Vascular Endothelial Growth Factor Levels Research Articles

Saponin Ⅰ from Shuitianqi () inhibits metastasis by negatively regulating the transforming growth factor-β1/Smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model.

To examine the influence of Saponin I from Shuitianqi (Rhizoma Schizocapasae Plantagineae) (SSPH I) on hepatocellular carcinoma (HCC) metastasis, and to elucidate the underlying mechanism. The intrahepatic metastasis Bagg's Albino/c (BALB/c) mouse model was established with human hepatocellular carcinomas (HepG2) cells, then treated with normal saline (once per day), cisplatin (2 mg/kg, once every 2 d), and SSPH Ⅰ (25, 50, and 75 mg/kg, once per day). Then, we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques. Based on our analysis, SSPH Ⅰ significantly alleviated hepatocyte necrosis and tumor cells infiltration. Moreover, SSPH Ⅰ suppressed extracellular matrix (ECM) degradation and angiogenesis viaa decrease in matrix etalloproteinase-2 (MMP-2), MMP-9, CD31, CD34, and vascular endothelial growth factor (VEGF) levels. Furthermore, SSPH Ⅰ repressed invasion and meta-stasis by suppressing the transforming growth factor-β1 (TGF-β1)/Smad7 axis and epithelial-mesenchymal transition (EMT), as evidenced by the scarce TGF-β1, N-cadherin, and Vimentin expressions, and elevated Smad7 and E-cadherin expressions. The SSPH Ⅰ-mediated negative regulation of the TGF-β1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

Valsartan as a prophylactic treatment against breast cancer development and niche activation: What molecular sequels follow chronic AT-1R blockade?

AimsTransactivation of insulin-growth-factor-receptor (IGF-1R) by angiotensin-II-type-1-receptor (AT-1R) was only demonstrated in vascular-smooth-muscle cells and has never been tested in breast-cancer (BC). This investigation addressed the impact of chronic AT-1R blockade by valsartan (Val) on possible concurrent AT-1R/IGF-1R signaling inhibition, regressing BC-tumor-microenvironment (TME) cellular components activation, and hindering BC development. Main methodsThe effect of different Val doses (10, 20, 40 & 80 mg/kg/day for 490 days) was tested on dimethylbenz(a)anthracene (DMBA)-induced progesterone-promoted-BC in rats. The influence on intratumoral/circulating angiotensin-II (ANG-II) levels and AT-1R/Mas-R immunofluorescent-expression were assessed. The potential AT-1R/IGF-1R crosstalk within TME-BC-stem-cells (BCSCs) and cancer-associated-fibroblasts (CAFs) was evaluated by fluorescently marking these cells and locating the immunofluorescently-stained AT-1R/IGF-1R in them using confocal-laser-microscopy and further quantified by flow cytometry. In addition, the molecular alterations following blocking AT-1R were inspected including determining Src; crucial for IGF-1R transactivation by AT-1R, Notch-1; IGF-IR transcriptional-regulator, and PI3K/Akt &IL-6/STAT expression. Further, the suppression of CSCs' capabilities to maintain pluripotency, stemness features, epithelial-to-mesenchymal-transition (EMT), and angiogenesis was evaluated by assessing NANOG gene, aldehyde-dehydrogenase (ALDH), N-cadherin and vascular-endothelial-growth-factor (VEGF), respectively. Furthermore, the proliferative marker; Ki-67, was detected by immunostaining, and tumors were histologically graded using Elston-Ellis-modified-Scarff-Bloom-Richardson method. Key findingsProphylactic Val significantly reduced tumor size, prolonged latency, reduced tumor histopathologic grade, decreased circulating/intratumoral-ANG-II levels, increased Mas-R, and decreased AT1R expression. AT-1R/IGF-1R were co-expressed with a high correlation coefficient on CAFs/BCSCs. Moreover, Val significantly attenuated IGF-1R transactivation and transcriptional regulation via Src and Notch-1 genes' downregulation and reduced Src/IGF-IR-associated PI3K/Akt and IL-6/STAT3 signaling. Further, Val significantly decreased intratumoral NANOG, ALDH, N-cadherin, VEGF, and Ki-67 levels. SignificanceChronic Val administration carries a potential for repurposing as adjuvant or conjunct therapy for patients at high risk for BC.

Hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway-based ulcer-healing mechanism of Astragalus Aqueous extract in diabetic foot rats.

The main objective of this work was to investigate the mechanism of Astragalus aqueous extract ulcer healing in diabetic foot model rats through the hypoxia-inducible factor 1-alpha (HIF-1ɑ)/vascular endothelial growth factor (VEGF) signalling pathway. Fifty specific-pathogen-free male Sprague Dawley rats were divided into blank (A), model control (B), Astragalus extract (C) and mupirocin (D) treatment groups. Group A received a regular diet, whereas the other groups received a high-fat/high-sugar diet and intraperitoneal streptozotocin injections to induce diabetes. Diabetic foot ulcers were created via skin excision. Subsequently, ulcers were debrided daily. Groups B, C and D received wet saline gauze, wet gauze with Astragalus extract and gauze with mupirocin, respectively, on the affected area. Group A received no treatment. After 14days, the rats were assessed for ulcer healing and general condition. Immunohistochemistry was used to detect HIF-1ɑ and VEGF levels in the dorsalis pedis artery, and ELISA was used to determine serum IL-6 and CRP levels. The results revealed that Groups C and D had significantly faster ulcer healing compared with Group B (p < 0.01), and ulcer healing was faster in Group C than in Group D (p < 0.01). Group C exhibited notably higher HIF-1ɑ and VEGF protein expression levels compared with Groups B and D (p < 0.01). IL-6 and CRP expression levels in Groups C and D were significantly lower than those in Group B (p < 0.01). In summary, Astragalus aqueous extract effectively treats diabetic foot ulcers by up-regulating HIF-1ɑ and VEGF expression, activating the HIF-1ɑ/VEGF pathway, improving local tissue ischaemia and hypoxia, promoting collateral circulation and enhancing dorsalis pedis artery formation, thereby accelerating ulcer repair in diabetic rats.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis.

Acute myeloid leukemia (AML) is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand, inhibiting hematopoiesis. The treatment and prognosis of this disease have always been unsatisfactory. To investigate the correlation between vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGFβ1) expression and prognosis in older adults with AML. This study enrolled 80 patients with AML (AML group), including 36 with complete response (AML-CR), 23 with partial response (AML-PR), and 21 with no response (AML-NR). The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls. Kaplan-Meier analysis was performed to assess overall survival (OS) and progression- or disease-free survival (DFS). Prognostic risk factors were analyzed using a Cox proportional hazards model. The AML group showed a VEGF level of 2.68 ± 0.16. VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR (P < 0.05). TGFβ1 expression in the AML group was 0.33 ± 0.05. Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR (P < 0.05). VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes, platelets, hemoglobin, and peripheral blood immature cells (P < 0.05); Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression (P < 0.05), whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels (P < 0.05). VEGF, TGFβ1, and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS (P < 0.05), while VEGF, TGFβ1, and white blood cell count were independent risk factors for DFS (P < 0.05). Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Higher levels of markers for early atherosclerosis in anti-citrullinated protein antibodies positive individuals at risk for RA, a cross sectional study

