WATER

The discovery in 2006 that loss-of-function mutations in the filaggrin gene ( FLG ) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.

Water has numerous functions necessary for survival including cellular homeostasis, solvent properties for dissolving ions and solutes, thermoregulation, and transport of waste and nutrients. Despite the established beneficial role of water in skin physiology, the optimal methods for skin hydration and requirements for daily water consumption remain elusive. This review summarizes the cellular and molecular biology of skin hydration, the debate and current recommendations of daily water requirements, and the latest research on interventions to improve skin hydration by both internal and external means of water exposure. We also explore the chemical properties of water, such as the concept of water "hardness" and environmental pollutants, and their impact on skin physiology.

Dry skin is a common condition that is attributed to a lack of water in the stratum corneum. With the availability of new technologies, light has been shed on the pathophysiology of dry skin at the molecular level. With the aim to discuss implications of this latest research for the optimal formulation of emollients designed to treat dry skin, five specialists met in November 2017. Research on three topics thereby provided particularly detailed new insights on how to manage dry skin: research on the lipid composition and organization of the stratum corneum, research on natural moisturizing factors, and research on the peripheral nervous system. There was consensus that latest research expands the rationale to include physiological lipids in an emollient used for dry skin, as they were found to be essential for an adequate composition and organization in the stratum corneum but are reduced in dry skin. Latest findings also confirmed the incorporation of carefully selected humectants into a topical emollient for dry skin, given the reduced activity of enzymes involved in the synthesis of moisturizing factors when skin is dry. Overall, the group of specialists concluded that the previous concept of the five components for an ideal emollient for dry skin is well in accordance with latest research.

Skin is among the most frequent sites of cancer diagnosis, and the global incidence of skin cancer continues to rise despite extensive public health initiatives and preventive strategies. Arsenic, a ubiquitous environmental metalloid classified as a Group 1 carcinogen, remains an important concern due to widespread exposure through contaminated drinking water, food sources and occupational contact. Arsenic‑associated skin carcinogenesis involves complex, interdependent molecular processes and has been linked to the disruption of redox signalling, altered DNA damage signalling and repair responses as well as epigenetic reprogramming. In keratinocytes, arsenic perturbs redox and stress‑response pathways and may disrupt genome maintenance and cellular stress signalling in experimental systems. Arsenic may also alter microRNA networks and affect telomere and mitochondrial homeostasis, although the contribution of these processes to malignant transformation remains context‑dependent; in melanoma, the carcinogenic mechanisms of arsenic are less well characterized. Clinically, arsenic is recognized as a carcinogen in non‑melanoma skin cancer (NMSC) and evidence from high‑exposure endemic regions, together with occupational cohorts, suggest a dose‑responsive association. For melanoma, clinical evidence is more heterogeneous and subject to substantial potential confounding, although some studies suggest modest risk elevation in high‑exposure or occupational settings. Collectively, convergent mechanistic, experimental and epidemiological data support arsenic as an independent carcinogen, particularly in NMSC. These findings underscore the need for heightened clinical vigilance, particularly in exposed populations, and call for renewed public health strategies and regulatory frameworks to mitigate the persistent global burden of arsenic‑associated skin cancer.

Dental caries is a major public health concern among children, with Streptococcus species, particularly Streptococcus mutans, playing a key role in its development. This study aimed to compare the effect of alkaline water, chlorhexidine mouthwash, and tap water on the salivary Streptococcus count in children aged 10-12 years. A single-blinded preliminary clinical study was conducted on 60 healthy children aged 10-12 years. Three groups of participants were randomly assigned: one group used alkaline water, another group used mouthwash containing 0.12% chlorhexidine, and the third group used tap water as a control. Participants were followed for three weeks. Children with systemic diseases, orthodontic appliances, or recent use of antibiotics or corticosteroids were excluded. Unstimulated saliva samples were collected at baseline and after the intervention. Salivary Streptococcus counts were determined using standard microbiological techniques. After 3 weeks, mean salivary Streptococcus mutans counts (CFU ×10 5 /ml) were 3.0 ± 0.36 in the alkaline water group, 2.1 ± 1.9 in the chlorhexidine group, and 7.9 ± 0.3 in the tap water group. Both intervention groups demonstrated significantly lower bacterial counts compared with the control group (p < 0.001), while chlorhexidine showed significantly lower counts than alkaline water. Within the short-term limitations of this study, rinsing with alkaline water demonstrated a significant reduction in salivary Streptococcus mutans counts, although chlorhexidine showed lower bacterial counts after 3 weeks under the conditions of this study. These preliminary findings suggest its potential as an adjunctive oral hygiene agent, and highlight the need for long-term clinical trials to assess its effectiveness in caries prevention.Trial registration: The trial was registered with the Clinical Trial.gov (Number and date NCT06511336, 07/09/2024).

