The hypothalamic-pituitary-adrenal axis regulates the secretion of glucocorticoids in response to environmental challenges. In the brain, a nuclear receptor transcription factor, the glucocorticoid receptor, is an important component of the hypothalamic-pituitary-adrenal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity. The glucocorticoid receptor influences cognitive processes, including glutamate neurotransmission, calcium signaling, and the activation of brain-derived neurotrophic factor-mediated pathways, through a combination of genomic and non-genomic mechanisms. Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor, thereby affecting the hypothalamic-pituitary-adrenal axis and stress-related cognitive functions. An appropriate level of glucocorticoid receptor expression can improve cognitive function, while excessive glucocorticoid receptors or long-term exposure to glucocorticoids may lead to cognitive impairment. Patients with cognitive impairment-associated diseases, such as Alzheimer's disease, aging, depression, Parkinson's disease, Huntington's disease, stroke, and addiction, often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression. This review provides a comprehensive overview of the functions of the glucocorticoid receptor in the hypothalamic-pituitary-adrenal axis and cognitive activities. It emphasizes that appropriate glucocorticoid receptor signaling facilitates learning and memory, while its dysregulation can lead to cognitive impairment. This provides clues about how glucocorticoid receptor signaling can be targeted to overcome cognitive disability-related disorders.

As a synthetic glucocorticoid, prednisone has been widely used in autoimmune diseases, recurrent abortion and asthma during pregnancy. Although studies suggested that glucocorticoid exposure during pregnancy have developmental toxicity, systematic research on the characteristics of the developmental toxicity of prednisone is lacking. This study intends to construct embryonic prednisone exposure (EPE) model to observe its bone developmental toxicity characteristics of prednisone and explore the mechanism. The results showed that EPE can shortened body and head length, reduced eye and head area, decreased operculum mineralization area, reduced mineralized vertebrae number, shortened ceratohyal and palatoquadrate cartilage length, and decreased expression of key osteogenic differentiation and cartilage development genes. The toxicity to osteogenesis is more severe than chondrogenesis. The toxicity caused by exposure in the middle and terminal stages of embryogenesis is more serious and shows a concentration-effect relationship. We confirmed that Gr/Hdac6 signaling activation mediates prednisone-induced inhibition of osteoblast differentiation by epigenetically regulating the Postnb/Wnt/β-catenin signaling pathway. The results of this study systematically demonstrate the characteristics of prednisone-induced systemic, bone, and cartilage developmental toxicity, and clarify the epigenetic mechanism of its osteogenic developmental toxicity. This provides theoretical and experimental evidence for the safe use of prednisone during pregnancy and the determination of early monitoring targets for bone developmental toxicity.

Pain is a complex sensory and emotional experience that severely affects an individual's quality of life and health status. Steroid hormones, as important regulatory substances in the human body, are extensively involved in various physiological and pathological processes. In recent years, remarkable progress has been made in the research of steroid hormones in the field of pain. They play a crucial role in the occurrence, development, and treatment of pain. This review comprehensively elaborates on the roles and therapeutic mechanisms of steroid hormones in pain, explores the performances of glucocorticoids, mineralocorticoids, sex hormones, etc. in different pain models, as well as the molecular mechanisms by which they regulate pain through genomic and non-genomic effects, aiming to provide a theoretical basis for the clinical treatment of pain.

Cochlear implantation is the standard of care for individuals with severe-to-profound sensorineural hearing loss. However, implantation itself can degrade residual hearing, for example due to insertional trauma and subsequent inflammatory processes. One potential method to mitigate this loss of residual hearing is through the local and sustained delivery of anti-inflammatory drugs released from the electrode array. To this end, a dexamethasone eluting electrode array (FLEX28 DEX) was developed by MED-EL. Here we present the results from a first-in-human feasibility study of the CIDEXEL system (the Mi1200 SYNCHRONY cochlear implant combined with the FLEX28 DEX array). A single-arm, exploratory, open-label, prospective, longitudinal, and monocentric study design with sequential block enrolment was used. Nine participants were implanted with the CIDEXEL and were followed up to 9 months post first fitting. The primary aim was to evaluate the safety of the device. The secondary aims were to assess: 1) electrode impedance levels; 2) hearing preservation rates; 3) speech perception outcomes; and 4) subjective feedback from the surgeons regarding their experience with the device during the operation. There were no device- or procedure-related serious adverse events. Low and stable impedance levels were observed across all electrode sites (basal, medial and apical). In the majority of participants, good preservation of residual hearing (≤15 dB hearing loss) was achieved. The participants showed speech perception test results which were comparable to those with a non-eluting FLEX28 array. Surgeons reported that the CIDEXEL had similar handling and insertion properties to a conventional electrode array.

Sepsis is characterized by a systemic inflammation disorder and multi-organ dysfunction caused by infection. Glucocorticoids (GCs), as anti-inflammatory properties drugs, are widely used for the management of patients with inflammatory diseases, including sepsis. However, the therapeutic effect and underlying mechanisms of GCs on sepsis remain incompletely understood.

Mouse sepsis models were constructed using intraperitoneal injection of lipopolysaccharide (LPS) and treated with synthetic GC dexamethasone (DEX). Systemic inflammation and organ injury were evaluated by histological staining, immunophenotypic analysis, and detection of inflammatory cytokines. Inflammatory signaling pathways were identified by western blot (WB) and RT-qPCR. Finally, targeted metabolomics were conducted to examine metabolic changes.

