Search Results (1,319)

Dex is a drug commonly used as an immunosuppressive and anti-inflammatory agent in humans and animals. GCs have a profound impact on melatonin expression and biological rhythm. However, the effect of chronic exposure to Dex on melatonin secretion and biological clock gene expression in ruminants is still unclear. Ten goats were randomly divided into two groups: the control group was injected with saline, and the Dex-treated group was intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The rhythm of melatonin secretion in the plasma was disturbed in the Dex group, and the plasma and colon levels of melatonin were lower in the Dex group compared to the control group (p < 0.05). Dex leads to a significant decrease in the expression of Arylalkylamine N-acetyltransferase (AANAT), a key melatonin synthase, in the pineal gland and colon. Detecting intestinal leakage-related indices showed that diamine oxidase (DAO) and lipopolysaccharide (LPS) content increased significantly in the Dex group (p < 0.05). We also detected genes associated with biological rhythms in the plasma. In the control group, the five tested genes showed circadian rhythms, but the circadian rhythms of Clock, Cry1, Cry2, and Per2 were abolished or blunted by the Dex (p < 0.05). Protein levels of CLOCK and BMAL1 in the colon changed significantly (p < 0.05). In conclusion, the above experimental results show that chronic exposure to Dex leads to the disorder of the circadian rhythms of melatonin secretion and clock genes. Full article

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G′ values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN’s composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9–1), depending on the IPN’s composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells. Full article

The analysis of cosmetic products represents an important field of analytical chemistry, since the demand for new formulations is continuously increasing. Regulations about prohibited/regulated compounds are applied in each country. Among the substances that are banned in cosmetics, corticosteroids represent a potential harm for consumers since the prolonged exposure to these compounds can affect health status. However, corticosteroids can be found in cosmetics as an illegal addition since they are able to alleviate the symptoms of inflammatory skin problems. In this work, two different approaches for detecting corticosteroids as potential adulterants in cosmetic products were compared. First, a reversed-phase HPLC-MS method was optimized and fully validated in order to identify and quantify eight corticosteroids (methylprednisolone, beclomethasone, flunisolide, budesonide, betamethasone 17-valerate, beclomethasone dipropionate, flumethasone, and dexamethasone). This reference method was then compared with an enzyme-linked immunosorbent assay (ELISA). Indeed, immunological techniques allow for rapid, low-cost, and sensitive detection of target analytes even in complex matrices, and they can be performed with simple instrumentation and by non-skilled personnel. The application of these methods on spiked cosmetic products was compared in terms of performance and advantages in order to evaluate the possibility of exploiting a complementary approach for optimizing the time for and costs of the analysis. Full article

The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% (w/w) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen’s egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions. Full article

Encephalitis affects 1.9 to 14.3 people per 100,000 each year, and the mortality rate varies but can be up to 40%. After the identification of a particular microorganism in a patient with encephalitis, appropriate antimicrobial therapy should be initiated. Corticosteroid therapy represents a therapeutic option in the treatment of primary central nervous system diseases due to its ability to reduce the inflammatory commitment of CNS and consequently reduce mortality rates regardless of the causative agent of injury. Corticosteroid therapy represents a therapeutic option in the treatment of primary central nervous system diseases. Their use is also recommended in meningitis with autoimmune etiology. While corticosteroids have repeatedly been used as adjunctive treatment in encephalitis of viral etiology, the scientific evidence supporting their effectiveness remains scarce. The use of standard doses recommended by the guidelines seems reasonable as an initial setting, especially when a definitive diagnosis of the causal agent is still awaited. The subsequent adjustment should be personalized based on the individual clinical response. Full article

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O₂ saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms—lethargy, discoordination, and impaired communication—without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as “brain fog”. Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections. Full article

Neural electrodes used for bidirectional communication between the nervous system and external devices like prosthetic limbs have advanced in neuroprosthetic applications. However, their effectiveness is hindered by the foreign body reaction, a natural immune response causing inflammation and fibrosis around the implanted device. This process involves protein adsorption, immune cell recruitment, cytokine release, and fibroblast activation, leading to a fibrous capsule formation and a decrease in electrode functionality. Anti-inflammatory and antifibrotic strategies have the potential to diminish the impact of the foreign body response. In this work, we have evaluated long-term metformin administration and short-term dexamethasone administration as a combined therapy to modulate the foreign body reaction induced by a polyimide intraneural implant in the sciatic nerve of rats. After a 12-week implant, the foreign body reaction was significantly reduced only in the group administered both drugs. Full article