The present study aimed to investigate the effects of the systemic administration of LY404187, a positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), on swallowing function. Experiments were conducted on 78 male Sprague-Dawley rats anesthetized with urethane. Upper airway distention with continuous airflow and the topical laryngeal application of distilled water or capsaicin were used to induce swallowing, which was identified by electromyographic activity recordings from the mylohyoid and thyrohyoid muscles. We investigated the effects of systemic administration of LY404187 (0.25-5.0 mg/kg), an angiotensin-converting enzyme inhibitor (perindopril), a dopamine agonist (amantadine), or a benzodiazepine inverse agonist (S-8510) on swallowing initiation. An optimal concentration of LY404187 (1.0 mg/kg) significantly increased the number of airflow-induced swallows compared with before administration. However, LY404187 did not modulate the initiation of chemically induced swallows. The pre-administration of talampanel, an AMPAR antagonist, diminished facilitatory effects of LY404187 on airflow-induced swallows. Perindopril, amantadine, and S-8510 did not facilitate both mechanically and chemically induced swallows. These results suggest that LY404187 facilitates the initiation of mechanically induced swallows via AMPAR activation.

Nanoemulgels are hydrocolloid-based structured systems that integrate nanoemulsions into polymeric gel networks, thereby enhancing dispersion stability, interfacial integrity, and functional performance. Hemp seed oil (HSO), rich in polyunsaturated fatty acids and γ-linolenic acid, represents a valuable lipid phase for the development of functional oil-based delivery systems. In this study, an HSO nanoemulsion (HSO-NE) and a hydrocolloid-based nanoemulgel (HSO-NE gel) were developed using a polymer matrix, and their physicochemical and structural properties were systematically investigated. Incorporation of nanoemulsion into the hydrocolloid gel network resulted in a modest increase in droplet size and polydispersity index, while inducing a pronounced increase in negative zeta potential (from -39.60 to -67.37 mV), indicating enhanced electrostatic stabilization and resistance to droplet aggregation. FTIR and TEM analyses confirmed that the hydrocolloid network physically entrapped the nanoemulsion droplets without disrupting interfacial integrity or lipid structure. As a functional validation model, the hydrocolloid-based HSO-NE gel was evaluated in an imiquimod-induced psoriasis-like mouse model. Topical application of the nanoemulgel significantly attenuated inflammatory responses, accompanied by downregulation of cytokine-cytokine receptor interaction and NF-κB signaling pathways. Collectively, this study demonstrates that hydrocolloid-based nanoemulgels represent an effective strategy for stabilizing oil-in-water nanoemulsions while preserving the functional properties of hemp seed oil, highlighting their potential as structured delivery systems for bioactive lipids.

This study investigated the development of hypromellose-based film-forming solutions (FFSs) containing ketoprofen, aiming to elucidate how key formulation variables (concentration and type of hypromellose (high-viscosity grades 2910 and 2208), plasticizers (macrogol 400 and propylene glycol) and volatile solvents (water and water/isopropanol mixtures)) influence FFSs performance and film properties. The FFSs were characterized in terms of pH, transparency, and rheological behavior, while the resulting films were evaluated for weight, stickiness, and mechanical properties. All FFSs exhibited pH values ranging from 4.10 to 5.83, high transparency (transmittance >90%), and shear-thinning behavior. The results demonstrated a critical role of polymer and plasticizer selection, with hypromellose 2910 outperforming hypromellose 2208 in both FFS and film properties, and macrogol 400 yielding films with superior mechanical performance compared to propylene glycol. The performance-defining characteristics and further in silico optimization of plasticizer concentration using a second-order polynomial regression model based on tensile strength, Young's modulus, and elongation at break, enabled identification of an optimal FFS composition (2% hypromellose 2910, 1.52% macrogol 400, 2.5% ketoprofen, and a 1:1 water/isopropanol mixture up to 100%). The optimized formulation formed a transparent film with favorable mechanical properties, including tensile strength (10.94 ± 2.26 MPa), elongation at break (75.97 ± 6.12%), and Young's modulus (33.79 ± 4.76 MPa). In vitro drug release was significantly enhanced from the optimized FFS compared to commercial gels, reaching 82.66% after 6 h and following the Korsmeyer-Peppas model, indicating its potential as a carrier for topical administration of ketoprofen.

