Development Of Blood Vessels Research Articles

In Silico Study Active Compounds of Jamu Against Pre-Eclampsia Through Anti-Vasoconstriction and Anti-Inflammation

Preeclampsia is one of serious pregnancy-related condition that marked by elevated blood pressure and proteinuria that typically emerges during the second trimester or above 20 week, this disease become the second common cause of maternal death globally per year. One factors that can initiate preeclampsia are immunologic factor. Preeclampsia is started with abnormal trophoblast development and poor or shallow placental blood vessel development. Several protein that are induce by pre eclampsia are ACE1 (as vasoconstrictor), p38α, and JNK (stress-related protein and induce inflammation). One of the natural medicine in Indonesia is a “Jamu” that refers to traditional herbal medicine derived from natural ingredients such as herbs, roots, and spices.. In this research we are trying to predict several compounds in early-month pregnant jamu to tackle activation of ACE1, JNK, and p38α. Firstly, all of jamu compound was screened using Lipinski and bioavaibility test. Then, all of the jamu compound that pass the test before will be docked with ACE1, JNK, and p38α using Vina wizard in PyRx. The highest affinity in docking result will be visualized using Biovia Discovery Studio 2019, and will advance to molecular dynamics simulation test to determine stability of the complex in cell environment. The result show that kaempferol can stabily bind to p38α protein, with only induce minimum fluctuation in all RMSD and RMSF result. Piperanine can stabily bind JNK protein with also minimum fluctuation in all RMSD and RMSF result. Both kaempferol and piperanine did’t violate any Lipinski rule and Bioavaibility test.

Differential vegfc expression dictates lymphatic response during zebrafish heart development and regeneration.

Vascular endothelial growth factor C (Vegfc) is crucial for lymphatic and blood vessel development, yet its cellular sources and specific functions in heart development remain unclear. To address this, we created a vegfc reporter and an inducible overexpression line in zebrafish. We found vegfc expression in large coronary arteries, circulating thrombocytes, cardiac adipocytes, and outflow tract smooth muscle cells. Notably, while coronary lymphangiogenesis aligns with Vegfc-expressing arteries in juveniles, it occurs only after coronary artery formation. Vegfc overexpression induced ectopic lymphatics on the ventricular surface prior to arterial formation, indicating that Vegfc abundance, rather than arterial presence, drives lymphatic development. However, this overexpression did not affect coronary artery coverage, suggesting a specific role for Vegfc in lymphatic, rather than arterial, development. Thrombocytes emerged as the initial Vegfc source during inflammation following heart injuries, transitioning to endocardial and myocardial expression during regeneration. Lower Vegfc levels in the amputation model corresponded with a lack of lymphatic expansion. Importantly, Vegfc overexpression enhanced lymphatic expansion and promoted scar resolution without affecting cardiomyocyte proliferation, highlighting its role in regulating lymphangiogenesis and promoting heart regeneration.

Metalloproteinases are involved in the regulation of prenatal tooth morphogenesis.

During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signalling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlights that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex-vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization and organization compared to control tooth germs. Additionally, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated Hif-1α expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.

Effects of guanidine acetic acid supplementation from gestation to lactation on reproductive performance, colostrum quality, blood biochemistry, and intestinal microflora diversity of sows.