Adipogenesis is a complex process influenced by various cellular interactions within adipose tissue, which plays a critical role in metabolic homeostasis. This study aimed to develop a novel in vitro three-dimensional (3D) co-culture model using murine 3T3-L1 pre-adipocytes, J774 macrophages, and NIH-3T3 fibroblasts to investigate adipogenic differentiation and inflammatory pathways. We first validated an adipogenic differentiation protocol in a two-dimensional (2D) model, where 3T3-L1 pre-adipocytes were subjected to a hormonal medium containing 3-isobutyl-1-methylxanthine, dexamethasone and insulin. After 7 days, differentiated cells were analyzed using Oil Red O and Nile Red staining, confirming lipid accumulation. Subsequently, spheroids were formed in 3D cultures, with monospheroids and heterospheroids maintained in either control medium or MDI for 11 days. Size measurements indicated significant growth in heterospheroids, particularly in the 3T3-L1:J774 combination, underscoring the importance of cellular interactions. Confocal microscopy and flow cytometry analyses demonstrated that even in the absence of hormonal stimuli, control spheroids exhibited adipogenic differentiation, evidenced by a notable proportion of Nile Red-positive cells (75.7 ± 1.7%). Inflammatory profiling revealed that the heterospheroid 3:J produced the highest levels of nitric oxide (NO), with no significant differences observed between control and MDI conditions. This study highlights the potential of 3D co-culture systems for elucidating the intricate interactions among adipocytes, macrophages, and fibroblasts. The findings may provide valuable insights into novel therapeutic targets for metabolic disorders. Full article

(1) Background: the objective of this study was to examine the impact of defatted mealworm hydrolysate (DMH), formulated through protein hydrolysis, on muscle protein synthesis in C2C12 cells and rats; (2) Methods: C2C12 cells were treated with dexamethasone and DMH, and cell viability was quantified using the MTT assay. Twenty-four Sprague–Dawley rats were divided into three groups (control, DEX, and DEX + DMH) and treated for 8 weeks. The DEX and DEX + DMH groups were administered intraperitoneal injections of DEX at a concentration of 2.25 mg/kg over a 3-d period. The control and DEX groups were fed a control diet, whereas the DMH group had part of the protein composition of the control diet replaced with 3.5% of DMH. The impact of DMH on muscle protein synthesis was evaluated through the measurement of grip strength, gastrocnemius and tibialis anterior muscle weights, and the investigation of muscle protein synthesis and degradation factor mRNA expression utilising the real-time PCR method; (3) Results: in vitro experiments demonstrated that treatment with DMH at concentrations greater than 5 mg/mL markedly alleviated DEX-induced injury in C2C12 cells. In vivo experiments demonstrated that the mRNA expression levels of myogenin and myoblast determination proteins, which promote muscle protein synthesis, were significantly increased. Furthermore, rats fed DMH exhibited significantly enhanced grip strength and tibialis anterior weight; (4) Conclusions: these findings indicate that DMH may serve as a functional material capable of promoting muscle protein synthesis and that the utilization of proteolytic enzymes is advantageous for the effective utilization of mealworms. Full article

Osteoporosis, a common metabolic bone disorder, leads to increased fracture risk and significant morbidity, particularly in postmenopausal women and the elderly. Traditional treatments often fail to fully restore bone health and may cause side effects, prompting the exploration of regenerative therapies. Adipose-derived stem cells (ADSCs) offer potential for osteoporosis treatment, but their natural inclination toward adipogenic rather than osteogenic differentiation poses a challenge. This study investigates a novel approach combining differentiation inducers (DIs), three-dimensional (3D) hydrogel scaffolds, and photobiomodulation (PBM) to promote osteogenic differentiation of immortalised ADSCs. A dextran-based 3D hydrogel matrix, supplemented with a DI cocktail of dexamethasone, β-glycerophosphate disodium, and ascorbic acid, was used to foster osteogenesis. PBM was applied using near-infrared (825 nm), green (525 nm), and combined wavelengths at fluences of 3 J/cm², 5 J/cm², and 7 J/cm² to enhance osteogenic potential. Flow cytometry identified osteoblast-specific markers, while inverted light microscopy evaluated cellular morphology. Reactive oxygen species assays measured oxidative stress, and quantitative polymerase chain reaction (qPCR) revealed upregulated gene expression linked to osteogenesis. The findings demonstrate that integrating DIs, 3D hydrogels, and PBM effectively drives osteogenic differentiation in immortalised ADSCs. The PBM enhanced osteogenic marker expression, induced morphological changes, and upregulated gene activity, presenting a promising framework for bone regeneration. Future research should assess the stability and functionality of these differentiated cells and explore their applicability in preclinical models of bone injury or degeneration. This integrative approach demonstrated specific efficacy in promoting the osteogenic differentiation of ADSCs, highlighting its potential application in developing targeted treatments for osteoporosis. Full article