Pseudomonas aeruginosa is a highly virulent bacterium that causes morbidity and mortality in fish farming practices. Therefore, the current work is accounted as a pioneer trial to assess Aloe vera or Barbados aloe gel (BAG, 8 mg/L) as an antimicrobial agent against P. aeruginosa infection in African catfish (Clarias gariepinus). In addition, hematological, biochemical, blood electrolytes, and histopathological investigations were applied, alongside tissue antioxidant response. For this, fish (n = 160) were arranged into four sets (control, BAG, P. aeruginosa, and P. aeruginosa-BAG), with four replicates (40 fish/set) for 15 days. The outcomes exhibited hematological-biochemical disruptions with high mortality (42.50%) resulting from P. aeruginosa challenge. This is evidenced by lowering hematological parameters (red and white blood cell count, hemoglobin, packed cell volume, and neutrophils, lymphocytes) and elevation of hepatic enzymes (aspartate and alanine aminotransferases). In addition, stimulation of stress response (high cortisol and glucose), hyperkalemia, and lipid peroxidation (increased malondialdehyde level) were obvious in the P. aeruginosa group. This was besides hyponatremia and inactivation of antioxidants (catalase and superoxide dismutase) of the skin, gills, and liver. These tissues also exhibited histopathological abnormalities, including epithelial desquamation, tissue hyperplasia, necrosis, leukocytic infiltration, vascular congestion, and cellular degeneration following P. aeruginosa infection. Conversely, watery exposure to BAG palliated these changes induced by P. aeruginosa. It improved blood profiles, electrolytes, and hepatic enzymes while boosting tissue antioxidant activity and regenerating the histopathological structure of skin, gills, and liver. This alleviation led to decreased mortality (12.50%). Taken together, the current report confirmed P. aeruginosa 's pathogenicity. It highlighted the promoting activity of aqueous addition of BAG (8 mg/L) as an antibacterial agent, besides its privileges for enhancing fish health for sustaining aquaculture.Clinical trial number: not applicable.

Endocrine-disrupting chemicals (EDCs) are ubiquitous and highly persistent environmental contaminants. Human exposure occurs through multiple routes, including dietary ingestion, water consumption, inhalation, and dermal contact, posing sustained health risks characterized by chronic, low-dose, and cumulative mixture exposure. Through interference with endocrine signaling and related biological pathways, EDCs have been implicated in the development and progression of several health outcomes, particularly reproductive, metabolic, neurodevelopmental, and hormone-related disorders. Of particular concern is their involvement in oncogenesis; throughout tumor progression, EDCs facilitate immune dysregulation and metabolic reprogramming via complex interactions across multiple targets and signaling pathways. Elucidating these underlying regulatory mechanisms is imperative for developing robust preventive strategies. This review synthesizes evidence regarding bisphenols, per- and polyfluoroalkyl substances (PFAS), heavy metals, pesticides, phthalates, polychlorinated biphenyls (PCBs), and other emerging pollutants. We specifically highlight their mechanistic roles across three critical domains: carcinogenesis, immune modulation, and metabolic reprogramming. Given the long latency periods, significant inter-individual variability, and synergistic mixture effects associated with EDC exposure, current risk assessments and causal inferences remain constrained. Future research must integrate high-precision exposure science, prospective longitudinal cohorts, and multi-omic mechanistic validation, while incorporating critical developmental windows and mixture-exposure frameworks. Ultimately, such advancements will provide a more reliable evidence base for exposure prevention, regulatory decision-making, and risk stratification and intervention strategies for exposure-related malignancies.

