Search Results (276)

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article

Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes. The investigation focused on alterations in the vascular endothelial growth factor (VEGF) and its receptor-1 (FLT-1) signaling pathways, as well as its potential to suppress inflammation and oxidative stress. A number of rats received a single dose of streptozotocin (STZ) 55 mg/kg (i.p.) to induce DM. Sitagliptin was administered orally (100 mg/kg/90 days) to normal and diabetic rats, after which samples were collected for investigation. Sitagliptin significantly mitigated weight loss in diabetic rats. Its administration significantly reduced blood glucose levels and improved serum troponin I and CK-MB levels. Heart sections from diabetic rats showed a marked increase in mTOR, VEGF, and FLT-1 immune reaction, while sitagliptin-treated diabetic rats’ heart sections showed moderate immune reactions. Sitagliptin’s protective effect was also associated with reduced inflammation, and apoptotic markers. In conclusion, Sitagliptin is suggested to offer beneficial effects on the vascular health of cardiac blood vessels, thereby potentially reducing myocardial stress in diabetic patients. Full article

Seed germination is recognized for enhancing the accumulation of bioactive compounds. Perilla frutescens (L.) Britt., commonly known as perilla seed, is rich in fatty acids that may be beneficial for anti-hair loss. This study investigated the hair regeneration potential of perilla seed extracts—non-germinated (NG-PS) and germinated in distilled water (0 ppm selenium; G0-PS), and germinated with 80 ppm selenium (G80-PS)—obtained from supercritical fluid extraction (SFE) and screw compression (SC). SFE extracts exhibited significantly higher levels of polyphenols, tocopherols, and fatty acids compared to SC extracts. Among the germinated groups, G0-PS showed the highest bioactive compound content and antioxidant capacity. Remarkably, treatment with SFE-G0-PS led to a significant increase in the proliferation and migration of hair follicle cells, reaching 147.21 ± 2.11% (p < 0.05), and resulted in complete wound closure. In addition, its antioxidant and anti-inflammatory properties were reflected by a marked scavenging effect on TBARS (59.62 ± 0.66% of control) and suppressed nitrite amounts (0.44 ± 0.01 µM). Moreover, SFE-G0-PS markedly suppressed SRD5A1-3 gene expression—key regulators in androgenetic alopecia—in both DU-145 and HFDPCs, with approximately 2-fold and 1.5-fold greater inhibition compared to finasteride and minoxidil, respectively. Simultaneously, it upregulated the expression of hair growth-related genes, including CTNNB1, SHH, SMO, GLI1, and VEGF, by approximately 1.5-fold, demonstrating stronger activation than minoxidil. These findings suggest the potential of SFE-G0-PS as a natural therapeutic agent for promoting hair growth and preventing hair loss. Full article

Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article

Diabetic retinopathy (DR), a leading cause of blindness in working-age adults, arises from chronic hyperglycemia-induced oxidative stress, inflammation, and vascular dysfunction. Current therapies such as laser photocoagulation, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and steroids target advanced stages but fail to prevent early neuronal and microvascular damage. Emerging evidence highlights oxidative stress as a key driver of DR pathogenesis, disrupting the blood-retinal barrier (BRB), promoting neurodegeneration and angiogenesis. Advances in imaging, particularly optical coherence tomography angiography (OCTA), enable earlier detection of neurodegeneration and microvascular changes, underscoring DR as a neurovascular disorder. Polyphenols, such as resveratrol, curcumin, and pterostilbene, exhibit multitarget antioxidant, anti-inflammatory, and anti-angiogenic effects, showing promise in preclinical and limited clinical studies. However, their low bioavailability limits therapeutic efficacy. Nanotechnology-based delivery systems enhance drug stability, tissue targeting, and sustained release, offering potential for early intervention. Future strategies should integrate antioxidant therapies and precision diagnostics to prevent early irreversible retinal damage in diabetic patients. Full article

This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1–27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden. Full article

Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study included 118 eyes from 115 patients who underwent IVI with anti-VEGF agents at Osaka Metropolitan University Hospital between September 2024 and January 2025. IOP was measured at three time points, namely before injection, within 1 min after injection, and at 30 min, in selected eyes with a post-injection IOP ≥ 25 mmHg. Differences in IOP elevation were analyzed according to the disease type and anti-VEGF agent. Univariate and multivariate linear regression analyses were performed to identify clinical factors associated with IOP elevation. Results: Mean IOP significantly increased from 13.9 ± 3.3 mmHg at baseline to 39.2 ± 12.4 mmHg immediately after injection (p < 0.001), with 79.7% of eyes showing an IOP ≥ 25 mmHg. Among those remeasured, IOP decreased to 17.7 ± 6.5 mmHg at 30 min. Significant differences in IOP elevation were observed among anti-VEGF agents (p < 0.001), with aflibercept at 2 mg and 8 mg showing greater increases than other agents. Multivariate analysis identified higher baseline IOP, history of glaucoma, absence of prior vitrectomy, and use of aflibercept (2 mg or 8 mg) as significant risk factors for greater post-injection IOP elevation. Conclusions: Transient IOP elevation ≥ 25 mmHg was observed in the majority of eyes after IVI but typically resolved within 30 min. Aflibercept use, high baseline IOP, glaucoma history, and absence of prior vitrectomy were associated with greater IOP elevation. Careful monitoring and attention to injection volume may be warranted, particularly in high-risk patients. Full article

Atrial fibrillation (AF), the most prevalent clinically significant cardiac arrhythmia, is characterized by chaotic atrial electrical activity and currently affects an estimated 2.5–3.5% of the global population. Its pathogenesis involves ion channel dysfunction, inflammatory cascades, and structural remodeling processes, notably fibrosis. Angiogenesis, the physiological/pathological process of new blood vessel formation, plays a multifaceted role in AF progression. This review synthesizes evidence highlighting angiogenesis’s dual role in AF pathogenesis: while excessive or dysregulated angiogenesis promotes atrial remodeling through fibrosis, and electrical dysfunction via VEGF, ANGPT, and FGF signaling pathways, compensatory angiogenesis exerts protective effects by improving tissue perfusion to alleviate ischemia and inflammation. Therapeutically, targeting angiogenic pathways—particularly VEGF—represents a promising strategy for modulating structural remodeling; however, non-selective VEGF inhibition raises safety concerns due to cardiovascular toxicity, necessitating cautious exploration. Emerging evidence highlights that anti-cancer agents (e.g., ibrutinib, bevacizumab) impair endothelial homeostasis and elevate AF risk, underscoring the need for cardio-oncology frameworks to optimize risk–benefit ratios. Preclinical studies on angiogenesis inhibitors and gene therapies provide mechanistic insights, but clinical validation remains limited. Future research should prioritize elucidating mechanistic complexities, developing biomarker refinement, and implementing interdisciplinary strategies integrating single-cell sequencing with cardio-oncology principles. This review emphasizes the imperative to clarify angiogenic mechanisms, optimize therapeutic strategies, and balance pro-arrhythmic versus compensatory angiogenesis, in pursuit of personalized AF management. Full article

(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted. Full article

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for natural bioactive compounds in therapeutic applications. Methods: The monosaccharide composition of PCS was analyzed using HPLC-RID, identifying glucuronic acid and xylose as major components. In vitro tests assessed antioxidant activity, while in vivo experiments on 24 rats evaluated wound healing. Rats were divided into four groups: control (saline), standard drug (CYTOL CENTELLA cream), glycerol, and glycerol+PCS. Wound healing was analyzed macroscopically, histologically, and biochemically. The chick chorioallantoic membrane (CAM) model assessed pro-angiogenic effects, and computational analyses explored COX-2 and VEGF pathways. Pharmacokinetic properties were also evaluated. Results: PCS demonstrated significant antioxidant activity and accelerated wound healing after 16 days, with improved wound appearance scores and increased collagen content. Histological analysis confirmed PCS outperformed the standard drug. The CAM model showed PCS increased blood vessel density, length, and junctions while reducing lacunarity. Computational analyses supported involvement of COX-2 and VEGF pathways. Pharmacokinetic assessments indicated good bioavailability, non-inhibition of CYP enzymes, and favorable skin permeability. Conclusions: PCS shows promise as a natural bioactive polymer for wound healing and tissue regeneration. Its antioxidant, anti-inflammatory, and pro-angiogenic properties, combined with favorable pharmacokinetics, highlight its therapeutic potential. This study provides new insights into the mechanisms of C. spinosa polysaccharides and their application in promoting tissue repair. Full article

Diabetic retinopathy (DR) is one of the leading causes of preventable blindness worldwide. It is characterized by a spectrum of disease that spans mild non-proliferative diabetic retinopathy (NPDR) all the way to neovascular glaucoma and tractional retinal detachment secondary to proliferative diabetic retinopathy (PDR). Most eyes with DR remain asymptomatic unless vision-threatening complications, such as diabetic macular edema (DME) and/or PDR, develop. Current treatment options include laser photocoagulation and/or anti-VEGF intravitreal injections. Patients under treatment with anti-VEGF agents usually require constant monitoring and multiple injections to optimize outcomes. This treatment burden plays a key role in suboptimal adherence to treatment in many patients, compromising their outcomes. Gene therapy has emerged as a promising therapeutic option for DR. The mechanism for current trials evaluating gene therapies for DR consists of delivering transgenes to the retina that express anti-angiogenic proteins that inhibit VEGF. Preliminary results from the SPECTRA (4D-150) and ALTITUDE (ABBV-RGX-314) studies are promising, demonstrating an improvement in the diabetic retinopathy severity score and a reduction in the treatment burden. In contrast, the INFINITY (ADVM-022) trial was complicated by several cases of severe inflammation and hypotony that led the sponsor to discontinue further development of this product for DME. Full article

Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose (PGG), through both in vitro and clinical studies. WRGE was obtained using a standardized extraction process, and PGG was identified via HPLC-DAD and HRESIMS/MS techniques. Human dermal papilla cells (HDPCs) are specialized fibroblasts that can regulate the hair growth cycle and hair follicle growth. HDPCs are widely used in research focused on anti-hair loss. In this study, the anti-hair loss effects of WRGE and PGG on HDPCs were confirmed. WRGE and PGG enhance cell proliferation in HDPCs. These results are associated with the activation of the Wnt/β-catenin signaling pathway and the upregulation of hair growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF). Furthermore, WRGE and PGG significantly inhibited dihydrotestosterone (DHT)-mediated DKK-1 secretion and H₂O₂-medicated cytotoxicity. Clinical trials further validated these results, demonstrating significant improvements in hair density and visual hair appearance scores in participants treated with WRGE compared to a placebo group. These results collectively suggest that WRGE and PGG may serve as promising natural agents for the prevention and treatment of hair loss by targeting multiple biological pathways, including the regulation of hair growth factors, oxidative stress, and hormonal imbalances. Full article

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. Its pathogenesis involves multiple factors, including aging, environmental influences, genetic predisposition, oxidative stress, metabolic dysfunction, and immune dysregulation. Currently, AMD treatment focuses primarily on wet AMD, managed through repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) therapies. While anti-VEGF agents represent a major breakthrough in wet AMD care, repeated injections may lead to incomplete responses or resistance in some patients, and carry a risk of progressive fibrosis. Artemisinin (ART) and its derivatives, originally developed as antimalarial drugs, exhibit a broad spectrum of pleiotropic activities beyond their established use, including anti-inflammatory, anti-angiogenic, antioxidant, anti-fibrotic, mitochondrial regulatory, lipid metabolic, and immunosuppressive effects. These properties position ART as a promising therapeutic candidate for AMD. A growing interest in ART-based therapies for AMD has emerged in recent years, with numerous studies demonstrating their potential benefits. However, no comprehensive review has systematically summarized the specific roles of ART and its derivatives in AMD pathogenesis and treatment. This paper aims to fill the knowledge gap by synthesizing the therapeutic efficacy and molecular mechanisms of ART and its derivatives in AMD, thereby providing a foundation for future investigations. Full article

Background/Objectives: Marinobufagenin (MBG) is a biomarker that is found to be high in pre-eclampsia (preE), and thus is relevant in the pathogenesis of obstetric complications. MBG is thought to possibly be implicated in harmful signaling within cytotrophoblasts (CTBs) of the placenta. In this study, we evaluated how anti-MBG human monoclonal antibody can alter cellular signaling in CTBs and in a rat model of preE. Methods: CTB cell proliferation, migration, and invasion as a result of MBG, both with and without anti-MBG present, were monitored via cell-based studies. Pro-angiogenic and anti-angiogenic factors in response to MBG with and without antibody were measured. Finally, we evaluated the lead anti-MBG antibody in comparison with the parent murine antibody in a rat model of preE. Results: CTB cells exposed to ≥1 nM MBG showed decreased (p < 0.05) proliferation, migration, and invasion, decreased secretion of VEGF and PIGF, and increased secretion of sFlt-1 and sEng. Pretreatment with anti-MBG significantly (p < 0.05) attenuated MBG-induced CTB dysfunction and modulation of VEGF, PIGF, sFlt-1, and sEng expression. In the rat model, anti-MBG treatment normalized blood pressure, reduced proteinuria, and eliminated fetal effects. Conclusions: MBG is a potential causative agent for preE, as it causes dysfunction in CTBs due to anti-angiogenic milieu. Our study suggests that anti-MBG antibody binds to MBG, neutralizing it and preventing downstream signaling in vitro. In a rat model of preE, treatment with anti-MBG antibody was effective at normalizing blood pressure, kidney function, and fetal birth weights. These data suggest that a human monoclonal antibody with high specificity and affinity for MBG has potential as a therapeutic agent for preE. Full article