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BACKGROUND: This study tested whether phloretin (a brain-edema inhibitors) would augment therapeutic impact of human-derived platelet-rich plasma (hPRP) on attenuating brain-hemorrhagic volume (BHV) and preserving the neurologic function in rodent following acute traumatic brain damage (TBD). METHODS: Rats (n=40) were separated into group-1 (sham-control), group-2 (TBD), group-3 [TBD + phloretin (80mg/kg/dose by intra-peritoneal administration at 30min and days 2/3 followed-by TBD), group-4 (TBD + PRP/80µL by left intra-carotid-artery injection at 3h after TBD) and group-5 (TBD + phloretin + hPRP) and cerebral tissues were harvested by day 28 after TBD. RESULTS: The brain MRI at day 28 revealed that the BHV was lowest in group 1, highest in group 2 and significantly lower in group 5 than in groups 3/4, but it was similar between groups 3/4, whereas neurological function displayed a opposite pattern of BHV among the groups (all p<0.0001). By 72h, the protein levels of upstream (HGMB1/TLR-2/TLR-4/MyD88/Mal/TRAM/ TRIF/TRAF6/IKK-α/IKK-ß/p-NF-κB) and downstream (IL-1ß/TNF-α/iNOS) inflammation signalings, apoptosis (caspase3/PARP) and fibrosis (Smad3/TGF-ß) biomarkers and flow cytometric assessment of inflammation cells (CD11b/c+//Ly6G+/PMO+) and early (AN-V+/PI-)/late (AN-V+/PI+) mononuclear-cell apoptosis displayed a similar manner of BHV among the groups (all p<0.0001). Cell number of inflammatory (CD68+/MMP9+) and brain-swelling/myelin-damaged (AQP4+/ GFAP+) mediators revealed a similar way, whereas the neuronal-myelin (Doublecortin+/NeuN/nestin) mediators exhibited an inverse manner of BHV among the groups (all p<0.0001). CONCLUSION: Combination of phloretin and hPRP regimen was better than just one treatment to offer synergic benefits for protecting the brain against TBD.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Sinusitis , Humanos , Infecciones por Pseudomonas/complicaciones , Pseudomonas aeruginosa/aislamiento & purificación , Sinusitis/microbiología , Sinusitis/complicaciones , Masculino , Síndrome de Inmunodeficiencia con Hiper-IgM/complicaciones , Enfermedades Orbitales/etiología , Enfermedades Orbitales/microbiología , Niño , FemeninoRESUMEN
This study tested whether combined dapagliflozin and entresto would be superior to mere one therapy on protecting the residual renal function and integrity of kidney parenchyma in hypertensive kidney disease (HKD) rat. In vitro results showed that the protein expressions of oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized-protein/cytosolic-cytochrome-C)/apoptotic (mitochondrial-Bax/cleaved caspeases 3, 9)/cell-stress (p-ERK/p-JNK/p-p38) biomarkers were significantly increased in H2O2-treated NRK-52E cells than those of controls that were reversed by dapagliflozin or entresto treatment. Adult-male SD rats (n = 50) were equally categorized into group 1 (sham-operated-control), group 2 (HKD by 5/6 nephrectomy + DOCA-salt/25 mg/kg/subcutaneous injection/twice weekly), group 3 (HKD + dapagliflozin/orally, 20 mg/kg/day for 4 weeks since day 7 after HKD induction), group 4 (HKD + entresto/orally, 100 mg/kg/day for 4 weeks since day 7 after HKD induction), and group 5 (HKD + dapagliflozin + entresto/the procedure and treatment strategy were identical to groups 2/3/4). By day 35, circulatory levels of blood-urine-nitrogen (BUN)/creatinine and urine protein/creatinine ratio were lowest in group 1, highest in group 2, and significantly lower in group 5 than in groups 3/4, but no difference between groups 3/4. Histopathological findings showed the kidney injury score/fibrotic area/cellular expressions of oxidative-stress/kidney-injury-molecule (8-OHdG+/KIM-1+) exhibited an identical trend, whereas the cellular expressions of podocyte components (synaptopodin/ZO-1/E-cadherin) exhibited an opposite pattern of BUN level among the groups. The protein expressions of oxidative stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D)/apoptotic (mitochondrial-Bax/cleaved-caspase 3)/mitochondrial-fission (PINK1/Parkin/p-DRP1)/autophagic (LC3BII/LC3BI ratio, Atg5/beclin-1)/MAPK-family (p-ERK/p-JNK/p-p38) biomarkers displayed a similar pattern, whereas the protein expression of mitochondria-biogenesis signaling (SIRT1/PGC-1α-Mfn2/complex I-V) displayed an opposite pattern of BUN among the groups. In conclusion, combined dapagliflozin-entresto therapy offered additional benefits on protecting the residual kidney function and architectural integrity in HKD rat.
