Subthreshold micropulse diode laser treatment in diabetic macular edema: biological impact, therapeutic effects, and safety.

PURPOSE: To introduce the treatment of diabetic macular edema (DME) with subthreshold micropulse diode laser (SMPL), to summarize the biological impact, therapeutic effects, and safety of this treatment, and to discuss the response to DME when SMPL is combined with anti-vascular endothelial growth factor (anti-VEGF) or steroid. METHODS: The literature search was performed on the PubMed database, with a selection of English-language articles published from 2000 to 2023 with the following combinations of search terms: diabetes macular (o) edema, micropulse laser or subthreshold micropulse laser, anti-vascular endothelial growth factor, and steroid. RESULTS: SMPL is a popular, invisible retinal laser phototherapy that is inexpensive, safe, and effective in the treatment of DME. It can selectively target the retinal pigment epithelium, reduce the expression of pro-inflammatory factors, promote the absorption of macular edema, and exert a similar and lasting clinical effect to traditional lasers. No significant difference was found in the therapeutic effects of SMPL between different wavelengths. However, HbA1c level and pretreatment central macular thickness (CMT) may affect the therapeutic outcomes of SMPL. CONCLUSION: SMPL has a slow onset and produces lasting clinical effects similar to conventional photocoagulation. It has been reported that SMPL combined with the intravitreal anti-VEGF injection can significantly reduce the number of injections without influencing the therapeutic effect, which is essential for clinical applications and research. Although 577 nm SMPL is widely used clinically, there are no standardized protocols for SMPL. Additionally, some important problems regarding the treatment of SMPL require further discussion and exploration.

FGF2, LIF, and IGF-1 supplementation improves mouse oocyte in vitro maturation via increased glucose metabolism†.

Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor-like factors, cumulus expansion factors, and glucose metabolism-related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor-like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.

AREDS2 Supplementation in Patients with Wet Age-Related Macular Degeneration.

BACKGROUND: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision. OBJECTIVES: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD. METHODS: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity. RESULTS: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively. CONCLUSIONS: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide-binding domain, leucine-rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85-90%) and wet (10-15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti-vascular endothelial growth factor (anti-VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option. Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro-oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone-induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE-19 cells). An age-related eye disease study (AREDS) formulation (incl. omega-3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone-induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance. The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). Hydroquinone induced an NLRP3-independent IL-18 release and NLRP3 accumulation inside the IL-1α-primed cells. Resvega treatment reduced the extent of hydroquinone-induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone- and impaired protein clearance-induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.

Determination of the effectiveness of Dorema ammoniacum gum on wound healing: an experimental study.

OBJECTIVE: For a long time, natural compounds have been used to accelerate wound healing. In this study, the topical effects of ammoniacum gum extract on wound healing were investigated in white male rats. METHOD: Following skin wound induction in aseptic conditions, 48 Wistar rats were divided into six equal groups; phenytoin cream 1% (standard), untreated (control), Eucerin (control), and 5%, 10% and 20% ointments of Dorema ammoniacum gum extract (treatment groups). All experimental groups received topical drugs daily for 14 days. The percentage of wound healing, hydroxyproline content, histological parameters, and growth factors (endothelial growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-α) were measured in experimental groups. RESULTS: The areas of the wounds in the treatment groups were significantly decreased compared with the wound areas of control groups at 5, 7 and 10 days after wounding. On the 12th day, the wounds in the treatment groups were completely healed. Hydroxyproline contents were significantly increased in the treatment groups compared with the control groups (p<0.001). In histological evaluation, the re-epithelialisation, increasing thickness of the epithelial layer, granulation tissue and neovascularisation parameters in the treatment groups showed significant increases compared with the control groups. Also, serum levels of TGF-ß, PDGF, EGF and VEGF in the treatment groups were significantly increased compared to the control groups. CONCLUSION: The topical application of ammoniacum gum extract significantly increases the percentage of wound healing in rats and reduces the time of wound closure.

Resvega, a Nutraceutical Preparation, Affects NFκB Pathway and Prolongs the Anti-VEGF Effect of Bevacizumab in Undifferentiated ARPE-19 Retina Cells.

