Dopamine-dependent functions of hyaluronic acid/dopamine/silk fibroin hydrogels that highly enhance N-acetyl-L-cysteine (NAC) delivered from nasal cavity to brain tissue through a near-infrared photothermal effect on the NAC-loaded hydrogels.

Hyaluronic acid/silk fibroin (HA/SF or HS) hydrogels with remarkable mechanical characteristics have been reported as tissue engineering biomaterials. Herein, the addition of dopamine/polydopamine (DA/PDA) to HS hydrogels to develop multifunctional HA/PDA/SF (or HDS) hydrogels for the delivery of drugs such as N-acetyl-L-cysteine (NAC) from nasal to brain tissue is examined. Herein, DA-dependent functions of HDS hydrogels with highly adhesive forces, photothermal response (PTR) effects generated by near infrared (NIR) irradiation, and anti-oxidative effects were demonstrated. An in-vitro study shows that the HDS/NAC hydrogels could open tight junctions in the RPMI 2650 cell line, a model cell of the nasal mucosa, as demonstrated by the decreased values of transepithelial electrical resistance (TEER) and more discrete ZO-1 staining than those for the control group. This effect was markedly enhanced by NIR irradiation of the HDS/NAC-NIR hydrogels. Compared to the results obtained using NAC solution, an in-vivo imaging study (IVIS) in rats showed an approximately nine-fold increase in the quantity of NAC delivered from the nasal cavity to the brain tissue in the span of 2 h through the PTR effect generated by the NIR irradiation of the nasal tissue and administration of the HDS/NAC hydrogels. Herein, dopamine-dependent multifunctional HDS hydrogels were studied, and the nasal administration of HDS/NAC-NIR hydrogels with PTR effects generated by NIR irradiation was found to have significantly enhanced NAC delivery to brain tissues.

The Negative Prognostic Role of Inflammatory Biomarkers in Patients With Chronic Cerebrospinal Venous Insufficiency.

BACKGROUND: The pathologic consequences of inflammatory responses in chronic cerebrospinal venous insufficiency (CCSVI) remains poorly understood. Hence, this study was aimed to evaluate the peripheral inflammatory biomarkers in patients with intracranial and extracranial CCSVI pathology. In addition, the relationship between inflammatory cytokine profile and CCSVI prognosis was also evaluated. METHODS: Patients diagnosed with CCSVI between July 2017 and July 2019 were included and subsequently divided into 3 groups based on the location of stenosis. The inflammatory biomarker assay included neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs), red blood cell distribution widths (RDW), C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, and neuron-specific enolase levels. Clinical outcomes were assessed using the modified Rankin Scale and Patient Global Impression of Change score. Univariate and multivariate regression analyses were performed to identify significant prognostic factors for poorer outcomes. Finally, we established a nomogram based on the multivariate regression analysis. RESULTS: We enrolled 248 patients in total, including 102 males and 146 females, with an average age of 57.85±12.28 years. Compared with patients with internal jugular vein stenosis, cerebral venous sinus stenosis (CVSS) patients were mostly younger and had been suffering from headaches and severe papilledema. Higher levels of NLR, RDW, and CRP were also observed in the CVSS group. Multivariate analysis indicated that NLR, PLR, and IL-6 were the independent prognostic factors for poor CCSVI outcomes. CONCLUSIONS: The clinical presentations and increases in NLR, PLR, IL-6, and CRP levels could be distinctly marked in patients with CVSS-related CCSVI than that in internal jugular vein stenosis-related CCSVI, indicating poor prognostic outcomes in these patients. A proinflammatory state might be associated with CCSVI pathology.

Potential Anti-Inflammatory and Anti-Coagulation Effects of One-Time Application of Remote Ischemic Conditioning in Patients With Subacute/Chronic Cerebral Arteriostenosis and Venostenosis.

BACKGROUND: Remote ischemic conditioning (RIC) is an extremely simple, non-invasive, and cost-effective method with a neuroprotective effect. This study aimed to evaluate the immediate effects of one-time application of RIC on inflammation and coagulation in patients with chronic cerebral vascular stenosis, and compare the different effects of RIC on cerebral arteriostenosis and cerebral venostenosis. METHOD: A total of 47 patients with defined cerebral arteriostenosis (n=21) or venostenosis (n=26) were prospectively enrolled. RIC intervention was given once with 5 cycles of inflating and deflating for 5 minutes alternately. Blood was sampled 5 minutes before and after RIC for inflammatory and thrombophilia biomarkers. Differences in inflammatory and thrombotic variables at differing time points in the group were assessed using paired t tests or Wilcoxon matched-pairs signed-rank test. RESULTS: Patients with cerebral arteriostenosis had a higher level of pre-RIC neutrophil-to-lymphocyte ratio ( P =0.034), high-sensitivity C-reactive protein ( P =0.037), and fibrinogen ( P =0.002) than that with cerebral venostenosis. In the arterial group, levels of fibrinogen ( P =0.023) decreased, and interleukin-6 levels were elevated ( P =0.019) after a single RIC. Age was negatively related to interleukin-6, C-reactive protein, and fibrinogen. CONCLUSION: One-time RIC interventions may show seemingly coexisted proinflammatory and anti-coagulation effects of a single bout on patients with cerebral arteriostenosis. Older age was a negative predictor for multiple biomarkers in the cerebral arteriostensosis group. The protective effect of RIC on cerebral venostenosis patients needs to be further studied in a larger sample size.

Developing photothermal-responsive and anti-oxidative silk/dopamine nanoparticles decorated with drugs which were incorporated into silk films as a depot-based drug delivery.

Photothermal-responsive (PTR) and anti-oxidative silk fibroin/dopamine nanoparticles (SD NPs) mediated by tyrosinase were produced, and decorated either by curcumin or albumin (BSA) to produce SD/curcumin or SD/BSA NPs as drug delivery vehicles, respectively. Both drug loaded NPs were further blended into SF solutions to produce SD films, as a depot-based drug delivery. The reaction mechanisms for producing new SD NPs were proposed. Anti-oxidative activities for SD NPs were examined by H2O2 scavenge capacities of NPs. NPs were not cytotoxic at concentration of 1000µg/mL. Moreover, heparin was coated to SD films to produce SDH films for temporary implants. Cumulative release profiles for drugs loaded SDH films showed fast releases and then sustained releases stages. Furthermore, the releases of curcumin in sustained stages for varying SD/curcumin NPs loaded into SDH films were dependent on amounts of NPs. BSA releases profiles for SD/BSA NPs loaded into SDH films were similar to those profiles for the films carried with SD/curcumin NPs but release periods of BSA were short. Degrees of PTR effects with irradiation of near infrared on the releases of two drugs loaded films were different. Blood clot at wound areas of rats with SDH films implantations was not found for 24 h study.

[Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.