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BACKGROUND: Rosacea, a chronic inflammatory skin condition, is marked by enduring redness, visible blood vessels, and inflammatory eruptions in facial areas. Managing rosacea remains a persistent challenge for dermatologists, especially in cases unresponsive to conventional treatments. Injectable poly-d,l-lactic acid (PDLLA) has shown promise in treating erythema and telangiectasia associated with rosacea in addition to age-related concerns. Employing Mirajet, a laser-induced microjet system, for administering PDLLA is a novel and promising treatment for rosacea. AIMS: We aimed to evaluate the efficacy and safety of injectable PDLLA delivered via a needle-free microjet system for managing rosacea. METHODS: Four Korean women with persistent and refractory rosacea received five monthly sessions of PDLLA needle-free injections. Clinical assessments were conducted using the Clinician's Erythema Assessment and Patient's Self-Assessment (PSA) at baseline, 4 weeks post-treatment, and 22 weeks post-final treatment. Adverse events were monitored throughout the study period. RESULTS: At 4 weeks post-treatment, both Clinician's Erythema Assessment and PSA scores indicated significant improvements in erythema that were sustained up to the 22-week follow-up. Patients reported high satisfaction with resolution of redness and improved skin texture. Mild swelling, redness, and petechiae were observed post-treatment but resolved spontaneously. No product-related adverse events were noted during the study period. CONCLUSION: Injectable PDLLA delivered via laser-induced microjet injection demonstrated promising efficacy in improving rosacea symptoms and skin quality for up to 22 weeks without significant adverse effects. Larger randomized controlled trials are needed to confirm these findings and evaluate long-term safety and sustainability of outcomes.
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The formation of polylactide stereocomplex (sc-PLA), involving the blending of poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), enhances PLA materials by making them stronger and more heat-resistant. This study investigated the competitive crystallization behavior of homocrystals (HCs) and stereocomplex crystals (SCs) in a 50/50 PLLA/PDLA blend with added polyethylene glycol (PEG). PEG, with molecular weights of 400 g/mol and 35,000 g/mol, was incorporated at concentrations ranging from 5% to 20% by weight. Differential scanning calorimetry (DSC) analysis revealed that PEG increased the crystallization temperature, promoted SC formation, and inhibited HC formation. PEG also acted as a plasticizer, lowering both melting and crystallization temperatures. The second heating DSC curve showed that the pure PLLA/PDLA blend had a 57.1% fraction of SC while adding 5% PEG with a molecular weight of 400 g/mol resulted in complete SC formation. In contrast, PEG with a molecular weight of 35,000 g/mol was less effective, allowing some HC formation. Additionally, PEG consistently promoted SC formation across various cooling rates (2, 5, 10, or 20 °C/min), demonstrating a robust influence under different conditions.
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AestheFill is a biostimulator based on poly-D,L-lactic acid. It is supplied as lyophilized powders and is referred to as a versatile biostimulator. According to the amount of water added, the suspensions can be vary in thickness which can be divided into four groups for different indications: the thickest suspension (D1.5-3) for nose or chin augmentation, thick suspension (D3-6) for deep wrinkle correction, thin suspension (D6-12) for shallow wrinkle correction, and super-thin suspension (D12-24) for skin rejuvenation. However, practitioners may be confused about which filler thickness, injection layer, method, and amount should be chosen for their patients. Biostimulators tend to form non-inflammatory nodules if technical mishaps occur during injection. Based on 10 years of AestheFill injection experience, the authors proposed the AestheCode system for the safe and effective injection of AestheFill.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Implants made from titanium are used as prostheses because of their biocompatibility and their mechanical properties close to those of human bone. However, the risk of bacterial infection is always a major concern during surgery, and the development of biofilm can make these infections difficult to treat. A promising strategy to mitigate against bacterial infections is the use of antifouling and antimicrobial coatings, where bioresorbable polymers can play an important role due to their controlled degradability and sustained drug release, as well as excellent biocompatibility. In the present study, poly(d,l-lactide) (PDLLA) and poly[d,l-lactide-co-methyl ether poly(ethylene glycol)] (PDLLA-PEG) were studied, varying the PEG content (20-40% w/w) to analyze the effectiveness of PEG as an antifouling molecule. In addition, silver sulfadiazine (AgSD) was used as an additional antimicrobial agent with a concentration ≤5% w/w and incorporated into the PEGylated polymers to create a polymer with both antifouling and antimicrobial properties. Polymers synthesized were applied using spin coating to obtain homogeneous coatings to protect samples made from titanium/aluminum/vanadium (Ti6Al4V). The polymer coatings had a smoothing effect in comparison to that of the uncoated material, decreasing the contact area available for bacterial colonization. It was also noted that PEG addition into the polymeric chain developed amphiphilic materials with a decrease in contact angle from the most hydrophobic (Ti6Al4V) to the most hydrophilic PDLLA-PEG (60/40), highlighting the increase in water uptake contributing to the hydration layer formation, which confers the antifouling effect on the coating. This study demonstrated that the addition of PEG above 20% w/w and AgSD above 1% w/v into the formulation was able to decrease bacterial adherence against clinically relevant biofilm former strains Staphylococcus aureus and Pseudomonas aeruginosa.