This experiment aimed to study the effects of guanidine acetic acid (GAA) on reproductive performance, lactation performance and blood biochemical indices of sows, as well as the performance of offspring piglets. A total of 20 sows (Landrace × Yorkshire, parity 4) were used. Half of the sows in each parity were fed a control diet (CG; basic diet, n = 10) or GAA diet (basic diet +1 g/kg GAA, n = 10) from the 85th day of gestation until weaning. The study results are presented as follows: Supplementation of GAA from late gestation to lactation did not adversely affect sow feed intake, backfat thickness, or blood routine indexes (p > 0.05). GAA supplementation showed a tendency to increase the number of healthy piglets and their birth activity (p = 0.06; p = 0.08), while significantly increasing the IUGR score of piglets (p < 0.05). GAA supplementation significantly increased colostrum protein content (p < 0.05) and tended to increase daily milk yield in sows (p = 0.07). GAA supplementation increased the level of immunoglobulin A in sow colostrum (p < 0.05) and showed a tendency to increase proline content (p = 0.10). GAA supplementation significantly decreased triglyceride content in sow cord blood (p < 0.05), with no significant effects observed on HDL-C, LDL-C, TC, and GLU (p > 0.05). GAA supplementation significantly increased eNOS levels in sow cord blood (p < 0.05), while showing no significant effects on IL-6 and IL-10 (p > 0.05). GAA supplementation did not significantly affect the α diversity of sow intestinal flora (ACE, Shannon, Chao1, Simpson, observed_otus, pielou_e, and good_cover), but PCoA analysis revealed differences in intestinal flora structure between groups. Additionally, GAA decreased the relative abundance of Sarciha and unidentified_ruminococcaceae and increased the relative abundance of Lactobacillus, Parabacteroides, and Pedobacter in the gut. GAA boosts nitric oxide synthase in sows' umbilical cord blood, enhancing placental blood vessel development. This improves piglet health and vitality, increases beneficial gut bacteria (Lactobacillus, Parabacteroides, Pedobacter), and raises colostrum protein levels and lactation volume, leading to better piglet growth and performance.

Therapeutic potency of marine collagen/pectin scaffolds - Fabrication, characterization and evaluation

Skin is an important vital organ that must be given proper care and protection from external damage and harmful microbes. If injured, it must be treated with an ideal wound dressing material with potent hemostatic and non-toxic properties. In the present study, fish collagen (FC) was extracted from the fins and tails of Black pomfret (Parastromateus niger). The isolated fish collagen was homogenized with pectin (P) and freeze dried to obtain fish collagen/pectin (FC/P) scaffolds. Scanning electron microscopic analysis showed the porous nature of scaffolds with intermittent holes. UV–Visible and Fourier infrared spectroscopic analyses demonstrated the physicochemical properties of FC/P scaffolds. Hemolytic assay performed using human blood demonstrated the percentage of hemolysis as 0.5 %. In vitro blood clotting assay carried out to determine the hemostatic behaviour displayed the formation of blood clot within 60 s in the presence of FC/P scaffolds. 95 % of cells were viable with the highest concentration of FC/P scaffold used for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Scratch wound assay demonstrated complete closure of wound in FC/P scaffold treated cells after 48 h of treatment. Chick embryo chorioallantoic membrane (CAM) assay showed the development of new blood vessels within 6 h of incubation with the FC/P scaffolds, thereby proving their angiogenic potency. These results indicate the potential use of FC/P scaffolds as effective biomaterials for tissue regenerative applications.

DNA methylation at AHRR as a master predictor of smoke exposure and a biomarker for sleep and exercise

BackgroundDNA methylation profiling may provide a more accurate measure of the smoking status than self-report and may be useful in guiding clinical interventions and forensic investigations. In the current study, blood DNA methylation profiles of nearly 800 Polish individuals were assayed using Illuminia EPIC and the inference of smoking from epigenetic data was explored. In addition, we focused on the role of the AHRR gene as a top marker for smoking and investigated its responsiveness to other lifestyle behaviors.ResultsWe found > 450 significant CpGs associated with cigarette consumption, and overrepresented in various biological functions including cell communication, response to stress, blood vessel development, cell death, and atherosclerosis. The model consisting of cg05575921 in AHRR (p = 4.5 × 10–32) and three additional CpGs (cg09594361, cg21322436 in CNTNAP2 and cg09842685) was able to predict smoking status with a high accuracy of AUC = 0.8 in the test set. Importantly, a gradual increase in the probability of smoking was observed, starting from occasional smokers to regular heavy smokers. Furthermore, former smokers displayed the intermediate DNA methylation profiles compared to current and never smokers, and thus our results indicate the potential reversibility of DNA methylation after smoking cessation. The AHRR played a key role in a predictive analysis, explaining 21.5% of the variation in smoking. In addition, the AHRR methylation was analyzed for association with other modifiable lifestyle factors, and showed significance for sleep and physical activity. We also showed that the epigenetic score for smoking was significantly correlated with most of the epigenetic clocks tested, except for two first-generation clocks.ConclusionsOur study suggests that a more rapid return to never-smoker methylation levels after smoking cessation may be achievable in people who change their lifestyle in terms of physical activity and sleep duration. As cigarette smoking has been implicated in the literature as a leading cause of epigenetic aging and AHRR appears to be modifiable by multiple exogenous factors, it emerges as a promising target for intervention and investment.

