bletilla striata polysaccharide (BSP), a bioactive compound from Bletilla striata, exhibits anti-inflammatory and wound-healing properties. However, its impact on angiogenesis modulation, particularly through the synaptopodin-2-like (SCEL) gene, remains poorly understood. The effects of BSP on HMEC-1 cells exposed to lipopolysaccharide (LPS) were assessed using cell viability, migration, apoptosis, and angiogenesis assays. SCEL's role was explored through lentiviral transfection to manipulate SCEL expression. Animal models were employed to evaluate BSP's therapeutic potential in burn wound healing, with histological analysis, immunohistochemistry (IHC), and molecular assays to assess tissue repair and angiogenesis. BSP significantly alleviated LPS-induced damage in HMEC-1 cells by promoting cell survival, reducing apoptosis, and enhancing migration and angiogenesis. BSP treatment downregulated SCEL expression, reversing LPS-induced cellular damage. In SCEL-overexpressing cells and mice, BSP's beneficial effects on wound healing were attenuated, indicating SCEL's regulatory role in angiogenesis. In vivo, BSP accelerated burn wound closure, improved tissue organization, and enhanced angiogenesis, as evidenced by increased CD31 expression. SCEL overexpression impaired these effects, highlighting the essential role of SCEL downregulation in BSP-mediated healing. BSP promotes burn wound healing by modulating angiogenesis via SCEL downregulation, facilitating cell survival, migration, and vascularization. These findings position BSP as a promising therapeutic agent for burn wound treatment, with further investigation into SCEL's molecular mechanisms offering potential for novel wound care strategies.

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia.

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms.

Utero-placental adaptations in response to intrauterine growth restriction in swine.

Intrauterine growth restriction (IUGR) is a common condition in swine associated with high piglet mortality and morbidity that develops in early gestation. This review article explores differences in uterine and placental tissues associated with IUGR fetuses compared to their normally-grown littermates at different stages of gestation. Specifically, we will review the available knowledge to date describing differences in 1) structure, 2) cellular apoptosis and proliferation, 3) adhesion, and 4) angiogenesis in endometrial and placental tissues associated with IUGR fetuses across gestation. Improved understanding of the mechanisms regulating IUGR is essential for the development of strategies to minimize the impact of IUGR in swine operations, thus improving reproductive efficiency and animal welfare.

VEGFA, MYC, and JUN are abnormally elevated in the synovial tissue of patients with advanced osteoarthritis

Osteoarthritis (OA), affecting > 500 million people worldwide, profoundly affects the quality of life and ability to work. The mitogen-activated protein kinase (MAPK) signaling pathway plays an essential role in OA. To address the lack of studies focused on synovial cells in OA, we evaluated the expression patterns and roles of the MAPK signaling pathway components in OA synovial tissues using bioinformatics. The JUN, MYC, and VEGFA expression levels were significantly higher in the synovial tissues of patients with OA than in control tissues. These loci were closely related to abnormal proliferation, inflammation, and angiogenesis in the synovial tissues of patients with OA. We speculate that Myc and VEGFA activate the p38-MAPK signaling pathway to further activate Jun, thereby promoting abnormal inflammation, proliferation, and angiogenesis in OA synovial tissue. The high MYC, JUN, and VEGFA expression was positively correlated with the patients’ K-L score, pain time, and synovial score. Furthermore, the high p38-MAPK and P-p38-MAPK expression confirmed that the abnormal expression and activation of the MAPK signaling pathway occurred in the synovial tissue of patients with OA. Our findings may provide a new direction for the clinical diagnosis and treatment of OA and insights into its pathogenesis.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight. IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG (fetal-acting) in adipocyte differentiation and placental angiogenesis. NOS3 (fetal and maternal-acting), NRK (fetal), and ADAMTS8 (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors.

Hypoxia-regulated miR-103-3p/FGF2 axis in adipose-derived stem cells promotes angiogenesis by vascular endothelial cells during ischemic tissue repair.