ObjectiveTo identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups.MethodsCross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Groningen (UMCG).Serum biomarkers of inflammation, endothelial cell activation, tissue remodeling and adipokine, which were previously associated with atherosclerosis, were measured with Luminex in four ACPA positive groups with different characteristics: without joint complaints, with joint complaints, RA risk and early RA groups.ResultsLevels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Receptor 1 (TNFR1) and vascular endothelial growth factor (VEGF) were significantly higher in the RA risk and early RA groups compared to the joint complaints and the no joint complaints groups. The difference remained statistically significant after correcting for renal function, smoking and hypertension in multivariate logistic regression analysis, with focus on ACPA positive with joint complaints group versus RA risk group: CRP OR = 2.67, p = 0.033; IL-6 OR = 3.73, p = 0.019; TNFR1 OR = 1.003, p < 0.001; VGEF OR = 8.59, p = 0.019.ConclusionIndividuals at risk for RA have higher levels of inflammatory markers and VEGF, which suggests that they might also have a risk of higher cardiovascular disease (CVD); however, this does not apply to individuals with ACPA positivity with self-reported joint complaints or without joint complaints only. Therefore, it is important that individuals with RA risk are referred to a rheumatologist to rule in or out arthritis/development of RA and discuss CVD risk.

TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins.

Previous studies reported the expression of toll-like receptors (TLRs), merely TLR2 and TLR4, and complement fragments (C3a, C5b9) in vitreoretinal disorders. Other than pathogens, TLRs can recognize endogenous products of tissue remodeling as damage-associated molecular pattern (DAMPs). The aim of this study was to confirm the expression of TLR2 and TLR4 in the fibrocellular membranes and vitreal fluids (soluble TLRs) of patients suffering of epiretinal membranes (ERMs) and assess their association with disease severity, complement fragments and inflammatory profiles. Twenty (n = 20) ERMs and twelve (n = 12) vitreous samples were collected at the time of the vitrectomy. Different severity-staged ERMs were processed for: immunolocalization (IF), transcriptomic (RT-PCR) and proteomics (ELISA, IP/WB, Protein Chip Array) analysis. The investigation of targets included TLR2, TLR4, C3a, C5b9, a few selected inflammatory biomarkers (Eotaxin-2, Rantes, Vascular Endothelial Growth Factor (VEGFA), Vascular Endothelial Growth Factor receptor (VEGFR2), Interferon-γ (IFNγ), Interleukin (IL1β, IL12p40/p70)) and a restricted panel of matrix enzymes (Matrix metalloproteinases (MMPs)/Tissue Inhibitor of Metallo-Proteinases (TIMPs)). A reduced cellularity was observed as function of ERM severity. TLR2, TLR4 and myD88 transcripts/proteins were detected in membranes and decreased upon disease severity. The levels of soluble TLR2 and TLR4, as well as C3a, C5b9, Eotaxin-2, Rantes, VEGFA, VEGFR2, IFNγ, IL1β, IL12p40/p70, MMP7 and TIMP2 levels were changed in vitreal samples. Significant correlations were observed between TLRs and complement fragments and between TLRs and some inflammatory mediators. Our findings pointed at TLR2 and TLR4 over-expression at early stages of ERM formation, suggesting the participation of the local immune response in the severity of disease. These activations at the early-stage of ERM formation suggest a potential persistence of innate immune response in the early phases of fibrocellular membrane formation.

Design and Optimization of Sesamol Nanosuspensions to Potentiate the Anti-Tumor Activity of Epirubicin against Ehrlich Solid Carcinoma-Bearing Mice.

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Tear fluid cytokine analysis: a non-invasive approach for assessing retinopathy of prematurity severity.

To determine whether there is a significant association between inflammatory cytokines in the tear fluid and the severity of Retinopathy of Prematurity (ROP). Retrospective cohort study. The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment. Significantly higher levels of CCL2 and vascular endothelial growth factor (VEGF) were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics' analysis. We found that combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for severe ROP (area under curve, 0.85). The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP.