Subcutaneous administration of DEX significantly alleviate LPS-induced acute organ injury and systemic inflammation, thereby reducing mortality in septic mice. DEX substantially reduced the amounts of intrahepatic neutrophils/macrophages, and inflammatory cytokines expressions in the livers of septic mice and in LPS-stimulated bone-marrow-derived macrophages (BMDMs). Mechanistically, DEX inhibit JAK1/STAT3 signaling pathway both in livers and BMDMs. Pharmacological inhibition of JAK1 or STAT3 via Upadacitinib or Stattic, respectively, partially mimic the anti-inflammatory function of GC, including the reduction of intrahepatic macrophages, proinflammatory cytokines production, and mortality in septic mice. Additionally, DEX could also promote the rewiring of tricarboxylic acid (TCA) cycle in the livers of septic mice.

This study provides important insights into the molecular and metabolic mechanisms underlying GCs-mediated anti-inflammatory reactions.

Chrysin (CHR) is the principal active compound in honey, propolis and plants. Its pharmacological effects include anti-inflammatory, antiallergic, and antioxidant capabilities. However, its poor solubility and bioavailability constitute a limitation. In this study, Poly-lactic-co-glycolic acid (PLGA) was used as a nanocarrier to enhance the stability, bioavailability, and effectiveness of CHR to protect mice from indirect acute lung injury (ALI) caused by lipopolysaccharide (LPS). CHR-loaded PLGA nanoparticle (CHR-NP) was prepared and characterized using techniques such as FTIR, zeta potential analysis, DLS, in vitro drug release assessment, encapsulation efficiency measurement, and TEM. Prior to the intraperitoneal injection of LPS (10mg/kg), C57BL/6 mice were orally administered CHR (50mg/kg), PLGA (50mg/kg), CHR-NP (50mg/kg), and dexamethasone (Dexa) (5mg/kg) for a duration of six days. Following 24hours of LPS or normal saline (control) injection, the mice were anesthetized. CHR-NP increased catalase, glutathione, and glutathione peroxidase while decreasing malondialdehyde, myeloperoxidase, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-12, and interferon (IFN)-γ. Moreover, treatment with CHR-NP augmented the gene and protein expression of the Keap1/Nrf2/ARE signaling pathway utilizing quantitative real-time PCR (RT-PCR), western blotting, and immunohistochemistry. Additionally, CHR-NP reduced histological alterations, pulmonary edema, damage, and iron deposition. Our findings indicate that CHR-NP significantly mitigated indirect ALI, primarily through the suppression of inflammation, oxidative stress, and ferroptosis via the activation of the Keap1/Nrf2/ARE signaling pathways.

Aging is a major risk factor for a variety of diseases, thus, translation of aging research into practical applications is driven by the unmet need for existing clinical therapeutic options. Basic and translational research efforts are converging at a critical stage, yielding insights into how fundamental aging mechanisms are used to identify promising geroprotectors or therapeutics. This review highlights several research areas from a clinical perspective, including senescent cell targeting, alleviation of inflammaging, and optimization of metabolism with endogenous metabolites or precursors. Refining our understanding of these key areas, especially from the clinical angle, may help us to better understand and attenuate aging processes and improve overall health outcomes.

Many studies indicate the gut microbiome is associated with diseases caused by administering high-dose glucocorticoids (GCs), such as hypertension, hyperglycemia, and osteoporosis. However, the association between intestinal flora and the use of high-dose GCs remains elusive. We aimed to characterize gut microbiome in Graves' ophthalmopathy (GO) patients after administering high-dose GCs. In this study, 20 primary GO patients were recruited. The differences in gut microbiota of GO patients before and after administering high-dose GCs were analyzed by 16S rDNA sequencing technology. Untargeted metabolomic analysis was used to examine the differences in gut metabolites between two groups. There were significant differences in α and β diversities of gut microbiota in GO patients before and after administering high-dose GCs. The random forest analysis indicated that three intestinal bacteria (Faecalibacterium, Streptococcus, and Prevotella) could distinguish the two groups with the highest accuracy, which was proven by receiver operator characteristic curve and linear discriminant analysis effect size analysis. The short-chain fatty acid-producing ability in GO patients' gut after high-dose GC administration was significantly decreased. The 5-hydroxytryptamine levels significantly increased in the gut of GO patients after administering high-dose GCs. Our study suggests that high-dose GC administration causes the changes in gut microbiome and metabolites. Moreover, the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.IMPORTANCEFor the first time, we revealed that gut microbiome and metabolome in Graves' ophthalmopathy patients after high-dose glucocorticoid (GC) administration significantly changed, and the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.

The utilization of dissolvable microneedles (MNs) is a promising and cutting-edge approach to drug delivery for the treatment of psoriasis, an autoimmune skin disorder characterized by the appearance of red, scaly patches on the skin. This study presents the development of a dissolving MN patch made of polyvinylpyrrolidone for the purpose of delivering Clobetasol 17-Propionate through the skin. The MN patches were evaluated for their physical characteristics, including morphology, solubility, strength, and ability to penetrate the skin. This evaluation was conducted on both unloaded and drug-loaded MN patches to determine their suitability for future applications. The manufacturing of 484 pyramidal-shaped tips, each measuring roughly 400 µm in height, was demonstrated by microscopy photographs. Compression tests revealed that the MN patch could endure a force greater than 1 N/needle while displacing around 300 µm, confirming the needle's ability to penetrate the stratum corneum. Following H&E staining, the penetration depth in mice skin was determined to be around 200 µm. The MN tips exhibited rapid drug release within a 10-minute timeframe, while the MN patch dissolved in the mice skin in roughly 20 min. An animal model was utilized to examine the effects of the produced patches on the treatment of psoriasis. Psoriasis was artificially induced in three groups of mice using imiquimod cream, applied for eight consecutive days to evaluate the inhibitory effect of clobetasol on exacerbating the disease. This assessment was accomplished using two methods: applying clobetasol ointment and using CP-loaded MNs. This innovative drug delivery system demonstrated encouraging results in terms of quick and effective administration, highlighting the potential of dissolvable MNs for psoriasis treatment.

