Search Results (298)

Skin wound management in veterinary medicine requires therapies able to control inflammation, limit microbial burden, and support tissue repair. This study evaluated the anti-inflammatory, wound-healing, and immunomodulatory effects of four novel topical formulations combining synthetic anti-inflammatory drugs, antibiotics, and plant extracts in rat experimental models. Burn injury was induced in male Wistar rats for wound-healing assessment, while kaolin- and dextran-induced paw edema models were used to assess anti-inflammatory activity. The tested formulations were meloxicam, dexamethasone, and levofloxacin; thyme extract with meloxicam and dexamethasone; burdock extract with dexamethasone and levofloxacin; and thyme extract combined with burdock extract. Wound evolution was monitored macroscopically, edema was quantified by plethysmometry, and selected inflammatory mediators were measured by immunoassay. In the burn model, the thyme-containing formulation with meloxicam and dexamethasone, and the thyme–burdock formulation, achieved complete wound closure by the end of follow-up, whereas the reference product did not. In the acute inflammation models, all innovative formulations significantly reduced edema at the main early time points compared with the negative control and outperformed the reference product. The thyme–burdock formulation also showed the most favorable immunomodulatory profile, including normalization of interleukin-10 and marked reduction in interleukin-1 beta in both models. These results support the potential of multi-component topical formulations, particularly plant extract-based combinations, as promising candidates for veterinary wound care. Full article

This case highlights a novel genotype–phenotype correlation in the field of endocrinology. Specific endocrine and imaging assessment, in addition to next-generation sequencing (NGS), was performed on the Illumina MiSeq platform, using a TruSight One Sequencing Panel kit for genomic analysis of coding regions of 4813 genes. A 54-year-old female was confirmed with a papillary thyroid carcinoma after total thyroidectomy and underwent radioiodine ablative therapy. Three years later, a left femoral enchondroma of almost 3 cm was identified at computed tomography (CT) scan and magnetic resonance imaging (MRI). She experienced hypertension (in addition to obesity, dyslipidaemia and impaired glucose tolerance) and was later confirmed with ACTH-independent cortisol excess [lack of cortisol suppression at 1 mg dexamethasone testing of 13.9 (normal < 1.8 µg/dL)], noting bilateral adrenal tumors, of 4.7 cm (right), respectively, and of 1.6 cm (left) at CT. Right laparoscopic adrenalectomy was performed with post-operative adrenal insufficiency, requiring glucocorticoid replacement and stopping the anti-hypertensive medication. Pathology report confirmed an adrenocortical adenoma (a Ki67 proliferation index of 2%). Noting the unusual association of the mentioned conditions, NGS was performed in the peripheral blood and identified a heterozygote missense variant of the APC gene (c.5759G>A, p.Arg1920Gln), a heterozygote missense variant of the MSH6 gene (c.2092C>G, p.Gln698Glu), and an incidental additional finding: a heterozygote stop gain pathogenic variant of the CACNA1S gene (c.2707C>T, p.Arg903*). The first two are currently classified as variants of uncertain significance. Whether the co-presence of a triple mutation may change the clinical picture and the life-long outcomes across reciprocal influence is still an open matter. Further research will point out the clinical implications of this genotype–phenotype association, which, to our best knowledge, has not been previously reported. Full article

