Stimulation Of Angiogenesis Research Articles

Possibility of stimulation of cerebral angiogenesis and neurogenesis with transcatheter intracerebral laser photobiomodulation therapy during dementia in patients with Alzheimer’s disease and in patients with distal cerebral atherosclerosis

AbstractBackgroundThe research is dedicated to stimulation of cerebral angiogenesis and neurogenesis with Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) in patients with dementia during Alzheimer’s disease (AD) and patients with distal forms of cerebral atherosclerosis.Materials & Methods350 patients with dementia were examined.We carried out determination of CDR, Tomography Dementia Rating scale (TDR), MMSE, cerebral CT, MRI, SG, rheoencephalography (REG), cerebral MUGA.48 (13.71%) patients with AD aged 34‐80 (mean age 67.5) were selected: 17 men (35.42%), 31 women (54.58%). According to their dementia severity, the patients were subdivided: preclinical stage (TDR‐0) ‐ 4, mild stage (TDR‐1) ‐ 16, moderately severe stage (TDR‐2) ‐ 21, severe stage (TDR‐3) ‐ 7.302 (86.29%) patients with distal cerebral atherosclerosis aged 58‐81 (mean age 78) were selected: 226 men (74.83%), 76 women (25.17%). According to their dementia severity, the patients were subdivided: mild stage (СDR‐1) ‐ 284 (94.04%), moderately severe stage (СDR‐2) ‐ 18 (5.96%).At hospital, all the patients underwent PBMT.ResultsAll 48 (100%) patients with AD showed improved cerebral microcirculation and 10‐20% increase in the volume of cerebral temporal lobes, which indicates cerebral neurogenesis development and tissue regeneration. The process was accompanied by a decreased level of dementia and restoration of cognitive functions. Consequently, the patients were transferred to milder TDR groups. Depending on the initial dementia severity, the resulting positive effect was observed during 2‐10 years.All 302 (100%) patients with distal cerebral atherosclerosis showed improved cerebral microcirculation and declining cerebral involutional changes, which indicates neurogenesis development and tissue regeneration. The process was accompanied by a decreased dementia level and cognitive functions restoration. The resulting positive effect was observed for over 10 years.ConclusionsDespite differences in the etiology of AD and distal cerebral atherosclerosis, PBMT is an effective treatment for dementia in these diseases. The method improves the blood supply of the brain; it stimulates neurogenesis and tissue structures restoration, which leads to an improvement in mental and cognitive functions. The resulting effect persists for a long time.

Altered expression of necroptotic, angiogenic and spermatogenic proteins in degenerate testes from aged stallions

We utilized RNA sequencing to compare the testis transcriptomes of fertile, adult stallions to those of adult stallions with age-related testicular degeneration (TD). Large-scale gene ontology analysis identified pathway-wide upregulation of inflammation and alterations in apoptotic pathways that likely play roles in the disease process (Woodward et al., Eq Vet J. 2022; 1-14). In humans and mice, inflammation, together with necroptosis, and alterations in capillary density, all contribute to age-related degenerative changes (Li et. al, ELife. 2017; 6:e27692 DOI: 10.7554/eLife.27692; Das et al, Cell. 2018;(173)74-89). One objective of the current study was to identify differentially expressed genes (DEGs) that may contribute similarly to TD in the horse. We also searched for DEGs that play roles in spermatogenesis. A second objective was to use immunohistochemistry (IHC) to determine if the protein products of these genes are differentially expressed between normal and diseased testes and to determine their patterns of expression. The hypothesis is that aberrations in necroptotic, angiogenic, and spermatogenic signaling pathways contribute to the pathophysiology of TD in stallions. RNA isolation and sequencing were performed on testicular tissue samples from 3 fertile adult stallions and from 3 adult stallions with confirmed TD as previously described (Woodward et al., Eq Vet J. 2022; 1-14). Transcript expression was compared between the 2 populations using either EdgeA or DESeq2, and a minimum of >1.5x fold change and Padj<0.05 asthe cutoffs for significance. Protein expression from selected DEGs was compared between normal adult and TD tissue using IHC. In degenerate testes, significant increases in gene expression were found in testicular-origin growth factors (BMP4 (9x increase), FGF2 (9x increase), and CSF1 (7x increase)). IHC confirmed increased expression of BMP4 and FGF2 proteins in germ cells from degenerate testes. Expression of CSF1R protein also was altered, with loss of expression of the protein in early germ cells, and increased expression in later stages of spermatogenesis. Upregulation of RIPK3 (3x increase) and VEGF (17x increase) transcripts also were confirmed in degenerate testes. These genes are central to necroptotic and angiogenic pathways, respectively. IHC confirmed diffuse upregulation of the RIPK3 protein in germ cells from degenerate testes. IHC for the VEGF protein is pending. In conclusion, alterations in expression of proteins responsible for stimulation of mitosis and meiosis in male germ cells were identified. Additionally, we provide evidence that chronic inflammation, necroptosis and aberrant angiogenesis may cause age-related degenerative changes in equine testes. In mice, inhibitors of the RIPK3 pathway and stimulation of angiogenesis can ameliorate clinical signs of aging in testes and muscle respectively (Li et. al, ELife. 2017; Das et al, Cell. 2018). Financial support: Grayson Jockey Club Research Foundation.

