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Background: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. Methods: In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.5, or 10 μmol/L. In the in vivo assays, streptozotocin-induced diabetic rats with excision wounds received daily topical applications of 0.2 g of 5% (w/w) hispolon ointment. Results: Hispolon improved cell viability; suppressed oxidative stress by reducing reactive oxygen species, lipid peroxidation, and oxidative DNA damage; and restored the reduced glutathione/oxidized glutathione ratio. The scratch assay demonstrated that hispolon at 10 μmol/L enhanced fibroblast migration impaired by high-glucose conditions. Treatment with 5% (w/w) hispolon ointment accelerated wound contraction, reduced the epithelialization time, and enhanced tissue regeneration with an efficacy comparable to that of Fespixon® cream, as shown by histological findings of increased fibroblast activity, collagen deposition, and capillary growth. Hispolon ointment also modulated macrophage polarization in diabetic wounds by reducing M1 markers and enhancing M2 markers. In a diabetic rat dead-space-wound model, 5% (w/w) hispolon ointment reduced the levels of pro-inflammatory cytokines, increased those of anti-inflammatory cytokines and growth factors, and stimulated Type I and III collagen synthesis, effectively promoting wound healing. In incisional wounds, hispolon ointment improved the wound-breaking strength, showing results comparable to that of Fespixon® cream. Safety assessments confirmed that hispolon ointment showed no acute dermal toxicity. These findings underscore hispolon's potential as a promising candidate for diabetic wound management by mitigating oxidative stress, enhancing tissue regeneration, and accelerating wound healing. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter baumannii complex (Abc) is currently a significant cause of difficult-to-treat pneumonia. Due to the high prevalence rates of carbapenem- and extensively drug-resistant (CR, XDR) phenotypes, limited antibiotic options are available for the effective treatment of pneumonia caused by CR/XDR-Abc. Areas covered: In vitro susceptibility data, relevant pharmacokinetic profiles (especially the penetration ratios from plasma into epithelial-lining fluid), and pharmacodynamic indices of key antibiotics against CR/XDR-Abc are reviewed. Expert opinion: Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation. [ABSTRACT FROM AUTHOR]

Background: Hispidin, a polyphenol component mainly derived from the medicinal mushroom species Phellinus and Inonotus, shows promise for biomedical applications, yet its potential in wound healing remains largely unexplored. This research investigates the wound healing effects of hispidin through in vitro and in vivo experiments, while also evaluating its antimicrobial properties and safety profile. Methods: In vitro scratch assays were conducted to evaluate the impact of hispidin on the migration of NIH-3T3 cells. The wound healing potential of hispidin was assessed in rats using excision wounds, dead space wounds, and linear incisions, treated with various topical ointments including a simple ointment, 2.5% (w/w) and a 5% (w/w) hispidin ointment, and a 0.2% (w/w) nitrofurazone ointment, administered at 0.2 g daily for 14 days. Results: Hispidin demonstrated antimicrobial properties and was particularly effective against Staphylococcus epidermidis. Hispidin enhanced NIH-3T3 cell viability, and promoted wound closure in scratch assays, correlating with increased levels of FGF21, TGF-β1, EGF, and VEGF. In excision wound models, the 5% (w/w) hispidin ointment improved wound contraction, epithelialization, tissue regeneration, fibroblast activity, and angiogenesis. In the granulation tissue from dead space wound models, hispidin reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and lipid peroxidation, while increasing anti-inflammatory cytokines (IL-10) and antioxidant activities (SOD, GPx, CAT), along with connective tissue markers like hydroxyproline, hexosamine, and hexuronic acid. Hispidin also enhanced wound breaking strength in incision models. Acute dermal toxicity studies indicated no adverse effects at 2000 mg/kg. Conclusions: These findings highlight hispidin's potential in wound care, demonstrating its antimicrobial, regenerative, and safety properties. [ABSTRACT FROM AUTHOR]

The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia. [ABSTRACT FROM AUTHOR]

The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future. [ABSTRACT FROM AUTHOR]

Degenerative diseases of the brain include Parkinson's disease (PD), which is associated with moveable signs and is still incurable. Hispidin belongs to polyphenol and originates primarily from the medicinal fungi Inonotus and Phellinus, with distinct biological effects. In the study, MES23.5 cells were induced by 1-methyl-4-phenylpyridinium (MPP+) to build a cell model of PD in order to detect the protective effect of hispdin and to specify the underlying mechanism. Pretreatment of MES23.5 cells with 1 h of hispdin at appropriate concentrations, followed by incubation of 24 h with 2 μmol/L MPP+ to induce cell damage. MPP+ resulted in reactive oxygen species production that diminished cell viability and dopamine content. Mitochondrial dysfunction in MS23.5 cells exposed to MPP+ was observed, indicated by inhibition of activity in the mitochondrial respiratory chain complex I, the collapse of potential in mitochondrial transmembrane, and the liberation of mitochondrial cytochrome c. Enabling C-Jun N-terminal kinase (JNK), reducing Bcl-2/Bax, and enhancing caspase-9/caspase-3/PARP cleavage were also seen by MPP+ induction associated with increased DNA fragmentation. All of the events mentioned above associated with MPP+-mediated mitochondrial-dependent caspases cascades were attenuated under cells pretreatment with hispidin (20 µmol/L); similar results were obtained during cell pretreatment with pan-JNK inhibitor JNK-IN-8 (1 µmol/L) or JNK3 inhibitor SR3576 (25 µmol/L). The findings show that hispidin has neuroprotection against MPP+-induced mitochondrial dysfunction and cellular apoptosis and suggest that hispidin can be seen as an assist in preventing PD. [ABSTRACT FROM AUTHOR]