Hibifolin protected pro-inflammatory response and oxidative stress in LPS-induced acute lung injury through antioxidative enzymes and the AMPK2/Nrf-2 pathway.

ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS-induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf-2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration-dependent improvement in LPS-induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf-2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS-induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries.

Ameliorative Effect of Imperatorin on Dermatophagoides pteronyssinus-Induced Allergic Asthma by Suppressing the Th2 Response in Mice.

Imperatorin is a furanocoumarin derivative and an effective ingredient in several Chinese medicinal herbs. It has favorable expectorant, analgesic, and anti-inflammatory effects. In this study, we investigated whether imperatorin has protective effects against Dermatophagoides pteronyssinus (Der p)-induced asthma in mice. Lung and bronchial tissues were histopathologically examined through hematoxylin-eosin staining. The concentrations of immunoglobin E (IgE), IgG1, IgG2a in serum and those of T helper 1 (Th1) and two cytokines and eosinophil-activated chemokines in bronchoalveolar lavage fluid (BALF) were detected using an enzyme immunoassay. Histological examination revealed that imperatorin reduced inflammatory cell infiltration, mucus hypersecretion, and endothelial cell hyperplasia. The examination also indicated that imperatorin could reduce the inflammatory cell count in BALF as well as IgE and IgG1 expression in serum, but IgG2a expression was significantly increased. Imperatorin reduced the production of interleukin (IL)-4, IL-5, and IL-13 by Th2, promoted the production of interferon-γ and IL-12 by Th1, and increased the production of IL-10 in bronchoalveolar lavage fluid. These findings suggest that imperatorin has a considerable anti-inflammatory effect on Der p-induced allergic asthma in mice.

3-Bromofluoranthene-induced cardiotoxicity of zebrafish and apoptosis in the vascular endothelial cells via intrinsic and extrinsic caspase-dependent pathways.

Fluoranthene, a high-molecular-weight polycyclic aromatic hydrocarbon (PAH), is widely present in air pollutants, including fine inhalable particulate matter. 3-Bromofluoranthene (3-BrFlu), which is a brominated fluoranthene and halogenated PAH, is generated from waste combustion, metallurgical processes, cement production, e-waste dismantling, and photoreaction. Vascular endothelial cells have key functions in the homeostasis and the development of the cardiovascular system. The zebrafish model has been widely employed to study cardiotoxicity and embryotoxicity. However, no evidence has indicated that 3-BrFlu induces cytotoxicity in vascular endothelial cells, or cardiotoxicity and embryotoxicity in zebrafish. In this study, 3-BrFlu induced concentration-dependent changes in embryo- and cardiotoxicity. Cytotoxicity was also induced by 3-BrFlu in a concentration-dependent manner through apoptosis and necrosis in vascular endothelial cells, SVEC4-10 cells. The activities of caspase-3, -8, and -9 were induced by 3-BrFlu via an intrinsic pathway constituting Bcl-2 downregulation, Bad upregulation, and mitochondrial dysfunction; the extrinsic pathway included the expression of death receptors, including tumour necrosis factor α and Fas receptors. These results indicated that 3-BrFlu caused cardio- and embryotoxicity in zebrafish through vascular endothelial cells cytotoxicity resulting from caspase-dependent apoptosis through intrinsic and extrinsic pathways.

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways.

Air pollution is a major environmental and public health problem worldwide. A nitro-polycyclic aromatic hydrocarbon and the most abundant air pollutant in diesel engine exhaust, 1-nitropyrene (1-NP), is caused by the incomplete combustion of carbonaceous organic substances. Macrophages are effector cells of the innate immune cells that provide resistance in the peripheral tissue. The overactivation of macrophages results in inflammation. The generation of proinflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumour necrosis factor alpha, is induced by 1-NP in a concentration-dependent manner in macrophages. In this study, the production of proinflammatory mediators, such as nitrogen oxide and prostaglandin E2, was induced by 1-NP in a concentration-dependent manner through the expression of iNOS and COX2. The generation of proinflammatory cytokines, iNOS, and COX2 was induced by 1-NP through nuclear factor (NF)-κB p65 phosphorylation and the degradation of its upstream factor, IκB. Finally, Akt phosphorylation was induced by 1-NP in a concentration-dependent manner. These findings suggest that 1-NP exhibits a proinflammatory response through the NF-κB pathway activation due to Akt phosphorylation.

