RESUMO
Ultrasound-modulated optical tomography (UOT), which combines the advantages of both light and ultrasound, is a promising imaging modality for deep-tissue high-resolution imaging. Among existing implementations, camera-based UOT gains huge advances in modulation depth through parallel detection. However, limited by the long exposure time and the slow framerate of modern cameras, the measurement of UOT signals always requires holographic methods with additional reference beams. This requirement increases system complexity and is susceptible to environmental disturbances. To overcome this challenge, we develop coaxial interferometry for camera-based UOT in this work. Such a coaxial scheme is enabled by employing paired illumination with slightly different optical frequencies. To measure the UOT signal, the conventional phase-stepping method in holography can be directly transplanted into coaxial interferometry. Specifically, we performed both numerical investigations and experimental validations for camera-based UOT under the proposed coaxial scheme. One-dimensional imaging for an absorptive target buried inside a scattering medium was demonstrated. With coaxial interferometry, this work presents an effective way to reduce system complexity and cope with environmental disturbances for camera-based UOT.
Assuntos
Iluminação , Tomografia Óptica , Imagens de Fantasmas , Ultrassonografia/métodos , Tomografia Óptica/métodos , Interferometria/métodosRESUMO
Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.
Assuntos
Angiotensina II/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Inativação Gênica , Subunidade p35 da Interleucina-12/metabolismo , Fator de Transcrição STAT4/metabolismo , Animais , Aorta , Apoptose , Modelos Animais de Doenças , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Gemcitabine has been used as a therapeutic drug combined with cisplatin for the treatment of lung cancer patients. However, the prognosis is poor due to acquired resistance. Accumulating studies have revealed that autophagy may contribute to the drug resistance. Therefore, the present study is aimed to clarify the mechanisms underlying gemcitabine-acquired resistance. METHODS: SPC-A1 and A549 cells were incubated with gemcitabine followed by assessment of cell viability with MTT assays. GFP-LC3 transient transfection, MDC staining, and transmission electron microscopy were used to detect the change of autophagy at morphological level. Flow cytometry was used to monitor the effect of 3-MA on gemcitabine-induced apoptosis. Western blot analysis was used to detect the expression of p62, LC3, Beclin-1, ATG5, activated caspase 3, Bax, BNIP3, BNIP3L, and Bcl-2. RESULTS: Our study showed that gemcitabine significantly induced both autophagy and apoptosis in human lung cancer cells SPC-A1 and A549. Of interest was that when autophagy was inhibited by 3-MA, the gemcitabine-induced apoptosis was effectively enhanced, suggesting that gemcitabine can activate autophagy to impair the chemosensitivity of lung cancer cells. Furthermore, the inhibition of autophagy by 3-MA further increased the expression of activated caspase 3, Bax, BNIP3, and BNIP3L, all are critical apoptotic mediators. Contrarily, 3-MA treatment further decreased the expression of Bcl-2, which is an important anti-apoptotic protein. CONCLUSION: Our study indicated that autophagy protected human lung cancer cells from gemcitabine-induced apoptosis, and the combined use of gemcitabine and an autophagic inhibitor in lung cancer patients may be an effective therapeutic strategy.
Assuntos
Adenina/análogos & derivados , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Células A549 , Adenina/farmacologia , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteína X Associada a bcl-2/metabolismo , GencitabinaRESUMO
To discuss the feasibility of the pharmacodynamic evaluation method for traditional Chinese medicine (TCM) formula particles, with traditional decoction for reference and the intervention of Magnoliae Officinalis Cortex in rats with ulcerative colitis (UC). First of all, the similarity of traditional Magnoliae Officinalis Cortex decoction and formula particles of different manufacturers was defined by using the IR fingerprint. The UC rat model was established and given Houpo formula particles of different doses and manufacturers, with the decoction for reference, in order to observe disease activity index (DAI), colon mucosa damage index (CMDI), pathologic changes, nitric oxide (NO), endothdin (ET), substance P, vasoactive intestinal peptide (VIP). Their intervention effects on UC rats were compared to study the difference between Sanjiu and Tianjiang Houpo formula particles, in order to demonstrate the feasibility of the pharmacodynamic evaluation method for Houpo formula particles. According to the results, Houpo formula particles showed similar pharmacodynamic actions with the traditional decoction. The pharmacodynamic comparison of Houpo formula particles of different manufacturers showed no statistical significance. The experiment showed that on the basis of the TCM compounds, a prescription dismantlement study was conducted to define target points of various drugs. The traditional decoction was selected for reference in the comparison of corresponding formula particles for their pharmacodynamic equivalence. This method could avoid controversies about single or combined boiling of formula particles, and give objective comments on the pharmacodynamic effect of the formula particles. The method is proved to be feasible.