H19 lncRNA triggers ferroptosis, exacerbating ox-LDL-induced artery endothelial cell damage in vitro.

The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Computer-Aided Design of VEGFR-2 Inhibitors as Anticancer Agents: A Review.

Due to its intricate molecular and structural characteristics, vascular endothelial growth factor receptor 2 (VEGFR-2) is essential for the development of new blood vessels in various pathological processes and conditions, especially in cancers. VEGFR-2 inhibitors have demonstrated significant anticancer effects by blocking many signaling pathways linked to tumor growth, metastasis, and angiogenesis. Several small compounds, including the well-tolerated sunitinib and sorafenib, have been approved as VEGFR-2 inhibitors. However, the widespread side effects linked to these VEGFR-2 inhibitors-hypertension, epistaxis, proteinuria, and upper respiratory infection-motivate researchers to search for new VEGFR-2 inhibitors with better pharmacokinetic profiles. The key molecular interactions required for the interaction of the small molecules with the protein target to produce the desired pharmacological effects are identified using computer-aided drug design (CADD) methods such as pharmacophore and QSAR modeling, structure-based virtual screening, molecular docking, molecular dynamics (MD) simulation coupled with MM/PB(GB)SA, and other computational strategies. This review discusses the applications of these methods for VEGFR-2 inhibitor design. Future VEGFR-2 inhibitor designs may be influenced by this review, which focuses on the current trends of using multiple screening layers to design better inhibitors.

A Brief Review on Adult-Onset Coats' Disease.

Adult-onset Coats disease is an uncommon and vision-threatening disease characterized by the development of abnormal blood vessels in the retina. Coats' disease commonly affects children in the first decade of life, but very rarely manifests in adults after the third decade of life, or who characteristically present with unilateral vision loss. Despite being a sight-threatening disease, the etiology remains inconclusive and various genetic and vascular abnormalities are implicated. Diagnosis relies on ophthalmologic examination, fundus photography, fluorescein angiography, and optical coherence tomography. Treatment modalities include laser photocoagulation, intravitreal injections of anti-vascular endothelial growth factor agents, and, in advanced cases, surgical interventions are needed and the treatment is aimed at avoiding complications like retinal detachment and neovascular glaucoma, which were comparatively rare in adult-onset Coats' disease. Despite therapeutic advancements, the prognosis varies, with some patients experiencing significant visual impairment. This review outlines the clinical features, diagnosis, management, and prognosis of adult-onset Coats' disease, underscoring the importance of early detection and intervention in optimizing visual outcomes.

Critical appraisal of the chorioallantoic membrane model for studying angiogenesis in preclinical research.

Angiogenesis, the biological mechanism by which new blood vessels are generated from existing ones, plays a vital role in growth and development. Effective preclinical screening is necessary for the development of medications that may enhance or inhibit angiogenesis in the setting of different disorders. Traditional in vitro and, in vivo models of angiogenesis are laborious and time-consuming, necessitating advanced infrastructure for embryo culture. A challenge encountered by researchers studying angiogenesis is the lack of appropriate techniques to evaluate the impact of regulators on the angiogenic response. An ideal test should possess reliability, technical simplicity, easy quantifiability, and, most importantly, physiological relevance. The CAM model, leveraging the extraembryonic membrane of the chicken embryo, offers a unique combination of accessibility, low cost, and rapid development, making it an attractive option for angiogenesis assays. This review evaluates the strengths and limitations of the CAM model in the context of its anatomical and physiological properties, and its relevance to human pathophysiological conditions. Its abundant capillary network makes it a common choice for studying angiogenesis. The CAM assay serves as a substitute for animal models and offers a natural setting for developing blood vessels and the many elements involved in the intricate interaction with the host. Despite its advantages, the CAM model's limitations are notable. These include species-specific responses that may not always extrapolate to humans and the ethical considerations of using avian embryos. We discuss methodological adaptations that can mitigate some of these limitations and propose future directions to enhance the translational relevance of this model. This review underscores the CAM model's valuable role in angiogenesis research and aims to guide researchers in optimizing its use for more predictive and robust preclinical studies. The highly vascularized chorioallantoic membrane (CAM) of fertilized chicken eggs is a cost-effective and easily available method for screening angiogenesis, in comparison to other animal models.