OP, a systemic bone disorder marked by reduced bone mass and heightened fracture risk, poses a significant global health burden, particularly among aging populations. Current treatments, including bisphosphonates and calcium supplementation, are limited by adverse effects and incomplete efficacy. Emerging research highlights ferroptosis-an iron-dependent cell death driven by lipid peroxidation-as a critical contributor to OP pathogenesis, characterized by dysregulated iron metabolism, oxidative stress, and lipid peroxide accumulation, which disrupt bone remodeling by impairing osteoblast function and enhancing osteoclast activity. This review elucidates the mechanistic interplay between ferroptosis and OP subtypes (diabetic osteoporosis (DOP), glucocorticoid-induced (GIOP), and postmenopausal osteoporosis (PMOP)) and evaluates the efficacy of Chinese herbal interventions in mitigating ferroptosis-driven bone loss. Key findings reveal that excess iron exacerbates lipid peroxidation via the Fenton reaction, while glutathione peroxidase 4 (GPX4) inactivation and system Xc- inhibition amplify oxidative damage. In DIOP, hyperglycemia-induced ROS and advanced glycation end products suppress osteogenesis, countered by melatonin and naringenin via nuclear factor -related factor 2 (Nrf2)/GPX4 activation. GIOP involves dexamethasone-mediated GPX4 downregulation, mitigated by exosomes and melatonin through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. PMOP driven by estrogen deficiency-induced iron overload is alleviated by aconitine and icariin (ICA) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Chinese herbs, including active compounds (quercetin, gastrodin, ICA, etc.) and formulations (Bugu Shengsui Capsule, Erxian Decoction (EXD), etc.), regulate iron metabolism, enhance antioxidant defenses (Nrf2/heme oxygenase 1(HO-1)), and inhibit lipid peroxidation, effectively restoring bone homeostasis. These findings underscore ferroptosis as a pivotal mechanism in OP progression and highlight the therapeutic promise of Chinese herbs in bridging traditional medicine with modern mechanistic insights. Future research should prioritize elucidating precise molecular targets, optimizing formulations, and validating clinical efficacy to address current therapeutic gaps.

The oxidative stress-induced premature senescence of trabecular meshwork (TM) represents a pivotal risk factor for the development of glucocorticoid-induced glaucoma (GIG). This study aimed to elucidate the pathogenesis of TM senescence in GIG. MethodsIntraocular pressure (IOP), transmission electron microscopy and senescence-associated protein expression in TM were evaluated in GIG mice. Protein expression of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and monoamine oxidase A (MAOA), phosphorylation of AKT were quantified. ROS and mitochondrial superoxide levels were measured to evaluate cellular oxidative stress. Cell cycle analysis, β-galactosidase staining, senescence-associated protein expression were employed to assess the aging status of primary human trabecular meshwork cells (pHTMs). ResultsmRNA-seq and KEGG analysis indicating PI3K/AKT pathway as a key regulator in TM of GIG. PI3K inhibitor significantly prevented IOP elevation and abnormal mitochondrial morphology of TM in the GIG mouse model. PI3K inhibitor or selective silencing of PIK3R1 alleviated dexamethasone (DEX)-induced oxidative stress, also mitochondrial dysfunction, inhibiting MAOA expression in pHTMs. The same phenomenon was observed in the GIG models with inhibition of MAOA. Further KEGG analysis indicates that cellular senescence is the key factor in the pathogenesis of GIG. TM senescence was observed in both GIG mouse and cell models. Inhibition of the PI3K/AKT/MAOA pathway significantly alleviated DEX-induced premature cellular senescence of TM in GIG models. Glucocorticoids activated the PI3K/AKT/MAOA pathway, leading to mitochondrial dysfunction, oxidative stress, and premature aging in TM, elevating IOP. This mechanism could be associated with the onset and progression of GIG, providing a potential approach for its treatment.

Hydrogen sulfide (H2S) plays crucial inflammatory modulating roles, representing a promising candidate for anti-inflammatory therapies. However, current H2S delivery approaches lack sufficient specificity against inflammatory response. Herein, regarding the overexpressed aminopeptidase N (APN) at the inflammation sites, an APN-activated self-immolative carbonyl sulfide (COS)/H2S donor (AlaCOS) was developed for inflammatory response-specific H2S delivery. The compound showed sustained H2S generation upon APN activation in the presence of carbonic anhydrase (CA), and the responsiveness could be well regulated by modulating the amino acid sequence. Due to the inflammatory response-specific sustained H2S delivery, AlaCOS provided potent anti-inflammatory capability, which was further validated by RNA sequencing. In vivo experiments on a full-thickness cutaneous wound murine model also showed the strong promoting effect on wound healing, mainly due to the regulation of the inflammatory response by AlaCOS. By introducing a caged coumarin fluorophore to the molecular architecture, self-reporting fluorescence could be generated accompanied with APN-mediated COS/H2S release, which achieved the visualization of H2S delivery in vitro and in vivo. This work not only offers a useful tool for studying the bioactivity of H2S on inflammation, but also provides new insights for developing novel therapies to cope with inflammation-associated diseases.

The body instinctively responds to external stimuli by increasing energy metabolism and initiating immune responses upon receiving stress signals. Corticosterone (CORT), a glucocorticoid (GC) that regulates secretion along the hypothalamic-pituitary-adrenal (HPA) axis, mediates neurotransmission and humoral regulation. Due to the widespread expression of glucocorticoid receptors (GR), the effects of CORT are almost ubiquitous in various tissue cells. Therefore, on the one hand, CORT is a molecular signal that activates the body's immune system during stress and on the other hand, due to the chemical properties of GCs, the anti-inflammatory properties of CORT act as stabilizers to control the body's response to stress. Inflammation is a manifestation of immune activation. CORT plays dual roles in this process by both promoting inflammation and exerting anti-inflammatory effects in immune regulation. As a stress hormone, CORT levels fluctuate with the degree and duration of stress, determining its effects and the immune changes it induces. The immune system is essential for the body to resist diseases and maintain homeostasis, with immune imbalance being a key factor in the development of various diseases. Therefore, understanding the role of CORT and its mechanisms of action on immunity is crucial. This review addresses this important issue and summarizes the interactions between CORT and the immune system.