Age-related macular degeneration (AMD) is an irreversible chronic degenerative pathology that affects the retina. Despite therapeutic advances thanks to the use of anti-vascular endothelial growth factor (VEGF) agents, resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, called Resvega®, was able to disrupt VEGF-A secretion in human ARPE-19 retina cells. We found that Resvega® inhibits VEGF-A secretion through decreases in both the PI3K-AKT-mTOR and NFκB signaling pathways. In NFκB signaling pathways, Resvega® inhibits the phosphorylation of the inhibitor of NFκB, IκB, which can bind NFκB dimers and sequester them in the cytoplasm. Thus, the NFκB subunits cannot migrate to the nucleus where they normally bind and stimulate the transcription of target genes such as VEGF-A. The IκB kinase complex (IKK) is also affected by Resvega® since the nutraceutical formulation decreases both IKKα and IKKß subunits and the IKKγ subunit which is required for the stimulation of IKK. Very interestingly, we highlight that Resvega® could prolong the anti-angiogenic effect of Avastin®, which is an anti-VEGF agent typically used in clinical practice. Our results suggest that Resvega® may have potential interest as nutritional supplementation against AMD.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

Evolución del cáncer papilar de tiroides en acromegalia: serie de casos / Evolution of papillary thyroid cancer in acromegaly: case series / Evolução do câncer papilar de tireoide na acromegalia: série de casos

Introducción: La acromegalia se produce por un adenoma hipofisario somatotropo, que secreta una excesiva producción de GH e IGF1, se relaciona con mayor riesgo de tumores malignos, no guardando asociación con un patrón especifico de presentación y el objetivo de este estudio es analizar la evolución del cáncer papilar de tiroides en acromegalia. Casos: Se trata de tres pacientes diagnosticados de carcinoma papilar de tiroides (CPT) con diferente pronóstico, con características faciales, y sintomatología como cefalea, alteraciones del campo visual, alteraciones menstruales, que condujeron a la realización de estudios bioquímicos, de imagen y al diagnóstico de acromegalia. Evolución: La aparición de cáncer de tiroides varía en el tiempo de evolución de la acromegalia, en dos de los casos lo antecedió y en el tercero se presentó a la par con esta patología. La respuesta al tratamiento en el CPT es indeterminada en la primera paciente y \excelente en los otros casos; en una paciente se alcanzó remisión. Conclusiones: la coexistencia de acromegalia con cáncer tiroides es posible, que los cambios acrales, faciales y la sintomatología expansiva del tumor conducen al diagnóstico de acromegalia y que la identificación de malignidades no guarda relación con la evolución de la enfermedad.

Introduction: Acromegaly is produced by a somatotropic pituitary adenoma, which secretes an excessive production of GH and IGF1, it is related to a higher risk of malignant tumors, not being associated with a specific pattern of presentation and the objective of this study is to analyze the evolution of papillary thyroid cancer in acromegaly. Cases report: These were three patients diagnosed with CPT with different prognosis, with facial characteristics, and symptoms such as headache, visual field alterations, menstrual alterations, which led to biochemical and imaging studies and the diagnosis of acromegaly. Evolution: The appearance of thyroid cancer in the time of evolution of acromegaly is different, in two of the cases it preceded it and in the third it was presented alongside this pathology. The re-sponse to treatment in CPT is indeterminate in the first patient and excellent in the other cases; re-mission was achieved in one patient. Conclusions: It is concluded that the coexistence of acromegaly with thyroid cancer is possible, that the acral and facial changes and the expansive symptomatology of the tumor lead to the diag-nosis of acromegaly and that the identification of malignancies is not related to the evolution of the disease.

Introdução: A acromegalia é produzida por um adenoma hipofisário somatotrópico, que secreta uma produção excessiva de GH e IGF1, está relacionada a um maior risco de tumores malignos, não estando associada a um padrão específico de apresentação e o objetivo deste estudo é analisar a evolução de câncer papilar de tireoide na acromegalia. Casos: São três pacientes com diagnóstico de carcinoma papilífero de tireoide (CPT) de prognóstico diferente, com características faciais e sintomas como cefaleia, alterações do campo visual, alterações menstruais, que levaram à realização de estudos bioquímicos, de imagem e diagnóstico de acromegalia. Evolução: O aparecimento do câncer de tireoide varia com o tempo de evolução da acromegalia, em dois dos casos ela o precedeu e no terceiro foi apresentado concomitantemente a esta patologia. A resposta ao tratamento no CPT é indeterminada no primeiro paciente e excelente nos demais casos; a remissão foi alcançada em um paciente. Conclusões: a coexistência de acromegalia com câncer de tireoide é possível, que as alterações acrais e faciais e a sintomatologia expansiva do tumor levam ao diagnóstico de acromegalia e que a identificação de neoplasias não está relacionada à evolução da doença.

