Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells

Abstract Objective: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. Methodology: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. Results: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). Conclusions: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

Mechanism of Shugan Huazheng Prescription Against Liver Fibrosis Based on HIF-1α/VEGF/TGF-β1 Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Shugan Huazheng prescription on hepatic fibrosis model rats induced by carbon tetrachloride （CCl4） and explore whether it plays its role through hypoxia-induced factor-1α/vascular endothelial growth factor/transforming growth factor-β1 （HIF-1α/VEGF/TGF-β1） pathway. MethodA total of 54 male SPF SD rats were randomly divided into six groups： blank group， model group， colchicine group （0.2 mg·kg-1）， and high-， medium-， and low-dose groups （29.52， 14.76， and 7.38 g·kg-1） of Shugan Huazheng prescription， with nine rats in each group. The molding was conducted three times a week for eight weeks. Administration began the day after the first injection， and the drug intervention was once a day for eight weeks. On the day after the last administration， the rats were deprived of food and water， and they were killed the next day， during which the physiological status of each group of rats was dynamically monitored. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining， and the content of hydroxyproline （HYP） and angiotensin Ⅱ （AngⅡ） in liver tissue were detected by enzyme-related immunosorbent assay （ELISA）. Real-time fluorescent quantitative PCR （Real-time PCR） was used to determine the mRNA expression levels of HIF-1α， VEGF， and TGF-β1 in liver tissue， and immunohistochemical method （IHC） and Western blot were used to detect the protein expression levels of HIF-1α， VEGF， and TGF-β1 in liver tissue. ResultCompared with the blank group， the overall condition of rats in the model group decreased significantly. The proliferation of connective tissue and the increase in adipose cells between hepatocytes were obvious. The content of HYP and Ang was increased. The mRNA and protein expressions of HIF-1α， VEGF， and TGF-β1 were increased to varying degrees （P<0.05）. Compared with the model group， the proliferation of connective tissue and inflammatory cell infiltration in the liver tissue of colchicine and Shugan Huazheng prescription groups were reduced. The content of HYP and Ang was decreased. The mRNA and protein expression levels of HIF-1α， VEGF， and TGF-β1 were decreased， and the colchicine group and high-dose group of Shugan Huazheng prescription were the most significant （P<0.05）. ConclusionShugan Huazheng prescription has an obvious therapeutic effect on CCl4-induced hepatic fibrosis model rats. Its therapeutic mechanism may be related to the regulation of the HIF-1α/VEGF/TGF-β1 signaling pathway and the improvement of hepatic hypoxia， vascular remodeling， and the syndrome of Qi deficiency and blood stasis in hepatic fibrosis.

Huanglian Jiedutang Regulates HIF-1α/VEGF Signaling Pathway to Improve Learning and Memory Abilities of APP/PS1 Transgenic Mice / 中国实验方剂学杂志

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg-1·d-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg-1·d-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

Risk of renal damage associated with intravitreal anti-VEGF therapy for diabetic macular edema in routine clinical practice

Purpose: Vascular endothelial growth factor inhibitors (anti?VEGF) have been shown to be effective in the treatment of diabetic macular edema. However, there is little information about the systemic effects of intraocular administration of anti?VEGF drugs in patients with coexistent diabetic nephropathy because it can produce adverse renal effects. Methods: This retrospective cohort study analyzed the effect of intravitreal anti?VEGF drugs (bevacizumab, ranibizumab, or aflibercept) on eFGR and microalbuminuria (MicA) in patients with diabetic macular edema and nonproliferative retinopathy without chronic kidney disease (CKD). Results: Sixty?six patients were included, 54.5% male and 45.5% female, with a mean age of 66.70 ± 11.6 years. The mean follow?up of patients with antiangiogenic treatment was 42.5 ± 28.07 months, and the mean number of injections was 10.91 ± 7.54. In 12.1% of the cases, there was a worsening of the glomerular filtration rate (eFGR) and a 19.7% worsening of the microalbuminuria (MicA). The number of injections was not related to the worsening of the eFGR (P = 0.74) or the MicA (P = 0.239). No relationship was found between the type of drug and the deterioration of the GFR (P = 0.689) or the MicA (P = 0.53). Conclusions: Based on the results, there is a small proportion of patients with increase in MicA and the decrease in eFGR after anti?VEGF therapy, and these was no associated with the number of injection or the drug type. Ophthalmologists should be aware of renal damage in order to do a close monitoring of renal function and proteinuria after intravitreal administration of anti?VEGF mainly in hypertensive patients.

