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PURPOSE: The development of the premaxillary-maxillary suture (PMS) in human fetuses and a possible association between the fusion time of the PMS and maxillary deficiency were investigated. Expression of transforming growth factor beta (TGF-ß1 and TGF-ß3) and of fibulins (fibulin1 and fibulin-5) were also investigated. METHODS: We analyzed 36 human fetus cadavers (19 males, 17 females; average age 23.97⯱ 2.57 gestational weeks [gws], range 11-35 gws). Two cases, diagnosed with Down syndrome (DS), were characterized with maxillary deficiency; 34 fetus cadavers did not show any craniofacial abnormalities. The PMS was analyzed anatomically, followed by semi-quantitative immunohistochemical (IHC)-based expression analyses (i.e., TGF-ß1/-ß3, fibulin-1/-5). Spearman correlation test was conducted to investigate correlations. RESULTS: In the fetuses without DS, the labial region of the PMS was open at 11 gws, after which it began to ossify from the middle to the upper and lower ends of the suture, typically fusing completely at 27 gws. Fetuses with DS demonstrated complete fusion of the labial region of PMS with a spongy bone structure at 23 gws and those without DS at 27 gws. IHC revealed similar patterns of TGF-ßs and fibulins expression in the PMS during the human fetal period. There were significant positive correlations between the expression of TGF-ß1 and TGF-ß3 (râ¯= 0.64, pâ¯= 0.009), TGF-ß1 and fibulin1 (râ¯= 0.66, pâ¯= 0.008), and TGF-ß3 and fibulin1 (râ¯= 0.67, pâ¯= 0.006). CONCLUSION: Premature fusion of the PMS in the labial region during the human fetal period may be associated with maxillary deficiency, which is related to a class III malocclusion. Overall, the similar expression patterns of TGF-ß1, TGF-ß3 and fibulin1 suggested a close relationship between these factors in regulating the development of the PMS.
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Background: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limiting inflammatory disease with low incidence and high misdiagnosis rate in children. Furthermore, cases where the clinical presentation resembles acute appendicitis are very rare. Case Presentation: A 14-year-old boy was misdiagnosed as acute appendicitis and received operative treatment at his early visit. He suffered from abdominal pain, vomiting, diarrhea, fever, and lymphadenitis at the ileocecal junction, which were found by B-ultrasonography examination and surgery. Lymphadenectomy, as well as appendectomy, was performed, and KFD was identified by pathological examination. The patient was transferred to our hospital for further therapy because of recurrent fever and abdominal pain after the appendectomy. His temperature became normal after methylprednisolone was administered, and no recurrence was observed till now during follow-up. Conclusions: Necrotizing lymphadenitis involving mesenteric lymph nodes may cause acute-appendicitis-like symptom; KFD should be a diagnostic consideration for mesenteric lymphadenitis.
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BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.
Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Oncolytic Viruses , Stomach Neoplasms/drug therapy , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Cisplatin/administration & dosage , Cisplatin/pharmacology , Disease Models, Animal , Drug Resistance, Neoplasm/drug effects , Drug Synergism , Humans , Male , Membrane Microdomains/metabolism , Mice , Mice, Nude , Sphingomyelin Phosphodiesterase/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathologyABSTRACT
The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.
