Epstein-Barr virus (EBV) infection in humans is ubiquitous and associated with various diseases. Remodeling of the immune microenvironment is the primary cause of EBV infection and pathogenesis; ...however, the underlying mechanism has not been fully elucidated. In this study, we used whole-transcriptome RNA-Seq to detect mRNAs, long non-coding RNAs (lncRNA), and microRNA (miRNA) profiles in the control group, 3 days, and 28 days after EBV infection, based on the tree shrew model that we reported previously. First, we estimated the proportion of 22 cell types in each sample using CIBERSORT software and identified 18 high-confidence DElncRNAs related to immune microenvironment regulation after EBV infection. Functional enrichment analysis of these differentially expressed lncRNAs primarily focused on the autophagy, endocytosis, and ferroptosis signalling pathways. Moreover, EBV infection affects miRNA expression patterns, and many miRNAs are silenced. Finally, three competing endogenous RNA regulatory networks were built using lncRNAs that significantly correlated with immune cell types, miRNAs that responded to EBV infection, and potentially targeted the mRNA of the miRNAs. Among them, MRPL42-AS-5 might act as an hsa-miR-296-5p "sponge" and compete with target mRNAs, thus increasing mRNA expression level, which could induce immune cell infiltration through the cellular senescence signalling pathway against EBV infection. Overall, we conducted a complete transcriptomic analysis of EBV infection in vivo for the first time and provided a novel perspective for further investigation of EBV-host interactions.
Epstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the ...composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV.
Six tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis.
16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine.
Collectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.
Objective
Diagnosis of cochlear malformation on temporal bone CT images is often difficult. Our aim was to assess the utility of deep learning analysis in diagnosing cochlear malformation on temporal ...bone CT images.
Methods
A total of 654 images from 165 temporal bone CTs were divided into the training set (
n
= 534) and the testing set (
n
= 120). A target region that includes the area of the cochlear was extracted to create a diagnostic model. 4 models were used: ResNet10, ResNet50, SE-ResNet50, and DenseNet121. The testing data set was subsequently analyzed using these models and by 4 doctors.
Results
The areas under the curve was 0.91, 0.94, 0.93, and 0.73 in ResNet10, ResNet50, SE-ResNet50, and DenseNet121. The accuracy of ResNet10, ResNet50, and SE-ResNet50 is better than chief physician.
Conclusions
Deep learning technique implied a promising prospect for clinical application of artificial intelligence in the diagnosis of cochlear malformation based on CT images.
Green tea catechins have been reported to have antitumor activity. The objective of this study was to examine the effect of catechins on the antitumor efficacy of doxorubicin (DOX) in a murine model ...for chemoresistant hepatocellular carcinoma (HCC). Epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) are the most abundant polyphenolic compounds in green tea. Here, we show that ECG or EGCG at higher doses had a slight inhibitory effect on cell proliferation in the resistant human HCC cell line BEL-7404/DOX in vitro and in vivo, whereas the administration of DOX with these compounds at lower doses significantly inhibited HCC cell proliferation in vitro and hepatoma growth in a xenograft mouse model, compared with treatment with either agent alone at the same dose. Furthermore, the administration of DOX in combination with ECG or EGCG markedly enhanced intracellular DOX accumulation, which implies that the catechins inhibited P-glycoprotein (P-gp) efflux pump activity. Consistent with these results, the intracellular retention of rhodamine 123, a P-gp substrate, was increased and the level of P-gp was decreased in cells concurrently treated with DOX and ECG or EGCG. EGCG increased topo II expression, but did not alter GST protein levels in tumor xenografts. The expression of MDR1 and HIF-1alpha mRNA was obviously reduced, whereas MRP1 and LRP expression was not changed significantly. These data suggest that tea catechins at non-toxic doses can augment DOX-induced cell killing and sensitize chemoresistant HCC cells to DOX. The chemosensitizing effect of catechins may occur directly or indirectly by reversal of multidrug resistance, involving the suppression of MDR1 expression, or by enhancement of intracellular DOX accumulation, involving inhibition of P-gp function.
The immune response plays a key role in the disease development of the organism, while immune function serves as an important indicator for animal models evaluation. The tree shrew (Tupaia belangeri ...chinensis), as a new laboratory animal with a close genetic relationship with primates, has been used to construct various disease models. However, the immune system of tree shrews, especially anatomical descriptions of lymph nodes, is still relatively unknown. In this study, a total of 16 different lymph nodes were identified, including superficial lymph nodes and deep lymph nodes. Superficial lymph nodes were located in the head and neck region (submandibular lymph node, parotid lymph node, deep and superficial cervical lymph nodes) and at the forelimb (axillary and accessory axillary lymph nodes, subscapular lymph node) and hindlimb (popliteal, sciatic, and inguinal lymph nodes). Deep lymph nodes comprise mediastinal lymph nodes located in thoracic cavity and abdominal lymph nodes that are mainly located in each mesentery (mesenteric, gastric, pancreatic-duodenal, renal lymph nodes) or along the major vessels (iliac lymph nodes). In addition, we described the spleen and thymus of the tree shrew, as well as two lymphoid tissues in the top wall of the nasal cavity and the oropharynx. This study mainly describes the tree shrew immune system from an anatomical and histopathological perspective and provides fundamental research references for the establishment of various animal models of tree shrews.