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Aminobutiratos , Compuestos de Bencidrilo , Compuestos de Bifenilo , Glucósidos , Hipertensión Renal , Nefritis , Sirtuina 1 , Valsartán , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Sirtuina 1/metabolismo , Creatinina , Peróxido de Hidrógeno , Proteína X Asociada a bcl-2/metabolismo , Riñón/patología , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Mitocondrias/metabolismo , Estrés Oxidativo , Homeostasis , Biomarcadores/metabolismo , Citocromos/metabolismo , Combinación de MedicamentosRESUMEN
BACKGROUND: This study tested the hypothesis that inflammatory and interleukin (IL)-17 signalings were essential for acute liver ischemia (1 h)-reperfusion (72 h) injury (IRI) that was effectively ameliorated by adipose-derived mesenchymal stem cells (ADMSCs) and tacrolimus. METHODS: Adult-male SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IRI), 3 [IRI + IL-17-monoclonic antibody (Ab)], 4 (IRI + tacrolimus), 5 (IRI + ADMSCs) and 6 (IRI + tacrolimus-ADMSCs) and liver was harvested at 72 h. RESULTS: The main findings included: (1) circulatory levels: inflammatory cells, immune cells, and proinflammatory cytokines as well as liver-damage enzyme at the time point of 72 h were highest in group 2, lowest in group 1 and significantly lower in group 6 than in groups 3 to 5 (all p < 0.0001), but they did not differ among these three latter groups; (2) histopathology: the liver injury score, fibrosis, inflammatory and immune cell infiltration in liver immunity displayed an identical pattern of inflammatory cells among the groups (all p < 0.0001); and (3) protein levels: upstream and downstream inflammatory signalings, oxidative-stress, apoptotic and mitochondrial-damaged biomarkers exhibited an identical pattern of inflammatory cells among the groups (all p < 0.0001). CONCLUSION: Our results obtained from circulatory, pathology and molecular-cellular levels delineated that acute IRI was an intricate syndrome that elicited complex upstream and downstream inflammatory and immune signalings to damage liver parenchyma that greatly suppressed by combined tacrolimus and ADMSCs therapy.
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Hepatopatías , Células Madre Mesenquimatosas , Daño por Reperfusión , Ratas , Masculino , Animales , Interleucina-17 , Tacrolimus/farmacología , Ratas Sprague-Dawley , Daño por Reperfusión/terapia , Daño por Reperfusión/patología , Células Madre Mesenquimatosas/patologíaRESUMEN
OBJECTIVES: To use convolutional neural network for fully automated segmentation and radiomics features extraction of hypopharyngeal cancer (HPC) tumor in MRI. METHODS: MR images were collected from 222 HPC patients, among them 178 patients were used for training, and another 44 patients were recruited for testing. U-Net and DeepLab V3 + architectures were used for training the models. The model performance was evaluated using the dice similarity coefficient (DSC), Jaccard index, and average surface distance. The reliability of radiomics parameters of the tumor extracted by the models was assessed using intraclass correlation coefficient (ICC). RESULTS: The predicted tumor volumes by DeepLab V3 + model and U-Net model were highly correlated with those delineated manually (p < 0.001). The DSC of DeepLab V3 + model was significantly higher than that of U-Net model (0.77 vs 0.75, p < 0.05), particularly in those small tumor volumes of < 10 cm3 (0.74 vs 0.70, p < 0.001). For radiomics extraction of the first-order features, both models exhibited high agreement (ICC: 0.71-0.91) with manual delineation. The radiomics extracted by DeepLab V3 + model had significantly higher ICCs than those extracted by U-Net model for 7 of 19 first-order features and for 8 of 17 shape-based features (p < 0.05). CONCLUSION: Both DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images, whereas DeepLab V3 + had a better performance than U-Net. CLINICAL RELEVANCE STATEMENT: The deep learning model, DeepLab V3 + , exhibited promising performance in automated tumor segmentation and radiomics extraction for hypopharyngeal cancer on MRI. This approach holds great potential for enhancing the radiotherapy workflow and facilitating prediction of treatment outcomes. KEY POINTS: ⢠DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images. ⢠DeepLab V3 + model was more accurate than U-Net in automated segmentation, especially on small tumors. ⢠DeepLab V3 + exhibited higher agreement for about half of the first-order and shape-based radiomics features than U-Net.