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BACKGROUND: Tonsillectomy is the most common procedure for treatment of pediatric recurrent acute tonsillitis and tonsillar enlargement that contributes to obstructive sleep apnea hypopnea syndrome. Postoperative hemorrhage of tonsillectomy is a life-threatening complication. AIM: To identify the risk factors that may contribute to primary and secondary post-operative hemorrhage in pediatric tonsillectomy. METHODS: The clinical data from 5015 children, 3443 males and 1572 females, aged 1.92-17.08 years, with recurrent tonsillitis and/or tonsil hypertrophy who underwent tonsillectomy in our hospital from January 2009 to December 2018 were retrospectively collected. The variables including sex, age, time of onset, diagnosis, method of tonsillectomy, experience of surgeon, time when the surgery started and monthly average air temperature were abstracted. The patients with postoperative hemorrhage were classiï¬ed into two groups, the primary bleeding group and the secondary bleeding group, and their characteristics were compared with those of the nonbleeding group separately. Statistical analysis was performed by chi-square test with SPSS 20. RESULTS: Ninety-two patients had post-tonsillectomy hemorrhage, and the incidence rate of post-tonsillectomy hemorrhage was 1.83%. The mean age was 5.75 years. Cases of primary hemorrhage accounted for approximately 33.70% (31/92), and cases of secondary hemorrhage occurred in 66.30% (61/92). The rate of reoperation for bleeding was 0.92%, and the rate of rehospitalization for bleeding was 0.88% in all patients. Multiple hemostasis surgery was performed in 6.52% (3/46) of patients. The method of tonsillectomy (coblation tonsillectomy) and experience of the surgeon (junior surgeon with less than 5 years of experience) were significantly associated with primary hemorrhage (χ 2 = 5.830, P = 0.016, χ 2= 6.621, P = 0.010, respectively). Age (over 6 years old) and time of onset (more than a 1-year history) were significantly associated with secondary hemorrhage (χ 2= 15.242, P = 0.000, χ 2=4.293, P = 0.038, respectively). There was no signiï¬cant difference in sex, diagnosis, time when the surgery started or monthly average air temperature. There was a signiï¬cant difference in the intervention measures between the primary bleeding group and the secondary bleeding group (χ 2= 10.947, P = 0.001). The lower pole and middle portion were the common bleeding sites, followed by the upper pole and palatoglossal arch. CONCLUSION: The incidence rate of post-tonsillectomy hemorrhage is low. Coblation tonsillectomy and less than 5 years' experience of surgeon contribute to the tendency for primary hemorrhage. Age and time of onset are responsible for secondary hemorrhage.
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OBJECTIVE: To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity. METHODS: The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry. RESULTS: The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05). CONCLUSIONS: Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.
Subject(s)
Immunity, Mucosal , Intestinal Mucosa , Adolescent , Age Distribution , Bacteria , Child , HumansABSTRACT
Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.
Subject(s)
Apoptosis , Measles virus/pathogenicity , Membrane Microdomains/virology , Oncolytic Virotherapy , Oncolytic Viruses/pathogenicity , Stomach Neoplasms/therapy , Animals , Cell Line, Tumor , Cell Proliferation , Chlorocebus aethiops , Cytopathogenic Effect, Viral , Humans , Male , Measles virus/genetics , Membrane Cofactor Protein/metabolism , Membrane Microdomains/metabolism , Membrane Microdomains/pathology , Mice, Nude , Oncolytic Viruses/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/virology , Tumor Burden , Vero Cells , Virus Internalization , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA. METHODS: Twenty-eight patients with BA were divided into three groups according to their age (< 2 months, 2-3 months, and ≥ 3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients preoperatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1ß, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-ß1 and liver expression of IL-1ß, IL-6, and TGF-ß1. RESULTS: The serum levels of IL-1ß, IL-12p70, IL-6, and IL-10 in patients aged ≥ 3 months were significantly higher than those in patients aged < 2 months. There were no significant age-related differences in the IL-1ß, IL-6 and TGF-ß1 expression levels in the liver tissue of patients with BA. CONCLUSIONS: The serum levels of IL-1ß, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient's age into consideration.
Subject(s)
Biliary Atresia/blood , Biliary Atresia/physiopathology , Cytokines/metabolism , Portoenterostomy, Hepatic/methods , T-Lymphocytes, Helper-Inducer/metabolism , Age Factors , Analysis of Variance , Biliary Atresia/surgery , Biomarkers/metabolism , China , Cohort Studies , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Hospitals, University , Humans , Immunohistochemistry , Infant , Male , Retrospective Studies , Risk Assessment , Treatment OutcomeABSTRACT
Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.
