CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.

Association between environmental mercury exposure and allergic disorders in Korean children: Korean National Environmental Health Survey (KoNEHS) cycles 3-4 (2015-2020).

Although previous studies have suggested potential adverse effects of mercury on a child's immune system, the associations have been inconsistent. We aimed to determine the association between urinary mercury levels and allergic diseases in Korean children with high mercury exposure. Data from 853 and 710 children aged 6-11 years in the Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017) and cycle 4 (2018-2020) were analyzed. We examined the association between mercury exposure and the prevalence of atopic dermatitis (AD), asthma, allergic rhinitis (AR), and allergic multimorbidity. After adjusting for all covariates, the urinary mercury level was positively associated with AD in the 2015-2017 study (OR = 1.34, 95% CI = 1.01, 1.79) and AR in 2018-2020 study (OR = 1.46, 95% CI = 1.01, 2.10). Pooled effects showed OR of 1.34 (95% CI = 1.01, 1.79) for AD and 1.47 (95% CI = 1.01, 2.12) for allergic multimorbidity. The association with allergic multimorbidity was greater in boys (OR = 1.88, 95% CI = 1.01, 3.49) than in girls (OR = 1.25, 95% CI = 0.73, 2.14). These results suggest that environmental mercury exposure may exacerbate symptoms of atopic dermatitis and allergic multimorbidity in children.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

Small testes: clinical characteristics and ultrasonographic findings.

The purpose of this pictorial essay is to describe the ultrasonographic and clinical findings of patients with small testes due to a wide range of causes. We retrospectively reviewed the ultrasonographic and clinical findings of various causes of small testes. We present various causes of small testes on ultrasonography including Klinefelter syndrome, testicular torsion, mumps orchitis, inguinal hernia, cryptorchidism, varicocele, and trauma. On ultrasonography, small testes in patients with testicular torsion, mumps orchitis, and trauma usually showed heterogeneous echogenicity. Atrophic testes were homogeneously hypoechoic in patients with cryptorchidism and inguinal hernia and were isoechoic to the normal testis in patients with varicocele. Klinefelter syndrome patients had small hyperechoic or hypoechoic nodules, but the echogenicity of the remnant portion of the testes was homogeneous. Ultrasonography is helpful for detecting small testes and for the differential diagnosis of the various possible causes of small testes.

Changes in Microvascular Morphology in Subcortical Vascular Dementia: A Study of Vessel Size Magnetic Resonance Imaging.

Background: Cerebral small vessel disease is the most common cause of subcortical vascular dementia (SVaD). Unfortunately, conventional imaging techniques do not always demonstrate the microvascular pathology that is associated with small vessel disease. The purpose of this study was to evaluate the changes in the microvascular structure of SVaD and to identify how the microvascular changes in vessel size, detected with imaging, affect the gray matter. Methods: Ten SVaD patients and 12 healthy controls underwent vessel size imaging with gradient-echo and spin-echo sequences before and after contrast agent injection. Four microvessel index maps, including total blood volume fraction (BVf), mean vessel density (Q), mean vessel diameter (mVD), and vessel size index (VSI) were calculated. ROI value of each microvessel parameter was compared between SVaD patients and controls. Voxel-wise comparison of microvessel parameters was also performed to assess the regional difference. The relationship between the microvessel parameters in white matter and total gray matter volume (TGV) were assessed. Results: Both mVD and VSI were significantly different between the SVaD and controls in the ROI-based comparisons (unpaired t-test, p < 0.05). mVD and VSI were significantly increased in the SVaD group at the subcortical, periventricular white matter, basal ganglia, and thalami compared with the controls (FDR corrected, p < 0.05). VSI in the white matter areas were significantly negatively correlated with TGV (r = -0.446, p < 0.05). Conclusions: The increase of mVD and VSI in SVaD patients reflects the damage of the microvessels in the white matter, and these changes may lead to the damage of the gray matter.

Testicular atrophy after mumps orchitis: ultrasonographic findings.

PURPOSE: The purpose of this study was to describe the ultrasonographic findings of testicular atrophy after mumps orchitis. METHODS: We retrospectively reviewed the case files of eight patients (14 to 24 years old; mean, 17 years) with mumps orchitis and testicular atrophy who were treated between January 2011 and September 2017. On gray-scale and color Doppler, the ultrasonographic features of volume, shape, echogenicity, and degree of blood flow in the testes were analyzed as part of both initial and follow-up ultrasonography. The duration between the initial diagnosis of mumps orchitis and the ultrasonographic diagnosis of testicular atrophy after mumps orchitis ranged from 25 to 230 days (mean, 95.9 days). RESULTS: Of the eight patients with testicular atrophy after mumps orchitis, the testes were affected unilaterally in seven patients (6 right-sided and 1 left-sided) and bilaterally in one patient. The affected testes (n=9) were 23%-55% (mean, 44.7%) smaller in volume (mean, 6.3±2.0 mL) than the contralateral normal testes (n=7) (mean, 10.8±2.3 mL) on follow-up ultrasonography (P=0.001). The shape of the atrophic testes was oblong in seven cases and elliptical in two cases. The atrophic testes were either heterogeneously hypoechoic with multiple hyperechoic islands (n=7) or heterogeneously hyperechoic (n=2). On follow-up color Doppler ultrasonography, the degree of vascularity of the atrophic testis was either similar to (n=3) or lower than (n=6) that of the contralateral testis. CONCLUSION: On ultrasonography, atrophic testes after mumps orchitis tended to exhibit an oblong shape, heterogeneous low echogenicity with multiple hyperechoic islands, and decreased vascularity.