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus.

(1) Background: The pathogenesis of systemic lupus erythematosus (SLE) involves complicated and multifactorial interactions. Inducible nitric oxide synthase overactivation (iNOS or NOS2) could be involved in SLE pathogenesis and progression. This study explored the relationship between NOS2-associated inflammation profiles and SLE phenotypes. (2) Methods: We developed a prospective, case control study that included a group of 86 SLE subjects, a group of 73 subjects with lupus nephritis, and a control group of 60 people. Laboratory determinations included serum C reactive protein (CRP-mg/L), enzymatic activity of NOS2 (U/L), serum levels of inducible factors of hypoxia 1 and 2 (HIF1a-ng/mL, HIF2a-ng/mL), vascular endothelial growth factor VEGF (pg/mL), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9-ng/mL), thrombospondin 1 (TSP-1-ng/mL), and soluble receptor of VEGF (sVEGFR-ng/mL). (3) Results: CRP, NOS2, HIF-1a, HIF-2a, VEGF, MMP-2, and MMP-9 were significantly increased, while TSP-1 and sVEGFR were decreased in the SLE and lupus nephritis groups compared with the control group. The variations in these biomarkers were strongly associated with the decrease in eGFR and increase in albuminuria. (4) Conclusions: The inflammatory phenotype of SLE patients, with or without LN, is defined by NOS2 and hypoxia over-expression, angiogenesis stimulation, and inactivation of factors that induce resolution of inflammation in relation with eGFR decline.

Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis.

Uterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions. This comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment. The prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis. Recognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk.

Cathelicidin LL-37 Expression in Human Breast Implant Capsules.

Capsular contracture is the most common complication following breast implant placement. Cathelicidin LL-37 is a cationic peptide involved in innate immunity. Initially investigated for its antimicrobial role, it was found to have pleiotropic activities, such as immunomodulation, angiogenesis stimulation, and tissue healing. The aim of the study was to investigate the expression and localization of LL-37 in human breast implant capsules and its relationship with capsular formation, remodeling, and clinical outcomes. The study enrolled 28 women (29 implants) who underwent expander substitution with definitive implant. Contracture severity was evaluated. Specimens were stained with hematoxylin and eosin, Masson trichrome, immunohistochemistry, and immunofluorescence for LL-37, CD68, α-smooth muscle actin, collagen type I and type III, CD31, and Toll-like receptor-4. LL-37 was expressed in macrophages and myofibroblasts of capsular tissue in 10 (34%) and nine (31%) of the specimens, respectively. In eight cases (27.5%), it was expressed by both macrophages and myofibroblasts of the same specimen. In infected capsules, expression by both cell types was found in all (100%) specimens. LL-37 expression by myofibroblasts positively correlated with its expression by macrophages ( P < 0.001). Moreover, LL-37 expression by macrophages of periexpander capsules negatively correlated with the severity of capsular contracture on definitive implants ( P = 0.04). This study demonstrates the expression of LL-37 in macrophages and myofibroblasts of capsular tissue and its negative correlation with the severity of capsular contracture following permanent implant placement. Expression or up-regulation of LL-37 may be involved in myofibroblast and macrophage modulation, thus playing a role in the pathogenic fibrotic process underlying capsular contracture. This is the first study to demonstrate LL37 expression in capsular tissue and to hypothesize its role in contracture and as a prognostic marker for contracture severity. If confirmed, medical strategies or implant coating could be implemented to reduce the risk of contracture for high-risk patients.

