Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.

Clinical efficacy of subthreshold micropulse laser combined with anti-VEGF drugs in the treatment of diabetic macular edema: A meta-analysis.

BACKGROUND: To systematically evaluate the efficacy and safety of subthreshold micropulse laser (SML) combined with anti-vascular endothelial growth factor (VEGF) drugs for the treatment of diabetic macular edema (DME). METHODS: The randomized controlled trials on SML combined with anti-VEGF drugs for DME were retrieved from China National Knowledge Infrastructure, Wan Fang Data, VIP Data, Sino Med (China Biomedical Literature Database), PubMed, Web of Science, The Cochrane Library, and Embase by computer from inception to April 19, 2022. The observation group was treated with SML combined with anti-VEGF drugs, while the control group was treated with anti-VEGF agents alone or SML. And the references of the included literature were manually searched. The Meta-analysis was performed using Revman 5.4 and STATA SE 15. RESULTS: This study finally included 15 randomized controlled trials involving 891 eyes for Meta-analysis. The results showed that there was no statistically significant difference between the 2 groups in best-corrected visual acuity at 1, 3, 6, 9, and 12 months after treatment. There was no statistical difference between the 2 groups in central macular thickness (CMT) at 1, 3, and 6 months after treatment (P > .05). CMT in the observation group was lower than that in the control group at 9 and 12 months (P < .05). There was no statistical difference between the 2 groups in total macular volume at 3, 6, 9, and 12 months in CMT (P > .05). The number of anti-VEGF drugs injections in the observation was lower than that in the control group (P < .05). The occurrence of complications between the 2 groups was not statistically significant difference (P > .05). CONCLUSION: SML in combination with anti-VEGF drugs in patients with DME are comparable in reducing the number of anti-VEGF drugs injections and CMT, thereby reducing the financial burden on patients. It does not differ in best-corrected visual acuity and total macular volume.

Neovascular age-related macular degeneration: disease pathogenesis and current state of molecular biomarkers predicting treatment response-a scoping review.

Age-related macular degeneration is a major cause of blindness, and the development of anti-vascular endothelial growth factor (VEGF) intravitreal treatments has revolutionised the management of the disease. At the same time, new challenges and unmet needs arose due to the limitations of the current therapeutic options. Neovascularisation development during the course of the disease has a complex pathogenetic mechanism, and several biomarkers and their association with treatment outcomes have been investigated. We reviewed the relevant literature about neovascularisation development and biomarkers related to response to treatment. Improving our knowledge on the field can improve patient outcomes and offer personalised care.

Effect of microaneurysms on the anti-VEGF treatment for diabetic macular edema: A retrospective cross-sectional study.

Although anti-vascular endothelial growth factor (VEGF) treatment is effective for treating diabetic macular edema (DME), the effect of the microaneurysm (MA) status on the therapeutic efficacy of an anti-VEGF treatment remains unclear. Our current study investigated the effects of the number and the presence or absence of leaking MAs on DME and the efficacy of anti-VEGF therapy. A total of 51 eyes of 47 DME patients were administered anti-VEGF treatment. Fluorescence angiography results were used to determine the number of MAs and the presence or absence of leakage, with these findings matched to the optical coherence tomography maps. The correlation between the number of MAs and the retinal thicknesses and the influence of the leaking MAs was examined in order to definitively determine the effect of the anti-VEGF treatment. There was a correlation between the number of MAs and the retinal thickness of the sector in both the 6 mm (correlation coefficients: 0.42) and 3 mm (0.34) sectors (P < .001). There was also a correlation between the number of MAs and the retinal thickness in both the 6 mm (0.31) and 3 mm (0.24) sectors after undergoing the treatment (P < .01). There was a significant difference between the mean thickness of the leaking versus the non-leaking MAs in the 6 mm (388 ±â€…87 µm) and 3 mm (477 ±â€…108 µm) sectors before treatment (P < .01). There was also a significant difference for the retinal thickness between the sectors with and without leaking MAs after the treatment (P < .01). The degree of retinal edema before treatment is associated with the number of MAs and the presence of leaking MAs. Anti-VEGF treatment is less effective for focal macular edema with large numbers of MAs, which includes leaking MAs.