Identifying factors mediating adipose-derived stem cells (ADSCs)-induced endothelial cell angiogenesis in hypoxic skin flap tissue is critical for reconstruction. While the paracrine action of VEGF by adipose-derived stem cells (ADSCs) is established in promoting endothelial cell angiogenesis, the role of FGF2 and its regulatory mechanisms in ADSCs paracrine secretion remains unclear. We induced hypoxia and examined the expression level of FGF2 in ADSCs using ELISA, qRT-PCR, and western blotting. Proliferation of ADSCs under hypoxia was assessed using a CCK-8 assay. Co-culture experiments of hypoxia-induced ADSCs with vascular endothelial cells were conducted, and migration and tube formation abilities were evaluated through wound healing assays, transwell cell migration, and tube formation experiments. Hypoxia treatment induced significant upregulation of FGF2 expression in ADSCs, along with enhanced cell proliferation. Co-culture of hypoxia-induced ADSCs with vascular endothelial cells showed increased migration and tube formation abilities of endothelial cells. Knockdown of FGF2 inhibited these processes, while overexpression of miR-103-3p mimics in ADSCs suppressed endothelial cell migration and tube formation. FGF2 is a direct target of miR-103-3p in ADSCs. miR-103-3p/FGF2 axis regulates ADSCs on the biological activity of co-cultured vascular endothelial cells. Moreover, in the ischemic skin flap nude mouse model, ADSCs injection showed increased blood vessel formation and reduced flap necrosis, with the most significant improvement observed with ADSCs of miR-103-3p inhibitor overexpressed. Hypoxia induces paracrine secretion of FGF2 from ADSCs, which enhances endothelial cell angiogenesis. FGF2 expression is regulated by miR-103-3p in ADSCs. The miR-103-3p/FGF2 axis induces endothelial cell migration and angiogenesis and finally modulates ischemic skin flap repair in nude mice in vivo.

ADAMTS7 Enhances Gastric Cancer Growth and Metastasis by Triggering the NF-κB Signaling Pathway.

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of metalloproteinases plays a vital role in various biological and pathological processes, including tissue remodeling, angiogenesis, and cancer progression. Among the 19 ADAMTS family members, our research focused on ADAMTS7, which exhibited significant overexpression in gastric cancer (GC). This overexpression was strongly correlated with poor clinical outcomes, including reduced overall survival and heightened metastatic potential. To investigate the role of ADAMTS7 in GC, we employed an integrated approach encompassing bioinformatics analysis, Western blotting, immunofluorescence, as well as in vitro and in vivo functional analyses. Our results showed that silencing ADAMTS7 expression significantly inhibited the proliferation, migration, and invasion of GC cells, and furthermore, silencing ADAMTS7 significantly inhibited the growth and metastasis of tumour cells in vivo in nude mice, highlighting its critical role in driving the malignant behaviour of GC cells. Further mechanistic studies identified the NF-κB signaling pathway as a key downstream target of ADAMTS7, with ADAMTS7 silencing resulting in a notable reduction in NF-κB pathway activity. These findings establish ADAMTS7 as a significant contributor to the aggressiveness of GC and a pivotal activator of the NF-κB pathway, a major regulator of inflammation and tumor progression. Consequently, ADAMTS7 emerges as a promising therapeutic target and prognostic biomarker for GC. Our study opens new avenues for the development of targeted therapies aimed at inhibiting ADAMTS7 activity, thereby potentially improving treatment outcomes and survival rates for patients with GC.

Enhancing Periodontal Ligament Regeneration via PDLSC Delivery Using Electrospun PCL/Collagen/Cellulose Acetate Scaffolds and Collagen Hydrogel Incorporated with Curcumin-Loaded ZIF-8 Nanoparticles.

Regenerating periodontal ligament (PDL) tissue is a vital challenge in dentistry that aims to restore periodontal function and aesthetics. This study explores a tissue engineering strategy that combines polycaprolactone (PCL)/collagen/cellulose acetate electrospun scaffolds with collagen hydrogels to deliver curcumin-loaded ZIF-8 nanoparticles fand periodontal ligament stem cells (PDLSCs). Scaffolds were fabricated via electrospinningand collagen hydrogels incorporated PDLSCs and curcumin-loaded ZIF-8 nanoparticles (CURZIF-8) were developed using cross-linking. In vitro assays evaluated biocompatibility, anti-inflammatory, and antioxidative properties. In vivo efficacy was assessed in a rat PDL injury model using histological and ELISA analyses examining tissue regeneration and inflammatory cytokine modulation. In vitro studies demonstrated that the scaffolds effectively supported PDLSC viability and migration. CURZIF-8 hydrogels enhanced anti-inflammatory and antioxidative activities. In vivo study showed that the combined scaffold-hydrogel system significantly promoted PDL regeneration. Tissue levels of bFGF, HGF, and TGF-β that are crucial for tissue repair, angiogenesis, and cell proliferation were evaluated. Whereas, pro-inflammatory cytokines TNF-α and IL-6=were downregulated. Histological analysis confirmed the formation of organized PDL structures and improved bone-cementum integration that arekey indicators of successful periodontal regeneration. The developed scaffold-hydrogel system facilitates PDL regeneration by modulating inflammation and promoting pro-healing factor expression. This approach shows promise for advancing periodontal tissue engineering and warrants further investigation in clinical settings.

