Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Comparative analysis of whole plant, flower and root extracts of Chamomilla recutita L. and characteristic pure compounds reveals differential anti-inflammatory effects on human T cells.

Introduction: Chronic inflammation is a hallmark of chronic wounds and inflammatory skin diseases. Due to a hyperactive and prolonged inflammation triggered by proinflammatory immune cells, transitioning to the repair and healing phase is halted. T cells may exacerbate the proinflammatory milieu by secreting proinflammatory cytokines. Chamomilla recutita L. (chamomile) has been suggested for use in several inflammatory diseases, implying a capability to modulate T cells. Here, we have characterized and compared the effects of differently prepared chamomile extracts and characteristic pure compounds on the T cell redox milieu as well as on the migration, activation, proliferation, and cytokine production of primary human T cells. Methods: Phytochemical analysis of the extracts was carried out by LC-MS/MS. Primary human T cells from peripheral blood (PBTs) were pretreated with aqueous or hydroethanolic chamomile extracts or pure compounds. Subsequently, the effects on intracellular ROS levels, SDF-1α induced T cell migration, T cell activation, proliferation, and cytokine production after TCR/CD3 and CD28 costimulation were determined. Gene expression profiling was performed using nCounter analysis, followed by ingenuity pathway analysis, and validation at protein levels. Results: The tested chamomile extracts and pure compounds differentially affected intracellular ROS levels, migration, and activation of T cells. Three out of five differently prepared extracts and two out of three pure compounds diminished T cell proliferation. In line with these findings, LC-MS/MS analysis revealed high heterogeneity of phytochemicals among the different extracts. nCounter based gene expression profiling identified several genes related to T cell functions associated with activation and differentiation to be downregulated. Most prominently, apigenin significantly reduced granzyme B induction and cytotoxic T cell activity. Conclusion: Our results demonstrate an anti-inflammatory effect of chamomile- derived products on primary human T cells. These findings provide molecular explanations for the observed anti-inflammatory action of chamomile and imply a broader use of chamomile extracts in T cell driven chronic inflammatory diseases such as chronic wounds and inflammatory skin diseases. Importantly, the mode of extract preparation needs to be considered as the resulting different phytochemicals can result in differential effects on T cells.

Abietane-Type Diterpenoids from the Arils of Torreya grandis.

A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1-7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 µM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 µM.

Study on the Compositional Analysis, Extraction Process, and Hemostatic and Anti-Inflammatory Activities of Cirsium japonicum Fisch. ex DC.-Cirsium setosum (Willd.) MB Extracts.

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1ß in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines.

Exploring the Biomedical Potential of Terpenoid Alkaloids: Sources, Structures, and Activities.

Terpenoid alkaloids are recognized as a class of compounds with limited numbers but potent biological activities, primarily derived from plants, with a minor proportion originating from animals and microorganisms. These alkaloids are synthesized from the same prenyl unit that forms the terpene skeleton, with the nitrogen atom introduced through ß-aminoethanol, ethylamine, or methylamine, leading to a range of complex and diverse structures. Based on their skeleton type, they can be categorized into monoterpenes, sesquiterpenes, diterpenes, and triterpene alkaloids. To date, 289 natural terpenoid alkaloids, excluding triterpene alkaloids, have been identified in studies published between 2019 and 2024. These compounds demonstrate a spectrum of biological activities, including anti-inflammatory, antitumor, antibacterial, analgesic, and cardioprotective effects, making them promising candidates for further development. This review provides an overview of the sources, chemical structures, and biological activities of natural terpenoid alkaloids, serving as a reference for future research and applications in this area.

In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams.

The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.

Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Pharmacological Potential of Kaempferol, a Flavonoid in the Management of Pathogenesis via Modulation of Inflammation and Other Biological Activities.