Anti-interferon-γ autoantibodies (AIGAs) syndrome is a recently recognized adult-onset immunodeficiency syndrome. Serum Immunoglobulin E (IgE) is increased in AIGAs syndrome, but the role of serum IgE levels in the clinical features and disease outcomes of AIGAs syndrome is not clear.

We retrospectively enrolled 163 patients diagnosed AIGAs syndrome with serum IgE examined at baseline from 2021 to 2024 and compared the clinical features between Group A (serum IgE level ≤ 212 IU/mL) and Group B (serum IgE level > 212 IU/mL). Multivariable logistic regression method was used to explore the risk factors associated with disease outcomes.

163 patients were included in this study, of whom 97 patients were in Group A (serum IgE level ≤ 212 IU/mL) and 66 patients in Group B (serum IgE level > 212 IU/mL). Group B showed higher number of infectious episodes, elevated levels of erythrocyte sedimentation rate (ESR), CD3 + T cells, immunoglobulin G (IgG), IgA, and globulins (GLB), shorter progression-free survival (PFS), and increased exacerbation numbers. Group B exhibited a higher incidence of fatigue, dyspnea, loss of appetite, rash, moist rales, hepatomegaly, and splenomegaly. Skin, bone marrow and spleen involvements were more common in Group B. IgE demonstrated correlations with IgG, GLB, Albumin (ALB), Eosinophils (EOS), IgG4, and ESR. During the follow-up, Group B exhibiting higher number of exacerbations compared to Group A (P < 0.0001). Multivariable Cox regression analysis revealed that High AIGAs titers (hazard ratio [HR], 2.418, 95% confidence interval [CI]1.037-5.642, P = 0.041), WBC > 22.52 × 109cells/L (HR2.199, 95%CI1.194-4.050, P = 0.012) were independent risk factors of disease exacerbation. Glucocorticoid treatment was commonly used in patients with AIGAs syndrome who had elevated IgE levels and skin involvement, demonstrating efficacy in improving condition.

Elevated serum IgE levels are associated with more severe clinical features in AIGAs syndrome, including increased infectious episodes, elevated inflammatory markers/immune markers, and multi-organ involvement, particularly skin. IgE serves as a marker of skin involvement and may indicate a potential response to glucocorticoid treatment.

Corticosteroids are frequently used in practice to treat patients with neurological disorders. However, its effect for stroke and traumatic brain injury (TBI) remains controversial. This study aimed to systematically review and evaluate efficacy and safety of corticosteroids for the treatment of stroke and TBI.

We searched Ovid-Medline and Ovid-Embase databases for randomised controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of corticosteroids in patients with ischaemic stroke, intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or TBI. The treatment intervention was corticosteroid, and the control was placebo or routine care. Outcome measures were death, functional outcomes and adverse events. We calculated odds ratio (OR) and 95% confidence interval (CI) for the effect size, pooled the results using random-effects modelling, and assessed heterogeneity by I2 statistic.

We identified 47 studies (41 RCTs and 6 cohort studies). Nine studies enrolled patients with ischaemic stroke (n = 2806), 6 studies for ICH (n = 1229), 1 study recruited both ischaemic stroke (n = 13) and ICH (n = 27), 10 studies for SAH (n = 1318) and 21 studies for TBI (n = 12,414). Dexamethasone was the most used corticosteroid (28 studies). Corticosteroids reduced risk of death at 3 months after ischaemic stroke (n = 1791; 31% vs. 26%, OR 0.77, 95% CI 0.62-0.95; df = 1, I2 = 0%) and after ICH (1 study; n = 850; 44% vs. 27%, OR 0.48, 95% CI 0.35-0.64), had no effect on death at 1 month after SAH (1 study; n = 140; 22% vs. 32%, OR 1.73, 95% CI 0.81-3.68), and increased risk of death at 6 months after TBI (n = 10,755; 23% vs. 27%, OR 1.20, 95% CI 1.10-1.32; df = 6, I2 = 0%). The pooled analyses found no significant effect of corticosteroids on functional outcome after ischaemic stroke, ICH, SAH or TBI, respectively.

Corticosteroids reduced the risk of death and in selected patients with stroke, such as those with large artery occlusion after thrombectomy, but increased the risk of death after TBI, had no effect on functional outcomes. Further trials are needed to identify individual stroke patients who may benefit from corticosteroids.

International Prospective Register of Systematic Reviews (CRD42023474473).

Pathogenic IgG autoantibodies play a crucial role in the pathogenesis of autoimmune diseases, and removal of pathogenic IgG autoantibodies is an important therapeutic approach and tool for such diseases. The neonatal Fc receptor (FcRn) interacts with IgG and protects it from lysosomal degradation. FcRn inhibitors accelerate the clearance of IgG antibodies, including pathogenic IgG autoantibodies, by targeting and blocking the binding of FcRn to IgG. Theoretically, FcRn inhibitors can be applied for the treatment of IgG-mediated autoimmune diseases. With successful completion of multiple relevant clinical trials, key evidence-based data have been provided for FcRn inhibitors in the treatment of IgG-mediated autoimmune diseases, and several FcRn inhibitors have been approved for these indications. Additional trials are being planned or conducted. This review examines all available high-quality clinical trials of FcRn inhibitors assessing IgG-mediated autoimmune diseases.

Atopic Dermatitis (AD) is a common continuous inflammation dermatosis requiring efficacious therapeutic intervention. Phellodendri Chinensis Cortex-Cnidii Fructus (PC) herb pair has shown effectiveness and security in traditional Chinese medicine (TCM) clinical applications, yet its pharmacological constituents and mechanisms are not fully elucidated.

