Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

An online preparative high-performance liquid chromatography system with enrichment and purification modes for the efficient and systematic separation of Panax notoginseng saponins.

In this study, an online preparative high-performance liquid chromatography (prep-HPLC) system based on the combination of the enrichment and purification modes for the efficient and systematic separation of Panax notoginseng saponins (PNS) was achieved. Five separation columns were used for the first and second separation of target components, eighteen trap columns were used to capture the effluents from the first separation or loading the trapped sample effluents, and a two-position eight-port valve was used to switch between the first and second separations. The conditions for the first and second separation of PNS were simulated and optimized with the online prep-HPLC system. Then, the PNS were separated using optimized chromatographic conditions. Notably, 14 monomer compounds with >90% purity (11 compounds with purity >97%) were simultaneously isolated from PNS using the above self-developed device, and their chemical structures were identified. Moreover, the separation time was less than 33.0 h. After 6 repeated enrichment and purification, the weight of each compound obtained was more than 5.0 mg, with compound 2 weighing over 900 mg. In brief, the self-developed prep-HPLC system, which integrated enrichment and purification, is suitable for the efficient and systematic separation of PNS and has broad application prospects, especially for the separation of complex chemical components in natural products.

Distinct expression and prognostic values of GATA transcription factor family in human ovarian cancer.

Accumulated studies have provided controversial evidences of expression patterns and prognostic value of the GATA family in human ovarian cancer. In the present study, we accessed the distinct expression and prognostic roles of 7 individual members of GATA family in ovarian cancer (OC) patients through Oncomine analysis, CCLE analysis, Human Protein Atlas (HPA), Kaplan-Meier plotter (KM plotter) database, cBioPortal and Metascape. Our results indicated that GATA1, GATA3, GATA4 and TRPS1 mRNA and protein expression was significantly higher in OC than normal samples. High expression of GATA1, GATA2, and GATA4 were significantly correlated with better overall survival (OS), while increased GATA3 and GATA6 expression were associated with worse prognosis in OC patients. GATA1, GATA2, GATA3 and GATA6 were closely related to the different pathological histology, pathological grade, clinical stage and TP53 mutation status of OC. The genetic variation and interaction of the GATA family may be closely related to the pathogenesis and prognosis of OC, and the regulatory network composed of GATA family genes and their neighboring genes are mainly involved in Notch signaling pathway, Th1 and Th2 cell differentiation and Hippo signaling pathway. Transcriptional GATA1/2/3/4/6 could be prognostic markers and potential therapeutic target for OC patients.

Ultrasound-guided transperineal laser ablation for percutaneous treatment of benign prostatic hyperplasia: a new minimally invasive interventional therapy.

BACKGROUND: Although there are different treatments for benign prostate hyperplasia, their efficacy and safety differ. We are currently exploring a new minimally invasive interventional therapy for benign prostatic hyperplasia (BPH). PURPOSE: To determine the feasibility, effectiveness, and safety of ultrasound-guided transperineal laser ablation (US-TPLA) for the treatment of BPH. MATERIAL AND METHODS: Twenty patients with BPH (mean age = 73.9 ± 9.2 years) who underwent US-TPLA from June 2018 to January 2020 with a subsequent six-month follow-up were retrospectively reviewed. After local anesthesia, a 21-G trocar was inserted into the prostate tissue under ultrasound monitoring, followed by 1064 nm diode laser irradiation. Changes in international prostate symptom score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), postvoid residual (PVR), prostate volume, and complications were evaluated six months after surgery. RESULTS: All patients underwent the operation successfully without serious complications. After six months, the average IPSS improved from 22.7 ± 5.3 to 9.1 ± 3.2 (P < 0.001), the QoL improved from 4.9 ± 1.7 to 2.3 ± 1.3 (P < 0.001), the Qmax improved from 8.5 ± 3.0 to 15.2 ± 4.8 mL/s (P < 0.001), the PVR increased from 78.7 ± 58.8 to 30.3 ± 34.2 (P < 0.05), and the mean prostate volume ranged from 70.8 ± 23.8 to 54.7 ± 20.9 mL (P < 0.05). CONCLUSION: US-TPLA is safe and feasible for the treatment of BPH. An evaluation at the six-month follow-up is effective.

