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Rush Spears posted an update 5 months, 4 weeks ago
Pyroptosis is a type of proinflammatory regulated cell death (RCD) in which caspase-1 proteolytically cleaves gasdermin D (GSDMD) to yield a cytotoxic pore-forming protein. Recent studies have suggested that additional cell death pathways may interact with GSDMD under certain circumstances to execute pyroptosis. Microglia/macrophages in the central nervous system (CNS) undergo GSDMD-associated pyroptosis in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) but the contribution of other cell death pathways to this phenomenon is unknown. Herein, we tested the hypothesis that multiple RCD pathways underlie microglial pyroptosis in the context of neuroinflammation.
A siRNA screen of genes with known RCD functions was performed in primary human microglia to evaluate their role in nigericin-induced pyroptosis using supernatant lactate dehydrogenase activity as a read-out of cell lysis. Activation of apoptotic executioner proteins and their contribution to pyroptosis wae-3/7 inhibition. Pharmacological and siRNA-mediated inhibition of caspase-1 diminished caspase-3/7 activation during pyroptosis. In mice with EAE-associated neurological deficits, activated caspase-3 colocalized with GSDMD immunopositivity in lesion-associated macrophages/microglia.
Activation of executioner caspases-3/7, widely considered key mediators of apoptosis, contributed to GSDMD-associated microglial pyroptosis under neuroinflammatory conditions. Collectively, these observations highlight the convergence of different cell death pathways during neuroinflammation and offer new therapeutic opportunities in neuroinflammatory disease.
Activation of executioner caspases-3/7, widely considered key mediators of apoptosis, contributed to GSDMD-associated microglial pyroptosis under neuroinflammatory conditions. Collectively, these observations highlight the convergence of different cell death pathways during neuroinflammation and offer new therapeutic opportunities in neuroinflammatory disease.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with several comorbidities and vascular risk factors, such as dyslipidemia. The present study aimed to assess the possible associations between the lipid profile and atherogenic indexes and the severity of HS.
This case-control study enrolled 78 HS patients and 62 healthy controls. Classic lipid profile and lipoprotein ratios, including the atherogenic index of plasma (AIP), were evaluated. The severity of HS was measured by the HS Physician Global Assessment (PGA).
HS-patients had lower serum total cholesterol and HDL-C levels and higher AIP than the control group. AIP was positively correlated to BMI, waist circumference, systolic and diastolic blood pressure, LDL-C, triglycerides, non-HDL-C, ApoB, HOMA, and hs-CRP and negatively to HDL-C and ApoA1. For the overall lipid profile, only AIP was related to a more severe HS (PGA ≥ 3) after controlling for age, sex, BMI, insulin resistance (IR), active smoking, and statin use (r =0.268; p = 0.023). Multiple logistic regression adjusted for age, sex, BMI, IR, smoking status and statin use, showed that AIP ≥ 0.11 was significantly associated with the severity of HS (OR, 4.38; CI 95%, 1.09-17.50; p = 0.037).
In conclusion, these results showed that AIP is significantly and independently associated with HS severity.
In conclusion, these results showed that AIP is significantly and independently associated with HS severity.
Anterior spinal cord herniation (aSCH) is a rare cause of myelopathy which may present as pure motor syndrome and mimic other degenerative diseases of the spinal cord. In slowly progressive cases, diagnosis may be impeded by equivocal imaging results and mistaken for evolving upper motor neuron disease. As early imaging studies are lacking, we aimed to provide a detailed description of imaging and neurophysiology findings in a patient with aSCH, focusing on the early symptomatic stages.
We here present the case of a 51-year old male patient with an episode of pain in the right trunk and a normal spinal MRI. After a symptom-free interval of 8 years, spasticity and paresis evolved in the right leg. There was subtle ventral displacement and posterior indentation of the thoracic spinal cord on MRI which, in retrospect, was missed as an early sign of aSCH. After another 3 years, symptoms spread to the left leg and a sensory deficit of the trunk became evident. Follow-up MRI now clearly showed an aSCH. BAY-593 Neurosurgical intervention consisted of remobilization of the herniated spinal cord and patch closure of the dura defect. Over the following years, motor and sensory symptoms partially improved.
The history of this patient with aSCH illustrates the importance of careful longitudinal clinical follow-up with repeated imaging studies in progressive upper motor neuron syndromes. Specific attention should be paid to a history of truncal pain and to MRI findings of a ventrally displaced spinal cord. Neurosurgical intervention may halt the progression of herniation.
The history of this patient with aSCH illustrates the importance of careful longitudinal clinical follow-up with repeated imaging studies in progressive upper motor neuron syndromes. Specific attention should be paid to a history of truncal pain and to MRI findings of a ventrally displaced spinal cord. Neurosurgical intervention may halt the progression of herniation.
This study investigated testicular oxidative stress status and physiomorphological function in Wistar rats fed with yaji and cadmium chloride (CdCl2).
Sixty male albino Wistar rats (12 per group) were randomly assigned to five groups group I (control), group II (300 mg/kg.bw of yaji), group III (500 mg/kg.bw of yaji), group IV (2.5 mg/kg.bw of CdCl2), and group V (2.5 mg/kg.bw of yaji+4 mg/kg.bw omega-3). Each group was evenly subdivided into two subgroups and treatment was administered for 14 days and 42 days, respectively. Semen quality (sperm count, progressive motility, normal morphology, and gonadosomatic index), hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone), testicular oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, and malonaldehyde) and testicular histomorphological features were examined.
Yaji caused significant (p< 0.05) dose- and duration-dependent reductions in semen quality, the gonadosomatic index, testosterone, follicle-stimulating hormone, and luteinizing hormone.
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