This study used serum pharmacochemistry, network pharmacology, and validation experiments to examine the impact of PC in the treatment of AD.

Initially, ultra performance liquid chromatography-mass spectrometry (UPLC-MS) had been applied to elucidate the components of PC that were absorbed. An integrative approach combining network pharmacology and in vivo research (general index observation, skin pathological tissue staining, ELISA, immunohistochemistry, immunofluorescence, and Western blotting) was employed to validate PC's mechanism in action after 2,4-dinitrochlorobenzene (DNCB) was used to create a mouse model of AD.

Fifty-three compounds and 18 serum prototype components were characterized within PC. The therapeutic efficacy of PC in AD was notably manifested in the alleviation of pruritus, improvement of skin histopathology, and reduction of cytokines involving IgE, IL-4, TNF-α and IL-6. Based on molecular docking studies, pharmacodynamic components such as phellodendrine, xanthotoxin, nomilin, and isopimpinellin strongly favored the main targets. Comprehensive investigations integrating serum pharmacochemistry, network pharmacology, and in vivo studies had revealed that PC prevented DNCB-induced AD through adjusting the TLR4/NF-κB signaling pathway.

The anti-AD effects of PC may be attributed to its modulation of the TLR4/NF-κB signaling pathway, reduction of NF-кB expression in the nucleusim, downregulation of inflammatory cytokine levels, provement of skin histopathological manifestations, and reduction of skin pruritus.

Rheumatoid arthritis (RA) is an autoimmune disorder that impacts around 1% of the global population. Up to 20% of people become disabled within a year, which has a severely negative impact on their health and quality of life. RA has a complicated pathogenic mechanism, which initially affects small joints and progresses to larger ones over time. It can damage the skin, eyes, heart, kidney, and lung. Oral medications, intra-articular injections, and other treatments are being used; nevertheless, they have drawbacks, including low bioavailability, numerous adverse effects, and poor patient compliance. Dissolving microneedles (DMNs) are a safe and painless method for transdermal drug delivery, achieved through their ability to physically penetrate the epidermal barrier. They enable targeted drug delivery, significantly enhancing the bioavailability of medications and improving patient compliance. DMNs are particularly effective in delivering both lipophilic and high molecular weight biomolecules. The superior bioavailability of DMNs is demonstrated by the fact that low-dose DMN administration can achieve up to 25.8 times higher bioavailability compared to oral administration. This paper provides a comprehensive review of recent advancements in the use of DMNs for RA treatment, encompassing various materials (such as hyaluronic acid, chitosan, etc.), fabrication techniques (such as the two-step casting method, photopolymerization), and performance evaluations (including morphology, mechanical properties, skin penetration capability, solubility, and pharmacodynamics). Additionally, a thorough safety assessment has been conducted, revealing that DMNs cause minimal skin irritation and exhibit low cytotoxicity, ensuring their safety for clinical application. DMNs provide a highly effective and promising alternative to oral and injectable drug delivery systems, offering a novel therapeutic approach for RA patients that significantly improves treatment outcomes and enhances their quality of life.

The risk factors for gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients are rarely reported. This study aimed to investigate the risk factors for gastrointestinal complications in internal medicine patients using glucocorticoids.

Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Gastrointestinal complications were identified by careful review of the electronic medical records of these patients. The risk factors for gastrointestinal complications during glucocorticoid therapy were analyzed by univariable and multivariable logistic regression. Receiver operating characteristic (ROC) curve with Youden's index was used to determine the best cutoff point of the identified continuous variables.

Of the 960 inpatients included, 88 had gastrointestinal complications, with the most common complications including 27 (30.7%) with abdominal discomfort, 26 (29.5%) with acid regurgitation and heartburn, and 14 (15.9%) with asymptomatic positive fecal occult blood. Multiple logistic regression analysis showed that age ≥ 65 years [OR = 2.014, 95% CI (1.096, 3.703), p = 0.024], history of gastroesophageal reflux disease (GERD) [OR = 1.810, 95% CI (1.009, 3.250), p = 0.047], history of peptic ulcer (PU) [OR = 5.636, 95% CI (1.505, 21.102), p = 0.010], maximum dose of glucocorticoids [OR = 1.003, 95% CI (1.001, 1.004), p = 0.001], and nonsteroidal anti-inflammatory drugs (NSAIDs) [OR = 2.788, 95% CI (1.023, 7.597), p = 0.045] were associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. ROC curve analysis revealed that when the maximum dose of glucocorticoids was greater than 160 mg, gastrointestinal complications were more likely to occur.

The study shows that age ≥ 65 years, history of GERD, history of PU, maximum dose of glucocorticoids, and NSAIDs are associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. Multidisciplinary teams, including physicians, pharmacists, and nurses, should consider increased monitoring to inpatients with high-risk factors.

Non-alcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD), can also manifest in patients classified as non-MAFLD who do not meet MAFLD criteria. The involvement of cortisol and thyroid hormones may play a role in the pathogenesis of FLD by modifying the metabolism of specific lipoproteins, particularly apolipoprotein M (Apo M). This study investigated cortisol and thyroid hormones levels and Apo M gene expression in white blood cells (WBCs) of individuals with MAFLD, non-MAFLD, and healthy controls.

The serum and WBCs of the study subjects were collected from patients with FLD (n=99) including 58 MAFLD and 41 non-MAFLD and healthy individuals (n=23). To investigate the gene expression of Apo M and thyroid and cortisol hormones, qRT-PCR and ELISA methods were used, respectively.

The Apo M gene expression was significantly lower in FLD patients, both non-MAFLD, and MAFLD patients compared to the control group (p<0.05). Total T4 and TSH hormone levels in the MAFLD patients were significantly decreased and increased compared to the control group, respectively (p<0.05). The cortisol level was significantly elevated in the FLD and MAFLD patients compared to the control group (p<0.01).