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Aleaciones , Antibacterianos , Biopelículas , Materiales Biocompatibles Revestidos , Ensayo de Materiales , Poliésteres , Staphylococcus aureus , Titanio , Biopelículas/efectos de los fármacos , Titanio/química , Titanio/farmacología , Aleaciones/química , Aleaciones/farmacología , Poliésteres/química , Poliésteres/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Humanos , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/farmacología , Propiedades de Superficie , Prótesis e ImplantesRESUMEN
Aim: This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Materials & methods: Synthesized nanoparticles were subjected to in vitro characterization, ex vivo permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. Results & conclusion: The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.
[Box: see text].
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Administración Cutánea , Nanopartículas , Piroxicam , Polietilenglicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Piroxicam/análogos & derivados , Piroxicam/administración & dosificación , Piroxicam/química , Polietilenglicoles/química , Animales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Tamaño de la Partícula , Inflamación/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Ratones , Ácido Láctico/química , Masculino , Ratas , Ácido Poliglicólico/química , Piel/metabolismo , Piel/efectos de los fármacosRESUMEN
BACKGROUND: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods. OBJECTIVE: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars. METHODS: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. RESULTS: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period. CONCLUSION: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.
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Cicatriz , Satisfacción del Paciente , Poliésteres , Humanos , Cicatriz/patología , Poliésteres/administración & dosificación , Femenino , Adulto , Masculino , Pueblo Asiatico , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Administración Cutánea , Resultado del Tratamiento , Atrofia/patología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Adulto JovenRESUMEN
To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p.
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Anticuerpos Antibacterianos , Vacunas Bacterianas , Infecciones por Chlamydia , Chlamydia muridarum , Citocinas , Ratones Endogámicos BALB C , Animales , Femenino , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Chlamydia muridarum/inmunología , Citocinas/metabolismo , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/inmunología , Ratones , Anticuerpos Antibacterianos/sangre , Inyecciones Intramusculares , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Inmunización Secundaria , Modelos Animales de Enfermedad , Inmunogenicidad Vacunal , Inyecciones Subcutáneas , Nanopartículas/administración & dosificación , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/administración & dosificación , Eficacia de las Vacunas , Células TH1/inmunología , NanovacunasRESUMEN
Biodegradable (BP) poly(D,L-lactic acid) (PDLLA) membranes are widely used in tissue engineering. Here, we investigate the effects of varying concentrations of PDLLA/gelatin membranes electrospun in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP; C3H2F6O) solvent on their mechanical and physical properties as well as their biocompatibility. Regardless of the environmental conditions, increasing the gelatin content resulted in elevated stress and reduced strain at membrane failure. There was a remarkable difference in strain-to-failure between dry and wet PDLLA/gelatin membranes, with wet strains consistently higher than those of the dry membranes because of the hydrophilic nature of gelatin. A similar wet strain (εw = 2.7-3.0) was observed in PDLLA/gelatin membranes with a gelatin content between 10 and 40%. Both dry and wet stresses increased with increasing gelatin content. The dry stress on PDLLA/gelatin membranes (σd = 6.7-9.7 MPa) consistently exceeded the wet stress (σw = 4.5-8.6 MPa). The water uptake capacity (WUC) improved, increasing from 57% to 624% with the addition of 40% gelatin to PDLLA. PDLLA/gelatin hybrid membranes containing 10 to 20 wt% gelatin exhibited favorable wet mechanical properties (σw = 5.4-6.3 MPa; εw = 2.9-3.0); WUC (337-571%), degradability (11.4-20.2%), and excellent biocompatibility.