Early growth response factor 3 may regulate coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression

AimThe present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1β, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. MethodsWe recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1β and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. ResultsThe levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1β in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r = 0.55, p < 0.001), IL-1β levels (r = 0.21, p = 0.004) and the Gensini score (r = 0.20, p = 0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. ConclusionsIn the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

Efficacy of tibial cortex transverse transport in treating diabetic foot ulcer and its effect on serum omentin-1 and irisin levels

ObjectiveDiabetic foot ulcer (DFU) is a common and debilitating complication of diabetes that is associated with an increased risk of lower-limb amputation and a reduced life expectancy. Tibial cortex transverse transport (TTT) has become a newly alternative surgical method to facilitate ulcer healing and prevent lower limb amputation. Herein, we investigated the efficacy of TTT in treating DFU and changes of serum omentin-1 and irisin levels.MethodsThis study prospectively recruited 52 consecutive patients with DFU who were treated with TTT. The follow-up was performed weekly during the first 12 weeks postoperatively and every 3 months until 1 year after TTT. The serum levels of vascular endothelial growth factor (VEGF), omentin-1, and irisin in DFU patients undergoing TTT were determined by ELISA methods on the preoperative 1st day, postoperative 2nd week and 4th week.ResultsThe wound healing rate was 92.3% (48/52) at the 1-year follow-up. The visual analog scale (VAS) pain scores of patients showed a significant reduction at the 4th week after TTT (p < 0.001). The dorsal foot skin temperature, ankle brachial index, and dorsal foot blood flow of patients were significantly increased at the 4th week after TTT (p < 0.001). Results of ELISA methods showed the serum levels of VEGF, omentin-1, and irisin on the 2nd week and 4th week after TTT were notably elevated compared to the levels determined on the preoperative 1st day (p < 0.001). The serum levels of VEGF, omentin-1, and irisin on the 4th week after TTT were also significantly higher than the levels determined on the 2nd week after TTT (p < 0.001).ConclusionTTT could promote the wound healing and reduce the risk of lower limb amputation, demonstrating promising clinical benefits in the treatment of DFU. Increased expressions of serum proangiogenic factors including VEGF, omentin-1, and irisin were noted in the early stage after TTT, which may provide a new mechanism of TTT promoting wound heal.

Effect of Dopamine as a Vascular Endothelial Growth Factor Antagonist on the Development of Acute Lung Injury in Sepsis Patients.

Sepsis is a dysregulated host immune response stemming from a systemic inflammatory response to microbial invasion, encompassing bacteria, viruses, and other pathogens. The vascular endothelial growth factor (VEGF) was initially identified for its potent induction of endothelial permeability. Studies have proposed a therapeutic role of dopamine in mitigating VEGF-induced permeability, shedding light on its potential in acute respiratory distress syndrome (ARDS) management. To determine the effect of dopamine as an inhibitor of VEGF and to prevent the progression of sepsis to acute lung injury (ALI) and ARDS. A total of 154 critical care unit patients with a diagnosis of sepsis were randomized into two groups:Group I (control group) and Group II (Study group). Both received standard treatment, as per ICU protocol. In addition, the study group (Group II) received a dopamine infusion of 2 micrograms/kg/min. Baseline routine investigation, procalcitonin, and chest X-ray were done. Day one and day seven blood samples were stored for analysis of VEGF levels. Murray's score and sequential organ failure assessment (SOFA) score (organ dysfunction) were calculated from day one to day seven. VEGF levels on day seven were significantly lower in the study group compared to the control group (p<0.05). The PaO2/FiO2 ratio at day seven was significantly increased in the study group than in the control group, indicating an improvement in oxygenation status in the study group. There was a mean ICU stay of 9.3 days in the study group versus 11.6 days in the control group (p<0.05). The SOFA score showed a significant improvement in the study group from day five onwards, indicating a therapeutic effect of dopamine on organ dysfunction in sepsis. Dopamine reduces VEGF and lung injury mediated by increased endothelial permeability.

Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study.

Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.

Preconditioning Local Injection of Activated Platelet-Rich Plasma Increases Angiogenesis, VEGF Levels, and Viability of Modified McFarlane Flap in Diabetes-Induced Rats.

