Efficacy and Safety of Loxoprofen Sodium Hydrogel Patch in Patients with Chronic Inflammatory Pain: A 4-Week Real-World Study.

Purpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data. Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks. Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%. Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.

Estradiol Ameliorates Acute Kidney Ischemia-Reperfusion Injury by Inhibiting the TGF-ßRI-SMAD Pathway.

Renal ischemia-reperfusion injury (IRI) is less extensive in females than males in both animals and humans; however, this protection diminishes after menopause, suggesting that estrogen plays a pivotal role in IRI, but the underlying mechanism remains largely unknown. Our study found that 45 min of warm ischemia was sufficient to induce significant pathological changes without causing death in model animals. Compared with male rats, female rats exhibited less extensive apoptosis, kidney injury, and fibrosis; these effects were worsened in ovariectomized (OVX) rats and ameliorated upon estradiol (E2) supplementation. Furthermore, the levels of TGF-ßRI, but not TGF-ßRII or TGF-ß1, were significantly increased in OVX rats, accompanied by phosphorylated SMAD2/3 activation. Interestingly, the alteration trend of the nuclear ERα level was opposite that of TGF-ßRI. Furthermore, dual luciferase reporter and chromatin immunoprecipitation assays showed that ERα could bind to the promoter region of TGF-ßRI and negatively regulate its mRNA expression. Moreover, an in vitro study using NRK-52E cells showed that ERα knockdown blocked E2-mediated protection, while TGF-ßRI knockdown protected cells against hypoxic insult. The findings of this study suggest that renal IRI is closely related to the TGF-ßRI-SMAD pathway in females and that E2 exert its protective effect via the ERα-mediated transcriptional inhibition of TGF-ßRI expression.

Versatile antibacterial surface with amphiphilic quaternized chitin-based derivatives for catheter associated infection prevention.

Microbial colonization of catheter surfaces is responsible for most healthcare-associated infections. Quaternized chitin and chitosan have excellent antimicrobial and biocompatible properties and can be used to provide safe and prolonged protection for biomedical catheters. Herein, we prepared quaternized ß-chitin derivative (QC)- and quaternized chitosan derivative (QCS)-based antimicrobial surfaces. The quaternized polysaccharides modified TPU surfaces exhibited hydrophilicity, good biocompatibility. Among these, QCS2-modified TPU exhibited excellent antibacterial properties against Gram-positive and Gram-negative bacteria, and prevented the adherence of bacteria compared with pristine TPU. The antibacterial activity of QCS2-modified surfaces maintained for 8 weeks under the condition of immersion in serum. An in vivo subcutaneous implantation experiment revealed 99.87% reduction of bacteria and reduced expression of inflammation-related factors in the surrounding tissue five days after implantation with QCS2-modified TPU. Therefore, quaternized polysaccharide-modified surfaces have promising potential in preventing medical catheter-associated infections.

Early Application of Quaternized Chitin Derivatives Inhibits Hypertrophic Scar Formation.

Various treatments for hypertrophic scars (HS) are applied after wound re-epithelialization. However, the lack of early intervention within the wound bed leads to poor HS treatment outcomes. In this study, quaternized chitin (QC) derivatives with different degrees of deacetylation (7.4% and 78.9%) are synthesized and their effects on HS formation are evaluated in a rabbit ear scar model. Early application of QC alleviates scar hypertrophy without delayed wound healing. Fibroblast count, collagen content, and α-smooth muscle actin expression are decreased, while matrix metalloproteinase-1 is upregulated on day 35 in the QC treatment group. QC suppresses inflammatory cell infiltration and IL-6 expression. A subsequent reduction in transforming growth factor ß1 expression is also observed. The inhibitory effect of QC on HS formation is eliminated through the administration of exogenous IL-6. Taken together, early application of QC inhibits HS formation by downregulating IL-6 expression, and QC with a low degree of deacetylation tends to be more effective. Considering its potential for accelerating wound healing, inhibiting HS formation, and its antibacterial activity, QC may be used as an effective dressing in clinical wound management.

Ultrabroad-spectrum, multidrug resistant bacteria-killing, and biocompatible quaternized chitin derivative for infected wound healing.

Wound infections have consistently been recognized as serious threats to human. The design of antimicrobial and biocompatible wound dressings for infected wounds is an area of constant research. Herein, we homogeneously synthesized an ultrabroad-spectrum antimicrobial and biocompatible quaternized chitin derivative (QC-4) in a high-efficiency and sustainable route using aqueous KOH/urea solution. Particularly, QC-4 displayed powerful multidrug resistant bacteria-killing activities even at a very low antimicrobial concentration range from 500 ng/mL to 5 µg/mL, including clinically prevalent multidrug-resistant Escherichia coli (MDR-E. coli), methicillin resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MRPA), and multidrug-resistant Acinetobacter baumannii (MDR-A. baumannii). With the aim to facilitate clinical translation, we validated the biocompatibility and safety of QC-4 both in vitro and in vivo, and further assessed the effects of QC-4 on infected wound healing in a porcine infectious full-thickness skin wound model. QC-4 demonstrated significant reduction of microbial aggregates and enhanced wound-healing effects by promoted re-epithelialization and collagen deposition, which were quite comparable to that of commercial Alginate-Ag dressing and absolutely superior to commercial Chitoclot Bandage dressing. Additionally, we provided clear evidences that QC-4 had a unique mechanism of action by attracting electrostatically to the negatively charged microbial surface, thus damaging the microbial cell wall and membrane. Findings of this work provided robust preclinical rationale for the future translational applications of QC-4 as a novel ultrabroad-spectrum and multidrug resistant bacteria-killing antimicrobial wound dressing for clinical wound management.