Disruptions in the skin restoration process can impair wound healing and lead to severe clinical complications, particularly in environments prone to microbial colonization and biofilm formation. Modern wound dressings are, therefore, designed not only to restore tissue integrity but also to actively modulate the wound microenvironment and mitigate infections caused by multidrug-resistant microorganisms. In this context, polymeric matrices play a fundamental role by providing structural support, moisture regulation, and controlled delivery capabilities that guide cellular responses and tissue regeneration. Recent advances have focused on integrating naturally derived bioactive agents, such as stem cell-derived components, vitamins, growth factors, and phytochemicals, into polymer-based systems to enhance their therapeutic performance due to their effectiveness depending strongly on the protective and regulatory functions of the polymeric carrier. Polymeric platforms enable stabilization, sustained release, and targeted activity of these molecules, thereby improving their bioavailability and functional impact within the wound site. This review examines the wound healing process from a polymer engineering perspective and discusses emerging strategies for incorporating natural and bioactive molecules into polymeric wound dressings to address the dual challenge of tissue regeneration and antimicrobial resistance (AMR). Emphasis is placed on how polymer properties govern therapeutic outcomes. Finally, we outline current advantages, limitations, and future directions in the design of advanced polymer-based wound dressings capable of enhancing healing while combating resistant microbial infections.

Traditionally, the grafting of vinyl acetate onto chitosan has relied on chemical initiators, such as redox or peroxide systems. Herein, we report for the first time the gamma radiation-induced graft polymerization of vinyl acetate onto chitosan, providing a clean, initiator-free, and controllable route for generating chitosan-graft-poly(vinyl acetate) copolymers. The central hypothesis is that gamma irradiation activates the reactive sites on chitosan, whose selectivity toward hydroxyl or amino groups is modulated by solvent polarity, thereby governing the structural and thermal behavior of the resulting copolymer. The reaction was carried out at 25 kGy in different solvents (ethanol, hexane, ethyl acetate, chloroform, acetone, and acetic acid), and the resulting products were characterized by Fourier transform infrared and solid-state Nuclear magnetic resonance cross-polarization magic angle spinning, confirming the successful grafting of short poly(vinyl acetate) chains onto the chitosan backbone. Thermogravimetric analysis and differential scanning calorimetry revealed solvent-dependent variations in the thermal stability and transition temperatures, indicating distinct polymeric architectures. Viability and scratch assays with human dermal fibroblasts demonstrated the high biocompatibility and enhanced cell proliferation of the copolymers synthesized in hexane or acetic acid. These findings establish gamma radiation as a versatile tool for tailoring chitosan functionalization through solvent-controlled radical mechanisms, thereby providing new opportunities for the rational design of biocompatible carbohydrate-based materials.

Ginsenoside Rg1 (GRg1), a major bioactive component of Panax ginseng, exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties, positioning it as a promising therapeutic agent in neurodegenerative and metabolic disorders. This review critically examines the current literature on GRg1, emphasizing its molecular mechanisms, pharmacological pathways, and clinical translation in complementary medicine. GRg1 demonstrates protective effects in conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, cardiovascular dysfunction, diabetes, and aging, acting primarily through the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and peroxisome proliferator-activated receptor gamma/heme oxygenase-1 (PPARγ/HO-1) signaling pathways. Evidence from in vitro, in vivo, and clinical studies indicates that GRg1 enhances cellular resilience, reduces oxidative damage, and regulates apoptosis. Despite its broad therapeutic potential, low bioavailability remains a major limitation, warranting the development of advanced delivery systems such as nanoparticles and liposomes. Overall, this review provides a comprehensive assessment of GRg1's pharmacological actions and highlights its growing relevance as a multifunctional therapeutic agent in complementary and integrative medicine.