Distance and near vision changes after intravitreal anti-vascular endothelial growth factor injection in eyes with center-involving diabetic macular edema

Purpose: To elucidate distance and near vision changes after intravitreal injections in center?involving diabetic macular edema (CIDME) in phakic and pseudophakic groups. Methods: A retrospective study was done on 148 eyes (72 phakic and 76 pseudophakic) with center?involving DME. All eyes were treated with intravitreal anti?vascular endothelial growth factor (VEGF) injection. All patients underwent distance best?corrected visual acuity (BCVA) testing, near BCVA testing, dilated fundus examination, and optical coherence tomography (OCT) at baseline and follow?up visits. Eyes that could not improve after the first injection were given 2nd, 3rd, and more injections in the subsequent visits. Results: On follow?up, post injections in the phakic group (n = 72), there were 65 eyes (90.3%) with stable/improved near vision and 59 eyes (81.9%) with stable/improved distance vision, whereas in the pseudophakic group (n = 76), 63 eyes (82.9%) and 60 eyes (78.9%), respectively. Both in phakic and pseudophakic eyes, 7.7%–13% of the cohort showed only near vision improvement. Conclusion: In DME, besides the changes in distance vision, there are also changes in near vision. These changes should be taken into account while determining the response to anti?VEGF in DME treatment.

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material & Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Inverse correlation of CD3 & vascular endothelial growth factor in incisional oral squamous cell carcinoma biopsies predicts nodal metastasis & poor survival of patients

Background & objectives: Oral squamous cell carcinoma (OSCC) is widely prevalent in the Indian subcontinent mainly due to habit-associated aetiologies. Immune regulation and angiogenesis are the part of tumourigenesis that play a crucial role in metastasis and survival. However, the concurrent expression of vascular endothelial growth factor (VEGF) and CD3 (immune regulator receptor on T-lymphocyte) in the same OSCC tissue samples has not been reported in the Indian population. The present study evaluated the expression of CD3+ T-cells and VEGF in OSCC tissue samples and studied the clinicopathological correlation and survival analysis in an Indian population. Methods: This was a retrospective study conducted on 30 formalin-fixed and paraffin embedded sections which were histologically diagnosed as OSCC cases comprising of 15 metastatic OSCC and 15 non- metastatic OSCC with available clinical data and survival status. Results: Reduced expression of CD3+ T-cells and increased VEGF expression were observed in metastatic OSCC samples. The correlation of expression of CD3+ T-cells and VEGF with clinicopathological parameters showed a significant association between these markers with age, nodal status, site of the lesion and survival. Interpretation & conclusions: Reduced expression of CD3+ T-cells in OSCC was found to be associated with a significantly poor survival. VEGF was found to be over expressed in metastatic OSCC as compared to that in non-metastatic OSCC. The study findings suggest that the evaluation of CD3 and VEGF in incisional OSCC biopsies can be considered for predicting the survival outcome and metastasis

Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases

Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio?similar product Zybev(Z) for macular edema because of retinal diseases. Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio?similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks. Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre?injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 ?m, and the post?injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 ?m; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (?m) decreased from 11.85 ± 1.96 pre?injection to 10.52 ± 1.75 post?injection, and the mean average cube volume (mm3) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow?up period after injection, no patient had inflammation, endophthalmitis, an increase in intra?ocular pressure, or systemic side effects. Conclusion: This short?term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio?similar products of bevacizumab for the treatment of macular edema because of retinal diseases

Role of Suprachoroidal Anti-VEGF Injections in Recalcitrant Serous Pigment Epithelium Detachment

