International journal of molecular sciences
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The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. ⋯ Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. ⋯ During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.
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The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. ⋯ Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001-0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the "impaired clearance of emboli" concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA.
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Randomized Controlled Trial Comparative Study Observational Study
Orofacial Manifestations and Temporomandibular Disorders of Systemic Scleroderma: An Observational Study.
Scleroderma is a disorder involving oral and facial tissues, with skin hardening, thin lips, deep wrinkles, xerostomia, tongue rigidity, and microstomia. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in Systemic Sclerosis (SSc) patients compared with healthy people. Eighty patients (6 men, 74 women) fulfilling ACR/EULAR SSc Criteria were enrolled. ⋯ SSc patients complained more frequently (78.8%) of oral symptoms (Xerostomia, dysgeusia, dysphagia and stomatodynia) than controls (28.7%) (χ² = 40.23 p = 0.001). TMD symptoms (muscle pain on chewing, difficulty in mouth opening, headaches) were complained by 92.5% of SSc patients and by 76.2% of controls (χ² = 8.012 p = 0.005). At the clinical examination, 85% of SSc patients showed restricted opening versus 20.0% of controls (χ² = 67.77 p = 0.001), 81.2% of SSc showed reduced right lateral excursion versus 50% of controls (χ² = 17.316 p = 0.001); 73.8% of SSc showed limited left lateral excursion versus 53.8% of controls (χ² = 6.924 p = 0.009); and 73.8% of SSc had narrow protrusion versus 56.2% of controls (χ² = 5.385 p = 0.02).
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Interference of the binding of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a new inspiring immunotherapy for resisting cancers. To date, the FDA has approved two PD-1 monoclonal antibody drugs against cancer as well as a monoclonal antibody for PD-L1. ⋯ In this review, we focused on the mechanism of the PD-1/PD-L1 signaling pathway and the monoclonal antibodies (mAbs) against PD-1 and PD-L1, which were approved by the FDA or are still in clinical trials. And also presented is the prospect of the PD-1/PD-L1 immune checkpoint blockade in the next generation of immunotherapy.