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Aprendizaje Profundo , Neoplasias Hipofaríngeas , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Hipofaríngeas/diagnóstico por imagen , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: We aimed to develop a deep learning artificial intelligence (AI) algorithm to detect impacted animal bones on lateral neck radiographs and to assess its effectiveness for improving the interpretation of lateral neck radiographs. METHODS: Lateral neck radiographs were retrospectively collected for patients with animal bone impaction between January 2010 and March 2020. Radiographs were then separated into training, validation, and testing sets. A total of 1733 lateral neck radiographs were used to develop the deep learning algorithm. The testing set was assessed for the stand-alone deep learning AI algorithm and for human readers (radiologists, radiology residents, emergency physicians, ENT physicians) with and without the aid of the AI algorithm. Another radiograph cohort, collected from April 1, 2020, to June 30, 2020, was analyzed to simulate clinical application by comparing the deep learning AI algorithm with radiologists' reports. RESULTS: In the testing set, the sensitivity, specificity, and accuracy of the AI model were 96%, 90%, and 93% respectively. Among the human readers, all physicians of different subspecialties achieved a higher accuracy with AI-assisted reading than without. In the simulation set, among the 20 cases positive for animal bones, the AI model accurately identified 3 more cases than the radiologists' reports. CONCLUSION: Our deep learning AI model demonstrated a higher sensitivity for detection of animal bone impaction on lateral neck radiographs without an increased false positive rate. The application of this model in a clinical setting may effectively reduce time to diagnosis, accelerate workflow, and decrease the use of CT.
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BACKGROUND: This study tested whether combined dapagliflozin and entresto treatment would be superior to either one alone for preserving the left-ventricular ejection-fraction (LVEF) in rat after ischemia-reperfusion (IR) injury. METHODS: Cell culture using H9C2 cells and IR injury in rat with dapagliflozin-entresto treatment were conducted in the present study. RESULTS: In vitro flow-cytometric result showed that the intracellular and mitochondrial reactive oxygen species and mitochondrial permeability transition pore, and protein levels of oxidative-stress/DNA-damaged markers [NADPH-oxidase-1 (NOX-1)/NOX-2/oxidized-protein/γ-H2A-histone-family member X (γ-H2AX)] were significantly higher in hydrogen peroxide (H2O2) (300µM)-treated H9C2 cells as compared with the controls that were significantly reversed in sacubitril/valsartan and dapagliflozin therapy in the same H2O2-treated condition, whereas the protein expressions of antioxidants [Sirtuin-1 (SIRT1)/SIRT3/superoxide dismutase/catalase/glutathione peroxidase) exhibited an opposite pattern among the groups (all p<0.001). Adult-male-Sprague-Dawley rat (n=40) were equally categorized into group 1 (sham-operated control), group 2 (IR), group 3 (IR+dapagliflozin/20mg/kg/orally at 3h and post-days 1/2/3 after IR), group 4 (IR+entresto/100mg/kg/orally at 3h and post-days 1/2/3 after IR) and group 5 (IR+dapagliflozin+entresto) and the hearts were harvested by day 3 after IR. The 3rd day's LVEF was highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3/4, but it was similar between the latter two groups (p<0.001). The protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), fibrotic (transforming-growth factor-ß/phosphorylated-Smad3), apoptotic [mitochondrial-Bax/cleaved-caspase-3/cleaved-poly (ADP-ribose) polymerase], mitochondria/DNA damaged (cytosolic-cytochrome-c/γ-H2AX), pressure-overload/heart-failure [brain natriuretic peptide (BNP)/ß-myosin heavy chain] and autophagic (ratio of meiotic cyclins CLB3-II/CLB3-I) biomarkers, and the upstream (high-mobility group box 1/Toll-like receptor-4/MyD88/phosphorylated-nuclear factor-κB and downstream [interleukin (IL)-1ß/IL-6/tumor necrosis factor-α] inflammatory signalings revealed an antithetical features of LVEF among the groups (all p<0.0001). The cellular levels of inflammatory (myeloperoxidase+/CD68+), pressure-overload/heart-failure (BNP+) and DNA-damage (γ-H2AX+) biomarkers as well as infarct area demonstrated an opposite pattern of LVEF among the groups (all p<0.0001). CONCLUSION: Incorporated entresto-dapagliflozin treatment was superior to either one alone on protecting the heart against IR injury.
