Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)–knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.
Recent findings of a link between high blood pressure (BP) and dementia have given new prospects. The aim of this study is to analyze a mixture of Chinese herbs, Tianma Gouteng Decoction (TGD), which was traditionally used to treat hypertension, and investigate its relation to ameliorating cognitive impairment. We discovered that TGD also had properties involving enhancement of memory acquisition (learning) skills in mice, but not memory consolidation. It was observed that TGD could prolong the step-through latency at doses of 1.0 and 2.5 g/kg on passive avoidance task in mice. TGD could be developed further to treat mice with amnesia, which was induced by scopolamine at the same dose under long-term (8 days) administration.
Accumulating evidence indicates that the high blood pressure (BP) is a potent risk factor for dementia in the elderly. In line with this theory, we had found the mixture of Chinese herbs (TGD) which were traditionally used to treat hypertension, could enhance the cognitive function. The aim of this study was to decrease the number of herbs used from 11 (TGD) to 4 herbs (TGDS) and further to search the active constituents. After administering a dose of 10 g/kg of TGDS0 to ICR mice, no cholinergic symptoms of lacrimation, salivation, emesis, eyeclosure, increased respiration and fibrillation were observed. All the mice survived without any deaths after 24 hours and 7 days. No changes were observed in control and experimental groups on locomotor activity (no stimulant or sedative effects). It was also revealed that TGDS could prolong the step-through latency at the dose of 1.0 and 2.5 g/kg on passive avoidance tasks in mice. This result was the same as the previous study. The active constituents which enhanced the memory acquisition were discovered in the butanol layer and ethyl acetate layer after the extraction.
The contents of the volatile principles, butylidenephthalide, ligustilide, butylphthalide, and the carboxylic acids, ferulic acid, nicotinic acid, in six tang-kuei (Angelicae radix) crude drugs were determined by high performance liquid chromatography. Experimental data showed great divergence in the medicinally active constituents and their ratios among the various tan g-kuei samples from different species with different prices. All parts of the tang-kuei plant contain the volatile active constituents, with the leaves and branching roots containing the most.
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