Background The risk of flap necrosis in tissue reconstruction surgery is elevated in patients with vascular disorders, such as diabetes mellitus. Chronic hyperglycemia causes endothelial cell dysfunction and increases inflammatory process, causing vascular insufficiency. Platelet-rich plasma (PRP) contains high levels of platelets, growth factors, and fibrinogens. Its regenerative properties spark interest in supporting flap survival in relation to diabetic complications. Methods Thirty Wistar rats were divided into three groups. The first group included diabetic rats without PRP injection, which underwent flap procedure. The second group included diabetes-induced rats receiving PRP subcutaneous injection 1 day prior to flap procedure. The third group included nondiabetic rats receiving PRP injection 1 day prior to flap procedure. Flap tissue samples were taken on the seventh day to measure vascular endothelial growth factor (VEGF) levels using enzyme-linked immunosorbent assay method; angiogenesis and collagen density were measured from histopathology examination, and flap viability was analyzed using digital measurements. Results Analysis showed that flap viability, angiogenesis, and VEGF levels were significantly higher in the PRP-injected diabetic rats compared with diabetic rats that did not receive PRP. The levels of VEGF, angiogenesis, and viability of flaps in diabetic rats given PRP did not differ significantly compared with nondiabetic rats that received PRP. Conclusion Flap preconditioning through local injection of activated PRP enhances flap viability, VEGF levels and angiogenesis, in random skin flaps in diabetic rats, to the level where it does not differ significantly to nondiabetic rats that were given PRP.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Continuous negative-pressure wound therapy improves the survival rate of skin grafts and shortens the time required for skin graft survival.

The effectiveness of negative-pressure wound therapy (NPWT) in skin graft fixation has been demonstrated in several clinical studies. However, in vitro and in vivo studies on skin graft fixation with NPWT have been scarce. In this in vivo study, we aimed to determine whether NPWT fixation enhances skin graft survival and how it contributes to improving skin graft survival biologically. We harvested skin from the bilateral abdominal wall of 88 mice after anesthetizing them. Full-thickness skin grafts (FTSGs) were performed on contralateral harvest sites, and grafts were fixed using NPWT (continuous and intermittent modes), conventional compression methods, and wrapping with polyurethane foam as a control group. On days 5 and 10 of grafting, the survival rates of the FTSGs were evaluated. Immunohistopathological analysis and measurement of the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and epidermal growth factor (EGF) were performed. The survival rates of FTSG in the continuous NPWT group were significantly higher than those in the other groups. The number of capillaries in the dermis was significantly higher in the continuous NPWT group than in the other groups. In the wound bed, VEGF levels were significantly higher in both NPWT groups than in the other groups. Continuous NPWT increases the survival rate of FTSGs and shortens the duration of skin graft survival.

A triple growth factor strategy for optimizing bone augmentation in mice.

With dental implant treatment becoming the gold standard, the need for effective bone augmentation prior to implantation has grown. This study aims to evaluate a bone augmentation strategy integrating three key growth factors: bone morphogenetic protein-2 (BMP-2), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Collagen scaffolds incorporating BMP-2, IGF-1, or VEGF were fabricated and categorized into five groups based on their content: scaffold alone; BMP-2 alone (BMP-2); BMP-2 and IGF-1 (BI); BMP-2, IGF-1, and VEGF (BIV); and BMP-2 and IGF-1 with an earlier release of VEGF (BI + V). The prepared scaffolds were surgically implanted into the calvarias of C57BL/6JJcl mice, and hard tissue formation was assessed after 10 and 28 days through histological, tomographic, and biochemical analyses. The combination of BMP-2 and IGF-1 induced a greater volume of hard tissue augmentation compared with that of BMP-2 alone, regardless of VEGF supplementation, and these groups had increased levels of cartilage compared with others. The volume of hard tissue formation was greatest in the BIV group. In contrast, the BI + V group exhibited a hard tissue volume similar to that of the BI group. While VEGF and CD31 levels were highest in the BIV group at 10 days, there was no correlation at the same time point between hard tissue formation and the quantity of M2 macrophages. In conclusion, the simultaneous release of BMP-2, IGF-1, and VEGF proved to be effective in promoting bone augmentation.