Relationship between the structure and function of the transcriptional regulator E2A.

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.

Inhibitor of DNA-binding family regulates the prognosis of ovarian cancer.

Aim: The mechanistic role of inhibitor of DNA binding or differentiation (ID) family in ovarian cancer (OC) has remained unclear. Materials & methods: We used the Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, SurvExpress, PROGgene V2, TIMER, and FunRich to evaluate the prognostic value of IDs in patients with OC. Results: the mRNA transcripts of all IDs were markedly downregulated in OC compared with normal tissue. The prognostic value of IDs was also explored within the subtypes, pathological stages, clinical stages and TP53 mutational status. The group with low-risk IDs showed relatively good overall survival (OS) compared with the high-risk group. Conclusion: ID1/3/4 may be exploited as promising prognostic biomarkers and therapeutic targets in OC patients.

Application of curved ablation in liver cancer with special morphology or location: Report of two cases.

BACKGROUND: Liver cancer is one of the most common malignant tumors with a high incidence and mortality. Hepatitis-liver cirrhosis-liver cancer is known as the trilogy of liver cancer. At present, due to significant development of imaging interventions, they occupy an irreplaceable position in the field of liver cancer treatment, especially ultrasound-guided ablation. Because patients with liver cancer often present with liver cirrhosis, which leads to morphological deformation of the liver, it is difficult to perform a linear ablation of liver cancer in the areas near the phrenic top and within large blood vessels, among others. The present study reports on two cases of liver cancer that have been subjected to curvilinear ablation. After 1 mo, magnetic resonance imaging showed complete ablation, demonstrating that ultrasound-guided curved ablation is feasible and effective in the treatment of liver cancer. CASE SUMMARY: Two patients were treated at the Liver Disease Department of the Xixi Hospital Affiliated to Zhejiang University of Chinese Medicine in 2019. Because the first liver cancer patient's tumor was located close to the diaphragm, it was difficult to complete a straight needle ablation procedure in one session. In order to achieve accurate and minimally invasive treatment of this tumor, a curved needle ablation procedure was designed. The second patient presented with a hepatic cyst in front of the tumor. In order not to damage the hepatic cyst, a looper needle ablation technique was used. The procedure was successfully completed in both cases. CONCLUSION: Curved ablation is a new technique that can be used to treat tumors situated in a variety of locations, providing new ideas for interventional techniques. Its operation difficulty is higher and further animal experiments are necessary to improve the operation procedure.

Peutz-Jeghers syndrome with mesenteric fibromatosis: A case report and review of literature.

BACKGROUND: Peutz-Jeghers syndrome (PJS) and mesenteric fibromatosis (MF) are rare diseases, and PJS accompanying MF has not been previously reported. Here, we report a case of a 36-year-old man with both PJS and MF, who underwent total colectomy and MF surgical excision without regular follow-up. Two years later, he sought treatment for recurrent acute abdominal pain. Emergency computed tomography showed multiple soft tissue masses in the abdominal and pelvic cavity, and adhesions in the small bowel and peritoneum. Partial intestinal resection and excision of the recurrent MF were performed to relieve the symptoms. CASE SUMMARY: A 36-year-old male patient underwent total colectomy for PJS with MF. No regular reexamination was performed after the operation. Two years later, due to intestinal obstruction caused by MF enveloping part of the small intestine and peritoneum, the patient came to our hospital for treatment. Extensive recurrence was observed in the abdomen and pelvic cavity. The MF had invaded the small intestine and could not be relieved intraoperatively. Finally, partial bowel resection, proximal stoma, and intravenous nutrition were performed to maintain life. CONCLUSION: Regular detection is the primary way to prevent deterioration from PJS. Although MF is a benign tumor, it has characteristics of invasive growth and ready recurrence. Therefore, close follow-up of both the history of MF and gastrointestinal surgery are advisable. Early detection and early treatment are the main means of improving patient prognosis.