Bacterial nanocellulose (BNC) is a promising biomaterial for wound healing due to its nanofibrillar architecture and high biocompatibility. In this study, BNC was produced using mango pulp waste as an alternative carbon source and subsequently modified through γ-radiation-induced grafting of poly(acrylic acid) (PAA) to alter its surface properties. Physicochemical characterization confirmed successful functionalization while preserving the native nanofibrillar structure, along with changes in hydration-related behavior consistent with increased surface polarity. The biological response of human adipose-derived mesenchymal stem cells (hADSCs) was evaluated in vitro. Compared with pristine BNC, the modified scaffolds were associated with changes in cell morphology, proliferation, and extracellular matrix (ECM)-related protein expression. In particular, pristine BNC supported greater cell spreading and proliferation, whereas BNC-g-PAA was associated with a distinct ECM-related profile. These findings suggest that γ-radiation-induced grafting can be used to)te the surface properties of BNC scaffolds and influence cell behavior. However, further studies are required to elucidate the contribution of grafting density, potential residual compounds from the carbon source, and long-term material-cell interactions. This work contributes to the development of sustainable, bioactive nanocellulose-based scaffolds for regenerative applications.

Cosmeceuticals are cosmetic formulations that are intended to alleviate skin conditions that affect its appearance and functionality. They are not considered medications but contain molecules that exert biological action on the skin beyond traditional cosmetic actions. Sometimes, the bioactives used have limitations for transdermal passage, and it has been suggested that the use of nanocarriers can increase the effectiveness of cosmeceutical products. The degree of sophistication of nanocosmeceuticals requires that safety and efficacy aspects be verified before going on the market. In this regard, the application of the Quality by Design (QbD) approach during product development ensures that products meet the consumer needs in full. This review analyzes the implementation of QbD in the development of nanocosmeceuticals, considering the main characteristics of the most used bioactive groups and nanocarriers that have proven to be ideal vehicles for topical and transdermal applications.

Mesenchymal stem cells (MSCs) are highly valuable for their potential in cell therapy and tissue engineering because of their self-renewal, multilineage differentiation, and immunomodulatory capabilities. Adipose-derived mesenchymal stem cells (AD-MSCs) are advantageous in regenerative medicine because of their accessibility and ease of isolation. However, the clinical application of MSCs faces challenges related to large-scale culture (LSC) expansion, which is required to generate enough cells for transplantation but also decreases their therapeutic properties. This review assesses the impact of LSC on MSC functionality, differentiation potential, and immunomodulatory properties, and identifies key factors, such as metabolic shifts, genetic instability, and altered secretory profiles, that can compromise their therapeutic potential. We explored how prolonged in vitro passaging decreases MSC functionality and increases the risk of genetic alterations. In addition, strategies to preserve the efficacy of MSCs during scaling are discussed. A comprehensive literature review was conducted using PubMed, focusing on in vitro and in vivo studies that evaluated the effects of LSC on MSCs. These findings provide insights into optimizing culture protocols to maintain the clinical efficacy of AD-MSCs in regenerative therapies, addressing the critical need to balance large-scale expansion and functional integrity.

[This corrects the article DOI: 10.3389/fphar.2020.602364.].

Abstract Within the intricate network of oncogenic pathways that orchestrate the insidious growth and spread of cancer, the Notch signaling pathway is well known for its multiple roles in regulating cell differentiation, influencing metastasis, cancer stem cells, angiogenesis, and immune evasion. This pathway can suppress tumors by promoting differentiation and inhibiting proliferation or, conversely, stimulate tumorigenesis by inhibiting apoptosis and maintaining stem cell properties. While current research proposes monoclonal antibodies as possible tools to regulate the Notch pathway, natural products offer a complementary approach, potentially providing a more nuanced and adaptable means of modulating this complex signaling cascade. With their long‐standing history of serving as a mainstay in developing successful cancer chemotherapeutic agents, natural products possess immense potential against cancer. The objective of this article is to examine the potential of natural products as therapeutic agents that modulate the Notch pathway in cancer, specifically focusing on its sophisticated role in both promoting and suppressing tumorigenesis in preclinical and clinical settings while comprehensively covering the state‐of‐the‐art research concerning Notch signaling in cancer. The article stands out by analyzing the preclinical and clinical scope of natural products targeting Notch signaling in cancer, especially mentioning the limitations in pharmacological and biopharmaceutical performance and highlighting the novelty of nanotechnology tools to overcome such limitations. It also highlights new aspects in the study of the Notch pathway.