Alterations in Apo M gene expression also cortisol and thyroid hormones levels in non-MAFLD patients were milder than MAFLD patients when compared to the control. Also, likely Apo M may be involved in FLD pathogenesis.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear.

This study aimed to identify the bioactive components of HXZQ responsible for its therapeutic effects on UC and to elucidate their underlying mechanisms.

The effect of HXZQ against dextran sodium sulfate (DSS)-induced colitis was investigated. Ingredients in HXZQ were characterized and analyzed in colitic mice using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). In vitro, biological activity of compounds was assessed using lipopolysaccharide (LPS)-induced Ana-1 cells and bone marrow-derived macrophages (BMDMs), tumor necrosis factor-alpha (TNF-α)-induced Caco-2 cells, and isolated intestinal crypts from colitic mice. These results were confirmed in vivo. The targets of the components were identified through bioinformatics analysis and validated via molecular docking, enzyme inhibition assays, and in vivo experiments. Hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time polymerase chain reaction (qPCR) were employed to confirm the pharmaceutical effects.

A clinical equivalent dose of HXZQ (2.5 mL/kg) effectively treated DSS-induced colitis. A total of 113 compounds were identified in HXZQ, with 35 compounds detected in colitic mice. Glycyrrhizic acid (GA) and patchouli alcohol (PA) emerged as key contributors to the anti-colitic effects of HXZQ. Further investigation revealed that HXZQ and its active components decreased the levels of pro-inflammatory cytokines TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) in colon, likely by inhibiting nuclear factor kappa-B (NF-κB) signaling pathway. This inhibition indirectly activated the intestinal farnesoid X receptor (FXR) signaling pathway, correcting bile acid imbalances caused by colitis. Additionally, these components significantly enhanced the expression of tight junction proteins ZO-1 and Occludin, as well as the adhesion protein E-cadherin, and reduced goblet cell loss, thereby repairing intestinal barrier injury. Mechanistically, GA and PA were found to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, leading to increased local active corticosterone levels in the intestine to exert anti-inflammatory effects. Notably, the inhibition of 11β-HSD1 with the selective inhibitor BVT2733 (BVT) ameliorated colitis in mice.

HXZQ exhibits therapeutic effects on UC, primarily through GA and PA inhibiting 11β-HSD1. This suggests new natural therapy approaches for UC and positions 11β-HSD1 as a potential target for colitis treatment.

Methylprednisolone (MP) is a synthetic glucocorticoid known for its anti-inflammatory and immunosuppressive effects, yet its application in global spinal cord injury (SCI) research has not been thoroughly summarized. This study aims to assess the current status and trends of methylprednisolone research in SCI, providing insights for future scholarly work.

Articles on methylprednisolone in SCI published from 1975 to 2023 were retrieved from the Web of Science database. Metrics such as publication counts, H-index values, and data on countries, institutions, authors, and journals were analyzed. Co-citation, collaboration, and co-occurrence analyses of keywords were performed using CiteSpace.

A total of 1,651 articles were identified, and publication numbers showed a consistent annual increase. The United States and Canada led in publication counts, H-index values, and citations, with the University of Toronto and the Veterans Health Administration being significant contributors. Bracken M.B. was the leading author. The most frequent keywords included 'trauma,' 'lipid peroxidation,' 'dose response,' 'ischemia,' and 'methylprednisolone.' A co-occurrence analysis classified 225 keywords into three clusters, highlighting key research areas in SCI.

These findings offer valuable insights into authors, countries, institutions, keywords, and research hotspots in SCI over the past 50 years, guiding future research directions in this field.

The nine human NR3 nuclear receptors translate steroid hormone signals in transcriptomic responses and operate multiple highly important processes ranging from development over reproductive tissue function to inflammatory and metabolic homeostasis. Although several NR3 ligands such as glucocorticoids are invaluable drugs, this family is only partially explored, for example, in autoimmune diseases and neurodegeneration, but may hold therapeutic potential in new areas. Here we report a chemogenomics (CG) library to reveal elusive effects of NR3 receptor modulation in phenotypic settings. 34 highly annotated and chemically diverse ligands covering all NR3 receptors were selected considering complementary modes of action and activity, selectivity and lack of toxicity. Endoplasmic reticulum stress resolving effects of N3 CG subsets in proof-of-concept application validate suitability of the set to connect phenotypic outcomes with targets and to explore NR3 receptors from a translational perspective.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by synovial hyperplasia, where inflammatory macrophages within the joint synovium produce multiple inflammatory cytokines, leading to cartilage damage. The development of therapeutic strategies that combine anti-inflammatory effects and cartilage repair mechanisms holds great promise for effective RA treatment. To address the limitations associated with the off-target effects of intravenous administration and the risk of synovial cavity infection with repeated local injections, we have innovatively developed a liposomal drug depot through hyaluronic acid (HA)-modified liposomes encapsulating dexamethasone sodium phosphate (DSP)-loaded nanogels, termed HA-Lipo@G/D. The nanogels were prepared by ionic cross-linking of chondroitin sulfate and gelatin, both of which have notable cartilage repair properties. In vitro studies demonstrated that this formulation exhibited sustained drug release, enhanced uptake by inflammatory macrophages, reduced secretion of inflammatory factors (TNF-α, IL-1β), and significantly decreased chondrocyte apoptosis induced by inflammatory factors. Moreover, in vivo assessments in a rat model of collagen-induced arthritis revealed effective accumulation of the liposomal drug depot at the inflamed joint site, resulting in macrophage repolarization and cartilage tissue repair. Our findings provide a synergistic strategy for inhibiting inflammation and mitigating cartilage damage through local joint cavity injection, thereby enhancing the therapeutic efficacy of RA.