Natural products and their bioactive compounds have been used for centuries to prevent and treat numerous diseases. Kaempferol, a flavonoid found in vegetables, fruits, and spices, is recognized for its various beneficial properties, including its antioxidant and anti-inflammatory potential. This molecule has been identified as a potential means of managing different pathogenesis due to its capability to manage various biological activities. Moreover, this compound has a wide range of health-promoting benefits, such as cardioprotective, neuroprotective, hepatoprotective, and anti-diabetic, and has a role in maintaining eye, skin, and respiratory system health. Furthermore, it can also inhibit tumor growth and modulate various cell-signaling pathways. In vivo and in vitro studies have demonstrated that this compound has been shown to increase efficacy when combined with other natural products or drugs. In addition, kaempferol-based nano-formulations are more effective than kaempferol treatment alone. This review aims to provide detailed information about the sources of this compound, its bioavailability, and its role in various pathogenesis. Although there is promising evidence for its ability to manage diseases, it is crucial to conduct further investigations to know its toxicity, safety aspects, and mechanism of action in health management.

Punicalagin attenuates isoproterenol-induced myocardial infarction through nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1-mediated inhibition of inflammation and cardiac stress markers in experimental animal models.

Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.

3-carene supresses inflammatory cytokine interleukin-4, interleukin-5 and interleukin-13 in a murine model of asthma.

Asthma is a common airway disease associated with allergic inflammation. Environmental factors, such as pollens, pollution, insect-borne antigens, or commercial chemicals, cause this disease. The common symptoms of this airway allergic reaction are increasing mucus, narrowing of the airway wall, coughing, and chest tightness. Medications, such as steroids, alleviate the disease but with severe side effects. Several studies have reported the anti-inflammatory effects of tree-based essential oil components, particularly 3-carene. Therefore, this study used 3-carene to determine if it alleviates asthmatic symptoms in the murine model. First, BALB/c mice were sensitized to an ovalbumin and aluminium hydroxide mixture on day 7th and 14th. From days 21st to 23rd, the mice were challenged with 3-carene and budesonide. The lung trachea, plasma, and bronchiolar lavage fluid (BAL fluid) were collected on day 24. The 3-carene treatment suppressed the cytokine gene expression, such as interleukin-4 (IL-4), IL-5, and IL-13, reducing the lung epithelial cell thickness in the asthmatic model. These results suggest that essential oil 3-carene has an anti-asthmatic effect.

Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Nutritional, molecular, and functional properties of a novel enzymatically hydrolyzed porcine plasma product.

In the present study, an enzymatically hydrolyzed porcine plasma (EHPP) was nutritionally and molecularly characterized. EHPP molecular characterization showed, in contrast to spray-dried plasma (SDP), many peptides with relative molecular masses (Mr) below 8,000, constituting 73% of the protein relative abundance. IIAPPER, a well-known bioactive peptide with anti-inflammatory and antioxidant properties, was identified. In vivo functionality of EHPP was tested in C. elegans and two different mouse models of intestinal inflammation. In C. elegans subjected to lipopolysaccharide exposure, EHPP displayed a substantial anti-inflammatory effect, enhancing survival and motility by 40% and 21.5%, respectively. Similarly, in mice challenged with Staphylococcus aureus enterotoxin B or Escherichia coli O42, EHPP and SDP supplementation (8%) increased body weight and average daily gain while reducing the percentage of regulatory Th lymphocytes. Furthermore, both products mitigated the increase of pro-inflammatory cytokines expression associated with these challenged mouse models. In contrast, some significant differences were observed in markers such as Il-6 and Tnf-α, suggesting that the products may present different action mechanisms. In conclusion, EHPP demonstrated similar beneficial health effects to SDP, potentially attributable to the immunomodulatory and antioxidant activity of its characteristic low Mr bioactive peptides.

Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Salvianolate ameliorates inflammation and oxidative stress in high-glucose induced HK-2 cells by blocking TGF-ß/Smad signal pathway.

The objective of this research is to assess how salvianolate impacts inflammation and oxidative stress in a laboratory setting, as well as to investigate the underlying mechanisms. HK-2 cells were subjected to different treatments, including normal glucose, mannitol, high glucose and high glucose plus salvianolate. Cell proliferation, death, MDA levels, IL-1ß, IL-6, TNF-α, MCP-1 concentrations, ROS levels, MMP, MPTP and ATP levels were assessed using various kits. The protein expressions of NOX4, TGF-ß1, P-Smad2, P-Smad3, Smad4 and Smad7 were ascertained through western blot analysis. Our results indicated salvianolate could reduce the release of IL-1ß, IL-6, TNF-α, as well as MCP-1, alleviate the levels of oxidative stress markers NOX4 and MDA, and improve mitochondrial function by increasing MMP and ATP levels while reducing ROS and MPTP opening. Furthermore, salvianolate inhibited the TGF-ß1/Smad2, Smad3 signaling pathway, suppressed Smad4 expression and increased Smad7 expression. Salvianolate seems to mitigate inflammation and oxidative stress through a variety of mechanisms. These discoveries offer valuable understanding into the possible mechanisms by which salvianolate may be employed in the treatment of diabetic nephropathy.