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Gelatina , Membranas Artificiales , Poliésteres , Materiales Biocompatibles/química , Gelatina/química , Ensayo de Materiales , Poliésteres/química , Estrés Mecánico , Ingeniería de Tejidos/métodos , Agua/químicaRESUMEN
In recent years, there has been a notable surge of interest in hybrid materials within the biomedical field, particularly for applications in bone repair and regeneration. Ceramic-polymeric hybrid scaffolds have shown promising outcomes. This study aimed to synthesize bioactive glass (BG-58S) for integration into a bioresorbable polymeric matrix based on PDLLA, aiming to create a bioactive scaffold featuring stable pH levels. The synthesis involved a thermally induced phase separation process followed by lyophilization to ensure an appropriate porous structure. BG-58S characterization revealed vitreous, bioactive, and mesoporous structural properties. The scaffolds were analyzed for morphology, interconnectivity, chemical groups, porosity and pore size distribution, zeta potential, pH, in vitro degradation, as well as cell viability tests, total protein content and mineralization nodule production. The PDLLA scaffold displayed a homogeneous morphology with interconnected macropores, while the hybrid scaffold exhibited a heterogeneous morphology with smaller diameter pores due to BG-58S filling. The hybrid scaffold also demonstrated a pH buffering effect on the polymer surface. In addition to structural characteristics, degradation tests indicated that by incorporating BG-58S modified the acidic degradation of the polymer, allowing for increased total protein production and the formation of mineralization nodules, indicating a positive influence on cell culture.
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Regeneración Ósea , Cerámica , Vidrio , Poliésteres , Andamios del Tejido , Cerámica/química , Andamios del Tejido/química , Regeneración Ósea/efectos de los fármacos , Vidrio/química , Porosidad , Poliésteres/química , Materiales Biocompatibles/química , Concentración de Iones de Hidrógeno , Humanos , Supervivencia Celular/efectos de los fármacos , Ensayo de MaterialesRESUMEN
Background/purpose: Peripheral neural regeneration is an interesting and challenging field. The aim of this study was to investigate the interactions of neural-like PC12 cells and Poly-D-Lysine (PDL)-coated 3D-printed polycaprolactone (PCL) scaffolds with different inner diameters of half tubular array (HTA) (0, 200, 300, and 400 µm), respectively. Materials and methods: This study used the fused deposition modeling (FDM) technique with 3D-printing to fabricate the thermoplastic polymer. Scaffold properties were measured by mechanical testing, and coating quality was observed under a scanning electron microscope (SEM). PC12 cell biocompatibility was examined by an MTT assay. Cell differentiation was evaluated by immunofluorescence staining. Results: The cell viability of PC12 cells on PDL-coated PCL scaffolds with a 200-µm inner diameter of HTA was shown with significant differences (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001) than other PCL groups at all experimental dates. The SEM observation showed that PDL-coated PCL scaffolds with 200-µm inner diameters of HTA promoted cell adhesion. An immunofluorescence staining of PC12 cells on the PDL-coated PCL scaffold with a 200-µm inner diameter of the HTA group showed that it stimulated PC12 cells for neurite formation much better than the other groups.A PDL-coated PCL scaffold with a 200-µm inner diameter of HTA can promote the growth and differentiation of PC12 cells better than other groups. It indicated that PDL-coated PCL scaffolds with a 200-µm inner diameter HTA can be used for further neural regeneration application.