Acute lung injury (ALI) is a severe inflammatory condition associated with high morbidity and mortality, and there are currently no specific pharmacological treatments available. In this context, plants and natural products have emerged as promising therapeutic alternatives. SteLL (Schinus terebinthifolia Raddi leaf lectin) has demonstrated several biological activities, including anti-inflammatory and immunomodulatory effects. This study evaluated the anti-inflammatory effects of SteLL in a murine model of lipopolysaccharide (LPS)-induced ALI. Female BALB/c mice received intraperitoneal (i.p.) administration of SteLL (1, 5, or 10 mg/kg), dexamethasone (2 mg/kg), or vehicle (PBS). Sixty minutes later, ALI was induced by intranasal instillation of 25 µL of LPS (1 μg/μL). After 24 h, the animals were euthanized. Bronchoalveolar lavage fluid (BALF) was obtained to evaluate inflammatory parameters and lungs were collected for histopathological analysis. The tested doses of SteLL resulted in a 45–66% lower leukocyte infiltration. The group treated with 5 mg/kg exhibited a lower proportion of neutrophils and a higher proportion of mononucleated cells. Pre-treatment with SteLL also minimized plasma leakage and myeloperoxidase (MPO) activity. Furthermore, SteLL attenuated the release of pro-inflammatory cytokines at all tested doses as well as prevented nitric oxide (NO) production at the highest dose (10 mg/kg). Histopathological analysis showed that SteLL (5 and 10 mg/kg) attenuated LPS-induced lung injury. Overall, SteLL demonstrated significant anti-inflammatory effects, showing its potential as a plant-derived compound for modulating pulmonary inflammation. Full article

Surgical site infections (SSIs) remain a major clinical challenge, particularly due to bacterial adhesion and biofilm formation on suture materials. In this study, we developed a dual drug-eluting suture incorporating chlorhexidine (CHX) and dexamethasone (DEX), with lauric acid used as a binding agent to enhance drug adhesion. The exact composition of the system was CHX/DEX/Lauric Acid, designed to enable localized delivery of both therapeutic agents at the implantation site. Vicryl sutures were dip-coated and characterized by means of FTIR-ATR and HPLC to confirm drug incorporation and release. Mechanical integrity was preserved, with no significant difference in tensile strength between coated and uncoated sutures. Antimicrobial activity was confirmed against Gram-positive and -negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in addition to the yeast Candida albicans. Cell viability assays demonstrated acceptable biocompatibility, with values exceeding 70%. These findings support the potential of dual-functionalized sutures to reduce SSIs and modulate inflammation, offering a promising strategy for improving postoperative outcomes. Full article

Intracranial meningiomas (ICMs) are the most common primary adult brain tumor. They are more frequent in women, respond to female hormones, are associated with breast cancer and are often progesterone receptor-positive (PR+), consistent with hormonal sensitivity. Yet <20% are weakly estrogen receptor-positive (ER+). This work reviews the literature to investigate this paucity of ER by first testing if Dexamethasone (Dex), which has been used since 1984 to reduce peritumoral brain edema, is suppressing ER. Ligand-binding assays after 1984 have shown a significant decrease in any and supra-threshold (>10 fmol/mg) ER+ from 68.5% and 39.6% to 25.5% and 12%, respectively (both p < 0.0001). This was confirmed as Dex-related in 93 patients with known Dex exposure (p = 0.0075). Immunohistochemical tests after 1984 have shown that 16% (95%CI 8.4–24.4) of ICMs have rare ER+ cells unrelated to PR and pS2 expression, consistent with Dex inhibition of ER transcription activity. Dex suppression of ER may be compounded by lower endogenous ER concentrations in ICMs compared to breast cancer. The difference in intra-tumoral estrogen concentration is proposed as a potential cause for lower ER in ICM. Replacement of Dex and more sensitive ER assays are needed to determine the role of hormones in the causation and treatment of ER+ ICM. Full article