Subject(s)
Magnetic Field Therapy , Neuroblastoma/therapy , Wilms Tumor/therapy , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/physiology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cell Survival/drug effects , Cell Survival/physiology , Cisplatin/adverse effects , Cisplatin/pharmacology , Combined Modality Therapy/adverse effects , Equipment Design , Humans , Kidney/drug effects , Kidney/physiopathology , Liver/drug effects , Liver/physiopathology , Magnetic Field Therapy/adverse effects , Magnets , Male , Mice, Nude , Neoplasm Transplantation , Neuroblastoma/pathology , Time Factors , Tumor Burden , Wilms Tumor/pathologyABSTRACT
BACKGROUND: Phalangeal microgeodic syndrome is an uncommon benign self-limiting condition that often occurs during cold weather. The etiology and the pathogenesis of the disease remain unclear. OBJECTIVE: To report a series of children with phalangeal microgeodic syndrome. MATERIALS AND METHODS: Twenty children with phalangeal microgeodic syndrome were retrospectively identified at our hospital after 2007. The clinical data, radiologic manifestation and pathologic appearance were analyzed. RESULTS: The average age was 10.3 years (range: 6.5-14.6 years). Twelve patients were boys. Twenty-five phalanges were affected radiographically (23 middle phalanges [92%] and 2 proximal phalanges [8%]). On radiographs, there were multiple small phalangeal lacunae in all cases. Metaphyseal rarefaction was seen in 15 phalanges, and metaphyseal transverse lucent bands were found in 7 phalanges. Epiphyseal rarefaction was seen in three phalanges. On magnetic resonance imaging (MRI), diffuse signal abnormalities of affected phalanges were observed in all cases. Multiple other phalanges and metacarpals also showed marrow edema in three cases. CONCLUSION: Phalangeal microgeodes may represent bone absorption and destruction in response to exaggerated peripheral circulatory impairment following chilblain, and mainly occur in bone growth spurts.
Subject(s)
Bone Diseases/diagnostic imaging , Finger Phalanges/diagnostic imaging , Magnetic Resonance Imaging , Adolescent , Biopsy , Bone Diseases/pathology , Child , Cold Temperature , Edema/diagnostic imaging , Edema/pathology , Female , Finger Phalanges/pathology , Humans , Male , Retrospective Studies , SyndromeABSTRACT
BACKGROUND: Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated. OBJECTIVE: This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma. METHOD: In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro. RESULTS: In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved. CONCLUSION: Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.
Subject(s)
Autophagy , Chloroquine/pharmacology , Cisplatin/pharmacology , Kidney Neoplasms/drug therapy , Vincristine/pharmacology , Wilms Tumor/drug therapy , Animals , Antimalarials/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Cell Proliferation , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Infant , Kidney Neoplasms/pathology , Male , Mice , Mice, Nude , Tumor Cells, Cultured , Wilms Tumor/pathology , Xenograft Model Antitumor AssaysABSTRACT
RATIONALE: Neuroblastoma is a common abdominal malignancy in children. The chemoresistant and relapsed cases have poor prognosis. The genetic background and the mechanism of resistance remain unelucidated. Next-generation sequence (NGS) is becoming a popular tool to unravel the genetic background and to guide precision medicine in oncology studies as well as in clinical practice. PATIENT CONCERNS: Here we report a neuroblastoma case of a boy aged 2 years and 8 months when first diagnosed, with multiple metastatic sites found in both lungs. The metastatic tumors were resistant to chemotherapy and the patient suffered from severe bone marrow suppression. NGS of the whole exon revealed somatic mutations including 9666 single-nucleotide variants (SNVs) from 5148 genes, 55 copy number variations (CNVs), and 140 insertion-deletion variations. The high frequency of SNVs makes it distinguished case. However, no mutation of key tumor driver genes with functional significance was identified. No abnormality was found in nucleic acid synthesis enzymes. No amplification of c-Myc and n-Myc was found by fluorescence in situ hybridization (FISH). Both NGS and immunohistochemistry (IHC) analysis indicated that DNA mismatch repair (MMR) system was intact. INTERVENTIONS: After initial diagnosis, the patient received combinational chemotherapy, which includes vindesine, an analogue of adriamycin suggested by NGS data, for 4 months. Radical section of the tumor together with the left kidney and the left adrenal gland was performed 5 months after diagnosis. Postsurgical chemotherapy protocols was similar with the previous. OUTCOMES: The patient died 2 years after initial diagnosis after 8 relapses following combinational chemotherapy. LESSONS: This case of neuroblastoma is with pronounced somatic mutations but unidentified driver gene and therapeutic target. Although NGS is a potentially powerful tool to guide precision medicine, at current stage, its application in the clinic certainly has its limits. The underlying mechanism of the substantially increased SNV number, as well as the malignant behaviors of the tumor, is yet to be revealed.