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d-Amino acids are signals for biofilm disassembly. However, unexpected metabolic pathways severely attenuate the utilization of d-amino acids in biofilm disassembly, resulting in unsatisfactory efficiency. Herein, three-dimensional poly(d-amino acid) nanoparticles (NPs), which possess the ability to block intracellular metabolism, are constructed with the aim of disassembling the biofilms. The obtained poly(α-N-acryloyl-d-phenylalanine)-block-poly(ß-N-acryloyl-d-aminoalanine NPs (denoted as FA NPs) present α-amino groups and α-carboxyl groups of d-aminoalanine on their surface, which guarantees that FA NPs can effectively insert into bacterial peptidoglycan (PG) via the mediation of PG binding protein 4 (PBP4). Subsequently, the FA NPs trigger the detachment of amyloid-like fibers that connect to the PG and reduce the number of polysaccharides and proteins in extracellular polymeric substances (EPS). Finally, FA NPs damage the structural stability of EPS and lead to the disassembly of the biofilm. Based on this feature, FA NPs significantly enhance the killing efficacy of encapsulated sitafloxacin sesquihydrate (Sita) by facilitating the penetration of Sita within the biofilm, achieving complete elimination of Staphylococcal biofilm in mice. Therefore, this study strongly demonstrates that FA NPs can effectively improve biofilm disassembly efficacy and provide great potential for bacterial biofilm infection treatment.
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Aminoácidos , Nanopartículas , Animales , Ratones , Aminoácidos/química , Peptidoglicano , Biopelículas , Polisacáridos , Nanopartículas/químicaRESUMEN
Polymeric nanoparticles (PNPs) are frequently researched and used in drug delivery. The degradation of PNPs is highly dependent on various properties, such as polymer chemical structure, size, crystallinity, and melting temperature. Hence, a precise understanding of PNP degradation behavior is essential for optimizing the system. This study focused on enzymatic hydrolysis as a degradation mechanism by investigation of the degradation of PNP with various crystallinities. The aliphatic polyester polylactide ([C3H4O2]n, PLA) was used as two chiral forms, poly l-lactide (PlLA) and poly d-lactide (PdLA), and formed a unique crystalline stereocomplex (SC). PNPs were prepared via a nanoprecipitation method. In order to further control the crystallinity and melting temperatures of the SC, the polymer poly(3-ethylglycolide) [C6H8O4]n (PEtGly) was synthesized. Our investigation shows that the PNP degradation can be controlled by various chemical structures, crystallinity and stereocomplexation. The influence of proteinase K on PNP degradation was also discussed in this research. AFM did not reveal any changes within the first 24 h but indicated accelerated degradation after 7 days when higher EtGly content was present, implying that lower crystallinity renders the particles more susceptible to hydrolysis. QCM-D exhibited reduced enzyme adsorption and a slower degradation rate in SC-PNPs with lower EtGly contents and higher crystallinities. A more in-depth analysis of the degradation process unveiled that QCM-D detected rapid degradation from the outset, whereas AFM exhibited delayed changes of degradation. The knowledge gained in this work is useful for the design and creation of advanced PNPs with enhanced structures and properties.
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BACKGROUND: The concept of "skin boosters" has evolved, marking a shift from traditional uses of hyaluronic acid (HA) fillers primarily for augmenting skin volume to a more diverse application aimed at improving dermal conditions. Restylane Vital and other HA fillers have been repurposed to combat skin aging and wrinkles by delivering HA directly to the dermis. OBJECTIVES: This review aims to define the term "skin booster" and to discuss the various components that constitute skin boosters. It seeks to provide a comprehensive overview of the different ingredients used in skin boosters, their roles, and their impact on enhancing dermal conditions. METHODS: A comprehensive review was conducted, focusing on representative skin booster ingredients. The approach involved analyzing the different elements used in skin boosters and their specific roles in enhancing dermal improvement. RESULTS: The findings indicate that skin boosters, encompassing a range of ingredients, are effective in improving the condition of the skin's dermis. The review identifies key ingredients in skin boosters and their specific benefits, including hydration, elasticity improvement, and wrinkle reduction. CONCLUSIONS: Skin boosters represent a significant development in dermatological treatments, offering diverse benefits beyond traditional HA fillers. This review provides valuable insights into the constituents of skin boosters and their effectiveness, aiding readers in making informed decisions about these treatments. The potential of skin boosters in dermatological practice is considerable, warranting further research and application.