Upper gastrointestinal bleeding remains an important gastrointestinal condition despite a decline in its incidence, the introduction of acid-suppressive therapy, and advances in endoscopic techniques. Based on etiology, it is classified as variceal or nonvariceal bleeding, with peptic ulcers constituting the majority of nonvariceal bleeding. Before endoscopy, it is essential to stabilize the patient by administering appropriate fluids, blood transfusions, proton pump inhibitors, vasoconstrictors, and antibiotics, followed by an early endoscopic examination and treatment whenever possible. Endoscopic management can be facilitated by accessories such as transparent caps, water-jet pumps, overtubes, and multi-bending endoscopes. Studies have reported emerging tools, including machine learning models for risk prediction, swallowable bleeding sensors, and hemostasis guided by endoscopic ultrasound or Doppler. Endoscopic hemostasis includes injections, mechanical therapy, electrocautery, and topical therapies. Once the bleeding source is identified, an appropriate endoscopic modality can be selected according to the lesion. For nonvariceal bleeding, injections, coagulation, and mechanical methods are used when endoscopic hemostasis is indicated. Band ligation is commonly used to treat esophageal variceal bleeding, whereas gastric variceal bleeding is typically treated with cyanoacrylate injections. If endoscopic therapy fails or rebleeding occurs, angiography with embolization or surgery may be required, and in acute variceal bleeding, a transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration can be considered. Second-look endoscopy may be performed selectively in patients at high risk of rebleeding or when repeat evaluation is needed. In peptic ulcer disease, early biopsy should be performed when malignancy is suspected, and Helicobacter pylori testing and eradication should be ensured.

Historically, Elaeocarpus sylvestris has served as a traditional medicinal agent for inflammatory disorders across East Asia. Recent studies have reported its antioxidant and anti-inflammatory activities, supporting its potential as a natural therapeutic resource for inflammatory skin diseases such as atopic dermatitis (AD). However, its pharmacological relevance to AD and the cellular signaling cascades remain insufficiently elucidated. This study aimed to pharmacologically validate the traditional use of E. sylvestris by investigating the anti-inflammatory and anti-atopic effects of its leaf ethanol extract (ESLE) and elucidating the associated molecular mechanisms. Inflammatory profiles of LPS-primed HaCaT cells were analyzed to evaluate the bioactivity of ESLE. We employed western blotting to dissect the intracellular signaling networks, focusing on the IRAK4-mediated MAPK, NF-κB, and JAK/STAT pathways. The study also extended to a DNCB-induced murine model of AD, facilitating a comprehensive assessment of efficacy of ESLE through histopathological examination and transepidermal water loss measurements. Geraniin was confirmed as a representative biomarker to verify ESLE's identity. ESLE significantly inhibited NO and PGE 2 production by downregulating iNOS and COX-2, while reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in keratinocytes. These effects were mediated by the suppression of IRAK4-dependent MAPK, NF-κB, and JAK/STAT signaling. Furthermore, ESLE improved skin barrier function and attenuated AD hallmarks, including mast cell infiltration, serum IgE elevation, and lymphoid organ hypertrophy. ESLE attenuates inflammatory responses and improves AD-like symptoms, potentially through modulation of inflammation-related signaling pathways. These findings support the pharmacological relevance of E. sylvestris and its traditional use in inflammatory skin conditions.