Prenatal exposure to low doses of benzophenone-3 elicits disruption of cortical vasculature in fetuses through perturbations in Wnt/β-catenin signaling correlating with depression-like behavior in offspring mice

Benzophenone-3 (BP-3), commonly used in personal care products, is routinely detected in environmental and human matrices. Evidence delineates a correlation between gestational BP-3 exposure and emotional and social disorders in children and adolescents. However, sensitive target cells and the mode of action underlying the early responses to environmentally relevant level of BP-3 exposure remain unclear. In this study, 0.3 and 3 mg/kg of BP-3 were administered to pregnant mice. Compared with the control group, the cortical blood vessel development process manifested the highest susceptibility to BP-3 exposure using transcriptomic sequencing at embryonic day 14 (E14). Notably, the diminution in vascular density and tight junction proteins presence was observed in the fetal cortex at E14, concomitant with the suppressed transcriptional activity of genes essential to angiogenesis and barrier formation. Strikingly, the investigation revealed that BP-3 exposure impeded vascular sprouting in aortic ring explants and neuroendothelial migration, implicating the Wnt/β-catenin signaling pathway. Moreover, BP-3 exposure compromised perivascular neural stem cell differentiation. Cortical vascular injury correlated with the exhibition of depression-like behavior in four-week postnatal progeny. These insights underscore the cerebrovasculature as an early sensitive target for low doses of BP-3 exposure, fostering the development of biomarkers and the establishment of the adverse outcome pathway framework for BP-3 hazard evaluation.

The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy.

G protein-coupled receptors (GPCRs) are vital cell surface receptors that govern a myriad of physiological functions. Despite their crucial role in regulating antitumor immunity and tumorigenesis, therapeutic applications targeting GPCRs in oncology are currently limited. This review offers a focused examination of selected protumorigenic chemokine and metabolite-sensing GPCRs. Specifically, the review highlights five GPCRs able to orchestrate tumor immunobiology at three main levels: tumor immunity, cancer cell expansion, and blood vessel development. The review culminates by illuminating emerging therapies and discussing innovative strategies to harness the full potential of GPCR-targeted treatments, by applying a multireceptor and patient-specific logic.

Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications.

Fine-tuning angiogenesis, the development of new blood vessels, is essential for maintaining a healthy circulatory and lymphatic system. The small glycoprotein vascular endothelial growth factors (VEGF) are the key mediators in this process, binding to their corresponding membrane-bound VEGF receptors (VEGFRs) to activate angiogenesis signaling pathways. These pathways are crucial throughout human life as they are involved in lymphatic and vascular endothelial cell permeability, migration, proliferation, and survival. Neovascularization, the formation of abnormal blood vessels, occurs when there is a dysregulation of angiogenesis and can result in debilitating disease. Hence, VEGFRs have been widely studied to understand their role in disease-causing angiogenesis. VEGFR1, also known as Fms-like tyrosine kinase-1 (FLT-1), is also found in a soluble form, soluble FLT-1 or sFLT-1, which is known to act as a VEGF neutralizer. It is incorporated into anti-VEGF therapy, designed to treat diseases caused by neovascularization. Here we review the journey of sFLT-1 discovery and delve into the alternative splicing mechanism that creates the soluble receptor, its prevalence in disease states, and its use in current and future potential therapies.

The angiogenic role of the alpha 9-nicotinic acetylcholine receptor in triple-negative breast cancers.