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Técnicas Cosméticas , Rellenos Dérmicos , Envejecimiento de la Piel , Humanos , Piel , Rejuvenecimiento , Ácido HialurónicoRESUMEN
OBJECTIVES: Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. METHODS: In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. RESULTS: The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. CONCLUSIONS: PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.
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Ácido Poliglicólico , Radio (Anatomía) , Animales , Conejos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Ácido Láctico , Microtomografía por Rayos X , Durapatita , Impresión Tridimensional , Andamios del TejidoRESUMEN
Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale.
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Artificial intelligence (AI) is a revolutionary technology that is finding wide application across numerous sectors. Large language models (LLMs) are an emerging subset technology of AI and have been developed to communicate using human languages. At their core, LLMs are trained with vast amounts of information extracted from the internet, including text and images. Their ability to create human-like, expert text in almost any subject means they are increasingly being used as an aid to presentation, particularly in scientific writing. However, we wondered whether LLMs could go further, generating original scientific research and preparing the results for publication. We taskedGPT-4, an LLM, to write an original pharmaceutics manuscript, on a topic that is itself novel. It was able to conceive a research hypothesis, define an experimental protocol, produce photo-realistic images of 3D printed tablets, generate believable analytical data from a range of instruments and write a convincing publication-ready manuscript with evidence of critical interpretation. The model achieved all this is less than 1 h. Moreover, the generated data were multi-modal in nature, including thermal analyses, vibrational spectroscopy and dissolution testing, demonstrating multi-disciplinary expertise in the LLM. One area in which the model failed, however, was in referencing to the literature. Since the generated experimental results appeared believable though, we suggest that LLMs could certainly play a role in scientific research but with human input, interpretation and data validation. We discuss the potential benefits and current bottlenecks for realising this ambition here.
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Inteligencia Artificial , Biofarmacia , Humanos , VibraciónRESUMEN
BACKGROUND: Skin aging is characterized by wrinkles, rough skin texture, pigmentation, facial erythema, and telangiectasia through structural and functional changes in the epidermis and dermis. Recently, injectable poly(D, L-lactic acid), a biodegradable polymer, has been used widely for skin rejuvenation. AIMS: This study aims to assess the efficacy and safety of injectable dermal poly D, L-lactic acid) for skin rejuvenation. PATIENTS/METHODS: A total of 16 patients who desired skin rejuvenation were included. All participants received two or three procedure sessions with a 4 weeks interval between sessions. Clinical and three-dimensional images at baseline, before each procedural session, and follow-up visits were obtained. Therapeutic effects were assessed by evaluating signs of aging skin and overall improvement by dermatologists and patients. Histologic examinations with special stains were performed on the posterior auricular areas of consenting patients at baseline and follow-up visits after injecting poly D L-lactic acid into the postauricular area as in the face. RESULTS: Overall, statistically significant differences were observed in all signs of aging skin, such as fine wrinkles, skin texture, irregular pigmentation, telangiectasia, and facial erythema before and after treatments. Half (50%) of patients responded that there was more than 50% overall improvement. There were no severe adverse events. Histologic examination demonstrated increases in collagen and elastic fibers in the dermis. CONCLUSIONS: Results of this preliminary study suggest that injectable dermal poly D, L-lactic acid can significantly affect skin rejuvenation without causing any serious adverse events.
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Técnicas Cosméticas , Envejecimiento de la Piel , Telangiectasia , Humanos , Ácido Hialurónico/efectos adversos , Rejuvenecimiento , Técnicas Cosméticas/efectos adversos , Eritema/etiología , Telangiectasia/tratamiento farmacológico , Ácido Láctico/efectos adversos , Resultado del Tratamiento , Satisfacción del PacienteRESUMEN
Cardiovascular tissue engineering is providing many solutions to cardiovascular diseases. The complex disease demands necessitating tissue-engineered constructs with enhanced functionality. In this study, we are presenting the production of a dexamethasone (DEX)-loaded electrospun tubular polymeric poly(l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA) construct which contains iPSC-CMs (induced pluripotent stem cell cardiomyocytes), HUVSMCs (human umbilical vein smooth muscle cells), and HUVECs (human umbilical vein endothelial cells) embedded in fibrin gel. The electrospun tube diameter was calculated, as well as the DEX release for 50 days for 2 different DEX concentrations. Furthermore, we investigated the influence of the polymer composition and concentration on the function of the fibrin gels by imaging and quantification of CD31, alpha-smooth muscle actin (αSMA), collagen I (col I), sarcomeric alpha actinin (SAA), and Connexin 43 (Cx43). We evaluated the cytotoxicity and cell proliferation of HUVECs and HUVSMCs cultivated in PLA and PLGA polymeric sheets. The immunohistochemistry results showed efficient iPSC-CM marker expression, while the HUVEC toxicity was higher than the respective HUVSMC value. In total, our study emphasizes the combination of fibrin gel and electrospinning in a functionalized construct, which includes three cell types and provides useful insights of the DEX release and cytotoxicity in a tissue engineering perspective.