Purpose: Retinal pigment epithelial detachments (PEDs) are characterized by a separation between the RPE and the innermost aspect of Bruch's membrane. Many chorioretinal diseases can lead to pigment epithelial detachment of which the most common is age-related macular degeneration; but a significant number of PEDs are idiopathic in etiology. PEDs can be classified as drusenoid, serous, vascularized, or fibrovascular type.Currently, serous PED has not shown much response to treatment, so no specific treatment guidelines are established. Whereas vascularized PEDs, have several treatment options such as intravitreal anti-Vascular endothelial growth factor (VEGF) therapy, laser photocoagulation, photodynamic therapy (PDT) and intravitreal steroids. Hence, the need of the hour is to formulate a treatment strategy for serous PED.Methods: We report an original study of thirty patients who were diagnosed with serous pigment epithelial detachment on Spectral-domain optical coherence tomography and fundus fluorescence angiography. All the patients presented to our outpatient department with the chief complaint of diminution of vision, central/paracentralscotoma and metamorphopsia. All of them underwent treatment with suprachoroidal anti-VEGF (bevacizumab).The patients were followed 8 weeks.Results: BCVA and Amsler grid assessment was recorded on the 3rd day,1st week, 2nd week, 4th week, 6th week, and 8th week. Post-injection SD-OCT macular scan was performed on the 6thweek. Functional improvement (BCVA) was reported by all patients. All the patients had reduced size and height of PED in SD-OCT.Conclusion: Thus, our result indicates that suprachoroidalbevacizumab is an efficacious treatment for serous PED. It can be hypothesized that as degenerative changes in bruch membrane due to metabolite deposit plays a key role in development of PED; injecting the anti VEGF drug in the suprachoroida space adjacent to the choroid has a superior effect.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Effects of Chitosan Nanoparticles with Long Synthetic siRNAs Targeting VEGF in Triple-Negative Breast Cancer Cells

Abstract Vascular endothelial growth factor (VEGF) is an essential angiogenic factor in breast cancer development and metastasis. Small interfering RNAs (siRNAs) can specifically silence genes via the RNA interference pathway, therefore were investigated as cancer therapeutics. In this study, we investigated the effects of siRNAs longer than 30 base pairs (bp) loaded into chitosan nanoparticles in triple-negative breast cancer cells, compared with conventional siRNAs. 35 bp long synthetic siRNAs inhibited VEGF gene expression by 51.2% and increased apoptosis level by 1.75-fold in MDA-MB-231 cell lines. Furthermore, blank and siRNA-loaded chitosan nanoparticles induced expression of IFN-γ in breast cancer cells. These results suggest that long synthetic siRNAs can be as effective as conventional siRNAs, when introduced into cells with chitosan nanoparticles

Retinopatía de la prematuridad agresiva posterior / Aggressive Posterior Retinopathy of Prematurity

Introducción: La retinopatía del prematuro es una enfermedad ocular provocada por una alteración en la vasculogénesis de la retina, que lleva a la pérdida parcial o total de la visión. Objetivo: Presentar el primer caso, en la provincia de Santa Clara, de retinopatía de la prematuridad agresiva posterior y el tratamiento realizado. Presentación del caso: Niña prematura con más de 5 factores de riesgo al nacer que presentó retinopatía de la prematuridad agresiva posterior y se le realizó tratamiento con bevacizumab intravítreo. Conclusiones: La evolución de la niña en un período de un 1 año resultó satisfactoria con regresión total de la enfermedad. El tratamiento establecido constituye un método alternativo con buenos resultados en algunas condiciones específicas como la retinopatía del prematuro agresiva posterior(AU)

Introduction: Retinopathy of prematurity is an ocular disease caused by an alteration in retinal vasculogenesis, leading to partial or total loss of sight. Objective: To present the first case, in the province of Santa Clara, of aggressive posterior retinopathy of prematurity and the treatment performed. Case presentation: Premature girl with more than 5 risk factors at birth who presented aggressive posterior retinopathy of prematurity and was treated with intravitreal bevacizumab. Conclusions: The evolution of the girl in a period of 1 year was satisfactory with total regression of the disease. The established treatment constitutes an alternative method with good results in some specific conditions such as aggressive posterior retinopathy of prematurity(AU)

YULINK regulates vascular formation in zebrafish and HUVECs

BACKGROUND: The distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation. METHODS: In this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs). RESULTS: Knockdown of YULINK during the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown of YULINK in HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased in YULINK knockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised in YULINK knockdown HUVECs, demonstrating to the involvement of YULINK. CONCLUSION: This study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs. Key points Knockdown of YULINK with morpholino in embryos of double transgenic zebrafish exhibited abnormal venous formation. Tube formation and phosphorylated EPHB4 were decreased in YULINK knockdown HUVECs. FLIM-FRET, immunoprecipitation, as well as other imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B and TICAM2) and endosome markers (Clathrin and RHOB). Knockdown of YULINK decreased the internalization of VEGF and VEGFR2 in HUVECs.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil

ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P&#x003C;0.05), the CMT in both groups was lower than that before the treatment(P&#x003C;0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P&#x003C;0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P&#x003C;0.001). In the injection group, only blurred vision was improved(P&#x003C;0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P&#x003C;0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.