Calcitonin-negative neuroendocrine tumor of the thyroid with metastasis to liver-rare presentation of an unusual tumor: A case report and review of literature.

BACKGROUND: Neuroendocrine tumors mainly occur in the stomach, intestine, pancreas, and lung and are rarely detected in the thyroid. Thyroid neuroendocrine tumors, designated medullary thyroid carcinoma, generally present with elevated calcitonin. Calcitonin-negative neuroendocrine tumors of the thyroid are extremely rare. CASE SUMMARY: Here, we present a case report of a 56-year-old female patient with a neck pain complaint. Total thyroidectomy was conducted after comprehensive evaluation, and diagnosis was confirmed as calcitonin-negative neuroendocrine tumor of the thyroid. Two months later, liver metastasis was detected, and transcatheter arterial chemoembolization was subsequently performed to control growth. However, the curative effect was unsatisfactory and multiple intrahepatic metastases occurred after 3 mo. CONCLUSION: Owing to the rarity of this disease, no clear guidelines are available for treatment. In addition to reporting this rare case, we have reviewed and summarized associated medical literature with an aim to provide a comprehensive reference platform for subsequent research.

Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain.

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

Dermatofibrosarcoma metastases to the pancreas: A case report.

BACKGROUND: In general, malignant tumors metastasize to the pancreas in < 1% of cases. Most patients miss the opportunity for further surgery due to distant metastases; however, for fibrosarcomas, aggressive surgery may be helpful even if distant metastases occur. Hence, we report such a case and share some valuable information about the disease. CASE SUMMARY: A 45-year-old man was admitted with recurrent epigastric pain for 10 days. The abdominal pain was mainly related to bloating with nausea, but no other associated symptoms. No particular signs were found on abdominal examination or laboratory testing. In 2003, a local distal expanded resection of the primary fibrosarcoma in the left chest wall was performed. Then, a left pneumonectomy was performed in 2017 due to diffuse metastases from the fibrosarcoma to the left lung. Enhanced computed tomography (CT) and magnetic resonance imaging of the upper abdomen suggested multiple masses of different sizes involving the head and tail of the pancreas; no local lymph node enlargement was noted. The postoperative pathologic diagnosis revealed a fibrosarcoma of the pancreas. A CT re-examination 6 mo postoperatively showed no local recurrence or distant metastases. CONCLUSION: A fibrosarcoma is a rare low-grade malignant tumor, and metastases to the pancreas are even rarer. Patients with a history of a fibrosarcoma should consider the possibility of metastasis when a pancreatic neoplasm is demonstrated. Surgical resection is the preferred treatment.

Primary renal synovial sarcoma: A case report.

BACKGROUND: Synovial sarcoma, a rare mesenchymal tumor type with unclear histological origin and direction of differentiation, accounts for 6%-10% of soft tissue tumors. It is mainly located near the joints and tendons of the limbs, and occurs primarily in children or young adults. Primary renal synovial sarcoma (PRSS) is very rare, accounting for approximately 1% of synovial sarcomas. It is a spindle cell tumor type affecting mesenchymal tissue, and has morphological, genetic, and clinical characteristics, and a certain degree of epithelial differentiation. It is highly malignant and has the fourth highest incidence among soft tissue sarcomas. Here, we report a case of PRSS and share some valuable information about the disease. CASE SUMMARY: A 54-year-old male patient was admitted to the hospital for a space-occupying lesion in the right kidney for 2 d upon ultrasound examination. The patient had no cold or fever; no frequency, urgency or pain of urination; and no other discomfort. The results of a hemogram, blood biochemistry, and tumor markers were in the normal range. The patient was examined by computed tomography (CT), which indicated the presence of a soft tissue density shadow with a diameter of approximately 6.8 cm in the right renal pelvis area, showing uneven enhancement. Ultrasound indicated a cystic solid mass of approximately 6.8 cm × 6.5 cm in the right kidney, with an unclear boundary and irregular shape. Meanwhile, color Doppler flow imaging showed dotted blood flow signals in the periphery and interior. Contrast-enhanced ultrasound (CEUS) showed "slow in and fast out" hyperenhancement of the right renal mass after contrast agent injection. The postoperative pathological diagnosis was (right kidney) synovial sarcoma. Despite postoperative adjuvant chemotherapy, tumor recurrence was detected two years later. CONCLUSION: PRSS is a rare malignant tumor. To date, no characteristic imaging findings have been observed. The diagnosis is confirmed primarily through postoperative pathological immunohistochemistry and SS18 (SYT) gene detection. In this case, CEUS was used preoperatively. We found that PRSS has the characteristic of "slow in and fast out" hyperenhancement, and its particular characteristics have diagnostic value. Postoperative adjuvant chemotherapy is not very effective.