Background/Objectives: Mild autonomous cortisol secretion (MACS) is increasingly recognized in patients with adrenal incidentalomas. While associated with cardiometabolic risk, management strategies remain controversial, particularly regarding functional outcomes. This retrospective comparative cohort study evaluated the impact of adrenalectomy versus conservative management on muscle strength in MACS patients. Materials and Methods: Forty patients with MACS (1-mg dexamethasone suppression test > 1.8 µg/dL) were enrolled: 15 underwent adrenalectomy and 25 received conservative management. Hand grip strength was measured using calibrated dynamometry, and gait speed was assessed with the 1-m walk test at baseline and 6 months. Results: Baseline characteristics are summarized descriptively for the surgical and conservative cohorts. At 6 months, the surgery group showed significant improvements in right hand grip strength (+1.19 ± 0.64 kg, p < 0.001) and left hand grip strength (+1.15 ± 0.49 kg, p < 0.001), representing approximately 5% improvement. In contrast, the conservative group exhibited significant decreases in strength over the same period (right: −0.40 ± 0.25 kg; left: −0.28 ± 0.28 kg, both p < 0.001). The post-surgical 1-mg dexamethasone suppression test decreased from 4.05 ± 1.44 to 1.01 ± 0.34 µg/dL (p < 0.001). Conclusions: Adrenalectomy results in significant improvement in objective muscle strength in MACS patients, with improvement observed in parallel to biochemical resolution of cortisol excess. In contrast, conservative management was associated with progressive decline in grip strength over 6 months. Hand grip dynamometry provides valuable functional outcome data that may guide surgical decision-making in MACS management. Full article

Background/Objectives: Fluoroscopically guided cervical nerve root corticosteroid injections are used for the treatment and diagnosis of radicular pain. Including a local anesthetic with the injected corticosteroid may decrease the pain associated with the procedure and add immediate diagnostic value. However, little is known about the safety of including a local anesthetic with a corticosteroid in these injections. Methods: A total of 299 consecutive cervical nerve root injections, performed between 2016 and 2024, were reviewed. Demographic and injection information (level/laterality and inclusion/exclusion of 1% preservative-free lidocaine with dexamethasone injectate) were documented. Charts were reviewed for major complications and increased pain post-procedure. Categorical data were compared between groups using Fisher’s exact test or Chi-square testing. Results: Injections were performed with 10 mg of dexamethasone only in 263 cases and with a mixture of 10 mg of dexamethasone and 1 mL of 1% lidocaine in 36 cases. There was no statistically significant difference in the incidence of major complications (p ≈ 1) or immediately increased pain post-procedure (p = 0.799). Conclusions: With proper technique, there is no evidence from this case–control study or in the available literature to suggest that including lidocaine with corticosteroid increases risks associated with cervical nerve root injections. However, serious adverse events are theoretically possible with injection of local anesthetic into a radicular artery, the vertebral artery, or subdural space. Given that such risks are not associated with the use of non-particulate steroids alone, large multi-institutional studies are needed to draw confident conclusions on the risks and benefits of the inclusion of local anesthetics with non-particulate corticosteroids for cervical transforaminal epidural steroid injection to inform clinical practice. Full article

Magnesium has attracted attention as an orthopedic implant material due to its excellent biocompatibility and biodegradability; however, rapid corrosion in physiological environments remains a major limitation. In this study, a polydopamine (PDA) intermediate layer and alginate/chitosan multilayer coating were formed on pure magnesium surfaces, with dexamethasone incorporation to simultaneously improve corrosion resistance and bioactivity. SEM observation revealed that uniform coating layers were formed on alginate/chitosan multilayer coated specimens, and the chemical structure of the coating layers was confirmed through FT-IR and XRD analyses. Electrochemical analysis revealed that the PDA/alginate/chitosan coating group exhibited higher corrosion potential (Ecorr: −0.7514 ± 0.022 V vs. −1.706 ± 0.001 V) and lower corrosion current density (icorr: 2.275 ± 0.15 × 10⁻⁷ A/cm² vs. 1.528 ± 0.47 × 10⁻⁴ A/cm²) compared to pure magnesium, with the highest impedance indicating superior corrosion resistance. In tape peel testing, the polydopamine-coated group demonstrated superior adhesion compared to the non-coated group, and sustained release of dexamethasone was confirmed. MC3T3-E1 cell culture results confirmed cell proliferation in all specimens, with the PDA/alginate/chitosan group exhibiting the highest ALP activity compared to other surface-treated groups. Based on these results, the PDA/alginate/chitosan multilayer coating was confirmed to be an effective surface modification method for corrosion control and promotion of osteoblast differentiation on magnesium. Full article