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IUBMB LifeVolume 75, Issue 6 COVER IMAGEFree Access Cover Image First published: 02 May 2023 https://doi.org/10.1002/iub.2731AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract On the Cover: Examples of the roles of proteases in prostate cancer development and progression. A simplified scheme of the roles of the major proteases discussed in this review is illustrated. The schematic representation of tumor growth and early steps of metastatic dissemination, shown in the center panel, include: 1) Proliferative and EMT signaling (interaction of cancer and stromal cells and inflammatory responses); 2) Cancer cell migration and invasion, involving ECM remodeling and signaling; 3) Stimulation of (lymph)angiogenesis and intravasation of invasive cancer cells, involving ECM remodeling, degradation of anti-angiogenic factors, production of angiogenic peptides and growth-factor activation; 4) Stromal cells, including cancer-associated fibroblasts (CAFs), are also involved in tumorigenic processes; 5) A small fraction of circulating tumor cells (CTCs) survive and eventually form distant metastases. These processes often involve autocrine-paracrine loops in the prostate cancer microenvironment, which due to simplicity have been omitted here by Koistinen et al.; Article first published: 04 Jan 2023; https://doi.org/10.1002/iub.2700 Volume75, Issue6June 2023 RelatedInformation

Vessel-Specific Shear Stress Distribution and Heterogeneity in Angiogenic Rat Mesenteric Microvascular Networks

Fluid shear stress has been identified as an important player in regulating endothelial cell behaviors and angiogenesis, defined as the sprouting of new blood vessels from existing vessels. However, the correlative or functional linking of shear stress to vessel-specific endothelial cell dynamics requires a better understanding of the shear stress values at the capillary level in microvascular networks. Critical questions remain unanswered. What is the shear stress experienced by endothelial cells along capillaries? Do all capillaries experience similar shear stress magnitudes? Can variations in shear stress along different capillary segments explain vessel-specific responses? The objective of this project was to estimate shear stress values in regions of angiogenic microvascular networks. Rat mesenteric tissues were harvested from adult male Wistar rats post the stimulation of angiogenesis via 48-80 mast cell degranulation. Microvascular networks were identified by perfusion of a 40kDa fixable dextran prior to harvesting and immunolabelling for PECAM. Dextran presence identified perfused segments along the hierarchy of microvascular networks, which were characterized by increased vessel density indicative of angiogenesis. Representative network regions with arteriole input and venule output vessels were selected for analysis. Vessel segments were defined by adjacent nodes, and the measurements of lengths and diameter. Assuming an inlet pressure of 75 mmHg and outlet pressure of 10 mmHg, a network segmental Newtonian flow model was used to computationally estimate vessel-specific shear stresses and velocities. Viscosity was set to 4 cP and assumed to be constant. In the results, shear stresses along vascular segments in 3 medium microvascular regions ranged from 0.1 to 1114.3 dyne/cm2 (average = 81.3 ± 3.5 dyne/cm2), in 4 small regions ranged from 0.1 to 518.7 dyne/cm2 (average = 61 ± 3.4 dyne/cm2), and in 1 large region ranged from 0.003 to 2328.1 dyne/cm2 (average = 39.8 ± 1.6 dyne/cm2). For all regions, the highest shear stress values located at capillary segments, defined as vascular segments with diameters lower than 10 μm. As segment diameters increased, the matched maximum shear stresses decreased accordingly. Also, the high heterogeneity of shear stresses in capillaries indicates the possibility for segment-specific regulation. For 3 medium regions, shear stresses along proximal capillaries branching from arteriolar inlets to venular outlets were higher than stresses along capillaries in regions distal to inlets and outlets. The results highlight the variability of segment-specific shear stresses along capillaries in microvascular regions and motivate research looking into how endothelial cells respond to segment-specific microenvironment and regulation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exogenous ketosis elevates circulating erythropoietin and stimulates muscular angiogenesis during endurance training overload.

