Objectives:The use of CAR technology in the treatment of cancer cells is progressing, as well as the use of CAR T-cell in the treatment of blood malignancies is in the clinical trial stage. In this study, have compared the second and third generation CAR expressed in NK cells in dealing with prostate cancer cells. Materials and Methods:To optimize the CAR design for detection of NK-92 cells, an in silico approach to select between two tags (Flag and c-Myc tags) was initially employed, ultimately favoring the Flag tag. By using lentiviral particles, transduced NK-92 cells with second- and third-generation CAR constructs were subsequently tested as effector cells against prostate cancer cells expressing the Prostate-Specific Membrane Antigen (PSMA). Then assessed both cytokine secretion and cytotoxic responses. Results:Computational analysis indicated that the NB/Flag/hinge configuration would provide superior PSMA recognition. Flow cytometry confirmed successful CAR expression in 47% of second-generation and 49% of third-generation NK-92 cells. Upon co-culture with PSMA-positive LNCaP cells and PSMA-negative PC-3 cells, the third-generation CAR NK cells demonstrated a noticeably stronger cytotoxic effect. Furthermore, higher levels of IL-2, TNF-α, and IFN-γ secretion were observed in the third-generation CAR group compared to the second. Conclusion:According to the computational studies, NB/Flag/hinge interacts with PSMA primarily through electrostatic forces. More importantly, third-generation CAR NK cells targeting PSMA displayed enhanced cytotoxicity and cytokine production relative to second-generation counterparts, pointing to their greater potential for therapeutic application.
Objectives:This study aimed to develop and evaluate a multifunctional five-layer wound dressing that meets essential requirements for effective wound healing, including exudate absorption, antimicrobial activity, moisture retention, gas exchange, and non-damaging adhesion. The specific objective was to assess the antibacterial efficacy, biocompatibility, and wound-healing performance of a dressing incorporating chitosan--LL37 nanoparticles (CS-LL37 NPs). Materials and Methods:A five-layer wound dressing was fabricated, consisting of a silicone adhesive layer, a polyurethane (PU) foam layer embedded with CS-LL37 NPs, a polypropylene diffusion layer, a cellulose-based retention layer, and a breathable, waterproof backing layer. The CS-LL37 NPs were incorporated into the PU layer, and their antibacterial activity and cytotoxicity were evaluated in vitro. The dressing's wound-healing performance, with and without CS-LL37 NPs, was assessed in vivo in a female Wistar rat model and compared with that of a commercial dressing (Mepilex Border). Results:The developed five-layer dressing demonstrated effective exudate management, antimicrobial activity, and favorable healing conditions. In vivo results showed wound closure rates and histological outcomes comparable to those of the commercial dressing. The inclusion of CS-LL37 NPs enhanced antibacterial performance without inducing significant cytotoxicity, indicating good biocompatibility. Conclusion:The prepared five-layer wound dressing exhibited healing performance comparable to a commercially available product. The incorporation of CS-LL37 nanoparticles showed significant potential to improve treatment outcomes, particularly for exudative wounds, and may be a promising option for patients with chronic or fragile-skin conditions such as Epidermolysis Bullosa.
Objectives:Atherosclerosis (AS) is caused by dyslipidemia, chronic inflammation, and oxidative stress. Ponicidin, a diterpenoid from Isodon species, has reported anti-inflammatory and antioxidant effects, but its role in AS remains unclear. In this study, we evaluated the therapeutic potential and safety of ponicidin in an experimental AS model. Materials and Methods:ApoE-/- mice were fed a Western diet and treated with ponicidin (10 mg/kg/day, intraperitoneally) for 12 weeks. Hepatic and renal safety were assessed using histological and serum biochemical markers. Aortic plaque burden was quantified using hematoxylin and eosin and Oil Red O staining. Plasma lipids, cytokines, oxidative stress markers, and antioxidant enzymes were measured using biochemical assays and ELISA. The effects on SIRT1 and PI3K/Akt/eNOS signaling were analyzed using immunohistochemistry, RT-qPCR, ELISA, and Western blotting. Results:Ponicidin showed no liver or kidney toxicity and moderately altered the body weight. Treatment significantly reduced aortic root plaque coverage and lesion area while improving plasma lipid profiles (↓TG, ↓TC, ↓LDL-C, and ↑HDL-C). Serum cytokine analysis revealed decreased TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1 levels, with elevated IL-10. Oxidative stress was attenuated, as evidenced by reduced malondialdehyde and myeloperoxidase levels, increased superoxide dismutase, catalase, and glutathione levels, and restored nitric oxide levels. Mechanistically, ponicidin up-regulated SIRT1 expression and enhanced the phosphorylation of PI3K, Akt, and eNOS, suggesting improved endothelial function. Conclusion:Ponicidin protects against AS by improving lipid metabolism, reducing vascular inflammation and oxidative stress, and enhancing endothelial signaling.
Brain cancers are among the most aggressive malignancies associated with significant global morbidity and mortality. Cancer immunotherapy has emerged as a promising novel approach for the treatment of brain cancer through regulating the PD-1/PD-L1 signaling and disrupting tumor immune escape. Several targeted therapies have been developed to inhibit the PD-1/PD‑L1 route, but reduced therapeutic responses and drug resistance remain a major challenge that needs to be addressed. Notably, non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), exert crucial effects on cell proliferation, invasion, and immune escape in the tumor microenvironment (TME). It has been shown that ncRNAs reduce tumor formation and progression by regulating the PD-1/PD-L1 pathway and by down-regulating key transcription factors, including NF-κB, JAK, and STAT. Therefore, identifying novel regulatory ncRNAs and their associated target genes offers promising opportunities for developing therapeutic interventions against brain cancer. This review highlights recent advances in understanding the regulatory role of ncRNAs on the PD-1/ PD-L1 pathway in brain cancer tumorigenesis.
Objectives:Vascular cognitive impairment (VCI) is a major cause of behavioral and cognitive abnormalities and dementia, but there are currently no specific drugs for VCI. Rosemary oil has been found to have a role in cognitive function. This study aims to evaluate whether inhalation of rosemary can improve learning and memory in VCI rats by regulating neuronal apoptosis and autophagy. Materials and Methods:Male SD rats were used to establish a VCI rat model by bilateral common carotid artery ligation. The rats were intervened with rosemary essential oil inhalation and EX527 injection. Cognitive function was evaluated by the Morris water maze test two weeks after the operation. The pathological changes of hippocampal tissue (HE, Nissl, TEM, TUNEL) and protein expression (WB) were analyzed. Results:Compared with the sham group, the VCI group exhibited cognitive deficits, neuronal loss, mitochondrial damage, and increased neuronal apoptosis (P<0.001). The levels of caspase-3, LC3B, and p-mTOR/mTOR in the hippocampal tissue were significantly elevated (P<0.0001, P<0.01, P<0.01), while the protein level of SIRT1 was significantly reduced (P<0.01). Compared with the VCI group, the rosemary group showed improved cognitive ability, ameliorated neuronal damage, and reduced neuronal apoptosis (P<0.05). The levels of caspase-3, LC3B, and p-mTOR/mTOR were decreased (P<0.0001, P<0.01, P<0.05), while the level of SIRT1 was increased (P<0.05). However, intervention with EX527 attenuated this protective effect. Conclusion:Rosemary inhalation can improve behavior and cognition in VCI rats by regulating SIRT1/mTOR pathway-mediated cell apoptosis and autophagy.
