Icariin contributes to recovery brain problems in bunnie product

Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder that affects movement coordination leading to a premature death. Despite several efforts, no disease-modifying treatment is yet available for this disease. Previous studies pinpointed the modulation of serotonergic signaling, through pharmacological inhibition of the serotonin transporter SERT, as a promising therapeutic approach for MJD/SCA3. Here, we describe the 5-HT1A receptor as a novel therapeutic target in MJD, using a C. elegans model of ATXN3 proteotoxicity. Chronic and acute administration of befiradol (also known as NLX-112), a highly specific 5-HT1A agonist, rescued motor function and suppressed mutant ATXN3 aggregation. This action required the 5-HT1A receptor orthologue in the nematode, SER-4. Tandospirone, a clinically tested 5-HT1A receptor partial agonist, showed a limited impact on animals' motor dysfunction on acute administration and a broader receptor activation profile upon chronic treatment, its effect depending on 5-HT1A but also on the 5-HT6/SER-5 and 5-HT7/SER-7 receptors. Our results support high potency and specificity of befiradol for activation of 5-HT1A/SER-4 receptors and highlight the contribution of the auto- and hetero-receptor function to the therapeutic outcome in this MJD model. Our study deepens the understanding of serotonergic signaling modulation in the suppression of ATXN3 proteotoxicity and suggests that a potent and selective 5-HT1A receptor agonist such as befiradol could constitute a promising therapeutic agent for MJD.Atopic dermatitis (AD) is a common yet complex skin disease, posing a therapeutic challenge with increasingly recognized different phenotypes among variable patient populations. Because therapeutic response may vary on the basis of heterogeneous clinical and molecular phenotypes, a shift toward precision medicine approaches may improve AD management. Herein, we will consider biomarkers as potential instruments in the toolbox of precision medicine in AD and will review the process of biomarker development and validation, the opinion of AD experts on the use of biomarkers, types of biomarkers, encompassing biomarkers that may improve AD diagnosis, biomarkers reflecting disease severity, and those potentially predicting AD development, concomitant atopic diseases, or therapeutic response, and current practice of biomarkers in AD. We found that chemokine C-C motif ligand 17/thymus and activation-regulated chemokine, a chemoattractant of TH2 cells, has currently the greatest evidence for robust correlation with AD clinical severity, at both baseline and during therapy, by using the recommendations, assessment, development, and evaluation approach. Although the potential of biomarkers in AD is yet to be fully elucidated, due to the complexity of the disease, a comprehensive approach taking into account both clinical and reliable, AD-specific biomarker evaluations would further facilitate AD research and improve patient management.
Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD).
We aimed to investigate the role of NKT cells in AD development, especially in skin.
Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy-controls and patients with AD. Mps1-IN-6 cell line Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4
NKT cells was further evaluated in models of mice with AD by using CXCR4-conditionally deficient or CXCL12 transgenic mice.
CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4
NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4
and CD69
. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4
NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4
tissue-resident NKT cells/CXCL12
cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD.
CXCR4
tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
Expandable cages have been increasingly used in cervical and lumbar reconstructions; however, there is a paucity in the literature on how they compare with traditional nonexpandable cages in the cervical spine. We present a systematic review and meta-analysis, comparing the clinical and radiologic outcomes of expandable versus nonexpandable corpectomy cage use in the cervical spine.
A database search identified studies detailing the outcomes of expandable and nonexpandable titanium cage use in the cervical spine. These studies were screened using the PRISMA protocol. Fixed-effects and random-effects models were used with a 95% confidence interval. Two analyses were carried out for each outcome one including all studies and the other including only studies reporting on exclusively 1-level and 2-level cases.
Forty-one studies were included. The mean change in segmental lordosis was significantly greater in expandable cages (all, 6.72 vs. 3.69°, P < 0.001; 1-level and 2-level, 6.81° vs. 4.31°, P < 0.001). The mean change in cervical lordosis was also significantly greater in expandable cages (all, 5.71° vs. 3.11°, P= 0.027; 1-level and 2-level, 5.71° vs. 2.07°, P= 0.002). No significant difference was found between the complication rates (all, P= 0.43; 1-level and 2-level, P= 0.94); however, the proportion of revisions was significantly greater in expandable cages (all, 0.06 vs. 0.02, P= 0.03; 1-level and 2-level, 0.08 vs. 0.01, P= 0.017).
The use of expandable cages may carry a modest improvement in radiologic outcomes compared with nonexpandable cages in the cervical spine; however, they may also lead to a higher rate of revisions based on our analyses.
The use of expandable cages may carry a modest improvement in radiologic outcomes compared with nonexpandable cages in the cervical spine; however, they may also lead to a higher rate of revisions based on our analyses.