Perinatal effects of combined use of heroin, methadone, and amphetamine during pregnancy and quantitative measurement of metabolites in hair.

OBJECTIVE: There has been very limited research on the clinical features of newborns exposed to combined use of heroin, methadone, and amphetamine in the uterus. We describe a technique for the quantification of drug metabolites in neonatal hair samples. METHODS: In a tertiary neonatal care center in Taiwan, three neonates whose mothers self-reported heroin abuse with methadone treatment during pregnancy were studied. Involuntary exposure to amphetamine was not suspected before the births. To assess long-term illicit drug exposure during pregnancy, a quantifying technique of gas chromatography/mass spectrometry (GC/MS) for hair samples from neonates was developed to replace current methods for urine and blood specimens. RESULTS: All three mothers were addicted to heroin and prescribed oral methadone treatment during pregnancy. Two males and one female were born and then admitted to the neonatal intensive care unit because of apparent neonatal abstinence syndrome (NAS) after birth. Additional hypertonicity and cerebral dysfunction were also diagnosed by electroencephalography in one case. Supportive care was given to the neonates, unless special treatments were needed in responding to tachypnea, fetal distress, or withdrawal symptoms. During follow-up periods from 10 months to 15 months, the signs of NAS remained and delays in milestones of development were observed. Further follow-up on the infants' neurobehavioral development is necessary. Measurement results of neonates' hair samples revealed high levels of metabolites of heroin, methadone, and amphetamine, reflecting the amount of illicit drug exposure 2-3 months before delivery. CONCLUSION: The current study suggested the possibility of polydrug exposure, which was previously unknown in pregnant women in Taiwan. Measurement of neonatal hair samples could provide a basis for clinical evaluation and potential corresponding treatment.

A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain.

Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder that affects development of midline structures and comprises hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene abnormalities include missense, nonsense, and splicing mutations, small insertions, small deletions, and complex rearrangements. Here, we present a patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T

Nine genes that may contribute to partial trisomy (6)(p22→pter) and unique presentation of persistent hyperplastic primary vitreous with retinal detachment.

We report on a newborn girl with facial anomalies, a congenital heart defect, severe pre- and postnatal growth retardation, feeding problems, and persistent hyperplastic primary vitreous. Cytogenetic analysis by high resolution GTG banding showed extra chromosomal material on the short arm of one chromosome 1 of the patient, but neither parent. SKY and CGH analysis demonstrated that the patient had a de novo 46,XX, der(1)t(1;6)(p36.3; p22). Compared with previously reported cases of partial trisomy 6p22 syndrome, this patient exhibited a unique condition for this syndrome: persistent hyperplastic primary vitreous (PHPV) with retinal detachment. The human genome database was searched for candidate genes and we propose the following nine genes located in the 6p22→6pter region for their potential contribution to the phenotype of partial trisomy 6p22→pter and persistent hyperplastic primary vitreous (PHPV) with retinal detachment: Forkhead box Q1 (FOXQ1), FOXF2, FOXC1, NRN1, EDN1, ATXN1, DEK oncogene, E2F3, and NRNS1.

Efficacy of intermediate-dose oral erythromycin on very low birth weight infants with feeding intolerance.

