This study investigates the long-term effects of deoxynivalenol (DON) consumption on avian growth performance, on the proliferation, apoptosis, and DNA damage of spleen cells, and on intestinal ...integrity. Two hundred and eight 5-day-old black-feathered Taiwan country chickens were fed diets containing 0, 2, 5, and 10 mg/kg of DON for 16 weeks. Body weight gain of male birds in the 2 mg/kg group was significantly lower than that in the 5 mg/kg group. At the end of trial, feeding DON-contaminated diets of 5 mg/kg resulted in heavier spleens. Moreover, the increase in DON induced cellular proliferation, apoptosis, and DNA damage signals in the spleen, the exception being female birds fed 10 mg/kg of DON showing reduced proliferation. Expression of claudin-5 was increased in jejunum of female birds fed 2 and 5 mg/kg of DON, whereas decreased expression levels were found in male birds. In conclusion, our results verified that DON may cause a disturbance to the immune system and alter the intestinal barrier in Taiwan country chickens, and may also lead to discrepancies in growth performances in a dose- and sex-dependent manner.
Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by ...modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene
as well as
(
)
and
in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile,
level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.
The pathogenesis of acute leukemia involves interaction among genetic alterations. Mutations of IDH1/2 and PHF6 are common and co-exist in some patients of hematopoietic malignancies, but their ...cooperative effects remain unexplored. In this study, we addressed the question by characterizing the hematopoietic phenotypes of mice harboring neither, Phf6 knockout, Idh2 R172K, or combined mutations. We found that the combined Phf6
Idh2
mice showed biased hematopoietic differentiation toward myeloid lineages and reduced long-term hematopoietic stem cells. They rapidly developed neoplasms of myeloid and lymphoid lineages, with much shorter survival compared with single mutated and wild-type mice. The marrow and spleen cells of the combined mutated mice produced a drastically increased amount of 2-hydroxyglutarate compared with mice harboring Idh2 R172K. Single-cell RNA sequencing revealed distinct patterns of transcriptome of the hematopoietic stem/progenitor cells from the combined mutated mice, including aberrant expression of metabolic enzymes, increased expression of several oncogenes, and impairment of DNA repairs, as confirmed by the enhanced γH2AX expression in the marrow and spleen cells. We conclude that Idh2 and Phf6 mutations are synergistic in leukemogenesis, at least through overproduction of 2-hydroxyglutarate and impairment of DNA repairs.
Skin tag over the scrotum in infancy Hung, Yi‐Li; Shen, Chun‐Min; Hsieh, Wu‐Shiun
Journal of paediatrics and child health,
September 2018, 2018-Sep, 2018-09-00, 20180901, Letnik:
54, Številka:
9
Journal Article
Protein glycosylation plays an important role in post-translational modification, which defines a broad spectrum of protein functions. Accordingly, infants with a congenital disorder of glycosylation ...(CDG) can have N-glycosylation, O-glycosylation, or combined N- and O-glycosylation defects, resulting in similar but different multisystem involvement. CDGs can present notable gastrointestinal and neurologic symptoms. Both protein-losing enteropathy and hypotonia affect the decision of using anesthetics. We reported a case of MPI-CDG with protein-losing enteropathy and muscular hypotonia that underwent different anesthesia approach strategies of vascular access. Here, we highlight why intubation with sevoflurane anesthesia and sparing use of muscle relaxants is the optimal strategy for such a condition.
A 25-month-old girl, weighing 6.6 kg and 64 cm tall, suffered chronic diarrhea, hypoalbuminemia, and hypotonia since birth. Protein-losing enteropathy due to MPI-CDG was documented by whole-exome sequencing. She underwent three sedated surgical procedures in our hospital. The sedation was administered twice by pediatricians with oral chloral hydrate, intravenous midazolam, and ketamine, to which the patient showed moderate to late recovery from sedation and irritability the following night. The most recent one was administered by an anesthesiologist, where endotracheal intubation was performed with sevoflurane as the main anesthetic. The patient regained consciousness immediately after the operation. She had no complications after all three sedation/anesthesia interventions and was discharged 7 days later, uneventful after the third general anesthesia procedure.
We performed safe anesthetic management in a 25-month-old girl with MPI-CDG using sevoflurane under controlled ventilation. She awoke immediately after the procedure. Due to the disease entity, we suggested bypassing the intravenous route to avoid excess volume for drug administration and that muscle relaxant may not be necessary for endotracheal intubation and patient immobilization when performing procedures under general anesthesia in CDG patients.
Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as ...the
family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of
in the disease remain unknown. Thus we analyzed
and global gene expression patterns in 347 newly diagnosed
AML patients in our institute. We found that higher
expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in
, and
, but negatively associated with acute promyelocytic leukemia, favorable karyotypes,
double mutations and
mutation. Patients with higher
expression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higher
expression was an independent unfavorable prognostic factor irrespective of other known prognostic parameters and gene signatures derived from multiple cohorts. Gene set enrichment analysis showed higher
expression was associated with both hematopoietic and leukemia stem cell signatures. While
and
family genes showed concordant expression patterns in normal hematopoietic stem/progenitor cells, their expression patterns and associated clinical and biological features were distinctive in AML settings, demonstrating
to be a unique homeobox gene. Therefore,
is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients.
The pathogenesis and clinical significance of lenticulostriate vasculopathy (LSV) are unclear. Our study aimed to determine the prevalence, presentation, and evolution of LSV, and the perinatal risk ...factors associated with LSV among very-low-birth-weight (VLBW) preterm infants.
One-hundred-and-thirty VLBW preterm infants were retrospectively enrolled in this study. Serial cranial ultrasound examinations were performed regularly from birth until a corrected age of 1 year. Infants with LSV were assigned to early-onset (≤10 postnatal days) and late-onset (>10 postnatal days) groups. Data describing the infants' perinatal characteristics, placental histopathology, and neonatal morbidities were collected, and the groups were compared.
Of the VLBW infants, 39.2% had LSV before they were 1 year old. Linear-type LSV was the most common presentation, and >50% of the infants had bilateral involvement. LSV was first detected at 112 ± 83 postnatal days, and its detection timing correlated negatively with gestational age (GA) (R
= 0.153,
= 0.005) and persisted for 6 months on average. The infants with and without LSV had similar perinatal characteristics, placental pathologies, cytomegalovirus infection rates, and clinical morbidities. The late-onset LSV group comprised 45 (88.2%) infants who had a significantly higher rate of being small for gestational age (SGA) and used oxygen for longer than the infants without LSV. After adjusting a multivariable regression model for GA and SGA, analysis showed that the duration of oxygen usage was an independent risk factor for late-onset LSV development in VLBW infants (odds ratio: 1.030,
= 0.032).
LSV may be a nonspecific marker of perinatal insult to the developing brains of preterm infants. Prolonged postnatal oxygen usage may predispose VLBW preterm infants to late-onset LSV development. The long-term clinical impacts of LSV should be clarified.
Vancomycin is commonly used for neonatal sepsis. However, consensus on an empirical neonatal vancomycin regimen remains uncertain. We aimed to reappraise the therapeutic optimum concerning vancomycin ...trough concentrations with empirical dosing and to evaluate the relationship between trough concentrations and predicted 24-h area under the curve (AUC24).
This was a 3-year retrospective study. Neonates who were admitted to the neonatal intensive care unit with available vancomycin trough concentrations were enrolled. Trough levels were obtained before the fourth dose. Achievement of goal trough after implementing the vancomycin dosing regimen was based on the Practical Neonatology Medical Manual, published by the National Taiwan University College of Medicine.
A total of 46 neonates were included for analysis. Coagulase-negative staphylococci were the most commonly identified pathogens of sepsis. Among these patients, 22 achieved goal trough levels of 10–20 mcg/mL. Trough levels of 5–10 or >20 mcg/mL occurred in 13 and 11 patients, respectively. A moderately positive correlation between trough and predicted AUC24 was found in all patients (Spearman's rho = 0.676, p < 0.001).
In patients with body weight 1200–2000 g and postnatal age >7 days, the serum creatinine of those with trough levels >20 mcg/mL was significantly higher than those with goal trough levels (0.61 vs. 0.45 mg/dL, p = 0.01). Among those with trough levels >20 mcg/mL, 5 patients received ibuprofen for patent ductus arteriosus closing prior to vancomycin treatment (45%, 5/11), compared to only 3 patients with trough levels <20 mcg/mL (9%, 3/35) (p = 0.013).
Only half of the neonates receiving empirical vancomycin regimen achieved goal trough levels of 10–20 mcg/mL. Higher serum creatinine or ibuprofen treatment may increase the risk of overly high trough levels. The vancomycin regimen needs further validation and modification to provide adequate dosing for optimal use in neonates.
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