YokoCo

Diseases affecting the retina, such as age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and retinal vein occlusions, are currently treated by the intravitreal injection of drug formulations. These disease pathologies are driven by oxidative damage due to chronic high concentrations of reactive oxygen species (ROS) in the retina. Intravitreal injections often induce retinal detachment, intraocular hemorrhage, and endophthalmitis. Furthermore, the severe eye pain associated with these injections lead to patient noncompliance and treatment discontinuation. Hence, there is a critical need for the development of a noninvasive therapy that is effective for a prolonged period for treating retinal diseases. In this study, we developed a noninvasive cerium oxide nanoparticle (CNP) delivery wafer (Cerawafer) for the modulation of ROS in the retina. We fabricated Cerawafer loaded with CNP and determined its SOD-like enzyme-mimetic activity and ability to neutralize ROS generated in vitro. We demonstrated Cerawafer's ability to deliver CNP in a noninvasive fashion to the retina in healthy mouse eyes and the CNP retention in the retina for more than a week. Our studies have demonstrated the in vivo efficacy of the Cerawafer to modulate ROS and associated down-regulation of VEGF expression in the retinas of very-low-density lipoprotein receptor knockout (vldlr-/-) mouse model. The development of a Cerawafer nanotherapeutic will fulfill a hitherto unmet need. Currently, there is no such therapeutic available, and the development of a Cerawafer nanotherapeutic will be a major advancement in the treatment of retinal diseases.

Vaccination decreases the risk of severe COVID-19 but its impact on postacute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC.

Psychological flexibility (PF) is a model of well-being and daily functioning that is applied to chronic pain, and is the model behind Acceptance and Commitment Therapy (ACT). However, studies of PF in chronic pain are limited by the lack of a single measure capturing all facets. The Multidimensional Psychological Flexibility Inventory (MPFI) assesses all facets of PF and psychological inflexibility (PI) and could remedy this problem. The current study employs this measure. Adult participants with chronic pain (N = 404) were recruited online and completed the MPFI, other validated measures of PF/PI, and measures of pain, work and social adjustment, and depression, at two time points. The reliability, factor structure, and validity of the MPFI were assessed. Confirmatory factor analysis results demonstrated a good model fit for the proposed factor-and subscale structure. Correlations between MPFI and theoretically similar measures were moderate to strong, and correlations with pain intensity, pain interference, work-and social adjustment, and depression, were small to large. In this first examination of the potential utility of the MPFI within a chronic pain population, we found it to be valid and reliable. It should be noted that the MPFI was less predictive of outcomes compared with more established measures in most cases. Despite this, results from the wide range of variables available from the MPFI highlights the potential importance of aspects of PF and PI not previously emphasized, including the greater predictive utility of the inflexibility facets. Further use and study of the MPFI is recommended. ClinicalTrials.gov ID: NCT05050565 Perspective: This article presents a comprehensive examination of a self-report measure assessing all facets of psychological flexibility and inflexibility, in a chronic pain sample. The results support the role of facets not previously emphasized. Comprehensive assessment of PF and PI appears possible and is recommended depending on research questions being asked.

Accumulating evidence indicating that inflammatory responses play crucial roles in Parkinson's disease (PD) development provided a hypothesis that physiological alpha-synuclein may contribute to inflammatory responses against infections during non-advanced stages of PD. Thus, we examined the risk of catching a common cold in patients with PD as compared to other common brain diseases.

Crotoxin (CTX) is a neurotoxin that is isolated from the venom of Crotalus durissus terrificus, which displays immunomodulatory, anti-inflammatory, and anti-tumoral effects. Previous research has demonstrated that CTX promotes the adherence of leukocytes to the endothelial cells in blood microcirculation and the high endothelial venules of lymph nodes, which reduces the number of blood cells and lymphocytes. Studies have also shown that these effects are mediated by lipoxygenase-derived mediators. However, the exact lipoxygenase-derived eicosanoid involved in the CTX effect on lymphocytes is yet to be characterized. As CTX stimulates lipoxin-derived mediators from macrophages and lymphocyte effector functions could be modulated by activating formyl peptide receptors, we aimed to investigate whether these receptors were involved in CTX-induced redistribution and functions of lymphocytes in rats. We used male Wistar rats treated with CTX to demonstrate that Boc2 (butoxycarbonyl-Phe-Leu-Phe-Leu-Phe), an antagonist of formyl peptide receptors, prevented CTX-induced decrease in the number of circulating lymphocytes and increased the expression of the lymphocyte adhesion molecule LFA1. CTX reduced the T and B lymphocyte functions, such as lymphocyte proliferation in response to the mitogen Concanavalin A and antibody production in response to BSA immunization, respectively, which was prevented by the administration of Boc-2. Importantly, mesenteric lymph node lymphocytes from CTX-treated rats showed an increased release of 15-epi-LXA. These results indicate that formyl peptide receptors mediate CTX-induced redistribution of lymphocytes and that 15-epi-LXA4 is a key mediator of the immunosuppressive effects of CTX.