Up-to-date knowledge on age-related macular degeneration

Age-related macular degeneration (AMD) is a major cause of central vision loss in developed countries. The incidence of AMD has increased rapidly in Korea. The objective of this article is to introduce the latest knowledge about the pathophysiology, diagnostic tools and therapeutic modalities of AMD. The risk factors for AMD are age, smoking, familial history, genetic factors related to the complement system, diet, and cholesterol levels. Inflammation plays an important role in the pathophysiology of AMD and is associated with the complement system. Genes associated with the complement system affect the pathophysiology, expression, progression and therapeutic response of AMD. The use of antioxidants, zinc, and omega-3 fatty acids inhibits progression from moderate AMD to advanced AMD. Although there is no established treatment for dry AMD, treatment with agents that inhibit the complement system or through other mechanisms is under study. A number of anti-vascular endothelial growth factor agents have been developed for the prevention of choroidal neovascularization in the treatment of wet AMD and are being used clinically. Therapeutic alternatives to anti-vascular endothelial growth factor agents are under study.

Treatment Outcome of Serous Macular Detachment in Circumscribed Choroidal Hemangioma

PURPOSE: To determine the clinical outcome of anti-vascular endothelial growth factor (anti-VEGF) and photodynamic therapy (PDT) for circumscribed choroidal hemangioma (CCH) with serous retinal detachment. METHODS: The medical records of patients having CCH with serous retinal detachment in macula were retrospectively reviewed. CCH and serous retinal detachment were evaluated via fundus photography, optical coherence tomography, indocyanine green angiography, and ultrasonography. RESULTS: A total of 9 eyes were enrolled in this study. The average follow-up period was 19.2 months. The mean visual acuity was 0.51 ± 0.52 (logMAR) and the mean maximum diameter and thickness of the tumor were 6,154.4 ± 2,019.9 µm and 2,224.4 ± 862.1 µm, respectively. Of the 6 eyes receiving anti-VEGF (mean number of injections: 3.16) as the first treatment for serous retinal detachment, 5 had sustained or recurred intraretinal/subretinal fluid (IRF/SRF) and needed additional PDT and transpupillary thermotherapy. In the 3 eyes that received PDT (mean number of treatments: 1.3) as an initial treatment, IRF/SRF was completely resolved. Finally, 8 eyes achieved complete resolution of SRF and IRF; however visual recovery was limited. CONCLUSIONS: PDT, even with a small number of treatments, can alleviate IRF/SRF in CCH, while anti-VEGF did not.

Astragalus polysaccharides exert protective effects in newborn rats with bronchopulmonary dysplasia by upregulating the expression of EGFL7 in lung tissue.

The aim of this study was to explore the effects of Astragalus polysaccharides (APS) on the mRNA expression of epidermal growth factor-like domain 7 (EGFL7) in lung tissue in newborn rats with bronchopulmonary dysplasia (BPD). For this purpose, a total of 96 newborn SD rats were randomly divided into 4 groups (n=24): the control group, air room plus APS group, BPD group and the APS group (20 mg/kg/day). Lung tissues were obtained on days 4, 10 and 14 after birth. Morphological changes were observed and the protein and mRNA expression levels of EGFL7, Bax and Bcl-2 were determined. The rats in the BPD group (BPD induced by hyperoxia) presented with an arrest in alveolar and vascular development and low mRNA and protein expression levels of of EGFL7, Bcl-2 and high levels of Bax compared with the rats in the control group. However, lung damage in the APS intervention group was attenuated compared with the BPD group. The protein and mRNA expression levels of EGFL7 and Bcl-2 were also increased and the level of Bax was decreased in the APS intervention group (P<0.01) compared with the BPD model group after birth on days 4, 10 and 14. Our data demonstrate that APS reduce airway remodeling and alveolar damage by upregulating the expression of EGFL7 and exert protective effects against BPD in neonatal rats. Thus, APS may have potential for use as a therapeutic strategy for BPD.

