Search Results (3,130)

The skin serves as the largest protective barrier organ of the human body and is easily impaired by trauma, infection and chronic diseases. Efficient wound dressings are indispensable for repairing infected wounds. Isochlorogenic acid A (IAA), the core active ingredient of Shanyinhua, has superior anti-inflammatory and antibacterial effects. However, low water solubility and weak structural stability restrict its direct application in wound treatment. In this work, IAA@Fe(III) nanoparticles (IAA@Fe(III) NPs) were synthesized through self-assembly and loaded into cross-linked amylopectin (Amy)/carboxymethyl chitosan (CMCS) (AC hydrogel) to construct Amy/CMCS@NPs composite dressings. Characterizations demonstrated that nanoparticles displayed a uniform spherical shape with a size of 114.20 ± 2.29 nm and stable coordination. The hydrogel featured a dense porous structure and outstanding mechanical performance, self-healing ability, adhesion, and swelling properties. In vitro tests proved that 50 mg/mL composite hydrogel exerted nearly 100% bacteriostatic activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with good biocompatibility, and enhanced cell migration capacity. In vivo assays indicated an 86.5% wound healing rate at day 7. This dressing could downregulate Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β), upregulate Cluster of Differentiation 31 (CD31) and Vascular Endothelial Growth Factor (VEGF), and accelerate wound repair. This study provides a theoretical and experimental basis for the exploitation of IAA-based wound dressings and high-value utilization of Shanyinhua resources. Full article

Aim: To evaluate the real-world effectiveness, durability, and safety of faricimab 6 mg in eyes with treatment-refractory retinal vein occlusion (RVO)-associated macular oedema (MO) in the United Kingdom (UK). Methods: This was a retrospective, single-centre observational study of eyes with RVO that were switched to faricimab after prior treatment with previous anti-vascular endothelial growth factor (anti-VEGF) agents. Baseline demographics, treatment history, pinhole visual acuity (VA), optical coherence tomography (OCT) biomarkers, and injection intervals were recorded. Eyes were treated using a treat-and-extend regimen without a loading phase. Functional, anatomical, durability, and safety outcomes were assessed over follow-up. Results: A total of 22 eyes from 22 patients were included, with a mean (SD) age of 67.9 (11.9) years and a mean (SD) RVO duration of 201.4 (153.1) weeks. Eyes had received a mean (SD) of 20.8 (16.9) prior anti-VEGF injections. The mean (SD) follow-up was 45.7 (15.8) weeks, with a mean (SD) of 5.9 (2.3) faricimab injections. There was no significant change in pinhole VA (53.5 (18.5) vs. 55.0 (18.8) letters, p = 0.08). The central subfield thickness (CST) reduced from 407.6 (102.1) to 377.0 (186.5) µm, and the maximum central retinal thickness from 483.6 (103.1) to 442.2 (187.2) µm, although these changes were not statistically significant (p > 0.05). The proportion of eyes with subretinal fluid (SRF) decreased from 18.2% to 4.5%, and intraretinal fluid (IRF) from 100% to 81.8%. Injection intervals between the first and second faricimab injections increased significantly from 4.9 (1.4) to 7.7 (3.4) weeks (final injection interval, p = 0.004). Six eyes (27.3%) discontinued faricimab, with three (13.6%) requiring an intravitreal dexamethasone implant following a suboptimal response. One eye (4.5%) developed transient intraocular pressure elevation; no cases of intraocular inflammation or endophthalmitis were observed. Conclusions: In this heavily pre-treated, chronic RVO cohort, switching to faricimab without a loading phase resulted in stable visual acuity, modest but non-significant anatomical improvements, and a significant extension in treatment intervals. These findings suggest that faricimab may provide durability benefits and disease stabilisation in treatment-refractory RVO, although functional gains may be limited in chronic disease. Further prospective studies are required to define optimal switching strategies. Full article

