Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.

Complex tumour ecosystem comprising tumour cells and its associated tumour microenvironment (TME) constantly influence the tumoural behaviour and ultimately impact therapy failure, disease progression, recurrence and poor overall survival of patients. Crosstalk between tumour cells and TME amplifies the complexity by creating metabolic changes such as hypoxic environment and nutrient fluctuations. These changes in TME initiate stem cell-like programmes in cancer cells, contribute to tumoural heterogeneity and increase tumour robustness. Recent studies demonstrate the multifaceted role of autophagy in promoting fibroblast production, stemness, cancer cell survival during longer periods of dormancy, eventual growth of metastatic disease and disease resistance. Recent ongoing studies examine autophagy/mitophagy as a powerful survival strategy in response to environmental stress including nutrient deprivation, hypoxia and environmental stress in TME. It prevents irreversible senescence, promotes dormant stem-like state, induces epithelial–mesenchymal transition and increases migratory and invasive potential of tumour cells. The present review discusses various theories and mechanisms behind the autophagy-dependent induction of cancer stem cell (CSC) phenotype. Given the role of autophagic functions in CSC aggressiveness and therapeutic resistance, various mechanisms and studies based on suppressing cellular plasticity by blocking autophagy as a powerful therapeutic strategy to kill tumour cells are discussed.

Recent development in immunotherapy for cancer treatment has substantiated to be more effective than most of the other treatments. Immunity is the first line of defence of the body; nevertheless, cancerous cells can manipulate immunity compartments to play several roles in tumour progression. Tumour-associated macrophages (TAMs), one of the most dominant components in the tumour microenvironment, are recognized as anti-tumour suppressors. Unfortunately, the complete behaviour of TAMs is still unclear and understudied. TAM density is directly correlated with the progression and poor prognosis of hepatocellular carcinoma (HCC), therefore studying TAMs from different points of view passing by all the factors that may affect its existence, polarization, functions and repolarization are of great importance. Different epigenetic regulations were reported to have a direct relation with both HCC and TAMs. Here, this review discusses different epigenetic regulations that can affect TAMs in HCC whether positively or negatively.

Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs 1, 2). Early management is important in order to avoid disability uphold quality of life (Ref. 3). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. 4). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs 5, 6, 7, 8). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. 9). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs 10, 11).

Consumption of edible insects has been widely suggested as an environmentally sustainable substitute for meat to reduce greenhouse gas emissions. However, the novel research field for edible insects relies on the content of bioactive ingredients and on the ability to induce a functional effect in humans. The goal of this manuscript is to review the available body of evidence on the properties of edible insects in modulating oxidative and inflammatory stress, platelet aggregation, lipid and glucose metabolism and weight control. A search for literature investigating the functional role of edible insects was carried out in the PubMed database using specific keywords. A total of 55 studies, meeting inclusion criteria after screening, were divided on the basis of the experimental approach: in vitro studies, cellular models/ex vivo studies or in vivo studies. In the majority of the studies, insects demonstrated the ability to reduce oxidative stress, modulate antioxidant status, restore the impaired activity of antioxidant enzymes and reduce markers of oxidative damage. Edible insects displayed anti-inflammatory activity reducing cytokines and modulating specific transcription factors. Results from animal studies suggest that edible insects can modulate lipid and glucose metabolism. The limited number of studies focused on the assessment of anti-coagulation activity of edible insects makes it difficult to draw conclusions. More evidence from dietary intervention studies in humans is needed to support the promising evidence from in vitro and animal models about the functional role of edible insect consumption.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case–control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography–tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose–response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Today, cancer is one of the leading causes of death worldwide. Lately, cytokine and chemokine imbalances have gained attention amongst different involved pathways in cancer development and attracted much consideration in cancer research. CXCL16, as a member of the CXC subgroup of chemokines, has been attributed to be responsible for immune cell infiltration into the tumour microenvironment. The aberrant expression of CXCL16 has been observed in various cancers. This chemokine has been shown to play a conflicting role in tumour development through inducing pro-inflammatory conditions. The infiltration of various immune and non-immune cells such as lymphocytes, cancer-associated fibroblasts and myeloid-derived suppressor cells by CXCL16 into the tumour microenvironment has complicated the tumour fate. Given this diverse role of CXCL16 in cancer, a better understanding of its function might build-up our knowledge about tumour biology. Hence, this study aimed to review the impact of CXCL16 in cancer and explored its therapeutic application. Consideration of these findings might provide opportunities to achieve novel approaches in cancer treatment and its prognosis.

Recurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen–thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33–614) pg/ml vs 119.92 (27–441) pg/ml; P-value = 0.030] and [82.54 (25.94–210.20) pg/ml vs 30.93 (13.62–193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.

The paper is based on the lecture that I gave on receiving the Nutrition Society's inaugural Gowland Hopkins Award for contributions to Cellular and Molecular Nutrition. It reviews studies on the adipose tissues, brown and white, conducted by the groups that I have led since entering nutrition research in 1975. The initial focus was on exploring metabolic factors that underpin the development of obesity using animal models. This resulted in an interest in non-shivering thermogenesis with brown adipose tissue being identified as the key effector of facultative heat production. Brown fat is less thermogenically active in various obese rodents, and major changes in activity are exhibited under physiological conditions such as lactation and fasting consistent with a general role for the tissue in nutritional energetics. My interests moved to white adipose tissue following the cloning of the Ob gene. Our initial contributions in this area included demonstrating nutritional regulation of Ob gene expression and circulating leptin levels, as well as a regulatory role for the sympathetic nervous system operating through β3-adrenoceptors. My interests subsequently evolved to a wider concern with the endocrine/signalling role of adipose tissue. Inflammation is a characteristic of white fat in obesity with the release of inflammation-related adipokines, and we proposed that hypoxia underlies this inflammatory state. O2-deprivation was shown to have substantial effects on gene expression and cellular function in white adipocytes. The hypoxia studies led to the proposition that O2 should be considered as a critical macronutrient.

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

The present study was performed to evaluate the effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM). This randomised, double-blind, placebo-controlled clinical trial was performed in sixty women with GDM. Participants were randomly divided into two groups to intake either 2 × 1000 mg/d n-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid in each capsule (n 30) or placebo (n 30) for 6 weeks. n-3 Fatty acid intake up-regulated PPAR-γ (P < 0·001) and LDL receptor (P = 0·004) and down-regulated gene expression of IL-1 (P = 0·002) and TNF-α (P = 0·001) in peripheral blood mononuclear cells of subjects with GDM. In addition, n-3 fatty acid supplementation reduced fasting plasma glucose (P = 0·001), insulin levels (P = 0·001) and insulin resistance (P < 0·001) and increased insulin sensitivity (P = 0·005) when compared with the placebo. Additionally, n-3 fatty acid supplementation was associated with a decrease in TAG (P < 0·001), VLDL-cholesterol (P < 0·001), total cholesterol (P = 0·01) and total cholesterol:HDL-cholesterol ratio (P = 0·01) when compared with placebo. n-3 Fatty acid administration was also associated with a significant reduction in high-sensitivity C-reactive protein (P = 0·006) and malondialdehyde (P < 0·001), and an increase in total nitrite (P < 0·001) and total glutathione levels (P = 0·006) when compared with the placebo. n-3 Fatty acid supplementation for 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipid and inflammation, glycaemic control, lipids, inflammatory markers and oxidative stress.

Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP’s depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships.

The hypovitaminosis D kyphotic pig provides a reliable model to study the initiation of bone lesions caused by maternal vitamin D (D) deficiencies. Matrix metalloproteinases (MMP; specifically, MMP9 and MMP13) and vascular endothelial growth factor (VEGF) are important in endochondral ossification and are potentially regulated by D. Fibroblast growth factor 23 (FGF23) is interrelated with D homoeostasis and bone mineralisation. Relative mRNA expression of MMP9, MMP13, VEGF and FGF23 was measured in pig femur and vertebra. Sows (n 37) were fed diets with 0 (−D), 8·125 (+D) or 43·750 (++D) µg D3/kg throughout gestation and lactation. At weaning (3 weeks), pigs were fed diets with 0 (−D) or 7·0 (+D) µg D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca and P requirements. Pigs at birth (n 27), 3 weeks (n 27) and after the nursery period (7 weeks; n 72) were euthanised for analysis. At 3 weeks, femur MMP9 expression of pigs produced by +D or ++D sows was reduced (P<0·05) to 0·5-fold and VEGF expression to 0·4-fold compared with pigs from –D sows. At 7 weeks, MMP9 expression was reduced (P<0·05) to 0·45-fold in femur and 0·58-fold in vertebra from pigs produced by +D or ++D sows compared with pigs from −D sows. Pig femur VEGF expression was reduced to 0·75-fold in pigs produced by ++D sows. MMP9 and VEGF mRNA expression offer potential markers for the initiation of bone lesions in the hypovitaminosis D kyphotic pig model.