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Peróxido de Hidrógeno , Daño por Reperfusión , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Valsartán/metabolismo , Estrés Oxidativo , Biomarcadores , ADN/metabolismoRESUMEN
BACKGROUND: Phlebosclerotic colitis (PC) is a rare form of nonthrombotic colonic ischemia. This retrospective study analyzed the clinical findings and temporal CT changes in 29 PC patients with long-term follow-up. METHODS: Twenty-nine patients with characteristic CT features of PC collected between 1997 and 2020 were stratified into the acute abdomen group (AA-group) (n = 10), chronic-progressive group (CP-group) (n = 14) and chronic-stable group (CS-group) (n = 5). Clinical and CT changes during follow-up, comorbidities and final outcomes were compared. RESULTS: The AA-group exhibited a significantly thicker colonic wall and more involved segments and pericolic inflammation than the CP-group and CS-group on initial CT (p = < 0.001-0.031). Seven patients in the AA-group who underwent right hemicolectomy had no recurrence during follow-up (mean ± SD, 7.1 ± 3.3 years), and the remaining three patients with renal or hepatic comorbidities who underwent conservative treatment died within 14 days. The CP-group showed significantly higher frequencies of chronic renal failure, urinary tract malignancies and liver cirrhosis than the AA-group (p = 0.005-0.008). In addition, CT follow-up (7.9 ± 4.3 years) showed significant increases in mesenteric venous calcifications, colonic wall thickening and involved colonic segments (p = 0.001-0.008) but conservative treatments were effective. The CS-group remained unchanged for years (8.2 ± 3.9 years). CONCLUSIONS: Early surgery offered excellent prognosis in PC-related acute abdomen denoted by marked right colonic wall thickening and pericolic inflammation on CT. Conservative treatments with a wait-and-watch strategy were appropriate for CP-PC and CS-PC, albeit CP-PC harbored significant increases in calcifications, colonic wall thickening and affected segments in long-term CT follow-up.
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This study tested the hypothesis that valsartan (Val) and melatonin (Mel)-assisted adipose-derived mesenchymal stem cells (ADMSCs) preserved the residual renal function in chronic kidney disease (CKD) rat through promoting cellular-prior-protein (PrPC) to upregulate PI3K/Akt/mTOR signaling and cell proliferation. In vitro study demonstrated that as compared with CKD-derived-ADMSCs, Val/Mel/overexpression of PrPC-treated CKD derived-ADMSCs significantly upregulated cell proliferation and protein expressions of PrPC and phosphorylated (p)-PI3K/p-Akt/p-mTOR, and downregulated oxidative stress (all p < 0.001). Rats (n = 42) were categorized into group 1 (sham-operated-control), group 2 (CKD), group 3 (CKD + ADMSCs/1.2 ×106 cells) + Mel/20 mg/kg/day), group 4 (CKD + siRNA-PrPC-ADMSCs/1.2 ×106 cells), group 5 (CKD + ADMSCs/1.2 ×106 cells + Val/20 mg/kg/day) and group 6 (CKD + Val + Mel). By day 35, the kidney specimens were harvested and the result showed that the protein expression of PrPC was highest in group 1, lowest in groups 2/4 and significantly lower in group 6 than in groups 3/5, but it was similar in groups 3/5 (all p < 0.0001). The protein expressions of cell-stress-signaling (p-PI3K/p-Akt/p-mTOR) and cell-cycle activity (cyclin-D1/clyclin-E2/Cdk2/Cdk4) exhibited an identical pattern, whereas the protein expressions of oxidative-stress (NOX-1/NOX-2)/mitochondrial fission (PINK1/DRP1)/apoptosis (cleaved-capsase3/cleaved-PARP) and fibrosis (TFG-ß/Smad3) as well as creatinine/BUN levels, ratio of urine-protein to urine-creatine and kidney-injured score exhibited an opposite pattern of PrPC among the groups (all p < 0.0001). In conclusion, Mel/Val facilitated-ADMSCs preserved renal architecture and function in CKD rat through promoting PrPC to regulate the cell proliferation/oxidative-stress/cell-stress signalings.