This study evaluated the prognostic significance of vasohibin-1 (VASH1) expression, cluster of differentiation 34 (CD34)-defined microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression, as well as the differences in these parameters between primary and metastatic colorectal cancer (CRC) lesions. Tissue microarrays were used to quantify VASH1 and VEGF expression and CD34-defined MVD. Receiver operating characteristic (ROC) analysis identified optimal cut-off values for overall survival (OS). Correlations among markers were analyzed with Spearman’s test, paired tissue comparisons by the Wilcoxon signed-rank test, and survival outcomes by Kaplan–Meier and Cox regression analyses. The study included 144 CRC patients (median age: 60 years; 59% male). ROC analysis determined optimal thresholds of 6 for VASH1 (area under the curve [AUC]: 0.79, 95% confidence interval [CI]: 0.72–0.87), 37 for CD34-defined MVD (AUC: 0.76, 95% CI: 0.68–0.84), and 6 for VEGF (AUC: 0.67, 95% CI: 0.58–0.76). Patients with high VASH1 expression, high CD34-defined MVD, and high VEGF expression had significantly shorter OS compared with their corresponding low-marker groups (VASH1, p < 0.001; CD34-defined MVD, p < 0.001; VEGF, p = 0.007). Among the 45 patients with paired primary and metastatic samples, metastatic lesions showed significantly lower VASH1 and VEGF expression and lower CD34-defined MVD than matched primary tumors, with median values decreasing from 6.0 to 4.0 for VASH1 (p = 0.002), from 4 to 3 for VEGF (p < 0.001), and from 32 to 27 for CD34-defined MVD (p < 0.001). In multivariate analysis, high VASH1 expression (hazard ratio [HR]: 2.05, 95% CI: 1.01–4.20, p = 0.048) and high CD34-defined MVD (HR: 2.12, 95% CI: 1.15–3.89, p = 0.015) remained independent predictors of poor OS. High VASH1 expression and high CD34-defined MVD were independent adverse prognostic factors for OS in CRC. Lower angiogenesis-related marker levels in metastatic lesions suggest heterogeneity in tumor angiogenesis. External validation is required before clinical application. Full article

Hypertension-induced vascular remodeling is a major contributor to cardiovascular morbidity and is characterized by endothelial dysfunction, vascular smooth muscle cell phenotypic switching, fibrosis, and inflammation. Sirtuin 3 (SIRT3), a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase, plays an important role in maintaining mitochondrial homeostasis, regulating redox balance, and modulating cellular energy metabolism. Emerging evidence suggests that SIRT3 deficiency accelerates hypertensive vascular remodeling through multiple mechanisms. In vascular smooth muscle cells (VSMCs), reduced SIRT3 activity enhances mitochondrial reactive oxygen species generation, promotes glycolytic reprogramming, and contributes to phenotypic switching and proliferation. In endothelial cells, SIRT3 mitigates oxidative stress (OS) by regulating the activity of superoxide dismutase 2, thereby preserving nitric oxide (NO) bioavailability and improving vascular function. SIRT3 also suppresses fibroblast-to-myofibroblast transformation by inhibiting the transforming growth factor-β/Smad3 pathway, thereby reducing vascular fibrosis. Furthermore, SIRT3 regulates macrophage metabolic reprogramming and autophagy, inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome activation, and attenuates vascular inflammation. In perivascular adipose tissue, SIRT3 deficiency exacerbates angiotensin II-induced fibrosis and cytokine secretion, thereby aggravating vascular dysfunction. Collectively, SIRT3 acts as a mitochondrial regulator against hypertension-induced oxidative and inflammatory injury. Targeting SIRT3-dependent pathways may represent a promising therapeutic approach to restore vascular homeostasis and prevent hypertensive vascular remodeling. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

Preeclampsia is a serious pregnancy complication characterised by maternal vascular dysfunction, placental dysfunction, and organ injury, with no effective treatment currently available. Kampo, a system of Japanese traditional medicine comprising standardised herbal formulations, could target pathophysiological pathways driving preeclampsia. We evaluated the effects of select Kampo formulations on markers of preeclampsia using primary human trophoblasts, placental explants, human umbilical vein endothelial cells (HUVECs), and uterine microvascular endothelial cells (UtMVECs). Twelve formulations were initially screened in HUVECs, and six formulations advanced for further study. TNFα was used to induce endothelial dysfunction, and angiogenic, antioxidant, inflammatory, and vascular dysfunction markers were assessed. Overall, Kampo formulations had minimal effect on sFlt-1 expression and only modest effects on sFlt-1 secretion by primary human trophoblast. In contrast, several formulations consistently increased placental growth factor (PlGF) expression and secretion, upregulated HMOX1 in trophoblasts, and enhanced PlGF secretion from placental explants. In endothelial cells, Kampo treatment partially reversed TNFα-induced dysfunction, demonstrated by reduced VCAM1 expression, and additional endothelial cell type-dependent effects on ET-1 and inflammatory pathways. These findings indicate that selected Kampo formulations modulate key pathways involved in the pathophysiology underpinning preeclampsia and warrant further investigation as potential therapeutic candidates. Full article