Tumor necrosis factor-α (TNF-α) is a central mediator of inflammatory pathology; thus, the selective suppression of TNF-α without causing broad immunosuppression remains a critical therapeutic goal. This study investigated the anti-inflammatory potential and underlying mechanisms of Dahlia pinnata (D. pinnata) extract in human monocytes and epithelial cells. We demonstrate that D. pinnata extract selectively suppresses basal TNF-α expression in THP-1 monocytes and BEAS-2B bronchial epithelial cells, with minimal impact on IL-1β, IL-6, or IL-10 and without inducing cytotoxicity. The extract also potently attenuated TNF-α induction triggered by Pseudomonas aeruginosa infection or lipopolysaccharide (LPS) stimulation. Notably, D. pinnata extract exhibited stronger and broader TNF-α-suppressive effects than dexamethasone, particularly in monocytes where dexamethasone was ineffective under the tested conditions. Mechanistic analyses revealed that the extract suppresses TNF-α expression primarily through the inhibition of NF-κB signaling, accompanied by enhanced p38 MAPK activation. Fractionation of the extract identified two active fractions (06 and 07) that robustly suppressed TNF-α expression under both basal and stimulated conditions while maintaining low cytotoxicity. These fractions recapitulated the signaling profile of the crude extract by inhibiting NF-κB activation and promoting p38 signaling. Collectively, our findings identify D. pinnata as a rich source of bioactive compounds that selectively suppresses TNF-α through the coordinated modulation of NF-κB and p38 pathways, highlighting its potential as a scaffold for developing targeted anti-inflammatory therapeutics. Full article

This study aimed to control rapid localized corrosion and inflammation of biodegradable magnesium implants by developing a pH-responsive mPEG-PLGA coating loaded with dexamethasone (Dex). The mPEG-PLGA layer was designed to selectively degrade in alkaline conditions, thereby moderating pH elevation at the implant surface while enabling controlled Dex release. By varying the molecular weight of mPEG and PLGA, the degradation rate and microsphere size were tunable, allowing adjustment of the drug release profile. Among the tested coating solution concentrations (1.5–7.5 mg/mL), the formulation with 3 mg/mL Dex yielded a final cumulative release concentration of 0.02 mg/mL over a two-week period, which suppressed inflammatory responses in RAW 264.7 macrophages with minimal cytotoxicity, while enhancing BMP-2 and RUNX2 expression in mesenchymal stem cells. In a rat femur defect model, Mg implants coated with mPEG-PLGA containing 3 mg/mL Dex significantly increased bone volume and bone mineral density and reduced early TNF-α expression, accompanied by continuous new bone formation and strong BSP-positive osseointegration. These findings suggest that the proposed pH-responsive mPEG-PLGA/Dex coating provides a promising strategy to simultaneously regulate corrosion, attenuate inflammation, and promote bone regeneration around magnesium implants. Full article

Chronic stress (CS) contributes to male infertility, reduced testosterone levels, and impaired semen quality. CS models induced by glucocorticoids, such as dexamethasone (DEX), negatively affect sperm parameters and testicular health, notably by promoting testicular apoptosis. While individual plant extracts have been studied for their ability to mitigate stress-induced reproductive dysfunction, the preventive effect of the Tri Garn Pis (TGP) polyherbal extract in DEX-induced CS (DexCS) has not previously been investigated. This study evaluated the effects of TGP extract on testicular function, sexual behavior, and sperm quality in DexCS male mice. Seventy-two ICR mice were randomly divided into six groups: control, DexCS, TGP (50, 100, and 200) + DexCS, and TGP200. Mice received TGP (50, 100, 200 mg/kgBW) for 14 days before DEX co-treatment for 28 days. Behavioral and reproductive assessments included depression-like behavior tests, sexual behavior, sperm quality, testicular histopathology, steroidogenesis proteins (AR, CYP11A1, StAR), and apoptosis markers (Hsp70, caspase-3, caspase-9). TGP extract—which is rich in phenolics and flavonoids with antioxidant activity—improved depressive behavior, sexual performance, testicular histology, and low sperm quality. TGP also upregulated testicular StAR expression while reducing caspase-3 and caspase-9 levels. TGP prevents testicular apoptosis, sexual dysfunction, and poor sperm motility induced by DexCS. Full article