This letter to editor would emphasise the position about topic fluoride into a choorte of children between 0-6 years of age after media messages, personal conviction by social media appeared in the last year about adverse fluoride effects in the topical application. After the preview letter to editor about the negative effects of water added with fluoride when had been highlighted that the hypothetical harmful effect of fluoride on intellectual quotient IQ of children is mainly an USA question because in Europe water is not fluoridated except for little areas of european's countries. Topic fluoride is safe and is a most strategy to carious lesion development if used in the correct modalities. No adverse effect of topic fluoride is possible to adress for yuong adult (> 18 yo) and 6 years old children. In that situation is suggest from paediatric scientific academy and ministerial guide lines to use the maximun concentration of fluoride permitted from European law and World Health Organisation WHO indications into toothpaste and mouthrinse (1500 ppm) for at home for oral hygiene. For children of age lower than 6 years old attention must be payed also for topic fluoride because an excess and not precise measurement of plasmatic fluoride may expose the children to dental fluorosis disease. In particullary the age from 0-2 years old is the most critically because during this stage some of the most important permanent teeth such first molars and incisor perform the mineralisation of protein matrix secreted by ameloblast during amelogenisis. Dose (rise o pea size) and toothpaste fluoride concentration (1000 ppm) are suggested from European Accademy of Paediatric Dentistry EAPD into a policy document and is highligted supervison of parents during at home children oral hygiene to avoid accidental ingestion of toothpate [Toumba et al., 2019]. Parents, Dentist and Paediatric must be pay attention about fluoride concentration of human use potable water and water to prepare the children food whilst there's not information about fluoride concentration into the child food. We just know that fish, tea and potatos peel are rich in fluoride. Avoid the final water rinse after toothbrush with fluoride toothpate is favourable as UK's National Health Service suggest to extend the contact time between fluoride and the dental enamel in order to form Fluoroapatite F-Ap more acid resistent than Hydroxiapatite HAp. We are talking about split the excess of foam at the end of toothbrushing and is very unlikely that this procedures could increase the fluoride concentration in the children lower 6 years old and expose those to dental fluorosis risk [Parakaw et al., 2024].

Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are potential wound dressings due to their lower critical solution temperature (LCST) of 32°C, close to physiological temperature, enabling injectable or spreadable formulations that quickly form a gel on irregular wounds while withstanding tissue motion. These systems aim to balance skin-like mechanical integrity, strong dry and wet adhesion and deliver stability after placement. This review summarizes the impact of the LCST driven phase transition on water content, pore structure, stiffness and interfacial hydration and how these effects regulate adhesion strength and failure mode. It compares major mechanical reinforcement strategies in PNIPAM-based dressings including hybrid nanocomposites, double network architectures, dynamic or sacrificial crosslinking strategies that enhance toughness, stretchability and recovery. It also describes multifunctional systems incorporating antibacterial activity, hemostasis, sensing, photothermal response or controlled drug release with emphasis on their effect on mechanics and adhesion. Since adhesion in soft hydrogels is strongly correlated with viscoelastic behavior, the review identifies rheological measures ( G '/ G ″ trends, shear thinning, yield behavior and recovery) as measures of injectability and wet adhesion stability. Lastly, essential translational barriers are defined, including limited biodegradability, additive cytotoxicity, sterilization, durability in exudate and motions and standardized testing and reporting to facilitate reliable comparison and clinical relevance.

Fluoroquinolone (FQ) antibiotics persist in the environment, posing risks to ecosystems and public health through antimicrobial resistance and bioaccumulation. Effective analytical methods are essential for monitoring these residues and enforcing regulations to limit antibiotic pollution. This study developed validated reversed-phase high-performance liquid chromatography (RP-HPLC) approaches for the simultaneous detection of five FQs: norfloxacin (NFX), levofloxacin (LFX), enrofloxacin (ENR), ofloxacin (OFX), and ciprofloxacin (CFX). Two chromatographic methods were required due to structural similarities between LFX and OFX. Method I, using an Eclipse Plus phenyl hexyl column, produced retention times of 5.2 min for NFX, 5.7 min for LFX, and 7.9 min for ENR. Method II, utilizing a YMC C18 column, yielded retention times of 8.9 min for OFX and 10.7 min for CFX. Both methods demonstrated high selectivity, specificity, linearity (R 2 > 0.998), and precision (relative standard deviation (RSD) < 2 %), with Photodiode Array (PDA) detection at 280 nm. Validation followed International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2R2 guidelines. Environmental samples from West Bengal, including water, soil, chicken muscle, and fish skin, were processed using solid-phase extraction. Residues of all five FQs were detected, ranging from 0.1 to 1.4 μg g -1 . Ofloxacin and CFX were more frequently found in animal-derived samples, whereas NFX and ENR were predominant in water and soil. The validated RP-HPLC methods provide robust tools for monitoring FQ residues in diverse matrices. The widespread contamination observed highlights the urgent need for stronger surveillance, stricter regulatory enforcement, and comprehensive risk assessment to mitigate antimicrobial resistance and protect public health. © 2026 Society of Chemical Industry.