Análise do perfil de expressão dos marcadores de angiogênese e das neurotrofinas na persistência da hiperatividade detrusora em pacientes submetidos à ressecção transuretal da próstata / Analysis of the expression profile of angiogenesis markers and neurotrophins in the persistence of detrusor overactive after transurethral resection of the prostate for treatment of bladder outlet obstruction due to benign prostatic hyperplasia

Introdução: A HD está presente em aproximadamente 50% dos pacientes com OIV devido HPB e 30% dos casos não apresentarão melhora após o tratamento cirúrgico. Até o momento, nenhuma característica clínica pode predizer acuradamente quais pacientes serão beneficiados. Neste estudo nós analisamos o papel de seis marcadores moleculares na resolução da HD após a RTUP. Método: Um estudo prospectivo e controlado analisou 43 pacientes com OIV devido HPB, submetidos a RTUP de 2011 a 2012. O grupo controle foi composto por espécimes de músculo vesical de 10 pacientes com menos de 60 anos, submetidos a prostatectomia radical devido câncer de próstata, apresentando IPSS menor que 8 e volume prostático menor que 30 gramas. Todos os pacientes realizaram estudo urodinâmico no pré-operatório e com 6 meses de pós-operatório. Nós analisamos a presença, o período de início (primeira vs segunda metade do enchimento vesical) e a amplitude (< 40 vs > 40 cmH2O) das CVIs, assim como sua resolução após 6 meses de tratamento cirúrgico. Uma biópsia de músculo vesical foi efetuada no final da RTUP para análise do perfil de expressão gênica do NGF, NGFr, VEGF, CD-105, CHRM2 e CHRM3. Para este propósito foi utilizado a técnica de qRT-PCR. Além disso, correlacionamos variáveis clínicas pré-operatórias com a evolução da HD no pós-operatório. Resultados: A idade média dos pacientes foi 63 anos (50 a 75). A HD estava presente em 21 (48,8%) pacientes. De acordo com aferições pré-operatórias, a média de expressão gênica do NGF foi 3,3 vezes maior nos pacientes que iniciaram CVI precocemente quando comparados àqueles que iniciaram as contrações na fase final de enchimento vesical (p=0,047). A presença e a amplitude das CVIs não apresentaram correlações estatísticas com os genes estudados. Em relação a resolução da HD, a média de expressão de CHRM2 foi 2 vezes maior entre os pacientes que evoluíram com melhora da HD (p=0,072). Após 6 meses da RTUP, 77,8% dos pacientes que possuíam...

Objective: Non-inhibited contractions (NIC) are present in about 50% of patients with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) and 30% of cases persist after surgery. To date, no clinical characteristic can predict accurately which patients are going to improve. We analyzed the role of six detrusor molecular markers in the resolution of NIC after transurethral resection of the prostate (TURP). Methods: We performed a prospective and controlled analysis of 43 patients with BOO due to BPH who underwent TURP from 2011 to 2012. The control group comprised 10 bladder specimens from patients younger than 60 years who underwent radical prostatectomy with an IPSS < 8 and prostate volume < 30 grams. All patients underwent urodynamic analysis pre and post operatively after 6 months. We analyzed the presence, time to occurrence (first vs second half of the filling phase) and grade (<40 vs >40 cmH2O) of NIC as well as its resolution after 6 months of surgery. A biopsy of the bladder muscle was performed at the end of TURP for analysis of nerve growth factor receptor (NGFr), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), endoglin (CD105), muscarinic cholinergic receptor 2 (CHRM2) and muscarinic cholinergic receptor 3 (CHRM3) genes expression. For this purpose, we used the quantitative real time polymerase chain reaction method (qRT-PCR). Results: Mean patient age was 63 years (50 to 75). NIC were present in 21 (48.8%) patients. According to pre-operative measures, NGF gene expression was 3.3 times greater in patients who presented early NIC as compared to those who presented late contractions (p=0.047). The presence or grade of NIC failed to present statistical correlations with the genes. With regard to the outcome, CHRM2 expression was 2.0 times greater among patients who presented resolution of NIC (p=0.072). After 6 months of TURP, 77,8% of patients with DO resolution had increased expression...