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta-analysis to elucidate the association. METHODS: A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random-effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test. RESULTS: Fifteen studies (eleven cross-sectional, two case-control, and two cohort studies) were included in this meta-analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11-1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37-23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected. CONCLUSIONS: Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them.

Distinct expression and prognostic value of members of the epidermal growth factor receptor family in ovarian cancer.

BACKGROUND: Increased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated. MATERIALS AND METHODS: In the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery . RESULTS: It was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis. CONCLUSION: These results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment.

The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus.

Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.

Chemopreventive effect of Myricetin, a natural occurring compound, on colonic chronic inflammation and inflammation-driven tumorigenesis in mice.

Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps. Histopathologic analysis showed that Myricetin could attenuate the degree of colonic inflammation and colorectal tumorigenesis. Further analysis showed that Myricetin strongly reduced the levels of inflammatory factors TNF-α, IL-1ß, IL-6, NF-κB, p-NF-κB, cyclooxygenase-2 (COX-2), PCNA and Cyclin D1 in the colonic tissues as analyzed by the assays of immunohistochemical staining, Western blotting and Q-RT-PCR. Our results demonstrated that Myricetin possesses the biological activities of chemoprevention colonic chronic inflammation and inflammation-driven tumorigenesis. We suggest that Myricetin could be developed as a promising chemopreventive drug for reducing the risk of colorectal cancer.

Analysis of the CDR3 length repertoire and the diversity of T cell receptor α and ß chains in swine CD4+ and CD8+ T lymphocytes.

The T cell receptor (TCR) is a complex heterodimer that recognizes fragments of antigens as peptides and binds to major histocompatibility complex molecules. The TCR α and ß chains possess three hypervariable regions termed complementarity determining regions (CDR1, 2 and 3). CDR3 is responsible for recognizing processed antigen peptides. Immunoscope spectratyping is a simple technique for analyzing CDR3 polymorphisms and sequence length diversity, in order to investigate T cell function and the pattern of TCR utilization. The present study employed this technique to analyze CDR3 polymorphisms and the sequence length diversity of TCR α and ß chains in porcine CD4+ and CD8+ T cells. Polymerase chain reaction products of 19 TCR α variable regions (AV) and 20 TCR ß variable regions (BV) gene families obtained from the CD4+ and CD8+ T cells revealed a clear band following separation by 1.5% agarose gel electrophoresis, and each family exhibited >8 bands following separation by 6% sequencing gel electrophoresis. CDR3 spectratyping of all identified TCR AV and BV gene families in the sorted CD4+ and CD8+ T cells by GeneScan, demonstrated a standard Gaussian distribution with >8 peaks. CDR3 in CD4+ and CD8+ T cells demonstrated different expression patterns. The majority of CDR3 recombined in frame and the results revealed that there were 10 and 14 amino acid discrepancies between the longest and shortest CDR3 lengths in specific TCR AV and TCR BV gene families, respectively. The results demonstrated that CDR3 polymorphism and length diversity demonstrated different expression and utilization patterns in CD4+ and CD8+ T cells. These results may facilitate future research investigating the porcine TCR CDR3 gene repertoire as well as the functional complexity and specificity of the TCR molecule.

Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection.

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirus relationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirus interaction.

Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model.

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model.