Immunological, histological and immunohistochemical alternations induced by zinc oxide nanoparticles and mureer plant in spleen albino rats with the prospective anti-inflammatory action of gallic acid.

The current study was proposed to evaluate the mortal impacts of either alone or mixed treatments of zinc oxide nanoparticles (ZnO NPs) and mureer or Senecio glaucus L. plant (SP) on spleen tissue via immunological and histological studies and to estimate the likely immunomodulatory effect of gallic acid (GA) for 30 days in rats. Rats were classified into eight groups with orally treated: Control, GA (100mg/kg), ZnO NPs (150mg/kg), SP (400mg/kg), GA+ZnO NPs (100,150mg/kg), GA+SP (100,400mg/kg), ZnONPs+SP (150,400mg/kg) and GA+ZnONPs+SP (100,150,400mg/kg). Interleukin-6 (IL-6) level was measured using an enzyme-linked immunoassay (ELISA). Also, the pro-apoptotic protein (caspase-3) expression was estimated using an immunohistochemistry assay. Our data revealed that ZnO NPs and SP triggered a significant increase in the levels of IL-6 and total lipids (TL) and the activity of lactate dehydrogenase (LDH), (p<0.001). Furthermore, they overexpressed caspase-3 and caused lymphoid depletion. They revealed that the immunotoxic outcome of mixed treatment was more than the outcome of the alone treatment. However, GA restored the spleen damage from these adverse results. Finally, this study indicated that ZnO NPs and SP might be immunotoxic and splenotoxic agents; however, GA may be displayed as an anti-inflammatory and splenic-protective agent.

The function and application of edible fungal polysaccharides.

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.

Vitreoretinal Interface Cells Correlate In Vivo With Uveitis Activity and Decrease With Anti-Inflammatory Treatment.

Purpose: To highlight the utility of en face swept-source optical coherence tomography angiography (SS-OCTA) in assessing vitreoretinal interface cells (VRICs) of patients with active uveitis and their dynamics. Methods: In this prospective, single-center study, 20 eyes from patients with active uveitis were analyzed using six 6 × 6-mm macular scans at three time points: active inflammation (baseline), clinically improving (T1), and resolved inflammation (T2). VRICs were visualized using 3-µm en face OCT slabs on the inner limiting membrane. The variation of VRIC number, density, and size over time was assessed, and VRIC measurements were compared with clinical grading. Results: At baseline, the VRIC count was significantly higher (552.5 VRICs) than that of the healthy controls (478.2 VRICs), with a density of 15.3 cells/mm2. VRIC number decreased significantly to 394.8 (P = 0.007) at T1, with a density of 10.9 cells/mm2 (P = 0.007). VRIC size reduced from 6.8 µm to 6.3 µm at T1 (P = 0.009) and remained stable at T2 (P = 0.3). Correlation coefficients between inflammatory parameters (anterior chamber cells and National Eye Institute vitreous haze), and VRIC count indicated a positive correlation at baseline (r = 0.53), weakening at T1 (r = 0.36), and becoming negative at T2 (r = -0.24). Conclusions: En face SS-OCTA revealed increased VRIC number and size in active uveitis, likely due to monocyte recruitment. Post-inflammation control, VRIC number, size, and density significantly decreased, returning to normal despite residual anterior chamber cells or vitreous haze. Translational Relevance: Visualization of VRICs by in vivo OCT opens up new opportunities for therapeutic targets.

Microbial Polysaccharides Extracted from Different Mature Muds of the Euganean Thermal District Show Similar Anti-Inflammatory Activity In Vivo.

The Euganean Thermal District, situated in North-East Italy, is one of Europe's largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.