Efecto potencial del ejercicio físico y del consumo de micronutrientes durante la gestación en factores maternos y placentarios asociados con enfermedades crónicas no transmisibles (ECNT) del adulto / Potential effect of physical exercise and consumption of micronutrients during pregnancy on the placental and maternal factors associated with chronic non-communicable diseases in adult

Introducción: En la actualidad casi todos los esfuerzos para prevenir las enfermedades crónicas no transmisibles (ECNT) a nivel poblacional, se han centrado en promover comportamientos saludables como el ejercicio, la actividad física, el consumo de frutas y verduras, y el desestimular el consumo de tabaco y alcohol en la población adulta, pero los resultados han sido poco alentadores. En los últimos años, múltiples estudios han señalado la relación entre alteraciones del crecimiento fetal y el desarrollo de ECNT en la edad adulta. Más recientemente, se ha propuesto que factores maternos (función endotelial, estrés oxidativo y alteraciones en adipoquinas) y placentarios (disfunción mitocondrial) pueden ser mecanismos precursores de alteraciones metabólicas fetales y del desarrollo posterior de ECNT y que intervenciones como el ejercicio físico y la complementación con micronutrientes durante la gestación podrían regular dichos factores maternos y placentarios. Objetivo: Realizar una revisión de la literatura para verificar el papel del ejercicio físico y los micronutrientes durante la gestación sobre factores maternos y placentarios relacionados con ECNT del adulto. Metododología: Se utilizaron las siguientes bases de datos: Medline, Scielo, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials y The Cochrane Libraryp Pregnancy, fetal development, oxidative stress, vascular endothelium, mitochondrial, adipokines, micronutrients, exercise. Resultados: El estrés oxidativo, como mecanismo central de otros eventos fisiopatológicos (alteración en los niveles de adipoquinas, disfunción endotelial y mitocondrial), tiene un papel importante en la programación fetal de ECNT, factores como la complementación con micronutrientes y el ejercicio físico, durante la gestación, podrían modular este estado y contribuir posiblemente a la prevención temprana de ECNT.

Introduction: Currently, most efforts to prevent nontransmissible chronic diseases at population level have centered on promoting healthy behaviors like physical activity, consumption of fruits and vegetables, and discouraging from the consumption of tobacco and alcohol in the adult population, but the results have been less than hopeful. During recent years, a number of studies have indicated the relation between metabolic alterations and fetal growth with the development of nontransmissible chronic diseases in adult age. More recently, it has been proposed that maternal factors (endothelial function, oxidative stress, and alterations in adipokynes) and placental factors (mitochondrial dysfunction) are the precursory mechanisms of fetal metabolic alterations and of the later development of nontransmissible chronic diseases. Also, it has been suggested that possibly supplementation with micronutrients and physical exercise during gestation could regulate these maternal and placental factors. Aim: To conduct a literature review to verify the role of physical exercise and micronutrients during pregnancy on placental and maternal factors related to nontransmissible chronic diseases in adults. Methods: Medline, SciELO, Embase, Science Direct, Cochrane Central Register of Controlled Trials, and the Cochrane Library were used in the last 10 years (1998-2008). The following topics were reviewed: pregnancy, fetal development, oxidative stress, vascular endothelium, mitochondrial dysfunction, adipokines, micronutrients, and exercise. Results: Oxidative stress, as the central pathophysiological event, such as changes in levels of adipokynes, mitochondrial and endothelial dysfunction, plays an important role in fetal programming of chronic diseases and factors such as micronutrient supplementation and physical exercise during pregnancy could modulate this state in a charity institution aiding in the early prevention of chronic diseases.

VEGF receptor antagonist Cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult.