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Melatonina/farmacología , Células Madre Mesenquimatosas/metabolismo , Insuficiencia Renal Crónica/patología , Valsartán/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Riñón/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Proteínas Priónicas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/efectos de los fármacos , Regulación hacia ArribaRESUMEN
BACKGROUND: This study tested the hypothesis that combined hyperbaric oxygen (HBO) and autologous adipose-derived mesenchymal stem cell (ADMSC) therapy was superior to either alone at protecting renal function in rodents after acute ischemia-reperfusion (IR) injury. METHODS AND RESULTS: Adult-male SD rats (n = 40) were equally categorized: group 1 (sham-operated control); group 2 (IR + 50 µg medium intra-renal artery administration); group 3 [IR + HBO (at 1.5 h and days 1 and 2 after IR)]; group 4 [IR + ADMSC (2.0×106 cells/5.0×105/per each renal artery and 1.0×106 by intravenous injection at 1.5 h after IR]; and group 5 (IR + HBO-ADMSC). By 72 hr after IR, the circulating levels of BUN/creatinine and ratio of urine protein/creatinine were significantly highest in group 2, lowest in group 1, significantly increased in group 5 than in groups 3 and 4, but not different between latter two groups, whereas the circulating levels of EPCs and soluble-angiogenesis biomarkers (SDF-1α/HIF-1α) exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.001). The kidney injury score, ROS (fluorescent intensity of H2DCFDA dye in kidney), inflammation (F4/80+, CD14+ cells) and glomerular-tubular injury score (WT-1/KIM-1) displayed an identical pattern whereas the integrity of podocyte components exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.0001). The protein expressions of inflammatory (MMP-9/TNF-α/NF-κB/ICAM-1), oxidative-stress (NOX-1/NOx-2/oxidized protein) and apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) markers showed an identical pattern to BUN/creatinine (all P<0.001). CONCLUSION: Combined ADMSC-HBO therapy was superior to either one alone at protecting the kidney from acute IR injury.
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Acute liver ischaemia-reperfusion injury (IRI), commonly encountered during liver resection and transplantation surgery, is strongly associated with unfavourable clinical outcome. However, a prompt and accurate diagnosis and the treatment of this entity remain formidable challenges. This study tested the hypothesis that 31 P-magnetic resonance spectroscopy (31 P-MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin-pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. Adult male SD rats were categorized into group 1 (sham-operated control), group 2 (IRI only) and group 3 (IRI + melatonin [ie mitochondrial donor rat received intraperitoneal administration of melatonin] pretreated mitochondria [10 mg/per rat by portal vein]). By the end of study period at 72 hours, 31 P-MRS showed that, as compared with group 1, the hepatic levels of ATP and NADH were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1. The liver protein expressions of mitochondrial-electron-transport-chain complexes and mitochondrial integrity exhibited an identical pattern to 31 P-MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial-damaged biomarkers displayed an opposite finding of 31 P-MRS, whereas the protein expressions of antioxidants were significantly progressively increased from groups 1 to 3. Microscopic findings showed that the fibrotic area/liver injury score and inflammatory and DNA-damaged biomarkers exhibited an identical pattern of cellular stress signalling. Melatonin-pretreated mitochondria effectively protected liver against IRI and 31 P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.
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Hígado/efectos de los fármacos , Melatonina/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Hígado/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Masculino , Mitocondrias Hepáticas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoRESUMEN
This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4-/- ) (n = 6 per each TLR4-/- group) mice were categorized into sham control (SCB6 ), SCTLR4-/- , ISB6 , ISTLR4-/- , ISB6 + Mel (i.p. daily administration) and ISTLR4-/- + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK-α/p-NF-κB/nuclear-NF-κB/nuclear-IRF-3&7/IL-1ß/IL-6/TNF-α/IFN-γ) and oxidative stress (NOX-1/NOX-2/ASK1/p-MKK4&7/p-JNK/p-c-JUN) downstream pathways as well as mitochondrial-damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group ISB6 , lowest in groups SCB6 and SCTLR4-/- , lower in group ISTLR4-/- + Mel than in groups ISTLR4-/- and ISB6 + Mel and lower in group ISB6 + Mel than in group ISTLR4-/- (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4-88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy.
