Puerarin is a naturally occurring isoflavone with reported anticancer activity, yet its topical translation is constrained by limited stability and suboptimal dermal delivery. A Puerarin-loaded proniosomal gel was developed as a potential dermal delivery platform, and we performed an initial assessment of its antimelanoma activity and safety. The gel was produced by coacervation–phase separation using Span 60, Tween 80, phosphatidylcholine, and cholesterol. Physicochemical characterization included pH, entrapment efficiency, rheology, FTIR, DSC, and vesicle properties (DLS, PDI, ζ-potential). In silico geometry optimization and docking were carried out for melanoma-associated targets (MITF and DNMT3B). Biological effects were investigated in vitro on A375 melanoma cells using MTT, morphological analysis, and nuclear/mitochondrial staining, while irritation potential was evaluated in ovo by HET-CAM. The optimized formulation exhibited a skin-compatible pH and an entrapment efficiency of 62 ± 0.26%. DLS indicated a multimodal population, with a major number-weighted vesicle population in the 100–200 nm range, and a ζ-potential of −34.9 ± 0.14 mV. FTIR and DSC supported component incorporation without evidence of chemical incompatibility. The gel showed non-Newtonian, pseudoplastic, thixotropic flow, which is advantageous for topical use. Docking predicted meaningful affinities of Puerarin toward MITF and DNMT3B. The formulation reduced A375 viability in a dose-dependent manner (to 44.66% at 200 µg/mL) and, at higher concentrations, produced nuclear condensation and disruption of the mitochondrial network. HET-CAM classified the gel as non-irritant. The Puerarin-loaded proniosomal gel represents a promising topical platform with preliminary in vitro antimelanoma cytotoxic potential, warranting additional studies to validate skin delivery, efficacy, and safety.
Geranium robertianum L. is used in traditional medicine to treat different systemic disorders and holds great therapeutic potential but remains understudied. To this aim, an ethanolic extract obtained from the aerial parts of G. robertianum L. (GR) was investigated in terms of phytochemical composition and biological activity. GR extract exhibited high levels of phenolic compounds and flavonoids. The antioxidant activity was determined by means of three different colorimetric assays (DPPH, ABTS, and FRAP), and the results obtained indicate that the ABTS assay showed the highest antioxidant capacity. Metal analysis was also performed. Fe was found to be the most abundant element in the analyzed extract, with a concentration of 363.65 ± 4.18 μg/g, followed by Zn, Mn, Ni, and Cr. Four potentially hazardous heavy metals, As, Co, Pb, and Cd, were found to be under the detection limit. The GR extract exhibited moderate antibacterial activity against both Gram-positive and Gram-negative bacteria, with inhibition zones generally comparable to those of levofloxacin. However, the extract was significantly less effective against the P. aeruginosa strain. On A253 human salivary gland carcinoma cells, GR extract elicited a dose-dependent antiproliferative effect, produced morphological changes, and increased ROS and both caspase-3/7 and caspase-9 levels.
Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of glucose-lowering drugs with beneficial pleiotropic effects that have been widely investigated in the past decade in several experimental models and patients in the absence of diabetes. There are two types of transporters: the SGLT1 isoform that is distributed across a broad range of tissues, including the cardiovascular system, and the SGLT2 isoform, which is mostly expressed in renal proximal tubular cells. It is known that inflammation and oxidative stress are key contributors to vascular damage and the progression of atherosclerosis. SGLT inhibitors have demonstrated multiple benefits that contribute to improved vascular health, including alleviation of endothelial function, anti-inflammatory and antioxidative effects, and mitigation of arterial stiffness, all contributing to blood pressure decrease. An increasing body of research has tackled the molecular and cellular mechanisms of their chronic and, more recently, acute cardiovascular beneficial effects. This narrative review specifically delves into the direct vasculoprotective effects of SGLT2 and dual SGLT1/2 inhibitors, summarizing their off-target mechanisms described in various experimental settings (animal models, animal and human cell lines/samples).