BACKGROUND: Erythromycin is generally used as a prokinetic agent for the treatment of feeding intolerance in preterm infants; however, results from previous studies significantly vary due to different medication dosages, routes of administration, and therapy durations. The effectiveness and safety of intermediate-dose oral erythromycin in very low birth weight (VLBW) infants with feeding intolerance was examined in this study. METHODS: Between November 2007 and August 2009, 45 VLBW infants with feeding intolerance, who were all at least 14 days old, were randomly allocated to a treatment group and administered 5mg/kg oral erythromycin every 6hours for 14 days (n=19). Another set of randomly selected infants was allocated to the control group, which was not administered erythromycin (n=26). RESULTS: The number of days required to achieve full enteral feeding (36.5±7.4 vs. 54.7±23.3 days, respectively; p=0.01), the duration of parenteral nutrition (p<0.05), and the time required to achieve a body weight ≥2500g (p<0.05) were significantly shorter in the erythromycin group compared with the control group. The incidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) ≥ stage II after 14 days of treatment were significantly lower (p<0.05) in the erythromycin group. No significant differences were observed in terms of the incidences of sepsis, bronchopulmonary dysplasia, or retinopathy of prematurity. No adverse effects were associated with erythromycin treatment. CONCLUSIONS: Intermediate-dose oral erythromycin is effective and safe for the treatment of feeding intolerance in VLBW infants. The incidences of PNAC and ≥ stage II NEC were significant lower in the erythromycin group.

Herlyn-Werner-Wunderlich syndrome consisting of uterine didelphys, obstructed hemivagina and ipsilateral renal agenesis in a newborn.

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare variant of Müllerian duct anomalies consisting of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome are usually asymptomatic until menarche, when they present with acute lower abdominal pain. Here we report a case of a female newborn with right renal agenesis diagnosed during the pregnancy. The patient presented with a protruding mass over the vaginal introitus that was associated with an obstructed hemivagina and uterine didelphys.

Congenital myotubular myopathy with a novel MTM1 gene mutation in a premature infant presenting with ventilator dependency and intrahepatic cholestasis.

Myotubular myopathy is a rare congenital disease characterized by hypotonia and respiratory compromise at birth in affected males. It causes high neonatal mortality. Most surviving newborns need prolonged ventilation and have significantly delayed motor development. Although all patients with congenital myotubular myopathy have respiratory problems such as atelectasis and recurrent lung infections, concurrent neonatal intrahepatic cholestasis is rare. We report a newborn with a myotubular myopathy, ventilator dependency, recurrent lung infections and pleural effusion, facial diplegia, ophthalmoplegia, and progressive intrahepatic cholestasis. A genetic study showed a novel mutation of the MTM1gene: c.1142 G>A (R381Q). We suggest that physicians consider probable concurrent disorders of other organs in neonates with congenital myotubular myopathy.

Ocular findings in a case of trisomy 18 with variant of Dandy-Walker syndrome.

Trisomy 18 is the second most common chromosomal syndrome and has multiple dysmorphic features. However, ocular findings in trisomy 18 are rarely reported. Retinal folds are the most common ocular finding described to date, although retinal hypopigmentation, dysplasia, and areas of hemorrhage and gliosis are also found in trisomy 18. Dandy-Walker syndrome is a brain malformation that has been reported in association with numerous chromosomal abnormalities, although it has rarely been reported in association with trisomy 18. Here, we present a case of trisomy 18 with ocular pathology and variant of Dandy-Walker syndrome, a combination that has not previously been reported.

Successful weaning of a laryngeal mask airway after a tongue-lip adhesion operation in a case with cerebro-costo-mandibular syndrome.

Cerebro-costo-mandibular syndrome (CCMS) consists of severe micrognathia, glossoptosis, posterior rib-gap defects and developmental delay. It may cause upper airway obstruction andflail chest, resulting in neonatal hypoxia, and possibly death. Early airway management or surgical intervention to maintain a patent airway is critical to avoid hypoxia in CCMS patients. We report a newborn with CCMS who was successfully weaned from a laryngeal mask after undergoing a tongue-lip adhesion operation at 164 days of age.

Exclusion of MYF5, GSC, RUNX2, and TCOF1 mutation in a case of cerebro-costo-mandibular syndrome.