Recurrent laryngeal nerve (RLN) injury is one of the most critical complications in thyroid surgery. Anatomic variations of the RLN often account for iatrogenic nerve injury. The coexistence of ...ipsilateral non-recurrent laryngeal nerve (NRLN) and RLN is an extremely rare variation with only few reports. Thus, surgeons should have a clear understanding of this variation. In this paper, we first present a case of left NRLN coexisting with left RLN and emphasize the importance of this rare anatomic pitfall.
Higher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the association between EA and prevention ...of oral cavity and pharyngeal cancer (OCPC).
Several databases were searched until October 1, 2022, and a meta-analysis was performed. A Mendelian randomization (MR) study was conducted with EA (i.e., the exposure) data derived from the Social Science Genetic Association Consortium and 6,034 cases of OCPC (i.e., outcome) selected from the Integrative Epidemiology Unit genome-wide association study. Five methods were used to evaluate the causality between EA and OCPC. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.
The meta-analysis included 36 eligible studies. EA was significantly and negatively associated with OCPC risk (odds ratio OR: 0.439, 95% confidence interval CI: 0.383-0.503,
< 0.001). MR analysis revealed that the risk of OCPC, oropharyngeal cancer, and oral cavity cancer decreased with an increase in education (OR: 0.349, 95% CI: 0.222-0.548,
< 0.001; OR: 0.343, 95% CI: 0.198-0.597;
< 0.001; OR: 0.342, 95% CI: 0.195-0.601,
< 0.001, respectively). Even after correcting for mediators, high EA still significantly reduced the risk of OCPC (OR: 0.361, 95% CI: 0.281-0.463,
< 0.001).
Both the meta-analysis and MR results demonstrated that high levels of EA can reduce the risk of OCPC in the general population.
Background
Animal models suitable for investigating mechanisms behind radiation-induced muscle injury are lacking. We developed a tree shrew model of such injury and investigated pathological changes ...and mechanisms.
Methods
Animals were divided into control (n = 5), radiation-induced acute injury (n = 5), and radiation-induced chronic injury (n = 5) groups. Tensor veli palatini (TVP) muscles of acute injury and chronic injury groups were dissected under a microscope at 1 and 24 weeks after radiation therapy, respectively. TVP muscles were stained with HE and Masson to visualize pathological changes. ELISA was performed to measure oxidative injury. RT-qPCR and immunohistochemical staining was performed to measure expression levels of miR-206 and histone deacetylase 4 (HDAC4).
Results
Compared to the control group, acute injury group showed a significant decrease in miR-206 expression (.061 ± .38, P < .05) and a significant increase in HDAC4 expression (37.05 ± 20.68, P < .05). Chronic injury group showed a significant decrease in miR-206 expression (.23 ± .19, P < .05) and a significant increase in HDAC4 expression (9.66 ± 6.12, P < .05).
Discussion
A tree shrew model of radiation-induced muscle injury was established by exposing TVP muscle region to radiation of 20-Gy. Experimental results indicated that injury caused by radiation persisted despite gradual healing of the TVP muscle and miR-206 regulatory pathway plays a key role in regulating radiation-induced muscle injury.
We report the emerging role of microRNA (miRNA) deregulation associated with activation of an oncogene SOX4 (a member of the SRY-related HMG-box) in esophageal carcinoma. Paired esophageal cancer and ...adjacent non-tumor tissues were obtained from 42 patients who underwent primary surgical resection for esophageal cancer. Experiments such as real-time PCR, western blot analysis, luciferase-reporter assay, cell proliferation and colony formation assays, in vitro migration and invasion assays, and a wound-healing assay were performed to determine the effects of miR-129-2. We found that SOX4 expression was elevated (P<0.005) in esophageal tumors (n=42) when compared with its expression in the controls (n=42). Compared with the normal esophageal tissues, the expression of miR-129-2 was downregulated in 27 of 31 primary esophageal tumors, while the expression of SOX4 was upregulated (P<0.001). Restoration of miR-129-2 by transfection with an miRNA expression plasmid led to a decrease in SOX4 expression, which was accompanied by reduced migration and proliferation of the cancer cells. These results suggest that aberrant expression of SOX4 is associated with repression of miR-129-2, and restoration of miR-129-2 suppresses the migration and proliferation of esophageal cancer cells. Our results demonstrated that the deregulation of miR-129-2 leads to aberrant SOX4 expression, presenting a new paradigm in which the restoration of miRNA suppresses its oncogenic target in esophageal cancer.
A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion ...method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an “S”-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.
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