Cancer remains one of the leading causes of mortality worldwide, driving the development of advanced drug delivery systems to improve therapeutic selectivity and overcome the complex defense mechanisms of malignant cells. Exosome-mimetic nanocarriers (EMNs) have emerged as an advanced biomimetic platform for cancer diagnosis and targeted drug delivery, combining the biological functionality of natural exosomes with the manufacturing flexibility and scalability of synthetic nanocarriers. This review analyzes the composition, design, and architecture of EMNs, as well as their applications in cancer drug delivery, drawing on fundamental concepts of pharmaceutical technology to provide a translational perspective. It also includes a dedicated section on cancer diagnosis and theranostic platforms, as well as a critical analysis of recent technological advancements in exosome-mimetic systems. Although the clinical translation of natural exosomes remains limited, emerging evidence suggests that engineered EMNs offer improved scalability, reproducibility, and therapeutic versatility. Recent studies highlight their potential to overcome key limitations of natural vesicles, positioning them as promising candidates for future clinical translation and commercialization.

Bisphenol S (BPS) is a recognized environmental contaminant that harms reproductive organs and fertility, affecting human health worldwide. Over the last few decades, the search for a compound that mitigates its harmful effects has increased. Vitamin E has not been evaluated in diabetic rats as a study model. We assessed for the first time the use of Vitamin E as a potential ameliorant compound. We used 26 Wistar rats, and assigned it randomly in five groups: (1) healthy rats (Ctrl, n = 6); (2) diabetic rats without treatment (Ctrl-D, n = 5); (3) diabetic rats treated with Vitamin E (100 mg/kg bw/day, VitE-D, n = 5); (4) diabetic rats treated with BPS (100 mg/kg bw/day, BPS-D, n = 5); and, (5) diabetic rats receiving a combination of Vitamin E (100 mg/kg bw/day) and BPS (100 mg/kg bw/day) (VitE + BPS-D, n = 5). All doses were administered orally (p.o.). We evaluated its effect on serum estradiol and testosterone levels, testis cellular apoptosis, antioxidant enzyme activity, and sperm and testicular histologic characteristics. BPS increases oxidative stress, promotes cell apoptosis, provokes structural changes in seminiferous tubules, and negatively affects spermatogenesis and sperm quality. As a result of our study, co-administration of Vitamin E did not reduce the negative impact provoked by BPS; indeed, in some cases, the vitamin exacerbated the injury. The beneficial effects of VitE on testosterone serum levels were nullified when combined with BPS. Our results show the dangers of BPS to male reproductive health in the diabetes model and stress the necessity for improved strategies to mitigate its deleterious impacts.

ABSTRACT Curcumin is a natural polyphenol derived from Curcuma longa with well‐documented anti‐inflammatory, antioxidant, antimicrobial, and wound‐healing properties. However, its clinical application in dermatology remains limited due to its low water solubility, low stability, and limited skin penetration. Recent advances in nanotechnology have enabled the development of curcumin delivery systems designed to improve dermal bioavailability, stability, and controlled release. Our novelty lies in integrating bibliometric analyses with a translational emphasis on food‐grade nanocarriers. This review highlights the therapeutic relevance of curcumin in major skin conditions, such as psoriasis, atopic dermatitis, acne, wound healing, burns, and skin cancer, with an emphasis on lipid‐ and polymer‐based nanoformulations, such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, and hydrogel‐based platforms. Furthermore, the bibliometric analysis highlights a growing scientific interest in curcumin nanotherapies, although clinical evidence remains limited. In general, curcumin nanoformulations represent promising strategies for topical dermatological applications, but further clinical validation and regulatory development are required to support their application in therapeutic products.

Early detection and accurate cancer diagnosis are crucial for improving patient outcomes and survival rates. This review presents a comprehensive and updated synthesis of emerging biomarkers, essential for providing non-invasive, efficient, and reliable methods to identify cancer in its early stages. An extensive literature review focuses on recent studies and advancements in both traditional and emerging biomarkers, including circulating tumor DNA (ctDNA), exosomes, liquid biopsies, microRNAs (miRNAs), and immunotherapy biomarkers, which show promising potential for early cancer detection. Liquid biopsies, nanobiosensors, artificial intelligence, and next-generation sequencing (NGS) are transforming biomarker discovery and application. Key challenges include low concentration and fragmentation, as well as clearance of ctDNA, the complexity of exosome isolation, inter-patient variability in miRNA expression, and the absence of clinical standardization. We also highlight the translational barriers in low-resource settings and suggest strategies for future implementation. We also underscore the limited diagnostic accessibility in low-resource settings, emphasizing the importance of equity in future applications. Future research should prioritize overcoming current challenges, promoting multidisciplinary collaboration, and creating standardized protocols to enhance the clinical utility of this approach.