Cerebro-costo-mandibular syndrome (CCMS) is an uncommon multiple congenital anomaly syndrome characterized by severe micrognathia, posterior rib-gap defects, and developmental delay. The cause of CCMS is unknown. Genes hypothesized to have a causal role in CCMS, include myogenic factor 5 (MYF5), goosecoid homeobox (GSC) and runt-related transcription factor 2 (RUNX2) [formerly known as core-binding factor (CBFA1)]. We report an infant with typical features of CCMS who, on prenatal ultrasound, was found to have severe micrognathia. We present the first image by three-dimensional computed tomography of posterior rib-defect, and we exclude mutations of the MYF5, GSC, RUNX2, and TCOF1 genes in our patient. Further molecular studies are needed to evaluate the cause of CCMS.

Associations of serum leptin with atopic asthma and allergic rhinitis in children.

BACKGROUND: There is growing evidence of positive correlations between asthma (AS) and obesity in adults and children. Leptin is an obesity gene product secreted by white adipose tissue; elevated serum levels are found in obese adults and children. Recently, leptin has also been found to be associated with allergic rhinitis (AR). However, the links between serum leptin, atopic AS, and AR remained undetermined. Because AS and AR share common allergic inflammatory mechanisms, our aim was to determine if there were any differences in serum leptin levels between asthmatic children and nonasthmatic children with AR. METHODS: We studied 114 children (67 boys and 47 girls): 68 with mild intermittent-to-moderate persistent atopic AS (AS children) and 46 with mild-to-moderate persistent AR without AS (AR children; overall mean age, 8.51 years; range, 5-18 years). Body mass index (BMI), serum leptin, pulmonary function, and atopy parameters (serum IgE and eosinophil levels) were measured. RESULTS: Compared with AR children, AS children had higher body weights (kg), body mass indices (kg/cm²), and serum leptin levels (ng/mL). Multiple linear regression analyses showed that serum leptin concentrations differed significantly for girls, being overweight and between disease groups (AS and AR children). CONCLUSION: Our results indicate that a higher serum leptin level has stronger association with mild-to-moderate persistent AS compared with AR. Hence, serum leptin may be a stronger predictor for childhood AS compared with AR. Among the asthmatic children, higher serum leptin levels also showed stronger associations with female gender and being overweight.

Do vacuum-assisted deliveries cause intracranial vessel injuries?

Vacuum-assisted deliveries are fairly commonly used in obstetrical practice. Most newborns who have a vacuum-assisted delivery undergo extracranial birth traumas that have no residual consequences. Vacuum-assisted deliveries that complicate intracranial vascular infarction are rarely reported. We present 2 cases of intracranial vessel infarction after vacuum-assisted deliveries. One newborn, with scalp erosion, showed an unusual left middle cerebral artery infarct, and the other, with a severe subgaleal hematoma, had a venous thrombosis. Before the diagnosis, made using brain ultrasonography, neither had specific observable neurological symptoms. In conclusion, vacuum-assisted deliveries should be given special attention, especially when they are combined with a severe extracranial birth trauma.

Rapidly declining unilateral hearing within 1 month in a newborn with internal auditory canal stenosis and facial palsy.

Most newborns with congenital unilateral facial palsy are expected to recover; however, when a patient has hearing loss, underlying developmental ear structure abnormalities should be investigated, particularly when the patient has internal auditory canal stenosis, which is rarely reported in newborns. All cases of internal auditory canal stenosis are accompanied by concomitant unilateral or bilateral hearing loss, but none with progressive hearing loss has been reported. We present the case of a newborn with rapidly declining hearing in the left ear within 1 month after birth. The hearing decline was associated with unilateral facial palsy. Using high-resolution computed tomography (CT) of the temporal bone, we diagnosed the patient with congenital internal auditory canal stenosis. This is the first case detected with progressive hearing loss after birth, which implies that prompt diagnosis and early habilitation are warranted, even when the hearing loss is initially mild.

