An antioxidative sophora exosome-encapsulated hydrogel promotes spinal cord repair by regulating oxidative stress microenvironment.

Spinal cord injury (SCI) is a severe traumatic disease because of its complications and multi-organ dysfunction. After the injury, the disruption of microenvironment homeostasis in the lesion demolishes the surrounding healthy tissues via various pathways. The microenvironment regulation is beneficial for neural and functional recovery. Sustained release, cellular uptake, and long-term retention of therapeutic molecules at the impaired sites are important for continuous microenvironment improvement. In our study, a local-implantation system was constructed for SCI treatment by encapsulating exosomes derived from Flos Sophorae Immaturus (so-exos) in a polydopamine-modified hydrogel (pDA-Gel). So-exos are used as nanoscale natural vehicles of rutin, a flavonoid phytochemical that is effective in microenvironment improvement and nerve regeneration. Our study showed that the pDA-Gel-encapsulated so-exos allowed rapid improvement of the impaired motor function and alleviation of urination dysfunction by modulating the spinal inflammatory and oxidative conditions, thus illustrating a potential SCI treatment through a combinational delivery of so-exos.

Evaluation of the efficacy of intervention in the management of AD chronic disease based on the theory of "prevention of the recrudescence of disease".

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease with a chronic course and a high recurrence. OBJECTIVE: Based on the theory of "prevention and recovery after ulceration", the application value and significance of compound ginseng cicada decoction in the intervention of chronic disease management in patients with AD were retrospectively analyzed. METHODS: Through clinical retrospective observation, 60 patients with spleen deficiency and moisture type AD admitted to the outpatient clinic of our hospital after January 2019 were analyzed. After comprehensive treatment until the patient's Investigator's Global Assessment (IGA) Scale score is lower than 2 points, the study group was divided into a research group and a control group, according to the actual clinical follow-up whether to take compound ginseng cicada soup. The control group carried out chronic disease management education, conventional emollient topical with no drug maintenance intervention, and the research group included clinical patients who were orally administered to compound ginseng cicada decoction for 1 month, observed for 3 months, and compared with the clinical recurrence (recurrence rate, time to first recurrence, severity at recurrence, degree of pruritus), and the quality of life. RESULTS: After 3 months, the relapse rate, recurrence severity, itching degree and quality of life impact scores of the study group were significantly lower than those of the control group, and there were no obvious adverse events. CONCLUSION: The combined application of compound ginseng cicada decoction in the management of chronic diseases in patients with atopic dermatitis has the positive significance of reducing AD recurrence, alleviating the severity of recurrence, and effectively improving the life quality of patients. This method has high safety and is worthy of wide application.

Phellinus igniarius polysaccharides induced mitochondrial apoptosis of hepatic carcinoma by enhancing reactive oxygen species-mediated AKT/p53 signalling pathways.

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5 ± 1.6% neutral carbohydrates. PIP consists of glucose, galactose, mannose, xylose, D-fructose, L-guluronic acid, glucosamine hydrochloride, rhamnose, arabinose and D-mannoturonic acid. PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Exosome-like nanoparticles derived from fruits, vegetables, and herbs: innovative strategies of therapeutic and drug delivery.

Over the past ten years, significant advancements have been made in exploring plant-derived exosome-like nanoparticles (PELNs) for disease therapeutics and drug delivery. PELNs, as inherent nanoscale particles comprised of proteins, lipids, nucleic acids, and secondary metabolites, exhibit the capacity for cellular uptake by human cells. This intercellular interaction transcends biological boundaries, effectively influencing biological functions in animals. PELNs have outstanding biocompatibility, low immunogenicity, enhanced safety, and environmentally friendly sustainability. This article summarized the preparation methods and characteristics of PELNs. It provided a systematic review of the varied roles of PELNs derived from fruits, vegetables, and herbs in disease therapeutics and drug delivery. The challenges in their production and application were discussed, and future prospects in this rapidly evolving field were explored.

HLA-A∗24:02 associated with lamotrigine-induced cutaneous adverse drug reactions: A systematic review and meta-analysis.

BACKGROUND: Several studies demonstrated a connection between human leukocyte antigen (HLA)-B∗1502 and lamotrigine (LTG)-induced cutaneous adverse drug reactions (cADRs). The correlation between the HLA-A∗24:02 and LTG-cADRs remains controversial. To examine the associations between HLA-A∗24:02 and LTG-cADRs, we conducted a systematic review and meta-analysis. METHODS: We performed a comprehensive search of the literature in several electronic database systems including Cochrane Library, EMBASE and PubMed from inception to January 2020. Review Manager was used to compare the frequencies of HLA-A∗24:02 carriers between the subgroups. RESULTS: A total of 5 studies were eligible, including 197 LTD-cADRs, 396 LTD-tolerant controls, and 2068 population controls. Compared with the LTG-tolerant controls, there was a statistically significant association between the HLA-A∗24:02 allele and LTG-induced cADRs (odds ratios: 1.94, 95% confidence intervals 1.06-3.54; P = .03). Compared with the general population, the relationship between the HLA-A∗24:02 genotype and LTG-induced cADRs was statistically significant (summary odds ratios: 2.12, 95% confidence intervals 1.04-4.30; P = .04). CONCLUSIONS: HLA-A∗24:02 may be a risk factor for LTG-cADRs.

Efficient detection of differentially methylated regions in the genome of patients with thoracic aortic dissection and association with MMP2 hypermethylation.

DNA methylation is known to regulate the expression of numerous genes but its role in the pathogenesis of thoracic aortic dissection (TAD) has remained largely elusive. In the present study, the DNA methylome of patients with TAD was analyzed using a methylation microarray and bisulfite pyrosequencing was used to determine whether the hypermethylation of matrix metalloproteinase 2 (MMP2) specifically is associated with TAD. Chip-based whole-DNA methylome analysis was performed on 4 male patients with TAD and 4 male healthy controls using an Illumina HumanMethylation EPIC 850K BeadChip. The resulting data were analyzed by clustering and principal component analysis, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the differentially methylated genes to interrogate their biological functions. Compared to the healthy controls, 3,362 loci were differentially methylated in the patients with TAD with a statistical significance of P<0.05, while 1,223 loci had a significance of P<0.01. Among these loci, 2,019 were hypermethylated and 1,343 were hypomethylated. From GO analysis within the biological process category, the MMP2, MMP14 and WNT2B genes were identified. enrichment was observed for loci involved in cellular component organization, enzyme-linked receptor protein signaling pathways (potentially having a key role in the development of cardiopulmonary function disorders) and vascular reconstruction. Bisulfite pyrosequencing of plasma samples indicated significantly increased methylation (P<0.01) of the CpG site at position 2 in the promoter of MMP2 in the TAD group relative to the healthy controls, and the mean methylation level of four CpG sites on the MMP2 gene in the TAD group was slightly higher than that in the control group, but not significantly. Hypermethylation of the MMP2 promoter may be a promising novel diagnostic and prognostic biomarker for TAD. Future studies on the epigenetics of biomarkers linked to vascular reconstruction and immune function may provide further insight into the pathogenesis and progression of TAD.

Single-dose of integrated bilayer microneedles for enhanced hypertrophic scar therapy with rapid anti-inflammatory and sustained inhibition of myofibroblasts.

Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.