De novo capillarization is a primary muscular adaptation to endurance exercise training and is crucial to improving performance. Excess training load, however, impedes such beneficial adaptations, yet we recently demonstrated that such downregulation may be counteracted by ketone ester ingestion (KE) post-exercise. Therefore, we investigated whether KE could increase pro-angiogenic factors and thereby stimulate muscular angiogenesis during a 3-week endurance training-overload period involving 10 training sessions/week in healthy, male volunteers. Subjects received either 25g of a ketone ester (KE, n=9) or a control drink (CON, n=9) immediately after each training session and before sleep. In KE, but not in CON, the training intervention increased the number of capillary contacts and the capillary-to-fibre perimeter exchange index by 44% and 42%, respectively. Furthermore, KE also substantially increased vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression both at the protein and at the mRNA level. Serum erythropoietin concentration was concomitantly increased by 26%. Conversely, in CON the training intervention increased only the protein content of eNOS. These data indicate that intermittent exogenous ketosis during endurance overload training stimulates muscular angiogenesis. This likely resulted from a direct stimulation of muscle angiogenesis, which may be at least partly due to stimulation of erythropoietin secretion and elevated VEGF activity, and/or an inhibition of the suppressive effect of overload training on the normal angiogenic response to training. This study provides novel evidence to support the potential of exogenous ketosis to benefit endurance training-induced muscular adaptation. KEY POINTS: Increased capillarization is a primary muscular adaptation to endurance exercise training. However, excess training load may impede such response. We previously observed that intermittent exogenous ketosis by post-exercise and pre-sleep ketone ester ingestion (KE) counteracted physiological dysregulations induced by endurance overload training. Therefore, we investigated whether KE could increase pro-angiogenic factors thereby stimulating muscular angiogenesis during a 3-week endurance training overload period. We show that the overload training period in the presence, but not in the absence, of KE markedly increased muscle capillarization (+40%). This increase was accompanied by higher circulating erythropoietin concentration and stimulation of the pro-angiogenic factors vascular endothelial growth factor and endothelial nitric oxide synthase in skeletal muscle. Collectively, our data indicate that intermittent exogenous ketosis may evolve as a potent nutritional strategy to facilitate recovery from strenuous endurance exercise, thereby stimulating beneficial muscular adaptations.

A mesenchymal stem cell-derived nanovesicle-biopotentiated bovine serum albumin-bridged gelatin hydrogel for enhanced diabetic wound therapy

The application of gelatin hydrogels is hampered by their poor mechanical properties, which are unfavorable for debridement and diabetic wound healing. Herein, bovine serum albumin (BSA)-bridged gelatin hydrogels biopotentiated by bone marrow mesenchymal stem cell (BMSC)-derived nanovesicles (NV), named NV@BSA-GEL, were fabricated by reinforcement of gelatin hydrogels with genipin and BSA in a one-pot, low-cost green approach based on amide bonding-guided crosslinking. Genipin introduction endowed the crosslinking of gelatin hydrogels with weak mechanical properties that were reinforced by BSA bridging to realize suitable mechanical properties for wound dressing, including excellent flexibility and appropriate rigidity. The bioactivity of NV released by the hydrogels resulted in efficient ROS scavenging and favorable immunomodulatory activity as well as promoted cell proliferation and migration of fibroblasts and vascular endothelial cells. Proteomic analysis confirmed that NV harbors a variety of growth factors that can promote wound healing. In vivo, the NV@BSA-GEL hydrogel had superior wound healing effects compared to BSA-GEL, including faster wound healing, stimulation of angiogenesis, contributing to an anti-inflammatory extracellular matrix, and promoting skin maturation, with no systemic toxicity. Thus, the combined merits of NV@BSA-GEL suggest that it has high potential as a new hydrogel dressing for the safe and efficient treatment of diabetic wounds.