Assuntos
Química Farmacêutica/métodos , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Magnolia/química , Animais , Colite Ulcerativa/metabolismo , Formas de Dosagem , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Masculino , Ratos , Ratos Wistar , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
The purpose of this study was to explore and compare the relationship among serum testosterone, systemic inflammatory response index (SIRI), lymphocyte-to-monocyte ratio (LMR) neutrophil-lymphocyte ratio (NLR), and carotid atherosclerosis in middle-aged and elderly men of Han nationality in the real world. With reference to the inclusion criteria, 89 middle-aged and elderly Han male patients were finally selected. Local weighted regression (LOESS) and multivariate logistic regression models were used to explore the independent correlation between serum testosterone, new inflammatory markers, and atherosclerosis. The diagnostic value of related indexes was evaluated by the receiver working curve characteristic curve (ROC), and the best critical value of testosterone and related inflammatory indexes was discussed. In the LOESS model, bioavailable testosterone (BT), free testosterone (FT), total testosterone (TT) and SIRI, NLR, LMR, and atherosclerosis were significantly correlated. After adjusting for confounding factors, BT, FT, TT, and LMR were negatively correlated with atherosclerosis (odds ratio [OR] < 1, p < .05), and SIRI and NLR were positively associated with atherosclerosis (OR > 1, p < .05). According to the ROC curve results, the area under the curve (AUG) of BT is 0.870, and the optimal threshold point is 4.875. The AUG of SIRI is 0.864, and the best threshold point is 0.769. Low testosterone and high inflammatory levels are closely related to atherosclerosis. Testosterone (TT, FT, and BT) and new inflammatory markers, SIRI, NLR, and LMR, are associated with carotid atherosclerosis in middle-aged and elderly men.
Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Idoso , Pessoa de Meia-Idade , Humanos , Masculino , Testosterona , Neutrófilos , Monócitos , População do Leste Asiático , Estudos Retrospectivos , LinfócitosRESUMO
Autophagy, a conversed response to stress, has recently been studied in human cancers. Two important autophagic genes-Beclin-1 and LC3 are reported in several human cancers. However, the expressions of Beclin-1 and LC3 in lung cancer have not yet been investigated. In the present study, we investigated the expression of Beclin-1 and LC3, and the relationship between the expression profile and the clinical or pathological changes in human lung cancer. 40 primary lung cancer patients are involved in present study. mRNA expressions of Beclin-1 and LC3-II were detected by Real Time PCR and the protein levels were assessed by immunohistochemistry and western blot. Relative lower expressions of Beclin-1 and LC3-II mRNA were found in the lung cancer tissues compared to counterpart normal tissues. Consistently, the lower amount of Beclin-1 and LC3-II protein was found in lung cancer tissues. However, the expressions of Beclin-1 and LC3-II in lung cancer tissues were not affected by patients' age, gender, smoking, histological type, lymph node metastasis and tumor-node-metastasis (TNM) stage. Both mRNA and protein levels of Beclin-1 and LC3-II were significantly decreased in lung cancer tissues which suggested that autophagy may be involved in the pathogenesis of lung cancer.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Pulmonares/fisiopatologia , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Análise de Variância , Proteína Beclina-1 , Western Blotting , Primers do DNA/genética , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Focusing light deep inside live scattering tissue promises to revolutionize biophotonics by enabling deep tissue noninvasive optical imaging, manipulation, and therapy. By combining with guide stars, wavefront shaping is emerging as a powerful tool to make scattering media optically transparent. However, for in vivo biomedical applications, the speeds of existing techniques are still too slow to accommodate the fast speckle decorrelation of live tissue. To address this key bottleneck, we develop a quaternary phase encoding scheme to enable single-exposure time-reversed ultrasonically encode optical focusing with full-phase modulations. Specifically, we focus light inside dynamic scattering media with an average mode time down to 29 ns, which indicates that more than 104 effective spatial modes can be controlled within 1 millisecond. With this technique, we demonstrate in vivo light focusing in between a highly opaque adult zebrafish of 5.1 millimeters in thickness and a ground glass diffuser. Our work presents an important step toward in vivo deep tissue applications of wavefront shaping.