Nicotine acts as an angiogenic factor by stimulating endogenous cholinergic pathways. Several subtypes of nicotinic acetylcholine receptors (nAChRs) have been demonstrated to be closely correlated to the formation and progression of different types of cancers. Recently, several studies have found that nicotinic acetylcholine receptors α9 (α9-nAChRs) are highly expressed in breast tumors, especially in tumors derived from patients diagnosed at advanced stages. In vitro studies have demonstrated that activation of α9-nAChRs is associated with increased proliferation and migration of breast cancer. To study the tumor-promoting role of α9-nAChRs in breast cancers, we generated a novel anti-α9-nAChR and methoxy-polyethylene glycol (mPEG) bispecific antibody (α9 BsAb) for dissecting the molecular mechanism on α9-nAChR-mediated tumor progression. Unexpectedly, we discovered the angiogenic role of α9-nAChR in nicotine-induced neovascularization of tumors. It revealed α9 BsAbs reduced nicotine-induced endothelial cell tube formation, blood vessel development in Matrigel plug assay and angiogenesis in microtube array membrane murine model (MTAMs). To unbraid the molecular mechanism of α9-nAChR in nicotine-mediated angiogenesis, the α9 BsAbs were applied and revealed the inhibitory roles in nicotine-induced production of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor A (VEGF-A), phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2), vascular endothelial growth factor receptor 2 (VEGFR2) and matrix metalloproteinase-9 (MMP9) from triple-negative breast cancer cells (MDA-MB-231), suggesting α9-nAChRs played an important role in nicotine-induced angiogenesis. To confirm our results, the shRNA targeting α9-nAChRs was designed and used to silence α9-nAChR expression and then evaluated the angiogenic role of α9-nAChRs. The results showed α9 shRNA also played an inhibitory effect in blocking the nicotine-induced angiogenic signaling. Taken together, α9-nAChR played a critical role in nicotine-induced angiogenesis and this bispecific antibody (α9 BsAb) may serve as a potential therapeutic candidate for treatments of the α9 positive cancers.

Expression of Autophagy Markers LC3B, LAMP2A, and GRP78 in the Human Kidney during Embryonic, Early Fetal, and Postnatal Development and Their Significance in Diabetic Kidney Disease.

Autophagy is the primary intracellular degradation system, and it plays an important role in many biological and pathological processes. Studies of autophagy involvement in developmental processes are important for understanding various processes. Among them are fibrosis, degenerative diseases, cancer development, and metastasis formation. Diabetic kidney disease is one of the main causes of chronic kidney disease and end-stage renal failure. The aim of this study was to investigate the immunohistochemical expression patterns of LC3B, LAMP2A, and GRP78 during different developmental stages of early-developing human kidneys and in samples from patients with type II diabetes mellitus. During the 7/8th DW, moderate expression of LC3B and LAMP2A and strong expression of GRP78 were found in the mesonephric glomeruli and tubules. In the 9/10th DW, the expression of LC3B and LAMP2A was even more pronounced in the mesonephric tubules. LC3B, LAMP2A, and GRP78 immunoreactivity was also found in the paramesonephric and mesonephric ducts and was stronger in the 9/10th DW compared with the 7/8th DW. In addition, the expression of LC3B, LAMP2A, and GRP78 also appeared in the mesenchyme surrounding the paramesonephric duct in the 9/10th DW. In the 15/16th DW, the expression of LC3B in the glomeruli was weak, that of LAMP2A was moderate, and that of GRP78 was strong. In the tubuli, the expression of LC3B was moderate, while the expression of LAMP2A and GRP78 was strong. The strongest expression of LC3B, LAMP2A, and GRP78 was observed in the renal medullary structures, including developing blood vessels. In postnatal human kidneys, the most extensive LC3B, LAMP2A, and GRP78 expression in the cortex was found in the epithelium of the proximal convoluted tubules, with weak to moderate expression in the glomeruli. The medullary expression of LC3B was weak, but the expression of LAMP2A and GRP78 was the strongest in the medullary tubular structures. Significantly lower expression of LC3B was found in the glomeruli of the diabetic patients in comparison with the nondiabetic patients, but there was no difference in the expression of LC3B in the tubule-interstitial compartment. The expression of LAMP2A was significantly higher in the tubule-interstitial compartments of the diabetic patients in comparison with the nondiabetic patients, while its expression did not differ in the glomeruli. Extensive expression of GRP78 was found in the glomeruli and the tubule-interstitial compartments, but there was no difference in the expression between the two groups of patients. These data give us new information about the expression of LC3B, LAMP2A, and GRP78 during embryonic, fetal, and early postnatal development. The spatiotemporal expression of LC3B, LAMP2A, and GRP78 indicates the important role of autophagy during the early stages of renal development. In addition, our data suggest a disturbance in autophagy processes in the glomeruli and tubuli of diabetic kidneys as an important factor in the pathogenesis of diabetic kidney disease.