Targeting senescent dermal fibroblasts responsible for hyperactive melanocytes in melasma

Targeting senescent dermal fibroblasts responsible for hyperactive melanocytes in melasma

Long-term results of coronary bypass grafting supplemented with surgical stimulation of extracardiac myocardial vascularization in patients with diffuse coronary artery disease

Highlights. In recent decades, the number of patients with diffuse, multivessel coronary artery disease has increased due to widespread use of endovascular methods of treatment, long-term conservative management of patients, and the expansion of indications for surgical revascularization. In order to improve the results of treatment, in 2007 academician Yu. L. Shevchenko developed and began using the method of stimulation of extracardiac angiogenesis – «YurLeon». The present article demonstrates the long-term results of supplementing coronary bypass surgery with this method in patients with diffuse coronary artery disease.Aim. To evaluate long-term results of coronary bypass surgery supplemented by extracardiac myocardial revascularization.Methods. The prospective, randomized study included 205 patients with diffuse, multivessel coronary artery disease who were treated at the St. George Thoracic and Cardiovascular Surgery Clinic, National Medical and Surgical Center named after N.I. Pirogov. The majority of patients were men – 75% (n = 153), whereas women accounted for 25% (n = 52), all patients were 60 to 78 years old (67.3±5.74 years). The group I consisted of patients with coronary bypass surgery supplemented with the «YurLeon» technique, the group II consisted of patients with coronary bypass grafting only. All patients provided consent to participate in the study. The clinical condition of patients, echocardiography, myocardial scintigraphy and coronary angiography data, quality of life indicators (the 36-Item Short Form Health Survey) were assessed.Results. In the long-term postoperative period (36 months), the group I, compared with the group II, presented with a statistically significant decrease in the functional class of angina pectoris (1[1–2] vs. 2[1–2], p = 0.02); fewer adverse events: myocardial infarction (4.5% vs. 11.6%, p = 0.011), recurrent angina pectoris (10% vs. 17.9%, p = 0.038); an increase in the left ventricular ejection fraction (59.0±5.15% vs. 53.2±6.13%, p = 0.001); a decrease in the Summed Rest Score (SRS) (4.5±3.5 vs. 8.4±5.7, p = 0.012) according to myocardial scintigraphy with technetril; a decrease in the Summed Thickening Score (STS) (6.1±3.3 vs. 10.7±2.9, p = 0.012); a decrease in the hibernating myocardium (3.5±2.2% vs. 7.4±5.1%, p = 0.03); additional extracardiac sources were found in the group I according to coronary graft angiography, there were no statistically significant differences between the groups by occluded autogenous venous bypass grafts (in the group I – 23 out of 46 venous conduits (49%), in the group II – 30 out of 49 venous conduits (51%), p = 0.089); The groups differed in terms of quality of life (the 36-Item Short Form Health Survey): physical functioning (87.3±10.32 vs. 75.3±14.15 points, p = 0.001); role-based functioning due to physical condition (90.1±10.50 vs. 79.7±7.01 points, p = 0.012); pain (93.10±6.37 vs. 80.5±5.21 points, p = 0.03); the total physical component of health (57.9±5.4 vs. 45.8±6.1 points, p = 0.012).Conclusion. We have accumulated 15 years of experience in conducting complex myocardial revascularization in patients with coronary artery disease and diffuse coronary atherosclerosis, which allowed us to prove the effectiveness and safety of the YurLeon technique.

Unraveling the Role of Peroxisome Proliferator-Activated Receptor β/Δ (PPAR β/Δ) in Angiogenesis Associated with Multiple Myeloma.