Subject(s)
Abdomen , DNA Copy Number Variations , DNA Mismatch Repair , Neuroblastoma/genetics , Neuroblastoma/pathology , Polymorphism, Single Nucleotide , Child, Preschool , Fatal Outcome , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , MutationABSTRACT
BACKGROUND: Extrauterine growth restriction (EUGR) plays an important role in the developmental origin of adult cardiovascular diseases. In an EUGR rat model, we reported an elevated pulmonary arterial pressure in adults and genome-wide epigenetic modifications in pulmonary vascular endothelial cells (PVECs). However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular consequences later in life remains unclear. METHODS: A rat model was used to investigate the physiological and structural effect of EUGR on early pulmonary vasculature by evaluating right ventricular systolic pressure and pulmonary vascular density in male rats. Epigenetic modifications of the Notch1 gene in PVECs were evaluated. RESULTS: EUGR decreased pulmonary vascular density with no significant impact on right ventricular systolic pressure at 3 weeks. Decreased transcription of Notch1 was observed both at 3 and 9 weeks, in association with decreased downstream target gene, Hes-1. Chromatin immunoprecipitation and bisulfite sequencing were performed to analyze the epigenetic modifications of the Notch1 gene promoter in PVECs. EUGR caused a significantly increased H3K27me3 in the proximal Notch1 gene promoter, and increased methylation of single CpG sites in the distal Notch1 gene promoter, both at 3 and 9 weeks. CONCLUSIONS: We conclude that EUGR results in decreased pulmonary vascular growth in association with decreased Notch1 in PVECs. This may be mediated by increased CpG methylation and H3K27me3 in the Notch1 gene promoter region.
Subject(s)
Epigenesis, Genetic/physiology , Fetal Growth Retardation/metabolism , Lung/metabolism , Microvessels/metabolism , Pregnancy, Ectopic/metabolism , Receptor, Notch1/physiology , Animals , Female , Fetal Growth Retardation/genetics , Fetal Growth Retardation/pathology , Lung/blood supply , Lung/pathology , Male , Microvessels/pathology , Pregnancy , Pregnancy, Ectopic/genetics , Pregnancy, Ectopic/pathology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR. METHODS: An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR. RESULTS: Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma. CONCLUSIONS: These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.
Subject(s)
Allergens , Asthma/genetics , Bronchial Hyperreactivity/genetics , Epigenesis, Genetic , Fetal Growth Retardation/genetics , Ovalbumin , Acetylation , Age Factors , Animals , Asthma/chemically induced , Asthma/immunology , Bronchial Hyperreactivity/chemically induced , Bronchial Hyperreactivity/immunology , DNA Methylation , Disease Models, Animal , Endothelin-1/genetics , Endothelin-1/metabolism , Female , Fetal Growth Retardation/physiopathology , Gene Expression Regulation , Genetic Predisposition to Disease , Histones/metabolism , Maternal Nutritional Physiological Phenomena , Nutritional Status , Pregnancy , Promoter Regions, Genetic , Rats, Sprague-Dawley , Risk FactorsABSTRACT
Atypical teratoid/rhabdoid tumor (AT/RT) is a very rare and highly malignant embryonal tumor in the central nervous system (CNS). Five patients (4 girls and 1 boy) with AT/RT were treated in our hospital. The clinical histories, symptoms, neuroimaging aspects, therapies, histological and immunohistochemical findings and follow-up information were reviewed. The patients ranged from 8 to 40 months with a mean age of 20.6 months. One tumor was located in the spinal cord, two in cerebellum and two in the pineal region. The imagings of the tumors resemble medulloblastomas. Pathological examinations showed that one patient had medulloblastoma differentiation, one had choroid plexus carcinoma differentiation, and one had mesenchymal components. Immunohistochemical staining showed that all of the tumors lost the nuclear expression of integrase interactor 1 (INI1), and were positive for Vimentin, S-100 protein and epithelial membrane antigen. One case with no recurrence after 24 months may have benefited from radical excision and postoperative radiotherapy. The other 4 patients died 8, 4, 1 and 1-month respectively after operation without radiotherapy. The diagnosis of AT/RT depends on full sampling, careful observation the morphological characteristics and INI1 examination, even when the tumor are presented in uncommon sites, such as the spinal cord and the pineal region.