Factors Affecting Compliance and Visual Outcomes in Patients Receiving Intravitreal Bevacizumab Injections.

Background Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients. Therefore, this study aims to determine the success rates of intravitreal bevacizumab therapy and the visual outcomes which may be increased by determining the factors affecting patient compliance and raising awareness about DR, neovascular AMD, and RVOamong patients and studying the factors responsible for non-compliance to treatment. Methodology This experimental pre-post study was conducted in the ophthalmology department at a tertiary care hospital and research center in western Maharashtra from September 2022 to June 2024. A total of 150 eyes of 150 patients who were diagnosed cases of DR, neovascular AMD, and non-ischemic RVOwere included in the study.Written informed consent was obtained from each patient. Data were entered in Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and statistical analysis was done using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). The chi-square test was employed to check the association between categorical variables. Pearson's correlation test was used, and p-values <0.05 were considered significant. Results The compliance rate in our study was 79.3% (113 individuals). In our study, 58% (87 individuals) were male while 42% (63 individuals) were females. Most patients were from urban areas 74.7% (112 individuals). Among the study participants, DR patients constituted 48.6% (73 individuals), while neovascular AMD and RVO were seen in 32% (48 individuals) and 19.4% (29 individuals), with 62% (93 individuals) being diabetic and 64.7% (97 individuals) being hypertensive. In our study, 92% (138 individuals) were willing to take treatment, with 88.7% (133 individuals) worried about their visual outcomes and 66% (99 individuals) afraid of getting injected. Appointments posed a financial burden to 30.7% (46 individuals) of patients, with 55.3% (83 individuals) having transportation issues. Overall, 18.7% (28 individuals) of patients had missed appointments between 14 and 90 days while 30.7% (46 individuals) had missed their appointments by 90 and 365 days. Younger patients with a shorter duration of diabetes had higher compliance rates. Post-injection, there was an overall significant improvement in vision as well as a reduction in the central subfield macular thickness, volume cube, and thickness average cube. Conclusions In the present study, four-fifths of the patients were compliant with treatment, and visual improvement was significant. In addition, there was a significant reduction in the macular thickness after the treatment. One of the factors for non-compliance included in our study was the need for follow-up. Younger patients and those with a shorter duration of diabetes had significantly higher compliance. We recommend further studies should be conducted to compare the effectiveness with the control group in randomized control trials.

New Interpretations for Sprouting, Intussusception, Ansiform, and Coalescent Types of Angiogenesis.

Angiogenesis, or the development of blood vessels by growing from already-formed vessels, is observed in embryonic development, physiological cyclical processes such as wound healing, the encapsulation of foreign bodies, tumor growth, and some other situations. In this review, we analyze the cellular mechanisms of angiogenesis, namely, angiogenesis by sprouting, ansiform (by loop formation) angiogenesis, coalescent angiogenesis, and angiogenesis by intussusception (splitting the capillary into two channels). The analysis of data revealed a lot of unanswered questions and contradictions. Here, we propose several new models of angiogenesis explaining these contradictions.

Comparison of colostrum and milk extracellular vesicles small RNA cargo in water buffalo