Predictors of visual outcome after pars plana vitrectomy secondary to proliferative diabetic retinopathy.

Objective: Advanced proliferative diabetic retinopathy can lead to serious ophthalmological complications, including blindness. This research aimed to determine visual outcomes after pars plana vitrectomy secondary to proliferative diabetic retinopathy, as well as to identify its predictors. Methods: This prospective clinical study was performed in the Ophthalmology Clinic of the Clinical Centre University of Sarajevo. 60 subjects (eyes) with performed pars plana vitrectomy secondary to proliferative diabetic retinopathy were included in the study. Results: After univariate linear regression analysis, glucose, HbA1c, vascular endothelial growth factor, previous pan-retinal laser photocoagulation, baseline best corrected visual acuity, gas injection, vitreous haemorrhage, iris rubeosis, and glaucoma were found to be statistically significant parameters associated with postoperative visual outcome (p<0.05). Multivariate linear regression analysis was performed to evaluate the association between factors and postoperative best corrected visual acuity. Only intravitreal vascular endothelial growth factor concentration, previous pan-retinal photocoagulation, and gas injection remained statistically significant associated with postoperative best corrected visual acuity (p<0.05). Conclusion: Vitrectomy is an effective treatment for advanced proliferative diabetic retinopathy. Factors correlated with the better visual outcome are good systemic control, previous pan-retinal photocoagulation, low intravitreal vascular endothelial growth factor concentration, younger age, intraoperative internal gas tamponade, combined phacoemulsification and pars plana vitrectomy surgery, and the absence of postoperative complications. Abbreviations: PDR = proliferative diabetic retinopathy, VEGF = vascular endothelial growth factor, TDR = tractional retinal detachment, BCVA = best corrected visual acuity, DR = diabetic retinopathy, RDD = rhegmatogenous retinal detachment, NVG = neovascular glaucoma, BRVO = branch retinal vein occlusion, CBC = complete blood count, DBT = differential blood count, ESR = erythrocyte sedimentation rate, HbA1c = glycosylated hemoglobin, PHACO = phacoemulsification, ILM = internal limiting membrane, PPV = pars plana vitrectomy, IOP = intraocular pressure, PRP = pan-retinal photocoagulation, ETDRS = Early treatment diabetic retinopathy study.

[Long-term outcome of macular neovascularization secondary to choroidal osteoma with and without intravitreal anti-VEGF(vascular endothelial growth factor)- treatment]. / Langzeitverlauf von makulären Neovaskularisationen bei chorioidalen Osteomen mit und ohne intravitreale Anti-VEGF(vascular endothelial growth factor)-Therapie.

BACKGROUND: Choroidal osteoma (CO) is a benign ossifying ocular tumor, which is unilateral in most cases. The CO may cause severe visual impairment, especially in the case of a secondary macular neovascularization (MNV). OBJECTIVE: Based on a case series of patients with MNV secondary to CO, the variability of the clinical course with and without intravitreal anti-vascular endothelial growth factor (VEGF) treatment is presented. METHODS: All patients diagnosed with secondary MNV due to CO between 2007 and 2023 were retrospectively assessed with respect to the clinical course. RESULTS: In this study 7 eyes of 5 patients (4 women, 1 man) were diagnosed with secondary MNV due to CO. Intravitreal anti-VEGF treatment was carried out in 2 patients with unilateral MNV and 1 patient was treated in both eyes for bilateral MNV. In another case with bilateral MNV, only 1 eye was treated because of fibrosis in the other eye. A further case with unilateral CO and MNV scars at the initial diagnosis was left untreated. Overall, in 3 out of 5 eyes treated with intravitreal VEGF inhibition stabilization or improvement of visual acuity could be achieved. CONCLUSION: In our case series intravitreal anti-VEGF treatment attained a functional stabilization or improvement in 3 out of 5 treated eyes. In one case of CO-associated MNV fibrosis rapidly developed without treatment. Therefore, the clarification for patients with CO about the lifelong risk for development of a secondary MNV is essential in individual cases for early treatment. As no standardized treatment scheme for intravitreal VEGF antibodies for CO-related MNV exists, the treatment is planned on an individual basis.

Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation.

INTRODUCTION: Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. SIGNIFICANCE: This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. METHODS: A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. RESULTS: SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). CONCLUSION: Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study.

AIM: To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. PRIMARY ENDPOINTS: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events. RESULTS: Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 µm at week 52 (mean change -60.9 µm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required. CONCLUSION: To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Intravitreal anti-vascular endothelial growth factor for the treatment of chronic central serous retinopathy: a meta-analysis of the literature.

OBJECTIVE: The purpose of this study was to evaluate the role of anti-vascular endothelial growth factor (anti-VEGF) treatment on the functional and structural parameters of chronic central serous retinopathy (CSR). METHODS: PubMed was used to systematically review literature published from 1 January 2009 to 1 July 2022. Studies were included if patients in their cohort had symptoms for more than 3 months, anti-VEGF treatment was provided and the following outcomes were reported: best-corrected visual acuity (BCVA), central macular thickness (CMT) and proportion of subretinal fluid (SRF) resolution. RESULTS: 339 eyes met inclusion criteria with a mean patient age of 45.8±4.9 years. The weighted mean baseline BCVA for the 20 studies was 0.39±0.23 logMAR, which improved to 0.28±0.24 after treatment with anti-VEGF injections (p=0.069). The weighted baseline CMT for the 20 studies decreased from 395.2±52.0 µm to 243.0±41.9 µm (p<0.001). The weighted overall percentage of SRF resolution was 68.4%. CONCLUSION: Anti-VEGF treatment demonstrated significantly decreased macular thickness and resolution of SRF in the treatment of chronic CSR without any reported adverse effects. However, BCVA did not significantly improve with pharmacotherapy.

Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Simulation of long-term impact of intravitreal anti-VEGF therapy on patients with severe non-proliferative diabetic retinopathy.

OBJECTIVE: A simulation model was constructed to assess long-term outcomes of proactively treating severe non-proliferative diabetic retinopathy (NPDR) with anti-vascular endothelial growth factor (anti-VEGF) therapy versus delaying treatment until PDR develops. METHODS AND ANALYSIS: Simulated patients were generated using a retrospective real-world cohort of treatment-naive patients identified in an electronic medical records database (IBM Explorys) between 2011 and 2017. Impact of anti-VEGF treatment was derived from clinical trial data for intravitreal aflibercept (PANORAMA) and ranibizumab (RISE/RIDE), averaged by weighted US market share. Real-world risk of PDR progression was modelled using Cox multivariable regression. The Monte Carlo simulation model examined rates of progression to PDR and sustained blindness (visual acuity <20/200) for 2 million patients scaled to US NPDR disease prevalence. Simulated progression rates from severe NPDR to PDR over 5 years and blindness rates over 10 years were compared for delayed versus early-treatment patients. RESULTS: Real-world data from 77 454 patients with mild-to-severe NPDR simulated 2 million NPDR patients, of which 86 680 had severe NPDR. Early treatment of severe NPDR with anti-VEGF therapy led to a 51.7% relative risk reduction in PDR events over 5 years (15 704 early vs 32 488 delayed), with a 19.4% absolute risk reduction (18.1% vs 37.5%). Sustained blindness rates at 10 years were 4.4% for delayed and 1.9% for early treatment of severe NPDR. CONCLUSION: The model suggests treating severe NPDR early with anti-VEGF therapy, rather than delaying treatment until PDR develops, could significantly reduce PDR incidence over 5 years and sustained blindness over 10 years.

Application of VEGF/VEGFR peptide vaccines in cancer: A systematic review of clinical trials.