Subject(s)
Central Nervous System Neoplasms/pathology , Rhabdoid Tumor/pathology , Teratoma/pathology , Age Factors , Biomarkers, Tumor/analysis , Biopsy , Cell Differentiation , Central Nervous System Neoplasms/chemistry , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/therapy , Child, Preschool , China , Female , Humans , Immunohistochemistry , Infant , Magnetic Resonance Imaging , Male , Predictive Value of Tests , Rhabdoid Tumor/chemistry , Rhabdoid Tumor/mortality , Rhabdoid Tumor/therapy , Teratoma/chemistry , Teratoma/mortality , Teratoma/therapy , Time Factors , Treatment OutcomeABSTRACT
Hamartomas are extremely rare splenic benign tumours in children. We present two cases, both in boys (6 and 8 years old), with left upper quadrant abdominal pain that were otherwise asymptomatic. Both patients showed a splenic mass on preoperative ultrasonography and magnetic resonance imaging (MRI). One patient had a focal splenic mass that was identified preoperatively with contrasted computed tomography (CT) scans. Both patients underwent a total splenectomy. Although multi-modality imaging findings were described preoperatively, the final diagnosis in each case was splenic hamartoma based on histology and immunohistochemistry. The postoperative courses were uneventful.
Subject(s)
Hamartoma/diagnosis , Splenectomy , Splenic Diseases/diagnosis , Abdominal Pain , Child , Hamartoma/surgery , Humans , Magnetic Resonance Imaging , Male , Prognosis , Splenic Diseases/surgery , Tomography, X-Ray ComputedABSTRACT
Early and accurate noninvasive means of identifying right ventricular (RV) dysfunction in children with tetralogy of Fallot (TOF) are needed. RV function was examined using tissue Doppler imaging (TDI), strain rate (SR), and strain analysis (SA) in children before (N = 37) and after (6-12 months; N = 32) TOF repair, and in a control group of children (N = 37). Plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase 9 (MMP-9) were measured. TDI, SR, and SA revealed that RV systolic and diastolic function indices were lower preoperatively in the TOF group compared with the control group, and did not improve after TOF repair. Plasma NT-proBNP concentrations were significantly higher in the TOF group pre- and postoperatively compared with the control group. In the preoperative TOF group, NT-proBNP concentration was significantly correlated with peak systolic SR and systolic strain in the mid segments of RV free wall. Plasma MMP-9 concentrations were significantly increased in the preoperative TOF group compared with the control group, and significantly correlated with plasma NT-proBNP and logNT-proBNP concentrations. RV function correlated with plasma NT-proBNP concentrations in children with TOF. Assessment of this noninvasive measure may help identify RV dysfunction in patients with TOF before they become clinically symptomatic.