Growing evidence suggests a role for peroxisome proliferator-activated receptor β/δ (PPAR β/δ) in the angiogenesis, growth, and metastasis of solid tumors, but little is known about its role in multiple myeloma (MM). Angiogenesis in the bone marrow (BM) is characteristic of disease transition from monoclonal gammopathy of undetermined significance (MGUS) to MM. We examined the expression and function of PPAR β/δ in endothelial cells (EC) from the BM of MGUS (MGEC) and MM (MMEC) patients and showed that PPAR β/δ was expressed at higher levels in MMEC than in MGEC and that the overexpression depended on myeloma plasma cells. The interaction between myeloma plasma cells and MMEC promoted the release of the PPAR β/δ ligand prostaglandin I2 (PGI2) by MMEC, leading to the activation of PPAR β/δ. We also demonstrated that PPAR β/δ was a strong stimulator of angiogenesis in vitro and that PPAR β/δ inhibition by a specific antagonist greatly impaired the angiogenic functions of MMEC. These findings define PGI2-PPAR β/δ signaling in EC as a potential target of anti-angiogenic therapy. They also sustain the use of PPAR β/δ inhibitors in association with conventional drugs as a new therapeutic approach in MM.

Proteases and their inhibitors involved in Schistosoma mansoni egg-host interaction revealed by comparative transcriptomics with Fasciola hepatica eggs

Schistosoma mansoni eggs are the main causative agents of the pathological manifestations of schistosomiasis. The eggs are laid in the host bloodstream, then they migrate through the intestinal wall into the lumen. However, a significant proportion of the eggs become lodged in the liver, where they cause inflammation and fibrosis. In this study, we focus on a specific group of proteins expressed by the egg, namely proteases and their inhibitors. These molecules are often involved in schistosome-host interactions, but are still unexplored in the egg stage. Using RNA-seq and comparative transcriptomics of immature and mature S. mansoni eggs, we mapped the portfolio of proteases and their inhibitors, and determined their gene expression levels. In addition, we compared these data with gene expression of proteases and their inhibitors in Fasciola hepatica eggs. Fasciola hepatica eggs served as a useful comparative model, as they do not migrate through tissues and inflict pathology. We detected transcription of 135 and 117 proteases in S. mansoni and F. hepatica eggs, respectively, with 87 identified as orthologous between the two species. In contrast, we observed only four orthologous inhibitors out of 21 and 16 identified in S. mansoni and F. hepatica eggs, respectively. Among others, we measured high and developmentally regulated levels of expression of metalloproteases in S. mansoni eggs, specifically aminopeptidase N1, endothelin-converting enzyme 1, and several leishmanolysin-like peptidases. We identified highly transcribed protease inhibitors serpin and alpha-2-macroglobulin that are unique to S. mansoni eggs, and antistasin-like inhibitor in F. hepatica eggs. This study provides new insights into the portfolio of proteases and inhibitors expressed by S. mansoni with potential roles in egg tissue migration, stimulation of angiogenesis, and interaction with host blood and immunity.

Influence of excessive body weight on cancer development and prognosis

Introduction and purpose&#x0D; According to the WHO, overweight and obesity are defined as excessive or abnormal accumulation of adipose tissue, leading to deterioration of health. Excessive body weight is a constantly growing public health problem that has reached the scale of a pandemic. Currently, there is ample evidence that excess body weight increases the risk of developing cancer and worsens the prognosis. The aim of this review is to analyze the impact of overweight and obesity on cancer development and prognosis, and to elucidate pathogenesis.&#x0D; State of knowledge &#x0D; Based on the current state of knowledge in epidemiology, it is estimated that approximately 20% of all malignancies are related to excessive body weight. So far, there is sufficient evidence to support an association between excess body fat and 13 out of 24 cancer sites: esophagus, gastric cardia, colon, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, meningioma, thyroid and multiple myeloma. Adipose tissue cells produce growth factors, hormones and cytokines that can interfere with the regulation of cell growth and survival. Excess adipose tissue leads to systemic chronic inflammation, oxidative stress, insulin resistance, hyperinsulinemia, increase in sex hormones, increase in leptin levels and a decrease in adiponectin levels. This leads to DNA defects, stimulation of angiogenesis, cell proliferation and inhibition of apoptosis, and thus promotes the development of cancer. In addition, studies have estimated that excess body weight is responsible for 14% of cancer deaths in men and 20% in women.&#x0D; Conclusions&#x0D; Due to the increasing problem of obesity and cancer worldwide and the proven causal relationship between these diseases, it is necessary to intensify nutrition education and promote a healthy lifestyle in order to minimize excessive body weight, and thus reduce the incidence of cancer.