Intelligent response agarose/chitosan hydrogel wound dressing: Synergistic chemotherapy, PDT and PTT effects against bacterial infection.

Bacterial infections impede skin wound healing, and antibacterial hydrogels have garnered significant attention in the field of wound care due to their combined therapeutic effects. In this study, an intelligent, responsive AC-Gel@Cur-Au hydrogel was developed using temperature-sensitive agarose and pH-responsive chitosan as the structural framework, infused with Gel@Cur and AuNR. The AC-Gel@Cur-Au hydrogels demonstrated excellent mechanical properties, swelling capacity, tissue adhesion, and biodegradability. Upon irradiation, the hydrogels exhibited effective photodynamic therapy (PDT), photothermal therapy (PTT), and heat-sensitive gel-sol conversion capabilities, allowing for the release of curcumin in response to temperature and pH changes. Through these synergistic effects, the AC-Gel@Cur-Au hydrogel displayed a rapid bactericidal effect against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), effectively treating persistent biofilms. In vivo studies using a full-thickness defect model of S. aureus infection demonstrated that the hydrogel possessed strong antibacterial activity and enhanced wound healing capabilities, significantly reducing inflammation. Furthermore, the hydrogel significantly promoted granulation tissue formation, collagen deposition, and angiogenesis. Importantly, all the components of the AC-Gel@Cur-Au hydrogel were found to be non-cytotoxic, indicating good biocompatibility. This safe, synergistic antibacterial hydrogel holds great promise for the treatment of bacterial infections in wound healing.

Placenta-derived biomaterials vs. standard care in chronic diabetic foot ulcer healing: A systematic review and meta-analysis.

This study explored the effectiveness of current placenta-derived biomaterials therapies in ulcer healing in DFU compared to standard of care (SOC). The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. Twelve randomized controlled trials (RCTs) with a total of 833 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving placenta-derived biomaterials therapies (OR=6.247 [4.425, 8.819], p<0.01, I2=41%) compared to control groups. Placenta-derived biomaterials therapies have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in DFU. The utilization of placenta-derived biomaterials in therapies for wound healing, particularly in chronic DFU, presents promising implications for clinical practice. These biomaterials offer a rich source of growth factors, cytokines, and extracellular matrix components, which can stimulate tissue regeneration and angiogenesis. Incorporating such therapies into clinical practice holds the potential to accelerate wound closure, reduce infection rates, and improve overall healing outcomes in people with diabetic chronic foot ulcers. Furthermore, the availability of these biomaterials can offer clinicians a readily-accessible and cost-effective alternative to traditional wound care approaches, ultimately enhancing patient care and quality of life. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Exosomes derived from human adipose mesenchymal stem cells act as a therapeutic target for oral submucous fibrosis.

Oral submucosal fibrosis is a highly malignant oral condition that necessitates the use of sophisticated therapeutic procedures. OSF is a multifactorial precancerous condition induced by areca nut chewing, deficiencies in vitamins and trace minerals, immunological aspects, and hereditary factors. Adipose tissue-derived mesenchymal stem cells possess the capability for multidirectional activation and are extensively distributed throughout the body. They have minimal immunogenicity and are extensively utilized in cancer treatment. Exosomes are extracellular vesicles produced by the intracellular route. They are biological carriers comprising microRNA, messenger RNA, lipids and proteins crucial for intercellular communication. ADSC exosomes, serving as a vehicle for miRNA, possess accessibility and little immunogenicity. They can significantly contribute to adipose tissue regrowth, angiogenesis, immunological modulation, and tissue repair. ADSC-Exo exhibits antifibrotic properties and may serve as a potential treatment for OSF. This review presents a novel therapeutic approach and clarifies the precise mechanisms involved in the clinical management of OSF using ADSC-Exo.

The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease.

Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays a critical role in the degradation and remodeling of the extracellular matrix (ECM). As a member of the gelatinase subgroup of matrix metalloproteinases, MMP-2 is involved in a variety of physiological processes, including tissue repair, wound healing, angiogenesis, and embryogenesis. It is primarily responsible for the degradation of type IV and V collagen, fibronectin, laminin, and elastin, which are essential components of the ECM. MMP-2 is secreted as an inactive pro-enzyme (proMMP-2) and activated through proteolytic cleavage, with its activity being precisely regulated by tissue inhibitors of metalloproteinases (TIMPs). Dysregulation of MMP-2 has been linked to a variety of pathological conditions, including cardiovascular diseases, diabetic complications, kidney diseases, and cancer. In cardiovascular diseases, it contributes to vascular remodeling, atherosclerosis, and aneurysms, while in fibrotic diseases, it mediates excessive ECM degradation leading to tissue scarring. In diabetes, elevated MMP-2 activity exacerbates complications such as nephropathy, retinopathy, and cardiovascular disease. In cancer, MMP-2 facilitates tumor invasion and metastasis by degrading ECM components and promoting angiogenesis. Despite its essential roles in both physiological and pathological processes, targeting MMP-2 for therapeutic purposes presents challenges due to its dual functions in tissue remodeling and repair, raising concerns about unplanned consequences such as impaired tissue healing or excessive tissue damage. These challenges underscore the need for future research to focus on developing selective modulators that can precisely balance their activity under specific disease environments. Clinical trials targeting MMP-2 modulation highlight the potential of gelatinase inhibitors, including those targeting MMP-2, to reduce tumor progression in fibrosarcoma, breast, and lung cancers. This paper reviews the structure, function, and regulation of MMP-2, its involvement in disease pathogenesis, and the potential challenges in the therapeutic implications of modulating its activity.

The Chicken Embryo: An Old but Promising Model for In Vivo Preclinical Research.

The chicken embryo has emerged as a valuable model for preclinical studies due to its unique combination of accessibility, affordability, and relevance to human biology. Its rapid development, external growth environment, and clear structural visibility offer distinct advantages over traditional mammalian models. These features facilitate the study of real-time biological processes, including tissue development, tumor growth, angiogenesis, and drug delivery, using various imaging modalities, such as optical imaging, magnetic resonance imaging, positron emission tomography, computed tomography, and ultrasound. The chicken embryo model also minimizes ethical concerns compared to mammalian models, as it allows for early-stage research without the complexity of a fully developed animal. Moreover, its ability to integrate human tumor cells into xenograft models provides a reliable platform for cancer research, enabling high-throughput screening of therapeutic interventions and tracking molecular dynamics in vivo. Advances in molecular imaging techniques further enhance the resolution and depth of data obtained from these studies, offering insights into cellular and molecular mechanisms underlying disease. Given its versatility, cost-effectiveness, and translational potential, the chicken embryo represents a promising tool for advancing preclinical research, particularly in drug development, cancer biology, and regenerative medicine.

Leptin/LPS-treated dendritic cells reduce the expression of genes involved in tumor tissue metastasis and angiogenesis in an animal model of breast cancer.

Leptin, an immune-regulating protein, enhances the maturation of dendritic cells (DCs). We previously demonstrated that leptin and lipopolysaccharide (LPS) promote the expression of co-stimulatory molecules on the surface of DCs. Leptin/LPS-treated DCs increased T cell responses against 4T1 breast cancer in mice. Therefore, in the present study, we investigate the effects of a DC vaccine treated with leptin and LPS on the genes involved in tumor metastasis, angiogenesis, and related cytokines in a mouse model of breast cancer. Tumor induction was achieved through subcutaneous injection of 4T1 cells into syngeneic mice. On days 12 and 19, the mouse groups received the DC vaccine treated with leptin and a combination of leptin and LPS. After sacrificing the mice on day 26, the levels of IL-6 and IL-33 in the serum were assayed using the ELISA technique, and the expression levels of the VEGF, CCL2, MMP9, and CCL5 genes in the tumors were measured by Real-Time PCR. Compared to untreated tumor-bearing mice, the leptin-treated mature DC (mDC) group exhibited a significant reduction in the expression of MMP9 (0.33-fold, p = 0.01) and CCL5 (0.81-fold, p = 0.02). The leptin-LPS-treated mDC group showed decreased expression of genes involved in metastasis and tumor growth, including VEGF (0.72-fold, p = 0.03), MMP9 (0.26-fold, p = 0.001), and CCL5 (0.3-fold, p = 0.006), indicating more efficient prevention of metastasis. The CCL2 gene expression levels in both treatment groups showed a slight decreasing trend, but these changes were not statistically significant. The leptin-treated mDC group reduced IL-6 production by approximately 16% (p = 0.02), while treatment with the leptin-LPS-treated mDC significantly decreased IL-6 production by approximately 22% (p = 0.01) and increased IL-33 production by approximately 42% (p = 0.03). The findings of the present study indicate that the leptin-LPS-treated mDC vaccine group reduced the expression of genes and cytokines involved in metastasis and angiogenesis, demonstrating greater efficacy compared to the leptin-treated mDC vaccine group.