Subject(s)
Heart Ventricles/physiopathology , Tetralogy of Fallot/complications , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Matrix Metalloproteinase 9/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Perioperative Period , Tetralogy of Fallot/blood , Tetralogy of Fallot/surgery , Ventricular Dysfunction, Right/bloodABSTRACT
OBJECTIVE: To study the impact of methionine restriction (MetR) on mucosal histopathology, permeability and tight junction composition in a dextran sulfate sodium (DSS)-induced colitis model, and to explore its underlying mechanism. METHODS: SD rats were randomly divided into 4 groups: normal rats fed by a complete amino acid (AA group) diet, normal rats fed by MetR diet (MetR group), DSS treated rats fed by a complete amino acid (DSS+AA group) and DSS treated rats fed by MetR diet (DSS+MetR group), each group had 15 rats.Abdominal aorta blood sampling was taken at day 21 after DSS model been established to analyze blood routine examination, liver and kidney function and level of electrolyte. Morphological changes in colonic mucosa were evaluated and scored by light microscopy. Myeloperoxidase (MPO) activity was measured. The effect of MetR on mucosal permeability of colon strips was detected by Ussing chamber. Claudin2, occludin, claudin3, ZO-1 expression were quantified by Western blot. RESULTS: The early clinical manifestation in the DSS treated rats were loose stool or diarrhea, hematochezia positive and bleeding, and weight losing. HE observation showed prominent colitis in distal colon with manifestations of crypt abscess and infiltration of inflammatory cells. Although MPO activity and WBC account between the DSS+MetR and DSS+AA group did not significantly changed, treatment with MetR diet significantly decreased the extent and severity of epithelial injury of DSS+MetR group (10.55 ± 3.62 vs 15.00 ± 4.89, P = 0.003). There were no significant difference in PCNA immunohistochemical result between the DSS+MetR group and DSS+AA group. Compared to the rats on AA diet, transepithelial electrical resistance (TEER) in DSS+AA group was obvious lower [(28.40 ± 6.78) Ω·cm² vs (46.53 ± 4.03) Ω·cm², P < 0.05], and TEER in MetR group were obviously higher [(60.64 ± 8.40) Ω·cm² vs (46.53 ± 4.03) Ω·cm², P < 0.05]. However, short-circuit current (Isc) in DSS+MetR group was obviously higher that of DSS+AA group [(35.01 ± 2.19) µA/cm² vs (29.61 ± 1.19) µA/cm², P < 0.05]. Western blot suggested that colon claudin2 expression was not found in colon epithelium of normal rats, and an obviously increase expression of claudin3 protein was found in the MetR group, compared to AA group; and an significantly increase in the abundance of claudin3 was found in the DSS+MetR group, but amount of claudin2 was decreased, compared with the DSS+MetR group. CONCLUSION: The MetR diet has obvious therapeutic effect on ulcerative colitis model rats induced by DSS, and its mechanism may not by regulating inflammatory cell infiltration and the way of promoting intestinal cell growth to alleviate inflammatory injury, but probably by changing the structure and function of tight junction protein and improve the intestinal mucosal barrier function, and promote the repair of damaged intestinal mucosa.
Subject(s)
Colitis/metabolism , Diet, Protein-Restricted , Methionine , Tight Junctions/metabolism , Animals , Disease Models, Animal , Male , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To summarize the clinical characteristics, diagnosis, treatments and outcomes of perinatal autosomal recessive polycystic kidney disease. METHODS: The clinical data of one case with infantile polycystic kidney disease diagnosed in perinatal stage and the reports of 11 cases seen in the past 15 years searched in Pubmed, OVID and Elsevier and CNKI, Wanfang database by using the polycystic kidney disease, infant, perinatal, autosomal recessive and case report as keyword were reviewed and analyzed. RESULTS: The infant was characterized by huge kidneys, severe respiratory and renal compromise. The kidneys were symmetrically enlarged and highly echogenic by ultrasonographic examination and showed high-signal intensity on T2-weighted images by MRI. Histologic analysis showed pulmonary hypoplasia, numerous dilated and elongated tubular structures in the kidney and dilated intrahepatic biliary ducts. Among the 12 cases, 8 cases' presumptive diagnosis was made by prenatal ultrasound revealed enlarged kidneys and oligohydramnios. All cases suffered respiratory distress after birth, and 5 cases complicated pneumothorax. 6 cases died in neonatal stage because of respiratory failure.1 case died 2 m after birth because of renal failure. Five cases are alive and underwent dialysis, nephrectomy or renal transplant. CONCLUSION: Newborn infants with perinatal autosomal recessive polycystic kidney disease often have poor outcome and died from respiratory and renal failure. Aggressive respiratory support and renal replacement therapy (including nephrectomy, dialysis and transplantation) may give these infants a favorable outcome.