Scrub typhus has become a leading cause of central nervous system (CNS) infection in endemic regions. As a treatable condition, prompt recognition is vital. However, few studies have focused on describing the symptomology and outcomes of neurological scrub typhus infection. We conducted a systematic review and meta-analysis to report the clinical features and case fatality ratio (CFR) in patients with CNS scrub typhus infection.

Eugenia gracillima is widely used by the population in the manufacture of pulps and jellies, with popular reports of its use in the treatment of infections in the urinary system, respiratory and dermatological problems. A previous study reports that EO from E. gracillima leaves proved to be a promising antioxidant agent in combating the promastigote forms of protozoa. Despite this, this species has been little studied due to its pharmacological properties.

Sorafenib-resistance leads to poor prognosis and high mortality in advanced hepatocellular carcinoma (HCC), and this study aims to investigate the functional role of a circular RNA ITCH (circITCH) in regulating the sorafenib-resistance of HCC and its underlying mechanisms.

Depression, a prognostic factor for prescription opioid misuse commonly occurs in people with chronic non-cancer pain (CNCP). However, the mechanisms linking depression and prescription opioid misuse remain unclear. This study examined the potential mediating role of pain catastrophizing in the association between depressive symptoms and prescription opioid misuse risk, and impulsivity traits as possible moderators of these relationships. Individuals (N = 198; 77% women) with CNCP using prescription opioids participated in a cross-sectional online survey with validated measures of depression, pain catastrophizing, rash impulsiveness, reward drive, anxiety, pain severity and prescription opioid misuse. Meditation analyses with percentile-based bootstrapping examined pathways to prescription opioid use, controlling for age, sex, pain severity, and anxiety symptoms. Partial moderated mediation of the indirect effect of depressive symptoms on prescription opioid misuse risk through pain catastrophizing by rash impulsiveness and reward drive were estimated. Pain catastrophizing mediated depressive symptoms and prescription opioid misuse risk. Indirect effects were stronger when moderate to high levels of reward drive were included in the model. Findings suggest the risk of prescription opioid misuse in those experiencing depressive symptoms and pain catastrophizing is particularly higher for those higher in reward drive. Treatments targeting these mechanisms may reduce opioid misuse risk. Perspective: This article identifies reward drive as a potentially important factor increasing the effects of depression-related cognitive mechanisms on risk of prescription opioid misuse in those with CNCP. These findings could assist in personalizing clinical CNCP management to reduce the risks associated with opioid misuse.

The amyloid precursor protein (APP) is critical for the pathogenesis of Alzheimer's disease (AD). The AD patients usually have lower pain sensitivity in addition to cognitive impairments. However, considerably less is known as yet about the role of APP and its two mammalian homologues, amyloid precursor-like protein 1 and 2 (APLP1, APLP2), in spinal processing of nociceptive information. Here we found that all APP family members were present in spinal cord dorsal horn of adult male C57BL/6J mice. Peripheral nerve injury specifically reduced the expression of spinal APLP2 that correlated with neuropathic mechanical allodynia. The loss of APLP2 was confined to inhibitory GABAergic interneurons. Targeted knockdown of APLP2 in GABAergic interneurons of GAD2-Cre mice evoked pain hypersensitivity by means of microglia activation. Our data showed that GABAergic terminals expressed APLP2, a putative cell adhesion protein that interacted with microglia-specific integrin molecule CD11b. Knocking down APLP2 in GAD2-positive neurons to disrupt the trans-cellular interaction led to microglia-dependent pain sensitization. Our data thus revealed an important role of APLP2 for GABAergic interneurons to control microglial activity and pain sensitivity.