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In this study, D-mannose was used to synthesize poly-D-mannose using a one-pot method. The molecular weight, degree of branching, monosaccharide composition, total sugar content, and infrared spectrum were determined. In addition, we evaluated the safety and bioactivity of poly-D-mannose including anti-pathogen biofilm, antioxidant, and anti-inflammatory activity. The results showed that poly-D-mannose was a mixture of four components with different molecular weights. The molecular weight of the first three components was larger than 410,000 Da, and that of the fourth was 3884 Da. The branching degree of poly-D-mannose was 0.53. The total sugar content was 97.70%, and the monosaccharide was composed only of mannose. The infrared spectra showed that poly-D-mannose possessed characteristic groups of polysaccharides. Poly-D-mannose showed no cytotoxicity or hemolytic activity at the concentration range from 0.125 mg/mL to 8 mg/mL. In addition, poly-D-mannose had the best inhibition effect on Salmonella typhimurium at the concentration of 2 mg/mL (68.0% ± 3.9%). The inhibition effect on Escherichia coli O157:H7 was not obvious, and the biofilm was reduced by 37.6% ± 2.9% at 2 mg/mL. For Staphylococcus aureus and Bacillus cereus, poly-D-mannose had no effect on biofilms at low concentration; however, 2 mg/mL of poly-D-mannose showed inhibition rates of 33.7% ± 6.4% and 47.5% ± 4%, respectively. Poly-D-mannose showed different scavenging ability on free radicals. It showed the best scavenging effect on DPPH, with the highest scavenging rate of 74.0% ± 2.8%, followed by hydroxyl radicals, with the scavenging rate of 36.5% ± 1.6%; the scavenging rates of superoxide anion radicals and ABTS radicals were the lowest, at only 10.1% ± 2.1% and 16.3% ± 0.9%, respectively. In lipopolysaccharide (LPS)-stimulated macrophages, poly-D-mannose decreased the secretion of nitric oxide (NO) and reactive oxygen species (ROS), and down-regulated the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Therefore, it can be concluded that poly-D-mannose prepared in this research is safe and has certain biological activity. Meanwhile, it provides a new idea for the development of novel prebiotics for food and feed industries or active ingredients used for pharmaceutical production in the future.
RESUMEN
Obesity is a global health problem caused by genetic, environmental, and psychological factors and is associated with various health disorders. As such, there is a growing focus on the prevention of obesity and related diseases. The gut microbiota plays a crucial role in these diseases and has become a therapeutic target. Prebiotics, such as poly-d-3-hydroxybutyric acid (PHB), have gained attention for their potential to alter the gut microbiota, promote beneficial bacterial growth, and alleviate obesity. In this study, we examined the prebiotic effects of PHB in obese mice. We found that, in C57BL/6N mice, PHB reduced blood lipid levels. Analysis of the intestinal microflora also revealed an increase in short-chain fatty acid-producing bacteria. When PHB was administered to obese mice, subcutaneous fat and dyslipidemia were reduced, and the number of beneficial bacteria in the intestinal microflora increased. Furthermore, fatty degradation and oxidative stress were suppressed in the liver. PHB regulates gut bacterial changes related to obesity and effectively inhibits dyslipidemia, suggesting that it could be a prebiotic agent for curing various obesity-related diseases. In summary, PHB increases the beneficial gut microbiota, leading to an alleviation of obesity-associated dyslipidemia.