Vascularization remains a fundamental bottleneck in tissue engineering, as the absence of functional vascular networks limits oxygen and nutrient delivery, resulting in necrotic cores and poor host integration. While structural scaffold design and cell sourcing have advanced considerably, emerging evidence indicates that paracrine signaling, rather than direct cell contact or scaffold architecture alone, is the primary driver of angiogenesis and vasculogenesis within engineered constructs. Key cell types, including endothelial cells (ECs) and mesenchymal stem cells (MSCs), engage in bidirectional paracrine crosstalk through the secretion of vascular endothelial growth factor (VEGF), angiopoietins, hepatocyte growth factor, and platelet-derived growth factor, among other mediators. While researchers have long focused on improving scaffold structure and cell selection, growing evidence shows that the chemical messages cells send to one another play a far more important role in driving blood vessel formation than previously appreciated. This review explores how cells embedded within engineered scaffolds communicate through secreted signals to coordinate the growth of new blood vessels. Two cell types, MSCs and ECs, are central to this process: cells that line blood vessels and bone marrow-derived stem cells. These cells exchange a variety of chemical messages that instruct neighboring cells to multiply, move, and organize into vessel-like structures. Importantly, the material properties of the scaffold itself, including its stiffness, surface texture, and degradation over time, influence the signals cells produce and how those signals spread through the tissue. Strategies to amplify paracrine signaling include growth factor-loaded delivery systems, hypoxic and genetic preconditioning of MSCs, and perfusion bioreactor culture. In vitro and in vivo evidence consistently demonstrates that coculture systems leveraging paracrine interactions produce superior vascular outcomes compared to single-cell or acellular constructs. Despite this progress, challenges related to signaling complexity, reproducibility, and clinical translation persist. Integration of transcriptomic and proteomic profiling, computational modeling, and machine learning approaches offers a path toward rationally designed scaffolds that recapitulate the spatiotemporal dynamics of native vascular signaling and ultimately support functional tissue regeneration. Full article

Background: To investigate the structural changes and visual outcomes in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor (anti-VEGF) compared with fellow eyes over a long-term follow-up period. Methods: A retrospective paired-eye cohort study was conducted, and 51 patients (80.4% female, mean age 51.8 years) with an average follow-up duration of 32.8 months were enrolled. The study included patients with active, treatment-naïve mCNV in one eye and a fellow eye without mCNV. Final visual outcomes and macular retinoschisis (MRS) progression were compared between mCNV eyes treated with intravitreal anti-VEGF injections and fellow eyes. Baseline parameters potentially associated with MRS progression in mCNV eyes were analysed. Results: The final VA increased in mCNV eyes but remained worse than that in fellow eyes (logMAR 0.3 vs. 0.16, p = 0.037). The percentages of treated mCNV eyes and fellow eyes showing MRS progression were similar (18.6% vs. 16.3%, p = 0.782). When mCNV eyes with and without MRS progression were compared (n = 10 and 41, respectively), MRS at baseline was the only significant predictor of MRS progression (70% vs. 17.1%, p = 0.002). A greater percentage of eyes with MRS progression exhibited higher vitreomacular interface (VMI) grading at baseline, although the difference was not statistically significant (40% vs. 14.7%; p = 0.083). Conclusions: Anti-VEGF treatment in mCNV eyes did not increase the incidence of MRS compared with fellow eyes or aggravate MRS. However, the presence of MRS at baseline may increase the risk of MRS progression after treatment, and close monitoring of this subgroup is warranted. Full article

Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact of mechanical processing CELT (Cell-Enriched Lipotransfer) and CELT^PLUS and electrical stimulation on the regenerative secretome of human lipoaspirates. qPCR analysis revealed that CELT^PLUS processing, which incorporates mechanical intersyringe shifting, significantly doubled the gene expression of nerve growth factor (NGF) (p = 0.015), vascular endothelial growth factor (VEGF) (p = 0.02), and brain-derived neurotrophic factor (BDNF) (p = 0.04) compared to CELT-processed lipoaspirate. Protein analysis via ELISA confirmed a time-dependent secretion of NGF and VEGF over 96 h. Furthermore, 24 h electrical stimulation (2 V) significantly enhanced NGF protein release (p < 0.001). These findings demonstrate that standardized mechanical processing effectively enriches regenerative cell populations and amplifies their neurogenic and angiogenic potential. The additional modulation of growth factor secretion via electrical stimulation highlights the potential of processed adipose tissue as a functional, autologous transplant for enhanced nerve reconstruction. Full article

Headache is a frequent and clinically relevant symptom in patients undergoing cranial radiotherapy, most often reflecting treatment-induced structural and inflammatory changes such as cerebral edema or radiation-related brain injury. Differentiating secondary headache from primary disorders, particularly migraine, is essential for appropriate management. This review aims to examine the pathophysiological mechanisms underlying headache following cranial radiotherapy, evaluate current pharmacological and complementary treatment strategies and highlight key aspects of differential diagnosis with migraine. Unlike existing literature that focuses primarily on radiological findings of radiation injury, this review adopts a symptom-driven approach, reframing headache as a critical clinical gateway for the early detection of structural complications. A structured narrative review of the literature was conducted using PubMed/MEDLINE, Scopus and Google Scholar to identify studies published between 2020 and 2025, focusing on cerebral edema, radiation-related complications, therapeutic approaches and migraine. Relevant clinical trials, systematic reviews and guidelines were included. Cerebral edema consistently emerges as the main mechanism of acute and subacute post-radiotherapy headache, whereas late-onset symptoms are most often linked to radiation necrosis. Corticosteroids remain first-line therapy, while bevacizumab has demonstrated benefit in steroid-refractory cerebral edema and radiation necrosis through inhibition of vascular endothelial growth factor (VEGF), thereby reducing vascular permeability and attenuating peritumoral edema. Its use in the context of cranial radiotherapy requires careful consideration, as the safety of concomitant administration with radiation has not been formally established, and headache itself is among its recognized adverse effects. Evidence for complementary therapies, including Boswellia serrata and plant-based compounds, remains limited. Migraine constitutes a distinct neurovascular disorder requiring careful differentiation from secondary headache in oncological patients. The review emphasizes headache as a clinically relevant indicator of underlying structural complications rather than an isolated symptom. Post-radiotherapy headache should be interpreted as a manifestation of underlying structural pathology. Accurate etiological diagnosis and individualized management are essential. Further research is needed to refine treatment strategies and clarify the role of complementary therapies. Full article

Despite reducing hernia recurrence, synthetic meshes often trigger persistent foreign body responses (FBRs). Mesh-enriched therapies (METs), incorporating autologous cellular components (MSCs, PRP, SVF), can regeneratively reprogram the host-prosthetic interactome. Following PRISMA-ScR guidelines, this scoping review involved a systematic search of PubMed, Embase, and Scopus (2000–2025). We utilized the PCC (Population, Concept, Context) framework to map evidence across systemic inflammation, local FBR, and bio-augmentation strategies. A total of sixty-five studies were synthesized and categorized into three primary thematic pillars. Regarding the Systemic Response (n = 25), the data established a predictable “foreign body signature” characterized by prominent C-reactive protein (CRP) and interleukin-6 (IL-6) spikes within the first 48 h post-implantation. For the Local Foreign Body Reaction (FBR, n = 19), human explant data extending up to 180 months revealed a perpetual, immune-mediated state driven by matrix metalloproteinase-2 (MMP-2) matrix remodeling and the development of “bridging fibrosis.” Finally, concerning Mesh-Enriched Therapy (MET) Integration (n = 21), biological enrichment successfully shifted the M1/M2 macrophage ratio toward a pro-regenerative, CD163+/CD206+ phenotype. While MET consistently enhanced vascular endothelial growth factor (VEGF)-driven angiogenesis and optimized the Collagen I/III ratio, a notable 22.2% discrepancy rate across the literature underscores the critical need for precise transforming growth factor-beta 1 (TGF-β1) dosing and release kinetics to prevent hyper-fibrosis. MET shifts hernia repair from passive mechanical reinforcement to active “biocamouflage” and integration. By modulating the Th1/Th2 rheostat, enriched therapies mitigate chronic inflammation and long-term complications. Standardized clinical trials are essential to optimize the therapeutic window for hybrid integration. Full article

