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Kilgore Hsu posted an update a month ago
Indeed, key analogs were also able to rescue cells from the cytopathic effect of SARS-CoV-2 infection, indicating relevance for therapeutic strategies targeting the COVID-19 pandemic.Despite numerous beneficial therapeutic effects namely antioxidant and anti-inflammatory activity, Vitamin E has limited clinical applications due to its low water solubility. Throughout the present work, α-tocopherol’s new PEGylated derivatives alongside with polyethylene glycol 300 (α-1TPGT300), 400 (α-TPGT400), and 1000 (α-TPGT1000) were synthesized. A 1,2,3-triazole ring was utilized as a linker for the attachment of alpha tocopherol to the PEGs through a click reaction. The purified derivatives were characterized by the means of 1H NMR, 13C NMR, mass spectroscopy, UV-vis and FT-IR methods. Synthesized derivatives’ capacity to produce self-assembly nanoparticles was evaluated employing the critical micelle concentration (CMC) values. The stability of the micelles was studied by size analysis. In vitro cytotoxicity of the products was investigated using MTT assay against MCF-7 breast cancer cells. The IC50 value for TPGT1000 after 24 h treatment was 15.0 ± 1.8 µM, whereas no significant cytotoxicity effect was observed following the treatment of MCF-7 cells by TPGT300, 400. WP1130 The present study showed that polymeric micelle TPGT1000 possessed better physicochemical and biological properties including relatively lower CMC value, higher stability in FBS environment in addition to higher cytotoxicity against MCF-7 breast cancer cells compared to the lower molecular weight PEGylated derivatives. These results confirmed that increasing PEG chain length left a positive effect on the polymeric micelle properties and also improved the cytotoxicity effect of new PEGylated vitamin E derivatives.
Arthroscopic anatomical reconstruction of the lateral ankle ligaments is an emerging technique for treating chronic ankle instability. One of the known complications of arthroscopic anterior cruciate ligament reconstruction is tunnel widening; this makes revision more complicated. The aim of this study was to look for tunnel widening in the postoperative course of arthroscopic ankle ligament reconstruction. We hypothesized that significant widening of the bone tunnels is present 1 year after anatomical ankle ligament reconstruction.
Twenty-one patients who underwent arthroscopic anatomical reconstruction of the lateral ankle ligaments with a gracilis graft were included prospectively. A CT-scan with 1-mm thick slices with multiplanar reconstruction was done 1 year after the surgery. The size and shape of the tunnels was analyzed, and the ratio of the preoperative to postoperative diameter was calculated. Based on this ratio, the tunnels were given a grade as described by Struewer. Tunnel widening was defined as a grade III tunnel, thus a ratio ≥ 1.3. The tunnel shape was classified as described by Peyrache as cone type, cavity type, line type.
None of the tunnels had widened 1 year after arthroscopic anatomical reconstruction of the lateral ankle ligaments. At the fibula, 81% of tunnels were grade I and 19% were grade II; 57% were cone type and 43% were line type. At the talus, 86% of tunnels were grade I and 14% were grade II. All were line type. At the calcaneus, 86% of tunnels were grade I and 14% were grade II; 57% were cone type and 43% were line type.
The main finding of this study was the absence of tunnel widening 1 year after arthroscopic reconstruction of the lateral ankle ligaments.
IV; retrospective study.
IV; retrospective study.
The treatment of infected nonunion requires radical debridement with stable fixation. Sever soft tissue compromise of the nonunion site might interfere with radical debridement. This study discussed the outcome of treatment of infected tibial nonunion with sever soft tissue compromise by a cyclic compression distraction technique using Ilizarov without radical debridement.
This study comprised 17 patients with unilateral infected tibial nonunion; 10 with diaphyseal and 7 with metaphysial locations.Their mean age was 21.9 years. There were 12 males and 5 females. The right side was affected in 11 patients and the left side in 6 patients. According toGustilo and Anderson classification, all patients were grade III. The mean limb shortening was 1.3cm. All patients were treated initially in another institute by uniplanner external fixator with rotational skin flap done in 11 patients and thiersch graft in 6 patients. One patient had common peroneal nerve affection. Distal circulation was sufficient in all patof a biological environment to achieve union.
IV; prospective case series.
IV; prospective case series.
Severe asthma with fungal sensitization (SAFS) is a complex clinical phenotype associated with poorly controlled type 2 inflammation and significant morbidity from both the disease itself and a high steroid burden.
To assess the effectiveness of biologic therapies targeting eosinophilic inflammation in SAFS.
We assessed the effectiveness of treatment with mepolizumab or benralizumab in patients with SAFS, and compared outcomes with patients with severe atopic asthma without fungal sensitization and patients with severe nonatopic asthma. Baseline clinical characteristics and clinical outcomes at 48 weeks were evaluated. A subgroup analysis was performed of patients who met the criteria for allergic bronchopulmonary aspergillosis (ABPA) rather than SAFS.
A total of 193 patients treated with mepolizumab (n= 63) or benralizumab (n= 130) were included. Patients with SAFS had higher baseline IgE level compared with patients with severe atopic asthma without fungal sensitization and severenonatopic asthma (7y, oral corticosteroid requirements, and patient-reported outcomes in patients with SAFS, with a reduction in exacerbations in the subgroup of patients with ABPA. These data highlight the potential clinical utility of targeting eosinophilic inflammation in SAFS and ABPA.The 57-amino acid Kunitz Protease Inhibitor (KPI) domain of Protease Nexin 2 inhibits Factor XIa (FXIa) and other proteases. We previously fused KPI to human serum albumin (KPIHSA). KPIHSA inhibits coagulation Factor XIa (FXIa) 6-fold more rapidly than plasmin. We screened a bacterial expression library of KPI variants randomized at M17, and selected M17D as having the highest anti-FXIa antiplasmin activity ratio. Expressed as HSA fusion proteins in Pichia pastoris, KPIHSA and KPI(M17D)HSA inhibited FXIa indistinguishably (Ki 9 nM) but KPI(M17D)HSA lacked detectable antiplasmin activity. Purified variant and wild-type KPIHSA were expressed and injected into mice with ferric chloride-treated carotid arteries, with or without systemic administration of tissue plasminogen activator (Tenecteplase, TNKase). The time to arterial occlusion (TTO) or reperfusion (TTR) was assessed by Doppler ultrasound. TTR did not differ between mice treated with TNKase alone or with TNKase supplemented with 38 mg/kg KPI(M17D)HSA but was significantly prolonged to >60 min in all mice treated with TNKase and 38 mg/kg KPIHSA.