Effect of high-fat diet on liver and placenta fatty infiltration in early onset preeclampsia-like mouse model

Background Preeclampsia, especially early onset of preeclampsia （PE）, is a common and serious disorder with high maternal and perinatal morbidity and mortality. Dietary factor is one of the most important factors which may affect the occurrence and development of the disease. The aim of this study is to investigate the effects of dietary factors on pathological changes of liver and placenta in preeclampsia-like mouse model by establishing the model at multiple stages of gestation. Methods Wild-type （WT） mice were injected subcutaneously with nitric oxide synthase （NOS） inhibitor L-arginine methyl ester （L-NAME, 50 mg·kg^-1·d^-1） to establish PE-like model （L-NAME group） at early-, mid-, and late- pregnant periods respectively; simultaneously, the control mice were injected with normal saline （NS group）. All the groups were divided into subgroups, standard chow group （SC）, and high-fat diet group （HF）. ApoE^-/- pregnant mice served as a control group. Systolic blood pressure （SBP）, urine protein, and histopathologic changes of placenta and liver in all groups were observed and statistically analyzed. Results In WT and apoE^-/- L-NAME subgroups, blood pressure and urine protein were significantly higher than those in all the gestational age matched NS groups （P 〈0.05）. Compared to other groups, remarkable liver fatty infiltration and lipid storage in placenta were found in early- and mid-L-NAME subgroups in apoE^-/- mice （P 〈0.05）, especially in the early- and mid-HF＋L-NAME subgroups in apoE^-/- mice （P 〈0.05）. More lipid storage droplets both in liver and placenta were found in ApoE^-/- mice than that of WT groups （P 〈0.05）. Morphology histopathologic examination of placentas showed varying degrees of fibrinoid necrosis and villous interstitial edema in early- and mid-L-NAME both in HF and SC of apoE^-/- and WT subgroups compared to NS controls （P 〈0.05）. But there was no significant difference between HF and SC subgroups （P 〉0.05）, and no difference between apoE^-/-and WT groups （P 〉0.05）. Conclusions Preeclampsia-like conditions could be induced by L-NAME in mice at different gestational stages. Both WT and apoE^-/- genotype mice with preeclampsia-like symptoms in early and mid stages of pregnancy presented lipid deposition in the placenta and hepatic fatty infiltration. To alter the environmental condition by feeding high-fat diet was harmful to the mother and the fetus. High-fat diet aggravated the impact of liver fatty infiltration at early and mid gestational stages especially in the apoE^-/- mouse model. These results further revealed the association between early-onset preeclampsia and the dysoxidation of fatty acids.

Rim^(18)F-fluorodeoxyglucose uptake of hepatic cavernous hemangioma on positron emission tomography/computed tomography:A case report

BACKGROUND Peripheral FDG accumulation in a hepatic hemangioma presenting in a patient with prolonged fever is rare.Therefore,clinicians should pay close attention to patients with hepatic mass.CASE SUMMARY A 54-year-old woman with a 4-wk history of daily fevers was admitted to our hospital.A whole body^(18)-Fluordesoxyglucose(PET-FDG)positron emission tomography/computed tomography(PET/CT)was performed to elucidate the source of the fever.However,whole body^(18)-FDG PET/CT raised the suspicion of a malignant lesion because of peripheral FDG accumulation(SUVmax 3.5 g/mL)higher than that of the normal liver parenchyma(SUVmax 1.6 g/mL)surrounding a hypoactive area,and no other abnormalities were showed.Subsequently,the patient underwent liver mass resection.Histopathology showed a hepatic cavernous hemangioma with fatty infiltration around the lesion.The fever disappeared four days after surgery and the patient did not present any complications during follow-up.CONCLUSION Fatty infiltration in the peripheral parts of hepatic cavernous hemangioma may lead to subacute inflammation which further activate the Kupffer cells.This may cause prolonged fever and peripheral rim FDG accumulation on PET/CT.

Regional differences in genetic susceptibility to nonalcoholic liver disease in two distinct Indian ethnicities

AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk(odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI(patients-14/93 and controls-7/138; P = 0.009) and NEI ethnicities(patients-17/163 and controls-7/109; P = 0.01). CONCLUSION Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants.

Quantification Threshold Pixel Technique of Magnetic Resonance Imaging in Paraspinal Muscles Atrophy among Discopathy Patients

Purpose: To evaluate the relationship between lumbosacral discopathy status and paraspinal atrophic changes (Cross-sectional area (CSA) and fatty infiltration (FI)) among different age groups. Materials and Methods: We retrospectively evaluated 200 patients with confirmed discopathy who were examined by lumbosacral Magnetic Resonance Imaging (MRI) at the two main governmental hospitals in Gaza Strip. Using ImageJ software and quantification threshold technique, we measured the CSA and FI of paraspinal muscles {multifidus (MF) & erector spinae (ES)}. The interpretation of MRI images was performed by two radiologists with a good inter-observer agreement between the radiological discopathy findings. Results: The highest percentage and severity of discopathy were noticed at the level of L4/5 (89.5%), followed by L5/S1 (14.5%). The FI is increased towards lower levels of L3/4 to L5/S1. No correlation was found between discopathy level, the severity of discopathy, and CSA of MF & ES muscles. In contrast, a correlation was observed between FI of MF & ES muscles, discopathy level, and severity. Also, the results illustrated no significant relation was observed between CSA of MF & ES muscles and age groups (P > 0.05), while a significant correlation was reported between FI and age groups (P Conclusion: The MRI quantification threshold pixel technique for paraspinal muscles reflected the atrophic changes like CSA and FI in discopathy patients.

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair

Electrospun fibers,with proven ability to promote tissue regeneration,are widely being explored for rotator cuff repairing.However,without post treatment,the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix(ECM).Moreover,during mechanical loading,the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells.Here,electrospun nanofiber scaffolds,with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion,were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy.The crimped nanofiber scaffold(CNS)features bionic tensile stress and induces chondrogenic differentiation,laying credible basis for in vivo experimentation.After repairing a rabbit massive rotator cuff tear using a CNS for 3 months,the continuous translational tendon-to-bone interface was fully regenerated,and fatty infiltration was simultaneously inhibited.Instead of micro-CT,μCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1μm.This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.