Herbal Products and Their Active Constituents for Diabetic Wound Healing-Preclinical and Clinical Studies: A Systematic Review.

The purpose of this review is to provide verified data on the current knowledge acquired in preclinical and clinical studies regarding topically used herbal products and their active constituents (formulations and dressings) with diabetic wound healing activity. Moreover, herbal products and their active constituents used for diabetic wound infections, and various cellular and molecular mechanisms of their actions will also be described. The electronic databases were searched for articles published from 2012 to 2022. Publications with oral or systemic administration of herbal products in diabetic wound healing, published before 2012, available only as an abstract, or in languages other than English were excluded from the study. The 59 articles comparing topically used herbal products in diabetic wound healing treatment versus control treatments (placebo or active therapy) were selected. Herbal products through different mechanisms of action, including antimicrobial, anti-inflammatory, antioxidant activity, stimulation of angiogenesis, production of cytokines and growth factors, keratinocytes, and fibroblast migration and proliferation may be considered as an important support during conventional therapy or even as a substitute for synthetic drugs used for diabetic wound treatment.

Utilizing Instilling Negative Pressure Wound Therapy with Vashe Wound Solution for an Infected Sternal Dehiscence: A Case Report

Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing through macrostrain, microstrain, and cyclic fluid instillation. Wounds benefit from additional superficial infection control with the removal of microorganisms, the release of proinflammatory mediators, stimulation of angiogenesis, as well as mechanical debridement. However, very few cases of utilizing NPWTi in the treatment of sternal wound infections have been reported in the literature. This case study describes the use of NPWTi with hypochlorous acid for the treatment of a sternal wound infection.

Effects of the Foam Massage Roller on VEGF-A and FGF-2 Blood Levels in Young Men.

Angiogenesis induced in muscles or massaged tissue is thought to support their regeneration and performance. Therefore, different methods that could promote angiogenesis are investigated. The aim of this study was to examine whether the use of the foam roller massager for lower limb muscles affects VEGF-A and FGF-2 levels in young men. The study group included 60 healthy young men attending Military University of Land Forces, Wroclaw, Poland. The participants were randomly divided into two groups. The experimental group included 40 individuals who performed self-massage of the lower limbs using a foam roller. The control group comprised 20 individuals who did not perform massage. Massage was applied to lower limb muscles four times a week for seven weeks. Blood was collected before the experiment and after weeks 1, 3, 5, and 7. ELISA was used to determine changes in VEGF-A and FGF-2 levels in blood serum. The results of the study demonstrated a significant increase in VEGF-A serum levels in the group of individuals who underwent massage each week compared to VEGF-A concentrations before the experiment. The increase in VEGF-A levels in the experimental group was observed throughout the experiment compared to the control group. No significant changes in serum FGF-2 levels were found. The use of a foam massage roller increased VEGF-A serum levels, which may indicate stimulation of angiogenesis.

Angiogenesis stimulation in bacteria-infected acute wound healing with honey treatment in BALB/C mice

Angiogenesis stimulation in bacteria-infected acute wound healing with honey treatment in BALB/C mice