Progress of anti-vascular endothelial growth factor drugs for the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

Retinopathy of prematurity(ROP)is a proliferative vascular disorder of the immature retina, and it is a major eye disease that causes blindness in children of developing and developed countries. Retinal laser photocoagulation and cryotherapy are the conventional treatment used for ROP but could cause permanent damage to retina, with a risk of complications such as visual field defect and high myopia. With more normal growth of retinal function and convenience and shorter time than coagulation therapy, intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has gradually gained popularity and has even been advocated as the treatment of choice in treating zone I, zone II posterior or aggressive ROP. However, the serious systemic complications, minimum effective dose and late recurrence caused by anti-VEGF drugs in the treatment of ROP still need to be further studied. This review focuses on the use of anti-VEGF agents for the treatment of ROP.

Application progress of laser photocoagulation in diabetic retinopathy treatment in the era of anti-vascular endothelial growth factor agents / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is the most prevalent and severe ocular complication in people with diabetes, and it is one of the leading causes of blindness in adults. In recent years, drug therapy represented by anti-vascular endothelial growth factor(VEGF)agents has become the first-line therapy in DR treatment, but it cannot reverse retinal non-perfusion areas, microaneurysms and abnormal teleangiectatic capillaries, those who cannot be treated on time are at risk of disease progression. Laser photocoagulation has been widely applied for more than 40 years, it can effectively reduce the rate of blindness by eliminating the non-perfusion areas of capillaries, and panretinal photocoagulation(PRP)has been the primary treatment for DR. With the continuing innovations in laser technology, on the basis of maintaining the curative effect, the aim of minimizing retinal damage and adverse side effects has been realized. A combination of laser photocoagulation and anti-VEGF agents can achieve complementary advantages and better efficacy. Deepening the clinical research on laser therapy and laser therapy combined with anti-VEGF agents in the treatment of DR may help to establish the personalized treatment corresponds with our national conditions. This article briefly reviews the latest application progress of laser therapy in DR treatment in the era of anti-VEGF agents.

Efficacy of different anti-vascular endothelial growth factor drugs in the treatment of diabetic macular edema and their relationship with optical coherence tomography classification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the clinical efficacy of different anti-vascular endothelial growth factor(VEGF)drugs in the treatment of diabetic macular edema(DME), and analyze their relationship with optical coherence tomography(OCT)classification.METHODS: A total of 45 DME patients treated with ranibizumab(admitted to our hospital from February 2020 to February 2022)were selected as the ranibizumab group, and 45 DME patients treated with conbercept during the same period were selected as the conbercept group. The ranibizumab group was treated with retinal photocoagulation combined with ranibizumab, and the conbercept group was treated with retinal photocoagulation combined with conbercept. The improvement of symptoms(improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage), levels of serum interleukin-6(IL-6)and VEGF, central macular thickness(CMT), best corrected visual acuity(BCVA), and complications were compared between the two groups, and the relationship between their clinical efficacy and different OCT types were analyzed.RESULTS: There was no significant difference in the improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage between the two groups(P&#x003E;0.05); After treatment, the values of IL-6, VEGF and BCVA in the two groups were significantly lower than those before treatment(P&#x003C;0.01), but there was no significant difference between the two groups(P&#x003E;0.05); compared with before treatment, CMT was significantly decreased in both groups after treatment(P&#x003C;0.05), and compared with ranibizumab group, the CMT was significantly decreased in the conbercept group(P&#x003C;0.01); there was no significant difference in the incidence of complications between two groups(P&#x003E;0.05); there were significant differences in the total effective rate among patients with serous retinal detachment(SRD), cystoid macular edema(CME)and diffuse retinal thickening(DRT; P&#x003C;0.05), among which DRT had the highest total effective rate and SRD had the lowest total effective rate.CONCLUSION: Both conbercept and ranibizumab in the treatment of DME can effectively improve the clinical symptoms of patients and reduce the inflammatory response, but conbercept can better reduce the level of CMT, and has better treatment effect on DRT-type DME patients.