The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and canine females. Immunocontraception via vaccination against gonadotropin-releasing hormone (GnRH), the luteinizing hormone receptor, zona pellucida proteins, and sperm, or use of viral-vectored delivery, is yet developing. Hormonal treatment (progestins, androgens, or GnRH) analogs act directly to block the reproductive axis. However, it produced essential side effects. Analogs of kisspeptin, non-steroid anti-inflammatory drugs such as firocoxib, and delivery of cytotoxins to the pituitary have shown non-conclusive results. Additional methods have also been tested, such as intraovarian injection of necrosing compounds or intravaginal and intrauterine devices. At present, neither of these methods offers permanent sterility that can replace surgical sterilization techniques. To our knowledge, none are currently authorized by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for contraceptive methods or sterilization of cats or dogs. Therefore, it is necessary to continue the development of a compound that warrants the sterility of cats and dogs.

In the last decades, the misuse and overuse of antimicrobial medications have precipitated the appearance of antimicrobial resistance, a phenomenon associated with around 4.95 million deaths per year worldwide. Control of this resistance represents the biggest challenge for antimicrobial therapies and novel drug formulations. Poloxamers are nonionic synthetic triblock copolymers used as excipients for formulating antibiotics, mainly as emulsifying agents, gelling agents, surfactants, and humectants. It has been discovered that poloxamers may have antimicrobial activity as microbicides or micro biostatics or can also potentiate other germicide drugs' efficacy. This review aims to examine the use of poloxamers and synthesize their potential mechanisms of action as antimicrobial drugs for treating microbial infections. This review's methodology included sourcing articles from PubMed, Google Scholar, and Scopus, using specific medical subject headings terms to warranty precision and pertinence. Poloxamer action mechanisms include quorum sensing inhibition, cellular membrane disruption, bacterial biofilm inhibition, and disruptions in bacteria cell walls. Results of Molecular docking demonstrated that poloxamers could interact directly with active sites of adhesion proteins and alter their functioning. Our experimental tests showed that poloxamers 188 and 407 possess the potential to be antimicrobial agents by effectively inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth. Despite the convincing evidence, further research is required to overcome challenges related to poloxamers' bioavailability and establish effective dosing regimens for different poloxamers to warrant their use and safety as antimicrobial drugs.

Cancer remains the second leading cause of death globally, driving the need for innovative therapies. Among natural compounds, maytansinoids have shown significant promise, contributing to nearly 25

The evaluation of biomaterial compatibility often relies on viability assays using tetrazolium salts, such as WST-8, to assess cytotoxicity. However, potential interference by bacterial nanocellulose (BNC) with these assays may compromise the accuracy of biocompatibility assessments. In this study, we examined the interference of BNC with tetrazolium salt-based viability assays by evaluating mesenchymal stem cells derived from adipose tissue (ASC) and dermal fibroblasts in contact with BNC. Our findings revealed significant interference of BNC with the hydrophilic tetrazolium salts WST-8 and WST-1, in contrast to the lipophilic MTT salt, which showed no such interference. Notably, the absorbance signal decreased by more than 50% when the BNC membrane was incubated with the supernatants of the blank solution compared with the conditions without BNC incubation. Critically, when BNC remained present during the reaction, absorbance-based viability values decreased by 78.71% (WST-8), 59.61% (WST-1), and 7.05% (MTT) compared to control wells where BNC was removed prior to the tetrazolium salt reaction. This study underscores the critical importance of accounting for possible interference in cytotoxicity assessments to ensure accurate biomaterial compatibility evaluations, thereby supporting the safe and effective application of these materials in biomedical contexts. Graphical abstract