Inflammatory bowel disease (IBD) arises from chronic dysregulation at the epithelial–stromal interface, creating a need for in vitro systems that better capture these interactions. In this study, we developed a 3D co-culture platform in which HT-29 intestinal epithelial cells and IMR-90 fibroblasts are embedded within an alginate–gelatin hydrogel, alongside a complementary interface model using a plasma-treated electrospun mesh to spatially compartmentalize stromal and epithelial layers. We first assessed metabolic activity, viability, and proliferation across several epithelial-to-fibroblast ratios and identified 1:0.5 as the most supportive of epithelial expansion. The A1G7 hydrogel maintained high viability (>92%) and sustained growth in all mono- and co-cultures. To evaluate inflammatory competence, models were stimulated with lipopolysaccharide (LPS), administered either within the hydrogel or through the culture medium. LPS exposure increased TNF-α and IL-1β secretion in both configurations, with the magnitude of the response depending on the delivery route. Treatment with dexamethasone consistently reduced cytokine levels, confirming the model’s suitability for pharmacological testing. Together, these results demonstrate that the alginate–gelatin system provides a reproducible epithelial–stromal platform with quantifiable inflammatory readouts, offering a practical foundation for mechanistic studies and early-stage screening of anti-inflammatory therapeutics in IBD. Full article

One highly consequential presentation of Venezuelan equine encephalitis virus (VEEV) infection is encephalitis. Here we considered anti-inflammatory interventions to limit the effects of this using a BALB/c subcutaneously challenged mouse model of disease. This disease model nearly ubiquitously presents with severe encephalitis, where viral neuroinvasion correlates with much of the outward clinical signs of disease. A selection of already licenced, commonly used anti-inflammatory drugs were tested in mice developing encephalitis (starting treatment at $24 \mathrm{h}$ post challenge). Drug regimens were used that had previously been shown to have pharmacodynamic effects in mice for unrelated conditions. None of the treatment regimens tested reduced brain inflammation. A single anti-inflammatory drug (dexamethasone) was further tested utilising ascending doses in an effort to provide an effective anti-inflammatory regimen. Higher doses of dexamethasone ($20$ and $50 \mathrm{m}\mathrm{g}/\mathrm{k}\mathrm{g}$) reduced inflammatory markers in the brain and lowered weight loss and clinical signs early on during infection. However, the $50 \mathrm{m}\mathrm{g}/\mathrm{k}\mathrm{g}$ regimen also caused the disease to become more severe at later time points when compared to controls. When combined with the antiviral drug molnupiravir, the negative effects of the dexamethasone treatment ($20$ and $50 \mathrm{m}\mathrm{g}/\mathrm{k}\mathrm{g}$) were absent, and the positive disease severity-reducing effects remained. When combined with a specific VEEV monoclonal antibody (1A3B7), dexamethasone significantly reduced the antibody’s protective effects. These data present currently unique insights into how anti-inflammatory approaches might benefit patients with VEEV disease and where caution might be advised. Full article