High altitude pulmonary edema (HAPE) is a life-threatening, non-cardiogenic pulmonary edema characterized by rapid onset and high mortality. Extracellular vesicles of mesenchymal stem cells are used in the treatment of a variety of lung diseases, but their use in HAPE remains underreported. This study explores the therapeutic potential of miRNA-486 modified extracellular vesicles from dental pulp stem cells (sEVmiR-486) against HAPE, aiming to decipher the associated molecular mechanisms. The rat HAPE model was established by exposing subjects to a simulated high-altitude, low-oxygen environment within a specialized chamber. The HAPE-afflicted rats received sEVNull and sEVmiR-486 intravenously, and the therapeutic effect was assessed through histopathological analysis, pulmonary artery pressure, lung water content, as well as markers of oxidative stress and inflammation. To supplement in vivo findings, pulmonary microvascular endothelial cells (PMVEC) were stressed with cobalt chloride to emulate hypoxic damage, and then treated with sEVNull and sEVmiR-486 to unravel the mechanism of action. The sEVNull mitigated pathological changes in the lungs, reduced pulmonary artery pressure and lung water content, and alleviated oxidative stress and inflammatory responses in cases of HAPE. Moreover, sEVNull enhanced vascular reactivity and restored pulmonary permeability and tight junction integrity, these effects were intensified by miRNA-486 overexpression. Notably, sEVmiR-486 attenuated oxidative damage in hypoxic PMVEC cells by modulating the PTEN/PI3K/Akt/eNOS signaling pathway. miRNA-486 fortified DPSC-sEVs intervention as a novel and potent treatment strategy for HAPE.

Accumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored.

The objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS.

The effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1.

We identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1β, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1).

This study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.

Vamorolone, a novel "dissociative" steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD).

To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD and to assess cortisol thresholds using a monoclonal antibody immunoassay.

Post hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of <500 nmol/L ("historical threshold") and <400 nmol/L ("revised threshold").

Mean age at enrolment was 5.41 ± 0.86 years (n = 118). At week 24, the proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day = 100% (25/25) and 92.0% (23/25); vamorolone 6 mg/kg/day = 95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day = 84.2% (16/19) and 47.5% (9/19); and placebo = 20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48 = 0.83).

AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone.

This case report describes a case of isolated adrenocorticotropic hormone (ACTH) deficiency that presented with arthritis. Initial investigations, including blood tests, imaging, and musculoskeletal ultrasonography, did not confirm any specific connective tissue disease, making it initially difficult to identify the cause of the arthritis. Subsequent adrenal crisis led to the diagnosis of isolated ACTH deficiency through comprehensive endocrine evaluation. The patient's musculoskeletal symptoms, together with generalised symptoms, were resolved following corticosteroid replacement therapy. This report highlights isolated ACTH deficiency as a rare but one of the causes of polyarticular joint pain and underscores the importance of considering endocrine disorders in the differential diagnosis of unexplained arthritis, particularly when accompanied by systemic symptoms.

Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis.

Gout is a common type of arthritis marked by monosodium urate (MSU) crystal deposition in joints, triggering an inflammatory response. Qu-Shi-Xie-Zhuo (QSXZ), a traditional Chinese medicine (TCM) formula, has been clinically used for the treatment of gouty arthritis (GA).

The study sought to examine the impact of QSXZ on GA and to delve into the pharmacological mechanisms that underlie its effects.

The chemical constituents of QSXZ were analyzed through UPLC-MS. MSU-induced acute gouty arthritis (AGA) and subcutaneous (SC) air pouch models in mice were employed to evaluate the anti-inflammatory properties of QSXZ and its primary active compound, Cryptotanshinone (CTS). To investigate the therapeutic mechanisms of QSXZ, we used MS-based network pharmacology, transcriptomic analysis, molecular docking and multiscale bioassays.

Treatment of QSXZ revealed a significant reduction of inflammatory cell infiltration and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin -1β (IL-1β). Based on UPLC/MS/MS results, 49 components were considered the active ingredients of QSXZ. Network pharmacology analysis indicated that QSXZ regulates multiple inflammation-related pathways. Subsequent transcriptomic analysis showed that QSXZ regulates gene expression of S100A8 and S100A9. Our investigation observed an increased expression of S100A8 and S100A9 in monocytes derived from gout patients. Molecular docking and molecular dynamics simulation analysis revealed the binding pattern and interaction between QSXZ active compound CTS and S100A8/A9, and subsequent surface plasmon resonance (SPR) and cell thermal shift assay (CETSA) experiments verified the direct interaction between them. To investigate the mechanisms of action, we conducted RT-PCR, Western blotting, immunohistochemistry, flow cytometry, and measured the inflammatory response. Our findings highlight the pathogenic role of S100A8/A9 mediated TLR4-NLRP3 axis in gout and review outstanding therapeutic effects of QSXZ and its primary active compound CTS on MSU-induced experimental models.

In summary, this study substantiates the therapeutic potential of QSXZ and its primary active compound CTS, as promising alternative treatments for GA. Our findings provide valuable insight into the critical pharmacological mechanism of QSXZ in regulating inflammation, highlighting its potential therapeutic effects in GA management.

The mortality and morbidity of emergency total aortic arch replacement (TAAR) for acute type A aortic dissection (ATAAD) is high, which is partly due to the excessively activated systemic inflammatory response. Methylprednisolone, an anti-inflammatory agent, might suppress the systemic inflammatory response and lead to improved outcomes. However, the protective effects of methylprednisolone on TAAR for ATAAD were not clarified. The usage and dosage varied in different centers across the world.