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Inflamación/patología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Melatonina/uso terapéutico , Estrés Oxidativo , Transducción de Señal , Accidente Cerebrovascular/tratamiento farmacológico , Alarminas/metabolismo , Animales , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Infarto Encefálico/complicaciones , Infarto Encefálico/tratamiento farmacológico , Infarto Encefálico/patología , Infarto Encefálico/fisiopatología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Imagen por Resonancia Magnética , Masculino , Melatonina/farmacología , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Extractos de Tejidos , Receptores Toll-Like/metabolismoRESUMEN
BACKGROUND: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). METHODS AND RESULTS: Adult male SD rats (n = 70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2 × 106 cells/by LICA administration 3 h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS), and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2, and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all P < 0.0001). By day 60, the endothelial cell markers at protein and cellular levels and number of small vessels exhibited an opposite pattern of BIV among the groups (all P < 0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy, and apoptosis were highest in group 2, lowest in group 1, and progressively increased from groups 3 to 7 (all P < 0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all P < 0.0001). CONCLUSION: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.
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Isquemia Encefálica , Células Progenitoras Endoteliales , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Isquemia Encefálica/terapia , Masculino , Pronóstico , Ratas , Ratas Sprague-Dawley , Roedores , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: This retrospective study evaluated the computed tomography (CT) features and clinical implications of a novel broken-crescent sign in patients with acute aortic intramural hematoma (IMH). METHODS: Out of 104 patients with aortic IMH encountered in our institution between 2003 and 2018, nine patients exhibited a positive broken-crescent sign, which was defined as a focal defect within the hyper-attenuating crescentic IMH on unenhanced CT, corresponding to a smooth out-bulging of the aortic lumen on enhanced study. The clinical findings, CT features, and outcomes of these nine patients were analyzed. RESULTS: Of five males and four females (age range 48-84 years, mean 69.7 years), six had type A and three had type B IMH. Five patients who had medical treatment and stable status for 1 to 3 days suffered sudden death, two of whom showed ascending aortic rupture with hemopericardium in one and adventitial tear with outward spillage of IMH in another at follow-up CT. The other four patients had early surgical or endovascular management survived; two demonstrated ascending aorta ecchymosis with adventitial tear and intact intima at surgery. Our results support the supposition that aortic IMH complicated with adventitial tear and partial outward seepage of IMH may generate a broken-crescent sign in CT. Despite initially stable clinical status, the residual intact inner aortic wall carries a high risk of sudden aortic rupture. CONCLUSIONS: In patients with acute aortic IMH, identification of a broken-crescent sign in CT is highly suggestive of impending aortic rupture, and early aggressive treatment is mandatory.
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This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral-cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale (NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). Between November 2015 and October 2017, a total of 99 IS patients were prospectively enrolled and categorized into three groups based on NIHSS, i.e., group 1 (NIHSS ≤ 8, n = 66), group 2 (NIHSS = 9-15, n = 14) and group 3 (NIHSS ≥ 16, n = 19), respectively. Blood samples were collected immediately after hospitalization, followed by transthoracic echocardiographic examination. The results showed that the flow cytometric analysis for assessment of inflammatory biomarkers of TLR2+/CD14+cells, TLR4+/CD14+cells, Ly6g+/CD14+cells, and MPO+/CD14+cells, and ELISA assessment for circulatory level of sST2 were significantly higher in groups 2/3 than in group 1 (all p < 0.01). However, these parameters did not show significant differences between groups 2 and 3 (all p > 0.05). The LVEF was significantly lower in group 3 than in group 1 (p < 0.001), but it displayed no difference between groups 1/2 or between groups 2/3. These inflammatory biomarkers ((TLR2+/CD14+cells// TLR4+/CD14+cells// MPO+/CD14+cells) and sST2)) were significantly positively correlated to NIHSS and strongly negatively correlated to LVEF (all p < 0.05). Multivariate analysis demonstrated that both MPO/CD14+cells >20% (p = 0.027) and sST2 ≥ 17,600 (p = 0.004) were significantly and independently predictive of moderate-severe CCS after acute IS. Receiver operating characteristic curve analysis demonstrated that sST2 was the most powerful predictor of CCS with a sensitivity of 0.929 and a specificity of 0.731 (p < 0.001). In conclusion, sST2 is a useful biomarker for prediction of CCS severity in patients after acute IS.