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most of them are non-functioning adrenal tumours (NFATs). Yet, 30–40% of them are not entirely “non-functioning”, due to mild autonomous cortisol secretion (MACS). Despite not being a guideline-based diagnosis, a lower ACTH might point to various NFATs/MACS complications. Objective. This study aimed to determine the relationship between the bone health status of post-menopausal women with NFATs/MACS and their baseline morning ACTH level. The bone health indicators were DXA, FRAX, and bone remodelling markers. Methods. This was a retrospective, real-life, transversal study in adult females who were hospitalized in a single tertiary centre of endocrinology. They were all anti-osteoporotic drug-naïve. The subjects underwent CT and DXA scanning and a 1 mg dexamethasone suppression test (DST). Results. The cohort (sample size of N = 84 patients, 61.49 ± 7.86 years) had a type 2 diabetes rate of 18%, arterial hypertension rate of 75%, and a dyslipidemia rate of 78%. Median ACTH was 11.89 pg/mL. The prevalence of MACS was 30.95%. The mean largest tumour diameter (LTD) was 2.25 ± 0.99 cm. ACTH correlated with second-day cortisol after the 1 mg DST (r = −0.301, p = 0.024), and LTD (r = −0.434, p < 0.001). ROC analysis for the bone resorption marker CrossLaps showed an AUC of 0.647 (p = 0.05), with the highest Youden index for the cut-off at 0.32 ng/mL (sensitivity 87.50%, specificity 39.50%). Bone impairment (osteoporosis + osteopenia) was found in 65% of patients, with an osteoporotic fracture prevalence of 4.76%. The lowest mean T-score (−1.12 ± 1.00) showed osteopenia, and the median trabecular bone score pointed a partially degraded microarchitecture [median (interquartile interval): 1.320 (1.230, 1.392)]. FRAX and FRAXplus estimations correlated with bone mineral density (BMD) at all three central DXA sites, regardless of the ACTH cut-off. Patients with a low ACTH (<10 pg/mL) displayed similar bone/adrenal features when compared to those with normal ACTH, except forbut they had a higher MACS rate (45.45% versus 21.57%, p = 0.021) and a larger LTD (2.67 ± 0.98 versus 1.98 ± 0.92 cm, p = 0.003). Fracture estimation showed that only in patients with a low ACTH, the 10-year fracture risk for major osteoporotic fractures (MOF) adjusted for lumbar BMD was lower than the risk for MOF adjusted for diabetes (p = 0.036), and the 10-year hip fracture risk was lower when adjusted for lumbar BMD (p = 0.007). ACTH correlated with lumbar BMD (r = 0.591, p = 0.002) only in the group with an ACTH < 10 pg/mL, suggesting its potential usefulness as a bone biomarker in these cases. On the other hand, MACS-negative subjects with a low ACTH versus those with a normal ACTH showed higher CrossLaps (0.60 ± 0.27 versus 0.42 ± 0.21 ng/mL, p = 0.022), indicating an elevated bone resorption even in patients with tumours that are regarded as true non-secretors. Conclusions. A subgroup of patients diagnosed with NFATs/MACS might be prone to skeletal damage, and biomarkers such as ACTH (specifically, suppressed ACTH) might serve as a surrogate pointer to help refine this higher risk in daily practice. Further research to address other ACTH cut-offs will place ACTH assays in the overall bone status evaluation in these patients, most probably not as a single biomarker, but in addition to other assays. Full article

Brown adipose tissue (BAT) has emerged as a promising therapeutic target for metabolic disorders such as type 2 diabetes and obesity. To advance research on BAT activation and elucidate the mechanisms underlying adipogenesis, it is crucial to develop a reliable in vitro model. This study aimed to optimize the differentiation of adipose-derived stem cells (ADSCs) into beige adipocytes and to validate the protocol using primary human ADSCs obtained from eight donors. Protocol optimization was first performed with commercial ADSCs, testing more than 30 combinations of adipogenic conditions. Differentiation was assessed by microscopy, Oil Red O staining, and uncoupling protein 1 (UCP1) expression via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Among the key adipogenic factors, rosiglitazone proved more effective than indomethacin. Extending the induction phase from 4 to 8 days and maintaining dexamethasone throughout the culture markedly enhanced differentiation efficiency. Serum concentration above 5% was inhibitory, while optimal conditions were identified as 5 μM rosiglitazone and 20 μg/mL insulin. The optimized protocol successfully induced beige adipogenesis in ADSCs from eight independent donors, though efficiency varied considerably which could be attributed to individual donor variability. These findings provide a robust in vitro model for studying beige fat biology and highlight the relevance of personalized approaches in metabolic research. Full article