Peptide vaccines that target vascular endothelial growth factor (VEGF) pathway have shown promising results in inducing strong anti-tumor immune responses with minimal toxicity in various clinical studies. This systematic review was conducted to provide a comprehensive evaluation of the therapeutic efficacy, immune response, survival rate, and side effects of VEGF/VEGF receptor-based peptide vaccines. VEGF/VEGFR2 peptide vaccines were found to be safe and effective in inducing anti-tumor immune responses, while induced moderate clinical benefit. In this regard, further clinical trials are necessary to fully evaluate their clinical effects and the exact correlation between induction of immune response and clinical outcomes.

The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF.

Angiogenesis is a double-edged sword; it is a mechanism that defines the boundary between health and disease. In spite of its central role in physiological homeostasis, it provides the oxygen and nutrition needed by tumor cells to proceed from dormancy if pro-angiogenic factors tip the balance in favor of tumor angiogenesis. Among pro-angiogenic factors, vascular endothelial growth factor (VEGF) is a prominent target in therapeutic methods due to its strategic involvement in the formation of anomalous tumor vasculature. In addition, VEGF exhibits immune-regulatory properties which suppress immune cell antitumor activity. VEGF signaling through its receptors is an integral part of tumoral angiogenic approaches. A wide variety of medicines have been designed to target the ligands and receptors of this pro-angiogenic superfamily. Herein, we summarize the direct and indirect molecular mechanisms of VEGF to demonstrate its versatile role in the context of cancer angiogenesis and current transformative VEGF-targeted strategies interfering with tumor growth.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Small Gauge Vitrectomy with or without Intravitreal Anti-Vascular Endothelial Growth Factor Agents Pretreatment for Proliferative Diabetic Retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a common visual threatening ocular disease, patients with nonclearing vitreous hemorrhage (VH), tractional retinal detachment (RD), or extensive fibrovascular proliferation are always in need for surgical treatment. Although several studies reported better surgical outcome in patients underwent surgery after anti-VEGF injection, the effect of anti-VEGF pretreatment for small gauge vitrectomy in PDR patients remains to be elucidated. OBJECTIVES: The objective of the study was to evaluate the benefits of preoperative anti-VEGF treatment in small gauge vitrectomy for PDR patients. METHODS: A comprehensive literature search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify relevant studies. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal breaks, surgical time, etc.) and postoperative outcome parameters (including best-corrected visual acuity (BCVA), postoperative VH, postoperative RD, etc.). RESULTS: Ten randomized controlled trials were identified and used for comparing small gauge vitrectomy alone (344 eyes, control group) and small gauge vitrectomy with preoperative anti-VEGF injection (355 eyes). The intraoperative findings showed that the surgical time, the incidence of clinically significant intraoperative bleeding, iatrogenic retinal breaks, silicone oil tamponade, and the frequency of endodiathermy were significantly less in the anti-VEGF pre-treated group than in the vitrectomy alone group (p < 0.01). The postoperative findings showed that the incidences of early postoperative VH, postoperative RD were significantly less in the anti-VEGF pre-treated group than in the control group (p < 0.05). The pooled result of postoperative rubeosis iridis/neovascular glaucoma was borderline (p = 0.072) between cases and controls, while no statistically significant differences in BCVA at last follow-up and incidences of late postoperative VH were found between these two groups (p > 0.05). CONCLUSIONS: Anti-VEGF injection prior to small gauge vitrectomy in PDR patients might facilitate easier surgical procedure and reduce intra- and postoperative complications. Further studies are needed to verify our findings and evaluate the optimal interval and dosage for preoperative anti-VEGF injection.

Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With Advanced Non-small Cell Lung Cancer Harboring Activating EGFR Mutations: A Systematic Review and Meta-analysis.

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non-small cell lung cancer. We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced non-small cell lung cancer harboring activating EGFR mutations, in comparison to EGFR TKIs alone. The electronic databases were searched for relevant randomized trials between 2000 and 2022. The primary endpoints were overall survival (OS) and progression-free survival. Secondary endpoints included objective response rate (ORR), disease control rate, and grade ≥3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. A total of 1528 patients from 8 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 37% (HR=0.63; 95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant difference in objective response rate or disease control rate between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension being the most significantly increased AEs. This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves progression-free survival, with no OS benefit, and increases AEs. Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results.

