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BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.
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Bruton's tyrosine kinase (BTK) is a central signaling node in B cells. BTK inhibition has witnessed great success in the treatment of B-cell malignancies. Additionally, in the immune system, BTK is also a prominent component linking a wide variety of immune-related pathways. Therefore, more and more studies attempting to dissect the role of BTK in autoimmune and inflammation progression have emerged in recent years. In particular, BTK expression was also found to be elevated within the central nervous system (CNS) during neuroinflammation. BTK inhibitors are capable of crossing the blood-brain barrier rapidly to modulate B cell functions, attenuate microglial activities and affect NLRP3 inflammasome pathways within the CNS to improve the outcome of diseases. Thus, BTK inhibition appears to be a promising approach to modulate dysregulated inflammation in the CNS and alleviate destruction caused by excessive inflammatory responses. This review will summarize the immunomodulatory mechanisms in which BTK is involved in the development of neurological diseases and discuss the therapeutic potential of BTK inhibition for the treatment of neuroinflammatory pathology.
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Objective: The aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson's disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD). Methods: In our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), ß-amyloid 42 (Aß42), and ß-amyloid 40 (Aß40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted. Results: In the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aß42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time (TT) delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of k PLI theta with HAMD and HAMA, especially in the prefrontal region, and k PLI gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and k PLI , and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group. Conclusion: These results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.
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Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in colorectal cancer (CRC). Stimulator of interferon genes (STING) is a novel potential target and STING agonists have shown potential anti-tumor efficacy. Combined therapy based on synergistic mechanism can overcome the resistance. However, STING agonists-based combination therapies are deficient. We designed different immunotherapy combinations, including STING agonist, indoleamine 2,3 dioxygenase (IDO) inhibitor and PD-1 blockade, with purpose of exploring which option can effectively inhibit CRC growth. To further explore the possible reasons of therapeutic effectiveness, we observed the combination therapy in C57BL/6Tmem173gt mice. Our findings demonstrated that STING agonist diABZI combined with IDO inhibitor 1-MT significantly inhibited tumor growth, even better than the three-drug combination, promoted the recruitment of CD8+ T cells and dendritic cells, and decreased the infiltration of myeloid-derived suppressor cells. We conclude that diABZI combined with 1-MT is a promising option for CRC.