Pfeiffer-like syndrome with holoprosencephaly: a newborn with maternal smoking and alcohol exposure.

We report the case of a female infant with Pfeiffer-like syndrome and holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and halluces, and variable accompanying anomalies compatible with Pfeiffer syndrome. She also displayed microcephaly, short palpebral fissures, and a smooth philtrum, which are clinical signs consistent with fetal alcohol syndrome. She suffered from multiple congenital anomalies and died at 41 days of age. Cardio-pulmonary failure, brain abnormalities, prematurity, and multiple complications contributed to her death. The patient displayed normal chromosomal numbers and type. DNA analysis did not reveal fibrobtast growth factor receptor (FGFR) genes FGFR1, FGFR2, FGFR3 or TWIST gene mutations. We review the previous reports of Pfeiffer syndrome and holoprosencephaly and describe our infant patient with Pfeiffer-like syndrome, holoprosencephaly, and heavy in utero maternal alcohol and smoking exposures.

Trisomy 18 syndrome with incomplete Cantrell syndrome.

The pentalogy of Cantrell was first described in 1958 by Cantrell and coworkers, who reported five cases in which they described a pentad of findings including a midline supraumbilical thoracoabdominal wall defect, a defect of the Lower sternum, abnormalities of the diaphragmatic pericardium and the anterior diaphragm, and congenital cardiac anomalies. Trisomy 18 has an incidence of about 0.3 per 1000 newborns. We present a case of trisomy 18 with incomplete Cantrell syndrome. The patient presented with hypogenesis of the corpus callosum, vermian-cerebellar hypoplasia (Dandy-Walker variant), ventricular septal defect, dextrocardia, patent ductus arteriosus, a defect of the lower sternum, a midline supraumbilical abdominal wall defect with omphalocele, congenital left posterior diaphragmatic hernia (Bochdalek hernia), micrognathia, low-set and malformed ears, rocker-bottom feet, dorsiflexed hallux, hypoplastic nails, short neck, and wrist deformity. Trisomy 18 syndrome was unusually combined with the pentalogy of Cantrell. We present this case because of its rarity and high risk of mortality.

Hydranencephaly associated with interruption of bilateral internal carotid arteries.

Hydranencephaly is a rare and fatal central nervous system disorder where all or nearly all of the bilateral cerebral hemispheres are absent. The extensive hollow cerebrum is replaced with cerebrospinal fluid. Clinically, the differential diagnoses of hydranencephaly include severe hydrocephalus and alobar holoprosencephaly. Nearly all cases are sporadic, involving approximately 1 in 5000 continuing pregnancies. The exact main cause is still unknown, but hydranencephaly is usually found to develop secondarily to the occlusion of cerebral arteries above the supraclinoid level. We present the case of a 1-month-old male infant with hydranencephaly initially thought to be severely hydrocephalus via routine antenatal intrauterine sonography performed at 35 weeks of gestation. Hydranencephaly was confirmed by brain sonography, brain magnetic resonance imaging and magnetic resonance angiography postnatally. We discuss several imaging features that are helpful in distinguishing hydranencephaly from extreme hydrocephaly. Different theories that have been recently proposed regarding the origin of hydranencephaly are reviewed.

Goldenhar syndrome (oculoauriculovertebral dysplasia): report of one case.

Goldenhar syndrome, also known as oculoauriculovertebral dysplasia, is an uncommon condition, characterized by a combination of anomalies: epibulbar dermoids or lipodermoids, preauricular appendices, malformation of the ears, hemifacial microsomia, vertebral anomalies, and others. The etiology of this disease has remained unclear; factors including chromosomal abnormalities, maternal diabetes mellitus or drug use, and influence of environment during pregnancy have been proposed. Here, we describe a case of Goldenhar syndrome in a 1-day-old female newborn, who presented with right external ear atresia, left preauricular appendices, cleft-like extension of the right oral angle, mandibular hypoplasia and relatively small hands. The literature on Goldenhar syndrome is briefly reviewed.