Factors That Can Prolong Ocular Treatment Duration in Age-Related Macular Degeneration.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are used to treat wet age-related macular degeneration (wAMD); however, they are associated with a considerable treatment burden and poor real-world outcomes. The molecular size and charge of anti-VEGF agents influence drug pharmacokinetics in the vitreous and peak drug efficacy. This article reviews the established and novel strategies to prolong drug action, in the vitreal cavity, and thus reduce dosing frequency. Increased ocular residency can be attained by increasing drug size as with large molecules, such as KSI-301; adding polyethylene glycol to pegcetacoplan (APL-2) or avacincaptad pegol to increase molecular size; or binding to other targets that increase molecular size, such as vitreal albumin in the case of BI-X. Faricimab is a bispecific antibody in which the fragment crystallizable portion is engineered to prolong ocular residency and reduce systemic exposure. Conversely, small VEGF-binding molecules, such as brolucizumab, can be administered at higher clinical doses, with the potential for prolonged clinical activity versus larger molecules. Other important considerations include sustained drug delivery routes, such as the ranibizumab port delivery system or subconjunctival or suprachoroidal injection. More effective and longer-lasting treatments are needed for wAMD to prolong drug action and reduce dosing frequency. Several strategies are under investigation and the prevention of vision loss in patients with AMD or other retinal diseases may be attainable in the near future.

Effects of acute aerobic exercise on cytokines, klotho, irisin, and vascular endothelial growth factor responses in rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes cartilage and bone damage as well as disability.  AIMS : The aim of this study was to examine the effects of acute aerobic exercise on cytokines such as serum interleukin-6 (IL-6), interleukin-1ß (IL-1ß), Tumor Necrosis Factor-α (TNF-α) and irisin, vascular endothelial growth factor(VEGF) and klotho in RA patients.  METHODS: Forty RA patient and 40 healthy volunteers of the same age participated in this study. All participants walked on the treadmill for 30 minutes at 60-80% of maximal heart rate. Blood samples were taken before and immediately after the exercise. Serum levels of IL-6, IL1ß, TNF-α and irisin, VEGF and klotho were measured by enzyme-linked immunosorbent analysis.  RESULTS: Baseline levels of inflammatory cytokines, irisin, VEGF and klotho were found to be higher in RA patients compared to the control group. In both groups, there was an increase in serum klotho levels after exercise compared to baseline (p<0.05), while a decrease in IL1ß, TNF-α levels were observed. While serum VEGF level decreased in RA group, it increased in the control group(p<0.05). Irisin levels decreased in both groups. IL-6 level did not change in the control group, while it increased in RA group. A single exercise session had an acute anti-inflammatory effect in RA patients. CONCLUSION: It can be concluded that acute aerobic exercise can be beneficial for patients with RA through cytokine, irisin, klotho and VEGF levels, and also it can be safely implemented to the RA rehabilitation program for additional anti-inflammatory effects. Trial registration ClinicalTrials.gov: NCT04439682.

Role of vascular endothelial growth factor in radiotherapy resistance to esophageal squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is related to the radiation resistance of tumors, resulting in the failure of tumor radiotherapy. The purpose of this study was to discuss the role of VEGF in radiotherapy resistance of esophageal squamous cell carcinoma (ESCC). We used the VEGF kit by ELISA to detect the serum VEGF level of ESCC patients who only received radiotherapy. The expression of VEGF in ESCC cells after siRNA treatment was verified by Western blot. The sensitivity of ESCC cells to radiation after knocking down VEGF was analyzed by Clonogenic assay and Cell counting kit (CCK-8). The results showed that the level of serum VEGF in patients with ESCC before and after radiotherapy was related to the clinical response, and it was confirmed that knocking down the expression of VEGF in ESCC cells improved the sensitivity to radiation.