Muscle atrophy, an age-related condition, presents a growing healthcare concern within the context of global population aging. While studies have investigated Hirsutella sinensis for its potential antifatigue properties, reports on its active components remain limited. This study evaluated the efficacy of H. sinensis mycelium extract on muscle health, utilizing a 1:1 water–ethanol preparation administered to C57BL/6 mice exhibiting acute hind leg atrophy. The results indicated no adverse effects, with significant improvements in muscle endurance and soleus muscle mass observed over a 14-day period. To further elucidate the mechanisms and effects of H. sinensis mycelium on dexamethasone-induced muscle atrophy, the water extract was fractionated into components of <3.5 kDa, 3.5–10 kDa, and >10 kDa using dialysis membranes. The investigation utilized a C2C12 cell atrophy model, induced by dexamethasone, to analyze the expression of relevant genes via qPCR. The results demonstrated that the <3.5 kDa and >10 kDa fractions significantly upregulated the expression of Myh2 and Myh7 genes while simultaneously downregulating the expression of MuRF-1 and Atrogin-1. It is noteworthy that the <3.5 kDa fraction exclusively enhanced MYHC protein expression and suppressed AMPK expression, as confirmed by Western blot analysis. This comprehensive pilot study suggests that the low-molecular-weight fraction of H. sinensis mycelium exhibits considerable potential for muscle mass preservation and atrophy mitigation. As a result, it offers a promising direction for the development of supplements aimed at addressing fatigue and preventing muscle atrophy. Full article

Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose–insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.5% protein, NP group). At 90 days of age, male rat offspring were challenged with food deprivation (72 h of fasting), intracerebroventricular (icv) injection of dexamethasone (2 µL, 2.115 mmol/L) or chronic intraperitoneal injection of dexamethasone (1 mg/kg body weight/5 days). Body weight, food intake, intravenous glucose tolerance test (ivGTT) results, insulin secretion and biochemical parameters were assessed. LP rats did not display significant metabolic changes after long-term starvation (p > 0.05) or under the central effect of dexamethasone (p = 0.999). Chronic dexamethasone induced rapid hyperglycemia (~1.2-fold, p < 0.001) and hyperinsulinemia (NP: 65%; LP: 216%; p < 0.001), decreased insulin sensitivity (NP: ~2-fold; LP: ~4-fold; p < 0.001), reduced insulinemia (20%) and increased glycemia (35%) only in NP rats under ivGTT conditions (p < 0.001). Glucose and acetylcholine insulinotropic effects, as well as the muscarinic receptor antagonist response, were reduced by chronic dexamethasone only in pancreatic islets from NP rats (p < 0.05). The direct effect of dexamethasone on pancreatic islets reduced insulin secretion (NP: 60.2%, p < 0.001; LP: 33.8%, p < 0.001). Peripheral glucose–insulin dyshomeostasis and functional failure of pancreatic islets in LP rats, as evidenced by an impaired acute and chronic response to metabolic stress, may be due to excessive corticosterone action as a long-term consequence. Full article

