146 research outputs found
A Novel Model of Atherosclerosis in Rabbits Using Injury to Arterial Walls Induced by Ferric Chloride as Evaluated by Optical Coherence Tomography as well as Intravascular Ultrasound and Histology
This study aim was to develop a new model of atherosclerosis by FeCl3-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (n = 15) by combination of a cholesterol-rich diet and FeCl3-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (n = 3), 8 weeks (n = 6), and 12 weeks (n = 6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl3. The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time
The First Human Infection with Severe Fever with Thrombocytopenia Syndrome Virus in Shaanxi Province, China
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. In July 2013, the first human infection with SFTS virus (SFTSV) was detected in Shaanxi Province, Western China. Methods: A seroprevalence study among humans was carried out in an SFTS endemic village; specifically, serum samples were collected from 363 farmers in an SFTS endemic village in Shaanxi Province. The presence of SFTSV antibodies in serum was determined using an ELISA. Results: SFTSV antibodies were found in a total of 20 people (5.51%), with no significant difference between males and females (6.93% and 4.42%, respectively; Chi-square = 1.29, p = 0.25). Moreover, the SFTSV antibody positive rate was not significantly different across different age groups (Chisquare = 2.23, p = 0.69). Conclusions: SFTSV readily infects humans with outdoor exposure. The results of the serological study indicate that the virus circulates widely in Shaanxi Province. SFTSV represents a public health threat in China
The significance of Notch ligand expression in the peripheral blood of children with hand, foot and mouth disease (HFMD)
BACKGROUND: Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. METHODS: Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias. RESULTS: Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3−CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3−CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3−CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05). CONCLUSIONS: The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3−CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes
Dynamic tear meniscus parameters in complete blinking: insights into dry eye assessment
AIM: To investigate the relationship between dynamic tear meniscus parameters and dry eye using an automated tear meniscus segmentation method. METHODS: The analysis of tear meniscus videos captured within 5s after a complete blink includes data from 38 participates. By processing video data, several key parameters including the average height of the tear meniscus at different lengths, the curvature of the tear meniscus's upper boundary, and the total area of the tear meniscus in each frame were calculated. The effective values of these dynamic parameters were then linearly fitted to explore the relationship between their changing trends and dry eye disease. RESULTS: In 94.74% of the samples, the average height of central tear meniscus increased over time. Moreover, 97.37% of the samples exhibited an increase in the overall tear meniscus height (TMH) and area from the nasal to temporal side. Notably, the central TMH increased at a faster rate compared to the nasal side with the temporal side showing the slowest ascent. Statistical analysis indicates that the upper boundary curvature of the whole tear meniscus as well as the tear meniscus of the nasal side (2, 3, and 4 mm) aid in identifying the presence of dry eye and assessing its severity. CONCLUSION: This study contributes to the understanding of tear meniscus dynamics as potential markers for dry eye, utilizing an automated and non-invasive approach that has implications for clinical assessment
Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma
Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22phox, which is upregulated following Kras activation. Both alterations are also detectable in PDAC cell lines and patient specimens. Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports increased glycolysis by generating NAD+, a substrate for GAPDH-mediated glycolytic reaction, promoting PDAC cell growth. Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22phox was induced by KrasG12V-activated NF-κB. In conclusion, we provide a biochemical explanation for the cooperation between p16 inactivation and Kras activation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC
Destabilization of Fatty Acid Synthase by Acetylation Inhibits De Novo Lipogenesis and Tumor Cell Growth
Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacological inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity and other diseases. Here we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin-ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels. Our results suggest opportunities to target FASN acetylation as an anticancer strategy
A modular assembly of spinal cord-like tissue allows targeted tissue repair in the transected spinal cord
Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs
The carbon stock of alpine peatlands on the Qinghai–Tibetan Plateau during the Holocene and their future fate
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