The pathogenesis of endotoxin-induced acute lung injury is fundamentally driven by dysregulated innate immune responses, where macrophage-mediated cytokine surges and subsequent signaling cascades trigger neutrophil infiltration and tissue damage.This study investigated whether curcumin modulates inflammatory signaling pathways and attenuates lung injury in experimental endotoxemia. Using endotoxin-stimulated murine macrophages and a mouse model of intratracheal lipopolysaccharide challenge, inflammatory cytokine production, mitogen-activated protein kinase activation, pulmonary edema, neutrophil accumulation, histopathologic injury, and short-term survival were assessed. Curcumin suppressed endotoxin-induced tumor necrosis factor- production and selectively inhibited ERK1/2 and JNK phosphorylation without affecting p38 signaling in macrophages. In vivo, curcumin reduced pulmonary cytokine levels, neutrophil infiltration, lung edema, and histologic injury, and was associated with improved survival following severe endotoxin exposure. These findings indicate that curcumin attenuates acute lung injury by selectively modulating intracellular inflammatory signaling pathways, supporting the concept that targeted inhibition of specific kinase cascades may mitigate inflammatory lung damage without broad immune suppression.

OBJECTIVE: Dysphagia is a common consequence of stroke with a negative effect on the clinical outcome. Given these potential outcomes, it is important to identify the precursors to dysphagia after stroke. The aims of this study were to identify lesions associated with dysphagia after an ischemic supratentorial stroke using voxel-based lesion symptom mapping (VLSM) and compare the difference in the lesion pattern between the oral and pharyngeal phase dysphagia. METHODS: Stroke patients who met the following inclusion criteria were screened retrospectively between January 2012 and November 2014: a first-ever stroke, supratentorial lesion and who underwent brain MRI and functional dysphagia scale (FDS) from videofluoroscopic swallowing study (VFSS). Finally, the MRI data of 83 patients were analyzed. Statistical maps of the lesion contribution related to dysphagia were generated using VLSM. RESULTS: VLSM showed that FDS was associated with damage to the putamen, caudate, insula, frontal precentral gyrus, and inferior frontal gyrus. The lesions were distributed more widely in the left than right hemisphere. Lesions correlated with the FDS oral score were distributed mainly in the frontal lobe and insula. Otherwise, the associated lesion with the FDS pharyngeal score was mainly the basal ganglia. CONCLUSION: In these results, lesions that correlated with dysphagia were distributed more widely in the left hemisphere, reflecting the possibility of lateralization of the swallowing function. Oral phase dysphagia was associated with left frontal lobe and insula; the lesion correlated with the cognitive function or apraxia. On the other hand, VLSM revealed the lesions associated with pharyngeal dysphagia to be the basal ganglia, which is a structure that plays a role in the automatic motor control network.
Apraxias ; Basal Ganglia ; Brain ; Brain Mapping ; Cognition ; Deglutition ; Deglutition Disorders ; Frontal Lobe ; Hand ; Humans ; Magnetic Resonance Imaging ; Neuroanatomy ; Prefrontal Cortex ; Putamen ; Retrospective Studies ; Stroke

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
3-Iodobenzylguanidine ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Anterior Wall Myocardial Infarction/*drug therapy/physiopathology ; Biphenyl Compounds/*therapeutic use ; Cardiotonic Agents/*therapeutic use ; Disease Models, Animal ; Echocardiography ; Fluorodeoxyglucose F18 ; Perindopril/therapeutic use ; Positron-Emission Tomography ; Pyrimidines/*therapeutic use ; Random Allocation ; Swine ; Tetrazoles/*therapeutic use ; Tomography, Emission-Computed, Single-Photon ; Valsartan/therapeutic use ; Ventricular Function, Left/*physiology

PURPOSE: Luciferase is one of the most commonly used reporter enzymes in the field of in vivo optical imaging. D-luciferin, the substrate for firefly luciferase has very high cost that allows this kind of experiment limited to small animals such as mice and rats. In this current study, we validated local injection of D-luciferin in the articular capsule for bioluminescence imaging in rabbits. MATERIALS AND METHODS: Chondrocytes were cultured and infected by replication-defective adenoviral vector encoding firefly luciferase (Fluc). Chondrocytes expressing Fluc were injected or implanted in the left knee joint. The rabbits underwent optical imaging studies after local injection of D-luciferin at 1, 5, 7, 9 days after cellular administration. We sought whether optimal imaging signals was could be by a cooled CCD camera after local injection of D-luciferin. RESULTS: Imaging signal was not observed from the left knee joint after intraperitoneal injection of D-luciferin (15 mg/kg), whereas it was observed after intraarticular injection. Photon intensity from the left knee joint of rabbits was compared between cell injected and implanted groups after intraarticular injection of D-luciferin. During the period of imaging studies, photon intensity of the cell implanted group was 5-10 times higher than that of the cell injected group. CONCLUSION: We successfully imaged chondrocytes expressing Fluc after intraarticular injection of D-luciferin. This technique may be further applied to develop new drugs for knee joint disease.
Adenoviridae ; Animals ; Chondrocytes* ; Fireflies ; Injections, Intra-Articular* ; Injections, Intraperitoneal ; Joint Capsule ; Knee Joint ; Luciferases ; Mice ; Optical Imaging ; Rabbits* ; Rats