RESUMO
The anaerobic fermentation of crop straw and animal wastes is increasingly used for the biogas and green energy generation, as well as reduction of the environmental pollution. The anaerobic cofermentation of corn stalks inoculated by cow dung was found to achieve higher biogas production and cellulose biodegradation. In this study, the effect of mixing corn stalks with cow dung at five different fermentation stages (0, 7, 15, 23, and 31 days of the total fermentation cycle of 60 days) on the further cofermentation process was explored, in order to optimize the corn straw utilization rate and biogas production capacity. In addition, the straw microstructure evolution was investigated by the SEM and XRD methods to identify the optimal conditions for the straw biodegradation process enhancement. The five test groups exhibited nearly identical total biogas productivity values but strongly differed by daily biogas yields (the maximal biogas generation rate being 524.3 ml/d). Based on the degradation characteristics of total solids (TS), volatile solids (VS), and lignocellulose, groups #1 and #3 (0 and 15 days) had the most significant degradation rates of VS (43.73%) and TS (42.07%), respectively, while the largest degradation rates of cellulose (62.70%) and hemicellulose (50.49%) were observed in group #4 (23 days) and group #1 (0 days), respectively. The SEM analysis revealed strong microstructural changes in corn stalks after fermentation manifested by multiple cracks and striations, while the XRD results proved the decrease in peak intensity of cellulose ã002ã crystal surface and the reduced crystallinity after cofermentation. The results of this study are assumed to be quite instrumental to the further optimization of the corn stalk anaerobic digestion by inoculation with digested manure for lignocellulose degradation enhancement and biogas productivity improvement.
Assuntos
Biodegradação Ambiental , Biocombustíveis , Lignina , Esterco , Zea mays/química , Anaerobiose , Animais , Bovinos , Fermentação , Lignina/análise , Lignina/química , Lignina/metabolismo , Difração de Raios XRESUMO
This article proposes a methane production approach through sequenced anaerobic digestion of kitchen waste, determines the hydrolysis constants and reaction orders at both low total solid (TS) concentrations and high TS concentrations using the initial rate method, and examines the population growth model and first-order hydrolysis model. The findings indicate that the first-order hydrolysis model better reflects the kinetic process of gas production. During the experiment, all the influential factors of anaerobic fermentation retained their optimal values. The hydrolysis constants and reaction orders at low TS concentrations are then employed to demonstrate that the first-order gas production model can describe the kinetics of the gas production process. At low TS concentrations, the hydrolysis constants and reaction orders demonstrated opposite trends, with both stabilizing after 24 days at 0.99 and 1.1252, respectively. At high TS concentrations, the hydrolysis constants and the reaction orders stabilized at 0.98 (after 18 days) and 0.3507 (after 14 days), respectively. Given sufficient reaction time, the hydrolysis involved in anaerobic fermentation of kitchen waste can be regarded as a first-order reaction in terms of reaction kinetics. This study serves as a good reference for future studies regarding the kinetics of anaerobic digestion of kitchen waste.
Assuntos
Reatores Biológicos/microbiologia , Fermentação , Metano/biossíntese , Eliminação de Resíduos/métodos , Anaerobiose , Humanos , Hidrólise , CinéticaRESUMO
Hypoxia which commonly exists in solid tumors, leads to cancer cells chemoresistance via provoking adaptive responses including autophagy. Therefore, we sought to evaluate the role of autophagy and hypoxia as well as the underlying mechanism in the cisplatin resistance of lung cancer cells. Our study demonstrated that hypoxia significantly protected A549 and SPC-A1 cells from cisplatin-induced cell death in a Hif-1α- and Hif-2α-dependent manner. Moreover, compared with normoxia, cisplatin-induced apoptosis under hypoxia was markedly reduced. However, when autophagy was inhibited by 3-MA or siRNA targeted ATG5, this reduction was effectively attenuated, which means autophagy mediates cisplatin resisitance under hypoxia. In parallel, we showed that hypoxia robustly augmented cisplatin-induced autophagy activation, accompanying by suppressing cisplatin-induced BNIP3 death pathways, which was due to the more efficient autophagic process under hypoxia. Consequently, we proposed that autophagy was a protective mechanism after cisplatin incubation under both normoxia and hypoxia. However, under normoxia, autophagy activation 'was unable to counteract the stress induced by cisplatin, therefore resulting in cell death, whereas under hypoxia, autophagy induction was augmented that solved the cisplatin-induced stress, allowing the cells to survival. In conclusion, augmented induction of autophagy by hypoxia decreased lung cancer cells susceptibility to cisplatin-induced apoptosis.