The Medal trial is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate whether 500 mg methylprednisolone IV before cardiopulmonary bypass could reduce the incidence of postoperative major organ injury, compared to placebo. Adult patients with the diagnosis with ATAAD, awaiting emergency total aortic arch replacement with hypothermic circulatory arrest and selective cerebral perfusion will be included in the trial. A total of 340 eligible subjects from 9 large cardiovascular centers will be randomized in a 1:1 ratio to receive 500 mg methylprednislone or placebo before cardiopulmonary bypass. The primary outcome is postoperative major adverse outcome [defined as all-cause death or postoperative neurological deficit or KDIGO II -III acute kidney injury or respiratory syndrome (tracheal intubation> 72 hours, tracheostomy or re-intubation) until postoperative day 30 or patient discharge]. The study has received approval from the local Ethics Committees of the 9 participating centers, and enrolled its first subject in June 24, 2022. As of September 5, 2024, 323 subjects have been enrolled. Results of the Medal trial will be published once data collection and analysis have been completed.

The Medal trial will determine the effectiveness of 500 mg methylprednisolone on the outcomes of patients with ATAAD undergoing TAAR.

URL https://www.chictr.org.cn/searchprojEN.html (Chinese Clinical Trial Registry). Unique identifier: ChiCTR2200059286.

Inflammation is a biological response to harmful stimuli, playing a crucial role in facilitating tissue repair by eradicating pathogenic microorganisms. However, when inflammation becomes chronic, it leads to numerous serious disorders, particularly in autoimmune diseases. Anti-inflammatory peptides (AIPs) have emerged as promising therapeutic agents due to their high specificity, potency, and low toxicity. However, identifying AIPs using traditional in vivo methods is time-consuming and expensive. Recent advancements in computational-based intelligent models for peptides have offered a cost-effective alternative for identifying various inflammatory diseases, owing to their selectivity toward targeted cells with low side effects. In this paper, we propose a novel computational model, namely, DeepAIPs-Pred, for the accurate prediction of AIP sequences. The training samples are represented using LBP-PSSM- and LBP-SMR-based evolutionary image transformation methods. Additionally, to capture contextual semantic features, we employed attention-based ProtBERT-BFD embedding and QLC for structural features. Furthermore, differential evolution (DE)-based weighted feature integration is utilized to produce a multiview feature vector. The SMOTE-Tomek Links are introduced to address the class imbalance problem, and a two-layer feature selection technique is proposed to reduce and select the optimal features. Finally, the novel self-normalized bidirectional temporal convolutional networks (SnBiTCN) are trained using optimal features, achieving a significant predictive accuracy of 94.92% and an AUC of 0.97. The generalization of our proposed model is validated using two independent datasets, demonstrating higher performance with the improvement of ∼2 and ∼10% of accuracies than the existing state-of-the-art model using Ind-I and Ind-II, respectively. The efficacy and reliability of DeepAIPs-Pred highlight its potential as a valuable and promising tool for drug development and research academia.

Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions.

This article investigates the effect of long-term cannabidiol (CBD) treatment on changes in the renal transcriptome in a mouse model. The main hypothesis was that systematic CBD treatment would affect gene expression associated with those processes in the kidney.

The study was conducted on male C57BL/6J mice. Mice in the experimental groups received daily intraperitoneal injections of CBD at doses of 10 mg/kg or 20 mg/kg body weight (b.w.) for 28 days. After the experiment, kidney tissues were collected, RNA was isolated, and RNA-Seq sequencing was performed.

The results show CBD's effects on changes in gene expression, including the regulation of genes related to circadian rhythm (e.g., Ciart, Nr1d1, Nr1d2, Per2, and Per3), glucocorticoid receptor function (e.g., Cyp1b1, Ddit4, Foxo3, Gjb2, and Pck1), lipid metabolism (e.g., Cyp2d22, Cyp2d9, Decr2 Hacl1, and Sphk1), and inflammatory response (e.g., Cxcr4 and Ccl28).

The obtained results suggest that CBD may be beneficial for therapeutic purposes in treating kidney disease, and its effects should be further analyzed in clinical trials.

To study the therapeutic effect of sinomenine hydrochloride (SH) on dextran sodium sulfate (DSS)-induced colitis in mice as an animal model and the changes of Notch signaling pathway in colon tissue of mice after treatment.

Twenty-four mice were randomly divided into control group, model group, SH low-dose group (20 mg/kg) and SH high-dose group (60 mg/kg), with 6 mice in each group. Disease activity index (DAI), colonic mucosal injury index and colonic histopathological score were calculated. The expression levels of related genes, proteins in Notch signaling pathway and inflammatory factors were quantified.

SH can significantly reduce the symptoms of colitis mice, and can significantly reduce the DAI score (Model: 3.44 ± 0.27; SH-20: 2.50 ± 0.18; SH-60: 1.89 ± 0.17; P < 0.001) and histopathological injury degree (Model: 7.67 ± 0.52; SH-20: 5.17 ± 0.75, P < 0.01; SH-60: 3.33 ± 0.52, P < 0.001). SH can down-regulate the expression levels of Notch1, NICD1, Jagged1 and Hes1 proteins in colon tissue of colitis mice (Model: 1.92 ± 0.16, 1.83 ± 0.21, 2.23 ± 0.22, 1.91 ± 0.17; SH-20: 1.56 ± 0.12, 1.39 ± 0.13, 1.58 ± 0.12, 1.38 ± 0.11; SH-60: 1.24 ± 0.09, 1.23 ± 0.10, 1.23 ± 0.11, 1.22 ± 0.09; P < 0.01), and reduce the contents of serum pro-inflammatory cytokines TNF-α, IL-1β and IL-6 (Model: 718.53 ± 81.81, 51.62 ± 2.80, 444.07 ± 67.77; SH-20: 544.72 ± 90.03, 34.10 ± 2.90, 345.43 ± 43.40; SH-60: 434.11 ± 71.75, 29.44 ± 3.70, 236.11 ± 29.35; P < 0.001).

The therapeutic effect of SH on DSS-induced colitis in mice may be related to inhibiting the overactivation of Notch signaling pathway.