Recently, much interest has been raised for the characterization of signaling molecules carried by extracellular vesicles (EVs), which are particularly enriched in milk (mEVs). Such interest is linked to the capability of EVs to cross biological barriers, resist acidification in the gastric environment, and exert modulation of the immune system, mainly through their microRNA (miRNA) content. We characterized the small-RNA cargo of colostrum EVs (colosEVs) and mEVs from Italian Mediterranean buffalo through next generation sequencing. Colostrum (first milking after birth) and milk (day 50 of lactation) were sampled from seven subjects from five farms. ColosEVs and mEVs were subjected to morphological characterization, followed by high-depth sequencing of small RNA libraries produced from total RNA. The main difference was the amount of EV in the two samples, with colostrum showing 10 to 100-fold higher content than milk. For both matrices, miRNA was the most abundant RNA species (95% for colosEVs and 96% for mEVs) and three lists were identified: colosEV-specific, mEV-specific and shared most expressed. Gene ontology (GO) enrichment analysis on miRNA targets highlighted many terms related to the epigenetic, transcriptional and translational regulations across the three lists, with a higher number of enriched terms for colosEV-specific miRNAs. Terms specific to colosEVs were related to “cell differentiation” and “microvillus assembly”, while for mEV “cardiac and blood vessel development” and “mitochondria” emergerd. Immune modulation terms were found for both sample-specific miRNAs. Overall, both matrices carry a similar molecular message in terms of biological processes potentially modulated into receiving cells, but there is significant difference in the abundance, with colostrum containing much more EVs than milk. Moreover, colosEVs carry molecules involved in signal transduction, cell cycle and immune response, as for mEVs and EVs of other previously characterized species, but with a special enrichment for miRNAs with epigenetic regulation capacities. These beneficial characteristics of colosEVs and mEVs are essential for the calf and could also be exploited for the therapeutic purposes in humans, although further studies are necessary to measure the sanitization treatment impact on EV conservation, especially in buffalo where milk is consumed almost exclusively after processing.

Chemical analogue based drug design for cancer treatment targeting PI3K: integrating machine learning and molecular modeling.

Cancer is a generic term for a group of disorders defined by uncontrolled cell growth and the potential to invade or spread to other parts of the body. Gene and epigenetic alterations disrupt normal cellular control, leading to abnormal cell proliferation, resistance to cell death, blood vessel development, and metastasis (spread to other organs). One of the several routes that play an important role in the development and progression of cancer is the phosphoinositide 3-kinase (PI3K) signaling pathway. Moreover, the gene PIK3CG encodes the catalytic subunit gamma (p110γ) of phosphoinositide 3-kinase (PI3Kγ), a member of the PI3K family. Therefore, in this study, PIK3CG was targeted to inhibit cancer by identifying a novel inhibitor through computational methods. The study screened 1015 chemical fragments against PIK3CG using machine learning-based binding estimation and docking to select the potential compounds. Later, the analogues were generated from the selected hits, and 414 analogues were selected, which were further screened, and as most potential candidates, three compounds were obtained: (a) 84,332, 190,213, and 885,387. The protein-ligand complex's stability and flexibility were then investigated by dynamic modeling. The 100ns simulation revealed that 885,387 exhibited the steadiest deviation and constant creation of hydrogen bonds. Compared to the other compounds, 885,387 demonstrated a superior binding free energy (ΔG = -18.80kcal/mol) with the protein when the MM/GBSA technique was used. The study determined that 885,387 showed significant therapeutic potential and justifies further experimental investigation as a possible inhibitor of the PIK3CG target implicated in cancer.

Vasculogenic mimicry-related gene prognostic index for predicting prognosis, immune microenvironment in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a highly aggressive cancer associated with higher death rates. However, traditional anti-angiogenic therapies have limited effectiveness due to drug resistance. Vascular mimicry (VM) provides a different way for tumors to develop blood vessels without relying on endothelial cells or angiogenesis. However, the intricate mechanisms and interplay between it and the immune microenvironment in ccRCC remain unclear. MethodsA PubMed and GeneCards literature review was conducted to identify VM-related genes (VMRGs). VMRGs expression profiles were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), developing a novel VM risk score model and nomogram for ccRCC. The EBI ArrayExpress database (the validation set) was obtained to validate the prognostic model. The relationship between VMRGs risk score clinical characteristics and immune infiltration was investigated. Finally, the expression of six model VMRGs was validated using single-cell analysis, GEPIA, Human Protein Atlas (HPA), and quantitative Real-time PCR (qRT-PCR). ResultsCox regression analysis and nomogram identified L1CAM, TEK, CLDN4, EFNA1, SERPINF1, and MALAT1 as independent prognostic risk factors, which could be used to stratify the ccRCC population into two risk groups with distinct immune profiles and responsiveness to immunotherapy. The results of single-cell analysis, GEPIA, HPA, and qRT-PCR validated the model genes’ expression. ConclusionsOur novel findings constructed a convenient and reliable 6 gene signatures as potential immunologic and prognostic biomarkers of VM in ccRCC.