Cancer involves uncontrolled cell growth, leading to tumor formation, and remains a major cause of mortality worldwide. Colorectal cancer (CRC) arises from abnormal proliferation of colon glandular epithelial cells. We assessed the cytotoxic and molecular effects of lithium carbonate (Li2CO3) and lithium chloride (LiCl) in two CRC cell lines (HCT-116 and SW-620) and a non-tumorigenic line (CRL-1790). Viability assays revealed dose-dependent cytotoxicity, with HCT-116 being the most sensitive cell line (IC50: 8.14 mM for Li2CO3). Notably, long-term lithium exposure reduced proliferation, lowering colony-forming efficiency (CFE) and a phenotypic shift from holoclones to meroclones and paraclones, indicating diminished self-renewal capacity. Minimal membrane damage was observed (LDH assay), suggesting non-lytic mechanisms consistent with apoptosis. TUNEL and Annexin-V/IP assays confirmed apoptosis in >40% of cells, without caspase-3 cleavage, suggesting a caspase-independent pathway. PARP-1 cleavage occurred only in SW-620 cells. Western blotting exposed cell-specific modulation of GSK-3β: increased inactive form (p-Ser9) in CRC cells and decreased in CRL-1790 cells, implying differential disruption of Wnt/β-catenin signaling. c-Myc levels remained unchanged, suggesting possible post-translational regulatory effects. Overall, these findings indicate that lithium salts selectively reduce CRC cell viability, impair stem-like characteristics, and induced caspase-independent apoptosis. Therefore, we expand the proof of concept of the potential of lithium-based compounds as low-toxicity adjuvant agents in colorectal cancer therapy.

Cancer represents a growing cause of death and a threat to public health worldwide; thus, there is an urgent need to understand its pathological mechanism and design effective therapies. The Hippo pathway regulates diverse cellular processes under physiological conditions; however, its dysregulation is associated with several types of cancer, including lung, pancreatic, colorectal, breast, and prostate cancer. Consequently, compounds targeting deregulated Hippo components represent potential treatments for a broad spectrum of cancers. Nonetheless, currently, there is limited information integrating the growing evidence of this potential. Therefore, the review's objective is to provide insight into the potential efficacy of targeting the Hippo/yes-associated protein (YAP) pathway for cancer therapy. First, we describe the molecular mechanisms of the Hippo signaling pathway in physiological conditions and several cancer types. We then provide an overview of natural products and synthetic compounds targeting this pathway, highlighting their potential applications in treating diverse cancers. We also discuss relevant preclinical and clinical studies of compounds targeting the Hippo pathway in cancer. Finally, we summarize our findings and offer recommendations for future research. This review emphasizes the role of the Hippo/YAP pathway in cancer and the potential of natural products and synthetic compounds targeting this pathway for cancer treatment.

The treatment of chronic and infected wounds remains a constant challenge; therefore, there is a need to develop multifunctional dressings that integrate mechanical resilience and antimicrobial activity via alternative drugs to prevent bacterial resistance. This study presents, for the first time, the design of self-healing hydrogels based on polyvinyl alcohol and polyvinylpyrrolidone, which were obtained by the freeze‒thaw method; these hydrogels enable physical crosslink formation without the use of toxic agents and serve as carriers for phenytoin repositioning, an antiepileptic drug recognized for its wound-healing properties. Phenytoin was incorporated via micelle-assisted solubilization, ensuring uniform distribution without damaging the hydrogel structure. The optimal formulation exhibited high swelling capacity ( 450

ABSTRACT The Jasminum genus, renowned for its aromatic flowers, has been used in traditional medicine across various cultures for its therapeutic properties. Recently, scientific interest has focused on the bioactive compounds present in Jasminum species, highlighting their potential applications in health and food preservation. This review evaluates the phytochemical composition of Jasminum species, emphasizing their therapeutic and preservative roles while identifying research gaps. A comprehensive literature search was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, focusing on studies from the last two decades. The review includes peer‐reviewed articles that provide robust methodologies and detailed results regarding the biological activities of Jasminum species. Findings reveal that Jasminum is rich in bioactive compounds such as terpenoids, flavonoids, and phenolic acids, contributing to significant antioxidant, anti‐inflammatory, antimicrobial, and anticancer properties. Scientific evidence supports traditional uses, such as treating headaches and infections. Additionally, Jasminum extracts have shown promise as natural food preservatives due to their potent antimicrobial activity. However, the review identifies significant variability in study methodologies and a lack of clinical trials, which limit the generalizability and application of these findings. Jasminum species possess a diverse phytochemical profile that holds promise for advancing health and food preservation applications. Future research should prioritize standardizing methodologies and conducting clinical trials to validate their efficacy. Bridging the gap between traditional knowledge and modern science will unlock the full potential of Jasminum as a multifaceted resource for health and nutrition.