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This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSCSPIONs ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSCSPIONs (1.0 × 106 cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSCSPIONs (0.5 × 106 cells)] and group 5 [CKD + iPS-MSCSPIONs (1.0 × 106 cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3ß/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-α/TNFR1/TRAF2/NF-κB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSCSPIONs that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.
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Pruebas de Función Renal , Riñón/patología , Riñón/fisiopatología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Administración Intravenosa , Animales , Apoptosis , Biomarcadores/metabolismo , Nitrógeno de la Urea Sanguínea , Diferenciación Celular , Proliferación Celular , Medios de Contraste/química , Creatinina/orina , Citoprotección , Humanos , Imagen por Resonancia Magnética , Masculino , Estrés Oxidativo , Podocitos/patología , Proteinuria/complicaciones , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/diagnóstico por imagen , Insuficiencia Renal Crónica/patología , Transducción de Señal , Factores de TiempoRESUMEN
PURPOSE: This study aimed to investigate the feasibility of diffusion tensor imaging (DTI) and T2-mapping to assess temporal renal damage in deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats and compare the results with histopathologic and immunohistochemical findings. PROCEDURES: After baseline renal magnetic resonance imaging (MRI), 24 out of 30 uninephrectomized Sprague-Dawley rats with DOCA-salt-induced hypertension were divided equally into four groups. Group 1 had renal MRI at weeks 2, 4, 6, and 8, and groups 2, 3, and 4 had MRI at weeks 2, 4, and 6, respectively. The remaining 6 rats were used as sham controls. The renal cortex and outer and inner stripes of the outer medulla were examined over time using fractional anisotropy (FA), apparent diffusion coefficient (ADC), and T2-mapping, and the results were compared with baseline values. The degree of glomerular and tubular injury, endothelial cell thickening, hyaline arteriolosclerosis, macrophage infiltration, microcyst formation, and fibrosis in different zones at different time points in the DOCA-salt rats were compared with controls. RESULTS: Compared with baseline values, DOCA-salt rats demonstrated a significant decrease in renal cortical FA from week 4 to week 8 (0.244 ± 0.015 vs 0.172 ± 0.014-0.150 ± 0.016, P = 0.018-0.002), corresponding to significantly more glomerular damage, arteriolosclerosis, macrophage infiltration, and fibrosis. The DOCA-salt rats had significantly increased cortical ADC and T2 values at weeks 6 and 8 (1.778 ± 0.051 × 10-3 mm2/s vs 1.872 ± 0.058-1.917 ± 0.066 × 10-3 mm2/s; 93.7 ± 4.9 ms vs 98.0 ± 2.9-100.7 ± 4.0 ms, respectively, all P < 0.05), consistent with excessively fluid-filled microcysts (aquaporin-2+). Despite DOCA-salt rats harbored markedly increased fibrosis in outer and inner stripes of the outer medulla at weeks 6 and 8, only nonsignificant decreases in FA were observed in comparison with the controls suggesting that only limited microstructural changes were present. CONCLUSIONS: Renal cortical FA is useful for the early detection and monitoring of renal damage in DOCA-salt hypertensive rats.