BACKGROUND: Excitotoxic brain insult is associated with extensive neuronal damage but could also cause inflammatory reactivity and vascular remodeling. The effects of the vascular endothelial growth factor (VEGF) inhibitor, Cyclo-VEGI on expression of VEGF, microgliosis and astrogliosis, blood-brain barrier (BBB) integrity and neuronal viability have been studied following intra-striatal injection of the excitotoxin, quinolinic acid (QUIN). The purpose of this study was to examine VEGF-dependent inflammatory responses in excitotoxin-injected brain and their dependence on pharmacological antagonism of VEGF receptors. METHODS: Single and double immunofluorescence staining of cellular (microglia, astrocyte, neuron) responses and dye and protein infiltration of blood-brain barrier have been applied in the absence, and presence, of pharmacological modulation using a VEGF receptor antagonist, Cyclo-VEGI. Dunn-Bonferroni statistical analysis was used to measure for significance between animal groups. RESULTS: Detailed analysis, at a single time point of 1 d post-QUIN injection, showed excitotoxin-injected striatum to exhibit marked increases in microgliosis (ED1 marker), astrogliosis (GFAP marker) and VEGF expression, compared with PBS injection. Single and double immunostaining demonstrated significant effects of Cyclo-VEGI treatment of QUIN-injected striatum to inhibit microgliosis (by 38%), ED1/VEGF (by 42%) and VEGF striatal immunoreactivity (by 43%); astrogliosis and GFAP/VEGF were not significantly altered with Cyclo-VEGI treatment. Leakiness of BBB was indicated by infiltration of Evans blue dye and plasma protein fibrinogen into QUIN-injected striatum with barrier permeability restored by 62% (Evans blue permeability) and 49% (fibrinogen permeability) with Cyclo-VEGI application. QUIN-induced toxicity was demonstrated with loss of striatal neurons (NeuN marker) and increased neuronal damage (Fluoro-Jade marker) with significant neuroprotection conferred by Cyclo-VEGI treatment (33% increase in NeuN and 38% decrease in Fluoro-Jade). CONCLUSION: An antagonist for VEGF receptor-mediated signaling, Cyclo-VEGI, has shown efficacy in a broad spectrum of activity against striatal excitotoxic insult including inhibition of microgliosis, reduction in leakiness of BBB and parenchymal infiltration of plasma fibrinogen and in conferring significant protection for striatal neurons. Antagonism of VEGF-mediated activity, possibly targeting VEGF receptors on reactive microglia, is suggested as a neuroprotective mechanism against inflammatory reactivity and a novel strategy to attenuate acute excitotoxic damage.

[Relationship of TCM syndrome type of gastric mucosal epithelial growth factor, vascular endothelial growth factor and proliferative cell nuclear antigen in patients with chronic atrophic gastritis].

OBJECTIVE: To study the relationship of TCM syndrome type of gastric mucosal epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) in patients with chronic atrophic gastritis (CAG) for exploring the essence of TCM type and providing a theoretical basis of clinical treatment. METHODS: TCM syndrome type of 200 patients with diagnosis of CAG confirmed by fibro-gastroscope and pathological examination were differentially classified, and the expressions of EGF, VEGF and PCNA in different types were determined using immunohistochemistry. RESULTS: Patients were differentiated as Pi-Wei deficiency type (Type I ) in 72; Gan-Wei disharmony type (Type II ) in 43; Pi-deficiency with qi stagnation type (Type III) in 32; Wei-yin deficiency type (Type IV) in 24; Pi-Wei damp-heat type (Type V) in 14; and Wei-collateral stasis obstruction type (Type VI) in 5. The difference of PCNA expression level between Type II with Type I , III and IV was significant (P < 0.05). No significant difference in expression levels of EGF and VEGF was found among the 6 types (P > 0.05). CONCLUSION: Type I and II were the dominant TCM syndrome types in CAG patients; the high expression of PCNA might be a diagnostic evidence for Gan-Wei disharmony syndrome.