WBC &amp; THEIR ROLE IN TUMOR MICROENVIRONMENT (TME) OF ORAL SQUAMOUS CELL CARCINOMA-A REVIEW

Oral premalignant lesions (OPLs) that affect approximately 4.5% of the world's population usually precede the occurrence of Oral squamous cell carcinoma. These lesions are now included in oral potentially malignant disorders (OPMD). Majority of OPLs regress, yet, up to 30% of them ultimately progress through increasingly grades of dysplasia &amp;culminate as oral cancer. Therefore, OPLs represent an intermediate phase during the evolution of normal mucosa into malignant tumor, owing to their acquisition of a subset of the genomic alterations from those necessary to develop into Oral Squamous cell Carcinoma(OSCC).(1) In India OSCC is responsible for more than 20% of new malignancies diagnosed every year, being the most prevalent malignancy in the nation. There are several prognostic factors which help to evaluate the risk associated with the OSCC and serve as subsequent treatment guidelines. Increasing evidence has, so far, suggested that inammation may be linked to pathogenesis of oral cancer. Also, the tumor microenvironment is considered a crucial component in the understanding of the biologic behavior of a neoplasm. Leukocytosis is common in patients with progressive oral squamous cell carcinoma, is related with T-classication, lympho-vascular permeation, and recurrence or metastasis, &amp;, therefore could decrease survival. Tumor-related leukocytosis results from hematopoietic colony-stimulating factors and inammatory cytokines from solid tumors. (2,4) One of the new most promising histopathological factor in prognostic evaluation of OSCC is, the density of tumour inltrating lymphocytes (TILs). Different subsets of lymphocytes have different or even opposing functions in the tumor microenvironment. (2,6,7) Neutrophils contribute to cancer progression or regression via multiple mechanisms, including the suppression of cytotoxic as well as helper Tcell responses and the stimulation of tumor angiogenesis.(8) B cells also act as antigen-presenting cells, promote differentiation of Th1 cells and Tcyt cells, and directly kill cancer cells through release of Granzyme B, thus, having a tumor suppressive role. (9) Inltrating eosinophils in the tumor microenvironment (TME), supply direct and indirect mitogenic growth mediators that stimulate proliferation of neoplastic cells, as well as educate other stromal cell types to induce paracrine and juxtacrine mitogenic signaling molecules to support neoplastic growth which also appears true for oral squamous cell carcinomas (OSCCs). (10) The plasmacytoid dendritic cells (pDC), are specically important in cancer immunity as, these cells have been identied in many solid malignant tumors, including those of head and neck &amp; may play a key role in tumor occurrence and development.(9,12) Mast cells have a long life and form a heterogeneous population of cells that seem to have both a positive and negative regulatory effect on the immune system. MCs accumulate into tumor microenvironment by the help of tumor cell-released chemoattractants such as SCF or CCL15 and actively recruit cells of the innate immune system mainly neutrophils, macrophages, and eosinophils and cells of the acquired immune system (B and T cells) to orchestrate antitumor immune responses (13) In cancer tissues, the inltration of macrophages is signicantly increased. Macrophages are recruited to this edge by tumor-derived chemotactic agents and are a major inltrating cell type in the leading edge of a carcinoma.(16) OSCC are highly immunogenic tumors that are often characterized by abundant inltration of immune cells, however, their function &amp; prognostic value vary. (19, 20)

Abnormal expression of long non-coding RNA FGD5-AS1 affects the development of ovarian cancer through regulating miR-107/RBBP6 axis.

Long non-coding RNAs (lncRNAs) are important players in cancer development. LncRNA FGD5-AS1 has been reported as a potential oncogene in ovarian cancer (OC). The present paper focused on the action mechanism of FGD5-AS1 in OC. Clinical OC samples were collected for expression analyses of FGD5-AS1, RBBP6, and miR-107. The expression of FGD5-AS1, RBBP6, and miR-107 in OC cells was altered by transfection. OC cell proliferation was assessed by MTT and colony formation assays, and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with OC cell supernatants by matrigel angiogenesis assay. The interactions among FGD5-AS1, miR-107, and RBBP6 were detected by luciferase reporter assay. FGD5-AS1 and RBBP6 were strongly expressed and miR-107 was poorly expressed in clinical OC samples and OC cell lines. FGD5-AS1 or RBBP6 overexpression in Hey and SKOV3 cells could potentiate OC cell proliferation and HUVEC angiogenesis, while FGD5-AS1 or RBBP6 knockdown in OC cells inhibited the above cellular processes. FGD5-AS1 targeted miR-107 to positively regulate RBBP6 expression. Additionally, miR-107 overexpression or RBBP6 knockdown in SKOV3 cells partially reversed the FGD5-AS1-dependent stimulation of OC cell proliferation and HUVEC angiogenesis. FGD5-AS1 may act as a promoter of OC via miR-107/RBBP6 axis.