A total of twenty-four healthy twin-bearing Liuyang black goats were allocated to two trials. In Trial 1, twelve goats received either the control diet (CG, n 6, 100 % feed) or restricted diet (RG, n 6, 60 % feed of CG) from gestation days 26 to 65 after synchronisation. In Trial 2, the remaining goats were randomly and equally divided into two treatments: CG and RG from days 95 to 125 of gestation. Placental traits, fetal weight, serum parameters, nitric oxide (NO), angiogenesis gene expression and cotyledon proteome were measured at the end of each trial. In early pregnancy, the total and relative weights of placenta, uterine caruncle and cotyledon, as well as fetus, were increased (P<0·05) in RG. The NO content in maternal serum was also increased (P<0·05) in RG. In all, fifty differentially expressed proteins were identified in cotyledon. The up-regulated proteins are related to proliferation and fission of trophoblast cell and the placenta angiogenesis. During the late pregnancy trial, placental weight was increased (P<0·05) in RG, but weight of the fetus was decreased (P<0·05). The capillary density in the cotyledon was also decreased (P<0·01). A total of fifty-eight proteins were differentially expressed in cotyledon. The up-regulated proteins in RG are related to placenta formation, blood flow regulation and embryonic development. These results indicated that feed intake restriction during gestation influenced the placental and fetal development in a stage-dependent manner. These findings have important implications for developing novel nutrient management strategies in goat production.

Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits. Methods: Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured. Results: Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (both p<0.01) when administered 5 or 8 hours after ischemia. The earlier the administration the better the neuroprotection. Conclusions: These results showed that the combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the time window of combination treatment should be at least 8 hours after ischemia, which was wider than monotherapy. RÉSUMÉ:Les effets d’une polythérapie combinant agents neuro-protecteurs et agents vasoprotecteurs dans les cas d’ischémie cérébrale.Contexte:Étant donné que la plupart des médicaments préalablement testés tendent à n’agir contre seulement un des processus de dommage associés aux AVC, il est possible que d’autres processus entraînent une mort cellulaire. À cet effet, il se pourrait qu’une combinaison d’agents protecteurs ciblant divers mécanismes physiopathologiques permette d’obtenir de meilleurs résultats qu’un simple agent. Après avoir suscité de façon contrôlée des lésions cérébrales ischémiques chez des lapins, l’objectif principal de la présente étude a donc été de se pencher sur l’impact d’une polythérapie combinant la protéine dite « facteur de croissance de l’endothélium vasculaire » (ou « VEGF » en anglais) avec le « facteur de croissance des nerfs » (ou « NGF » en anglais). Méthodes: Les animaux ont été attribués au hasard à l’un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d’un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d’administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d’administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5 heures à la suite d’un AVC). Tant le volume des infarctus, le contenu en eau, les déficits neurologiques ainsi causés, l’apoptose des neurones que l’expression des protéases caspase 3 et des protéines Bcl-2 ont été mesurés. Résultats: Si on la compare au traitement à base de solution saline administré au groupe témoin, la polythérapie à base de VEGF et de NGF, lorsqu’administrée 5 heures ou 8 heures à la suite de l’AVC, a su réduire de façon notable le volume des infarctus, le contenu en eau, l’apoptose des neurones et l’expression des protéases caspase 3. Elle a également permis de réguler à la hausse l’expression des protéines Bcl-2 en plus d’entraîner une amélioration de la récupération fonctionnelle (p < 0,01 pour ces deux aspects). Ainsi donc, plus tôt l’on opte pour cette polythérapie, meilleure sera la neuroprotection encourue. Conclusions: Ces résultats démontrent que la polythérapie à base de VEGF et de NGF procure des effets neuroprotecteurs. Quant au délai d’administration de ce traitement combinatoire, il devrait être d’au moins 8 heures à la suite d’un AVC, ce qui est plus élevé que la monothérapie.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.