Background/Objectives: Post-COVID follow-up may provide an opportunity to reassess persistent and modifiable cardiometabolic risk. We characterized six-month cardiometabolic and vascular trajectories after COVID-19 hospitalization and explored associations with routinely documented dietary counseling and omega-3 recommendations. Methods: This single-center retrospective longitudinal cohort included 238 adults hospitalized with COVID-19 between March 2020 and December 2024. Patients were classified according to recorded post-discharge management as usual care (n = 64), dietary management (n = 60), omega-3 supplementation (n = 59), or combined management (n = 55). Outcomes were assessed at the index visit and at visits labeled approximately three and six months later. Longitudinal changes were estimated using generalized estimating equations; six-month associations were evaluated using baseline-adjusted ANCOVA with robust standard errors and Benjamini-Hochberg correction. Results: Mean age was 54.0 ± 10.6 years, 54.6% were women, 82.4% had hypertension, 40.8% had diabetes, and mean body mass index was 33.8 ± 4.6 kg/m2. At six months, endpoint-specific data were available for 182 participants for blood pressure, total cholesterol, triglycerides, and HDL-C; 180 for waist circumference; 179 for SCORE; 177 for LDL-C and bilateral carotid IMT analyses; 173 for HOMA-IR; and 164 for IL-6. Across the cohort, systolic and diastolic blood pressure decreased by 7.91 and 4.75 mmHg; several lipid, anthropometric, and insulin-resistance markers also improved. No omnibus group-by-time interaction was significant. After false-discovery-rate correction, only higher six-month HDL-C in the dietary and combined-management groups versus usual care remained statistically significant; all other between-group findings were nonsignificant after correction. Conclusions: Several cardiometabolic risk markers improved during follow-up, but no recorded management category showed consistent trajectory-level superiority. Because intervention content and adherence, time-updated medication use, acute COVID-19 severity, and lifestyle changes were not captured, the comparative findings are exploratory and noncausal. The isolated HDL-C associations should not be interpreted as evidence of cardiovascular benefit. No cardiac biomarkers, echocardiographic measures, incident heart failure, or cardiovascular events were assessed.
Objective:Orbital wall fractures require precise reconstruction to restore orbital volume and visual function, and bio-inert titanium implants benefit substantially from osteoconductive surface modifications. This study evaluated the biocompatibility and osteogenic potential of hydroxyapatite-collagen (HAP-COL) composites used in titanium implants intended for orbital fracture repair, comparing a sprayed HAP coating with a robocasting-deposited, 3D-printed HAP-COL layer. Methods:HAp-COL hybrid powder (HAp:COL mass ratio 4:1) was prepared by hydrothermal synthesis at 100 °C and 104 Pa, followed by spray drying, and characterized by FAAS, ICP-OES, FT-IR, XRD, and SEM-EDS. Two implant configurations were tested: Sample 1 (titanium with sprayed HAp) and Sample 2 (titanium with three robocasting-deposited 3D-printed HAP-COL layers). Cytotoxicity was assessed on a normal human osteoblast cell line (NHOst, Lonza CC-2538) in accordance with ISO 10993-12, using sample extracts at stock concentration and binary dilutions (1/2, 1/4, 1/8) and quantified by MTT assay at 24 and 48 hours. Results:Both samples showed dose- and time-dependent viability profiles within the acceptable limits of ISO 10993-5. Sample 1 viability ranged from 70.62% (stock) to 89.72% (1/8) at 24 h, and from 77.28% to 93.63% at 48 h. Sample 2 consistently outperformed Sample 1, with values from 80.61% to 91.28% at 24 h and from 83.35% to 96.47% at 48 h. Discussion:Both HAP-COL application techniques proved highly biocompatible and compliant with ISO 10993-5 non-cytotoxic safety limits. However, the 3D-printed robocast layer (Sample 2) consistently outperformed the sprayed coating, exhibiting superior osteoblast viability and proliferation. This demonstrates that a layered, biomimetic robocast architecture optimizes cell survival and successfully mitigates the bio-inert properties of standard titanium. Conclusions:The 3D-printed HAP-COL coating produced by robocasting exhibited superior biocompatibility and osteoconductive behavior compared with the sprayed alternative, supporting sustained osteoblast proliferation. HAP-COL robocast layers on titanium represent promising candidates for personalized orbital wall reconstruction, although in vivo validation remains necessary.