CD105-microvessel density analysis and its clinical value in urothelial carcinoma of bladder patients

Background Endoglin/CD105-microvessel density (CD105-MVD) is identified as one of the most potential methods for semi-quantification of angiogenesis in human cancer tissues. Present study aimed to examine the diagnosticand prognostic value of CD105-MVD in two clinically distinct subtypes of urothelial carcinoma of bladder (UCB) namely non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients. Methods Message expression of endoglin was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and MVD measurement was done by immunohistochemical staining in 90 UCB [NMIBC: 60; MIBC: 30] patients. SEM studies were carried out to examine tumor vasculature and extent of neoangiogenesis in NMIBC and MIBC patients. Results Elevated message expression of CD105 showed statistical significance with tumor stage, grade, smoking/tobacco chewing history in NMIBC andage in MIBC cohort. Higher values of CD105-MVD showed statistical relevance with tumor stage, grade, size, smoking/tobacco chewing history in NMIBC cohort. Kaplan Meier test identified high CD105-MVD as strong predictor of poor RFS in NMIBC patients. Conclusions Association of CD105 expression and MVD with the clinicohistopathological features as well as poor survival outcomes potentially identify it as a preferred marker of clinical significance in a given cohort of UCB patients. Clinical significance Strong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients. Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients. Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients. The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients.

TREM2-mediated Macrophage Glycolysis Promotes Skin Wound Angiogenesis via the Akt/mTOR/HIF-1α Signaling Axis.

The trigger receptor expressed on myeloid cells-2 (TREM2) pathway in myeloid cells is a key disease-inducing immune signaling hub that is essential for detecting tissue damage and limiting its pathological spread. However, the role and potential mechanisms of TREM2 in wound repair remain unclear. The purpose of this study was to determine the role and mechanism of TREM2 in skin wound healing in mice. Immunofluorescence staining was used to determine the expression and cellular localization of TREM2 and test the effects of TREM2 knockout on angiogenesis, glycolysis, and lactylation in skin tissue. Western blotting was used to analyze the expression of the Akt/mTOR/HIF-1α signaling pathway in the wounded skin tissues of wild-type (WT) and TREM2 knockout mice. A coimmunoprecipitation assay was used to determine whether HIF-1α, which mediates angiogenesis, is modified by lactylation. The number of TREM2+ macrophages was increased, and TREM2+ macrophages mediated angiogenesis after skin injury. TREM2 promoted glycolysis and lactylation in macrophages during wound healing. Mechanistically, TREM2 promoted macrophage glycolysis and angiogenesis in wounded skin tissues by activating the Akt/mTOR/HIF-1α signaling pathway. HIF-1α colocalized with Klac to mediate lactylation in macrophages, and lactate could stabilize the expression of the HIF-1α protein through lactylation. Lactate treatment ameliorated the impaired angiogenesis and delayed wound healing in wounded skin in TREM2 knockout mice. TREM2+ macrophage-mediated glycolysis can promote angiogenesis and wound healing. Our findings provide an effective strategy and target for promoting skin wound healing.

Peptidergic G-Protein-Coupled Receptor Signaling Systems in Cancer: Examination of Receptor Structure and Signaling to Foster Innovative Pharmacological Solutions

Background. Peptidergic GPCR systems are broadly distributed in the human body and regulate numerous physiological processes by activating complex networks of intracellular biochemical events responsible for cell regulation and survival. Excessive stimulation, ill-function, or blockade of GPCRs produces cell disturbances that may cause disease should compensatory mechanisms not suffice. Methods and Results. Revision of updated experimental research provided an evident relationship associating peptidergic GPCR malfunction with tumor formation and maintenance resulting from uncontrolled cell proliferation and migration, colonization, inhibition of apoptosis or altered metabolism, and increased angiogenesis in tumoral tissues. Conclusion. Determination of the implication of GPCR peptide signaling in specific neoplasia is crucial to designing tailored pharmacological treatments to counteract or dismantle the origin of the signaling circuitry causing cellular disruption. In some cases, particular ligands for these receptors may serve as concomitant treatments to aid other pharmacological or physical approaches to eradicate neoplasias.