Beneficial effects of dietary omega 3 polyunsaturated fatty acids on offspring brain development in gestational diabetes mellitus

Various mechanisms through which maternal diet influences offspring brain development in gestational diabetes mellitus (GDM) remains unclear. We speculate that prenatal omega 3 fatty acids will improve the levels of brain neurotrophins and vascular endothelial growth factor (VEGF), an angiogenic factor leading to improved cognitive performance in the offspring. GDM was induced in Wistar rats using streptozotocin. They were assigned to either control, GDM or GDM+O (GDM + omega-3 fatty acid supplementation). The offspring were followed till 3 mo of age and cognitive assessment was undertaken. Data analysis was carried out using one-way ANOVA followed by LSD test. GDM induction increased (p < 0.01) dam glucose levels and lowered brain derived neurotrophic factor (BDNF) levels (p = 0.056) in the offspring at birth. At 3 months, GDM group showed significantly lower levels of neurotrophic tyrosine kinase receptor-2 (NTRK-2) and VEGF, lower mRNA levels of NTRK-2 and cAMP response element-binding protein (CREB) (P < 0.05 for all) as compared to control. The GDM offspring had a higher escape latency (p < 0.01), made lesser % correct choices and more errors (p < 0.05 for both). Prenatal supplementation with omega 3 polyunsaturated fatty acids was beneficial since it ameliorated some of the adverse effects of GDM.

HGF, HNRPD, and sFLT1 Interfere with the Induction of VEGF in Patients with Severe Psoriasis.

Restructuring of dermal microcapillaries is one of the hallmarks of plaque psoriasis. To control the proliferation of vascular endothelial cells, vascular endothelial growth factor (VEGF) promotes the remodeling of the existing blood vessels and angiogenesis. This study aimed to explain the lowering protein and mRNA levels of VEGF in lesional skin of patients with severe psoriasis (the Psoriasis Area and Severity Index, PASI > 25). Using the method of qPCR, we assessed the expression of VEGF mRNA in lesional and nonlesional psoriatic skin. Using ELISA, we also compared the levels of VEGF in skin homogenates of psoriasis patients and healthy volunteers. We found that the exacerbation of psoriasis induced VEGF on mRNA and protein levels 12 and 20 times, respectively. We also confirmed a strong correlation between VEGF and PASI score in patients with PASI < 25. In addition, we showed that several factors, namely HGF, HNRPD, and sFLT1 interfere with the biosynthesis of VEGF in skin lesions of patients with PASI > 25%. Thus, using VEGF as a biomarker to monitor the disease shall be done cautiously in patients with severe psoriasis.

A Glucose-Responsive Hydrogel Inhibits Primary and Secondary BRB Injury for Retinal Microenvironment Remodeling in Diabetic Retinopathy.

Current diabetic retinopathy (DR) treatment involves blood glucose regulation combined with laser photocoagulation or intravitreal injection of vascular endothelial growth factor (VEGF) antibodies. However, due to the complex pathogenesis and cross-interference of multiple biochemical pathways, these interventions cannot block disease progression. Recognizing the critical role of the retinal microenvironment (RME) in DR, it is hypothesized that reshaping the RME by simultaneously inhibiting primary and secondary blood-retinal barrier (BRB) injury can attenuate DR. For this, a glucose-responsive hydrogel named Cu-PEI/siMyD88@GEMA-Con A (CSGC) is developed that effectively delivers Cu-PEI/siMyD88 nanoparticles (NPs) to the retinal pigment epithelium (RPE). The Cu-PEI NPs act as antioxidant enzymes, scavenging ROS and inhibiting RPE pyroptosis, ultimately blocking primary BRB injury by reducing microglial activation and Th1 differentiation. Simultaneously, MyD88 expression silence in combination with the Cu-PEI NPs decreases IL-18 production, synergistically reduces VEGF levels, and enhances tight junction proteins expression, thus blocking secondary BRB injury. In summary, via remodeling the RME, the CSGC hydrogel has the potential to disrupt the detrimental cycle of cross-interference between primary and secondary BRB injury, providing a promising therapeutic strategy for DR.