Relationship of TCM syndrome type of gastric mucosal epithelial growth factor, vascular endothelial growth factor and proliferative cell nuclear antigen in patients with chronic atrophic gastritis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the relationship of TCM syndrome type of gastric mucosal epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) in patients with chronic atrophic gastritis (CAG) for exploring the essence of TCM type and providing a theoretical basis of clinical treatment.</p><p><b>METHODS</b>TCM syndrome type of 200 patients with diagnosis of CAG confirmed by fibro-gastroscope and pathological examination were differentially classified, and the expressions of EGF, VEGF and PCNA in different types were determined using immunohistochemistry.</p><p><b>RESULTS</b>Patients were differentiated as Pi-Wei deficiency type (Type I ) in 72; Gan-Wei disharmony type (Type II ) in 43; Pi-deficiency with qi stagnation type (Type III) in 32; Wei-yin deficiency type (Type IV) in 24; Pi-Wei damp-heat type (Type V) in 14; and Wei-collateral stasis obstruction type (Type VI) in 5. The difference of PCNA expression level between Type II with Type I , III and IV was significant (P < 0.05). No significant difference in expression levels of EGF and VEGF was found among the 6 types (P > 0.05).</p><p><b>CONCLUSION</b>Type I and II were the dominant TCM syndrome types in CAG patients; the high expression of PCNA might be a diagnostic evidence for Gan-Wei disharmony syndrome.</p>

Treatment of Exudative Age-Related Macular Degeneration

Age-related macular degeneration (ARMD) is characterized by both primary and secondary damage of macular retinal pigment epithelial cell, resulting in the formation of drusen, choroidal neovascularization, and atrophy of photoreceptors and choriocapillaris layer of the choroid. After ARMD becomes exudative, laser photocoagulation, transpupillary thermotherapy, photodynamic therapy, intravitreal steroid injection, intravitreal anti-vascular endothelial growth factor injection, and surgical intervention are treatments to control choroidal neovascularization. In photodynamic therapy, a light-sensitive drug is administered by intravenous infusion and activated by a low-powered laser. Activated photosensitizer induces occlusion of the pathologic vasculature. Pegatanib, ranibizumab, and bevacizumab are anti-angiogenic agents, inhibiting the formation of neovascular membranes to prevent further development of the condition and to improve vision. This is thought to be due to the inhibition of vascular endothelial growth factor.

Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53.

Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin.

VE-statin, an endothelial repressor of smooth muscle cell migration.

The recruitment and proliferation of smooth muscle cells and pericytes are two key events for the stabilization of newly formed capillaries during angiogenesis and, when out of control in the adult, are the main causes of arteriosclerosis. We have identified a novel gene, named VE-statin for vascular endothelial-statin, which is expressed specifically by endothelial cells of the developing mouse embryo and in the adult, and in early endothelial progenitors. The mouse and human VE-statin genes have been located on chromosome 2 and 9, respectively, they span >10 kbp and are transcribed in two major variants arising from independent initiation sites. The VE-statin transcripts code for a unique protein of 30 kDa that contains a signal peptide and two epidermal growth factor (EGF)-like modules. VE-statin is found in the cellular endoplasmic reticulum and secreted in the cell supernatant. Secreted VE-statin inhibits platelet-derived growth factor (PDGF)-BB-induced smooth muscle cell migration, but has no effects on endothelial cell migration. VE-statin is the first identified inhibitor of mural cell migration specifically produced by endothelial cells.

[Study on effects of Astragalus, Angelica and their combination on vascular endothelial cell proliferation in vitro].

OBJECTIVE: To study the effects of Astragalus membranaceus (AM), Angelica sinensis (AS) and their combination on human umbilical vein endothelial cell (HUVEC) proliferation and cells cycle. METHODS: The effects were observed and studied by means of taking the cultured HUVECs as model to determine the cell proliferation with MTT method, cell cycle was analyzed with cytometry, and vascular endothelial growth factor (VEGF) expression with SABC method. The regulatory effects of AM, AS and their combination on the HUVEC proliferation promoting were observed and studied. RESULTS: AM and AS, used singly or in combination, could promote the growth of endothelial cells, increase the cell population in S phase, the effects showed more significant when used in combination (P < 0.05 or P < 0.001). Meanwhile, VEGF expression in all the medicated group was up-regulated, but in the PBS control group, it showed only weak expression (P < 0.05 or P < 0.01). CONCLUSION: AM and AS have effect in promoting vascular endothelial cell proliferation and DNA synthesis, and showed synergistic effect when they were used in combination, suggesting that these two Chinese herbs could have certain effect on the genesis and development of neogenetic vascularization in ischemic myocardium.