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Acetatos/toxicidad , Desoxicorticosterona/toxicidad , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Hipertensión/complicaciones , Enfermedades Renales/patología , Riñón/patología , Animales , Hipertensión/inducido químicamente , Hipertensión/patología , Riñón/diagnóstico por imagen , Riñón/lesiones , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/etiología , Masculino , Ratas , Ratas Endogámicas Dahl , Ratas Sprague-DawleyRESUMEN
PURPOSE: In this prospective study, we sought to compare the clinical utility of fluorodeoxyglucose PET/MRI, MRI, and PET/CT in the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: We examined 198 consecutive patients with biopsy-proven OHSCC who agreed to receive chemoradiation. All patients underwent pretreatment PET/MRI and PET/CT on the same day. Patients were followed-up for a minimum of 12 months or until death. The McNemar's test and receiver-operating characteristic (ROC) curves were used to compare sensitivity/specificity and the diagnostic capabilities of PET/MRI, MRI, and PET/CT, respectively. RESULTS: We identified 55 patients (27.7%) who had synchronous cancers and/or distant metastases (number of involved sites: 83). The results of site-based analysis revealed that the sensitivity of PET/MRI was 15.7% higher than that of MRI (73.5% versus 57.8%, p < 0.001) and 3.6% higher compared with PET/CT (73.5% versus 69.9%, p = 0.083), whereas the sensitivity of PET/CT was 12.1% higher than that of MRI (69.9% versus 57.8%, p = 0.012). On a patient-basis, ROC curve analysis demonstrated that PET/MRI yielded a greater area under curve than MRI (0.930 versus 0.905, p = 0.023). There were no significant differences in terms of diagnostic capability between MRI and PET/CT (0.905 versus 0.917, p = 0.469) and between PET/MRI and PET/CT (0.930 versus 0.917, p = 0.062). CONCLUSIONS: In our cohort, PET/MRI showed a significantly higher diagnostic capability than MRI and no significant difference compared with PET/CT for the detection of synchronous cancers or distant metastases in patients with OHSCC.
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Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
INTRODUCTION: Duplications of the alimentary tract are a rare congenital malformation. Most of the cases are symptomatic and diagnosed before 2 years of age. Here, we report a young female presented with a huge abdominal mass, and colonic duplication was confirmed during laparotomy. CASE PRESENTATION: A 29-year-old female had chronic constipation treated with laxative agents. She presented to the emergency room with abdominal cramping for 3 days, accompanied with intermittent fever and vomiting. A huge movable abdominal mass was noted during physical examination. Computerized tomography showed a long segmental dilated bowel lumen with stool impaction and bowel wall thickening of the dilated lumen in the left abdomen, highly suggestive of a long tubular colon duplication. The patient underwent subtotal colectomy. Specimen subsequently confirmed the diagnosis for colonic duplication from cecum to sigmoid colon, and the duplicated colon was found on the antimesenteric side of the native colon. She had a stable postoperative course and was discharged 9 days later. DISCUSSION: Duplications of the alimentary tract are a rare congenital anomaly. Colonic duplication is an even more unusual malformation of this type. It can be classified into cystic or tubular type according to the gross morphology and may or may not be associated with other congenital anomalies. Most common presentation includes abdominal distention, refractory constipation, and bowel obstruction like many other colorectal conditions. Thus, its indistinct symptoms make it difficult to be diagnosed preoperatively. The recommended treatment is surgical resection of the duplicated lumen along with the attached native colon.
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Colon/anomalías , Adulto , Bario , Colon/diagnóstico por imagen , Enema , Femenino , Humanos , Tomografía Computarizada por Rayos XRESUMEN
This study tested the hypothesis that combined hyperbaric oxygen (HBO) and melatonin (Mel) was superior to either one for protecting the brain functional and parenchymal integrity from acute ischemic stroke (IS) injury. Adult-male Sprague-Dawley rats were divided into groups 1 (sham-operated control), 2 (IS), 3 (IS + HBO), 4 (IS + Mel), and 5 (IS + HBO-Mel). By day 28 after IS, the brain infarct area (BIA) was lowest in group 1, highest in group 2, significantly higher in groups 3 and 4 than in group 5, but not different between groups 3 and 4. The neurological function at day 7, 14, and 28 exhibited an opposite pattern to BIA among the 5 groups. The protein expressions of inflammatory (IL-1ß/IL-6/iNOS/TNF-α/p-NF-κB), apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial Bax), mitochondrial/DNA-damaged (cytochrome-C/γ-H2AX), oxidative stress (NOX-1/NOX-2), and autophagy (i.e. ratio of CL3B-II/CL3B-I) biomarkers displayed an identical pattern of BIA among 5 groups. Cellular expressions of inflammation (F4/80+/GFAP+) and DNA-damaged biomarker (γ-H2AX+) exhibited an identical pattern, whereas the integrities of myelin sheath/neuron (MPB+/NeuN+), endothelial cell (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIA among the 5 groups. Combined HBO-Mel therapy offered an additional benefit in protecting the brain against IS injury.