Background/Objectives: Sarcopenia is characterized by the loss of muscle mass and function, increases in mortality rate, and risk of comorbidities in the elderly. This study evaluated the effects of Alnus japonica hot water extract (AJHW) and its active compound, oregonin, on muscle atrophy and apoptosis in vitro. Methods: AJHW underwent phytochemical analysis. C2C12 cells were subjected to H₂O₂ and dexamethasone to induce oxidative stress and muscle loss, after which AJHW and oregonin were administered to assess their impacts on cell viability, apoptosis, muscle protein synthesis stimulation, and muscle protein degradation inhibition. Cell viability was assessed via an MTT assay, and apoptosis was analyzed by measuring Bcl-2, Bax, cleaved caspase-3, and cleaved PARP through Western blotting. Western blotting and RT-PCR were utilized to analyze MyoD, Myogenin, Atrogin-1, and MuRF1 protein and gene expression in a muscle atrophy model, as well as the Akt/mTOR and FoxO3α pathways. Results: AJHW was confirmed to contain oregonin, an active compound. AJHW and oregonin significantly increased cell viability and reduced apoptosis by upregulating Bcl-2 and downregulating Bax, cleaved caspase-3, and cleaved PARP. They significantly enhanced muscle protein synthesis through the upregulation of MyoD and Myogenin, while diminishing muscle degradation by downregulating Atrogin-1 and MuRF1. The activation of the Akt/mTOR pathway and inhibition of the FoxO3α pathway were also observed. Conclusions: AJHW and oregonin effectively prevented muscle cell apoptosis, promoted muscle protein synthesis, and inhibited muscle protein degradation in vitro. These results suggest that AJHW and oregonin could serve as therapeutic agents to prevent and treat sarcopenia. Full article

Background: Melasma is a challenging, acquired hyperpigmentary disorder. The gold standard treatment is Kligman’s formulation, which contains hydroquinone, tretinoin, and dexamethasone, but its long-term use is limited by the risk of exogenous ochronosis. Cysteamine, a tyrosinase inhibitor, reduces melanocyte activity and melanin production, showing strong depigmenting effects in patients resistant to Kligman’s formulation. Nonetheless, clinical studies have yielded inconsistent efficacy results. This meta-analysis aimed to assess the efficacy of cysteamine in treating melasma and to identify potential factors that may impact its therapeutic outcomes. Methods: A systematic search of PubMed, Embase, Web of Science, and CENTRAL, from the earliest record until August 2024, was conducted. Randomized controlled trials and quasi-randomized design studies related to topical cysteamine on melasma patients were included. The primary outcome was MASI or mMASI assessment after treatments. The current meta-analysis was conducted with a random-effects model. Subgroup analyses and meta-regressions were performed based on baseline MASI, disease duration of melasma, patient age, and sample size of the included studies. Funnel plots and Duval and Tweedie’s trim and fill method were adopted to assess the publication bias. Results: Eight studies were included for quantitative analysis. The analysis of MASI after topical cysteamine demonstrated a significant decrease compared to the placebo (p = 0.002). Compared to other melasma treatments, cysteamine did not show superior efficacy in mMASI (p = 0.277). The treatment efficacy of hydroquinone, modified Kligman’s formula, and tranexamic acid mesotherapy for melasma was not statistically different when compared to cysteamine (p = 0.434). Further analyses showed no benefit when allowing extended cysteamine application time (p < 0.0001). The meta-regression revealed the efficacy of cysteamine decreased as the duration of melasma increased (coefficient = 0.38, p = 0.0001, R² = 0.99). The funnel plot displayed some asymmetry. The trim and fill method suggested the adjusted effect size was 0.607 (95% CI = −0.720 to 1.935). Conclusions: Cysteamine exhibited efficacy in treating melasma patients; however, its depigmentation effect was comparable to hydroquinone-based regimens, tranexamic acid mesotherapy, and modified Kligman’s formula. Using cysteamine in patients with a short duration of melasma may result in better efficacy. Full article

Mandarin fish ranavirus (MRV) is a distinctive member among the genus Ranavirus of the family Iridoviridae. The persistently covert infection of MRV was previously observed in a natural outbreak of MRV, but the underlying mechanism remains unclear. Here, we show that mandarin fish peripheral B lymphocytes are implemented as viral reservoirs to maintain the persistent infection. When mandarin fish were infected with a sublethal dosage of MRV under a nonpermissive temperature (19 °C) and a permissive temperature (26 °C), all of the fish in the 19 °C group survived and entered the persistent phase of infection, characterized by a very low viral load in white blood cells, whereas some of the fish died of MRV infection in the 26 °C group, and the survival fish then initiated a persistent infection status. Raising the temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigation showed that IgM⁺-labeled B lymphocytes, but not CD3Δ⁺-labeled T lymphocytes and MRC-1⁺-labeled macrophages, are target cells for the persistent infection of MRV. Moreover, the reactivation of the quiescent MRV was confirmed through a non-TLR5 signal pathway manner. Collectively, we demonstrate the presence of the B cell-dependent persistent infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus. Full article