Cancer remains one of the most frightening global health challenges, contributing substantially to morbidity and mortality across diverse populations. In recent years, naturally derived compounds have attracted considerable attention due to their potential therapeutic efficacy and fewer adverse effects. Among these, the flavokawain subclass of chalcones, comprising Flavokawains A, B, and C, obtained from various plant sources, has emerged as a promising group of bioactive phytochemicals exhibiting a broad spectrum of pharmacological activities, with notable anticancer potential. This review critically compiles and evaluates the existing preclinical evidence regarding the anticancer mechanisms of flavokawains across various cancer models. It was found that these compounds have significant potential to inhibit cancer cell proliferation, induce apoptosis, disrupt cell-cycle progression, and modulate multiple molecular pathways implicated in tumorigenesis, including phosphoinositide 3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular-signal regulated kinase/c-Jun N-terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK) and so on. Importantly, flavokawains exert significant modulatory effects within the tumor microenvironment by suppressing angiogenesis through downregulation of vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1), attenuating epithelial-mesenchymal transition via restoration of E-cadherin and suppression of vimentin and Snail1, inhibiting matrix metalloproteinase (MMP)-mediated extracellular matrix remodeling, and disrupting cancer stem cell (CSC)-supportive niches. Preclinical toxicity profiles suggest a favorable safety margin, though further investigation is required to fully elucidate their therapeutic index. Due to their multifaceted mechanisms of action and selective cytotoxicity toward cancer cells, flavokawains are considered promising preclinical candidates for development as adjuncts or alternatives to conventional chemotherapeutic agents. Full article

Papillary thyroid cancer (PTC) exhibits Warburg-type metabolic reprogramming with enhanced glycolysis and dependence on glucose-driven pathways. This study evaluated the effects of antihyperglycemic interventions on cytokine secretion, angiogenic signaling, metabolic activity, and proliferation in thyroid-derived cell models. Two PTC cell lines (MDA-T32 and SCC147) and a normal thyroid line (Nthy-ori) were analyzed for intracellular and extracellular cytokines, secretion efficiency (index), relative metabolic index (RMI), and marker of proliferation (Ki-67) expression following exposure to vandetanib (VDT), sodium–glucose cotransporter 2 (SGLT2), or dipeptidyl peptidase (DPP) inhibitors. Baseline analysis revealed distinct cell line-specific profiles. Compared with Nthy-ori cells, MDA-T32 cells exhibited increased vascular endothelial growth factor (VEGF) concentrations in lysates and conditioned medium (p < 0.001, q < 0.001) with enhanced VEGF secretion efficiency (p = 0.002, q = 0.008), elevated intracellular fibroblast growth factor (FGF) (p < 0.001, q < 0.001) with reduced FGF secretion index (p = 0.004, q = 0.01), and lower interleukin 8 (IL-8) concentrations accompanied by increased IL-8 secretion efficiency (p = 0.006, q = 0.02). In contrast, SCC147 cells demonstrated reduced VEGF secretion (p < 0.001, q < 0.001), decreased intracellular IL-8 (p = 0.008, q = 0.02), reduced chemokines of the growth-regulated oncogene GROβ family (GROβ) secretion (p = 0.01, q = 0.04), increased IL-8 secretion efficiency (p = 0.01, q = 0.03), and decreased GROβ secretion efficiency (p = 0.008, q = 0.02). Nthy-ori cells displayed a balanced profile. Among the investigated interventions, VDT produced the most pronounced effects. In MDA-T32 cells, VDT significantly reduced VEGF levels (p < 0.001, q < 0.001) and increased IL-8 and GROβ concentrations in conditioned medium (q < 0.05), whereas no significant effects after FDR correction were observed in SCC147 or Nthy-ori cells. SGLT2 and DPP inhibitors produced only nominal effects (p < 0.05), which did not remain significant after correction for multiple testing. VDT reduced RMI by approximately 50% in MDA-T32 cells while Ki-67 expression increased, whereas SCC147 cells remained largely unchanged. In Nthy-ori cells, SGLT2 inhibition increased RMI and decreased Ki-67 expression. These findings demonstrate marked heterogeneity among PTC cell lines and suggest that alterations in metabolic activity were not consistently accompanied by proportional changes in proliferative status under the experimental conditions used. VDT predominantly affected angiogenic and inflammatory signaling in MDA-T32 cells, whereas SGLT2 and DPP inhibition exerted limited measurable effects at clinically achievable concentrations. Full article

Background/Objectives: Faricimab is a novel bispecific antibody simultaneously inhibiting vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2). Its efficacy in vitrectomized eyes with diabetic macular edema (DME), a setting with altered intravitreal pharmacokinetics, remains poorly characterized. We evaluated the 12-month outcomes of intravitreal faricimab (IVF) for DME in eyes vitrectomized for proliferative diabetic retinopathy (PDR). Methods: We retrospectively reviewed 12 consecutive eyes of 11 patients (mean age 59.4 ± 10.5 years) with DME after pars plana vitrectomy (PPV) for PDR who received IVF (6 mg/0.05 mL) between September 2022 and August 2024 with at least 12 months of follow-up. Best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were assessed at baseline (BL), 6 months (M6), and 12 months (M12). Results: Eight eyes were treatment-naïve and 4 had been switched from prior anti-VEGF therapy. Two eyes (16.7%) required a change in therapy: one for intraocular inflammation and one for inadequate anatomical response. In the 10 eyes that continued IVF, the mean number of injections was 4.1 ± 1.9. CRT decreased significantly from 489.5 ± 95.9 µm at BL to 328.5 ± 74.7 µm at M6 (p = 0.0065) and 307.0 ± 64.3 µm at M12 (p = 0.0023; repeated-measures ANOVA with Dunnett’s post hoc test). Mean BCVA improved from 0.33 ± 0.26 to 0.23 ± 0.21 logMAR at M12 (p = 0.0894). Conclusions: In this small retrospective study of vitrectomized eyes with DME after PPV for PDR, IVF was associated with significant anatomical improvement, while visual acuity remained stable over 12 months, with a relatively low injection burden. Faricimab may be a useful therapeutic option in this challenging population, although larger prospective studies are warranted to confirm these findings. Full article

Although estrogen has been identified to play crucial roles in the development of melasma, the exact mechanism of estrogen’s effect on pigmentation is incompletely elucidated. Recent studies have highlighted the pivotal role of immune cells in melasma. Interestingly, infiltrated macrophages are significantly enhanced in melasma lesions. Estrogen could facilitate M2 polarization. However, whether estrogen could stimulate melanogenesis via skewing M2 phenotype remains unknown. This study attempted to determine the significance and molecular mechanism of estrogen-induced M2 phenotype in melasma. We found that M2 infiltration was significantly increased in melasma lesions compared with perilesional skin. Arginase 1 was identified as the hub gene, and its expression was positively correlated with that of microphthalmia-associated transcription factor and tyrosinase-related protein 1 in melasma through transcriptome analysis. Moreover, β-estradiol (E2) was confirmed to promote M2 skewing while inhibiting M1 polarization via activating STAT6 signaling. Importantly, E2-induced M2 polarization robustly increased melanogenesis by increasing tyrosinase activity and expression of microphthalmia-associated transcription factor and tyrosinase in melanocytes, which were profoundly inhibited by VEGF knockdown or antagonism both in vitro and in ex vivo skin. Furthermore, VEGF was revealed to enhance melanogenesis through activating p38 MAPK and ERK1/2 signaling pathways in melanocytes. Additionally, dermal VEGF was significantly increased, and most of it colocalized with M2 macrophages in melasma lesions. Crucially, E2 administration potently reversed ovariectomy-decreased M2 skewing and subsequently promoted dermal VEGF expression and epidermal melanogenesis in the mouse tail skin, which were significantly suppressed by macrophage depletion. These findings suggest that estrogen may stimulate melanogenesis in melasma through increasing M2 skewing and VEGF expression and secretion in macrophages. Full article