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Menopause-associated mood disorder is characterized by emotional depression, anxiety, and stress, which accompany hypogonadism in women in the menopausal phase. The current treatment for menopause-associated mood disorder provides only symptomatic relief and is associated with many side effects. Supplementation with vitamin E has been shown to be effective in ameliorating anxiety and depression. However, the effects of vitamin E and its underlying mechanism in ameliorating menopause-associated mood disorders remain uncertain. This work evaluated the effects of α-tocopherol and tocotrienol-rich palm oil extract on depressive and anxiety-related phenotypes induced by estrogen deficiency through ovariectomy in mice. Our study revealed that ovariectomized mice exhibited alterations in behavior indicative of depressive- and anxiety-like behaviors. The serum corticosterone level, a glucocorticoid hormone associated with stress, was found to be elevated in ovariectomized mice as compared to the sham group. Oral administration of α-tocopherol (50 and 100 mg/kg) and tocotrienol-rich palm oil extract (100 and 200 mg/kg) for 14 days alleviated these behavioral changes, as observed in open field, social interaction, and tail suspension tests. However, treatment with tocotrienol-rich palm oil extract, but not α-tocopherol, modulated the depressive- and anxiety-like responses in ovariectomized mice subjected to chronic restraint stress. Both treatments suppressed the elevated serum corticosterone level. Our findings suggested that α-tocopherol and tocotrienol-rich palm oil extract alleviated menopause-associated mood disorder, at least in part, by modulating the hypothalamic-pituitary-adrenal (HPA) axis. The findings of this study can provide a new foundation for the treatment of menopause-associated depressive- and anxiety-like phenotypes, for the betterment of psychological wellbeing.

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Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis.

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BackgroundAlthough the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, patients with severe liver disease have been shown to have higher mortality. Overall, the mechanism behind the liver injury remains unclear. Approach and resultsWe showed that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. ConclusionOur findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

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ObjectiveCOVID-19 patients presenting with gastrointestinal (GI) symptoms occur in both adults and children. To date, however, no large sample size study focusing on gastrointestinal symptoms in pediatric cases has been published. We analyzed COVID-19 infected children in Wuhan who presented with initial GI symptoms to determine the GI characteristics and epidemiological trend of the disease. DesignWe retrospectively analyzed 244 children patients confirmed with COVID-19 at Wuhan Childrens Hospital from 21 Jan to 20 Mar 2020. Symptomatic cases were divided into two groups according to whether the patients presented with or without GI symptoms on admission. Demographic, epidemiological, symptoms, and laboratory data were compared. We also analyzed the respective trends of case number changes of GI cases and asymptomatic cases. Results34 out of 193 symptomatic children had GI symptoms. They had lower median age and weight, a higher rate of fever, a longer length of stay and more hematological and biochemical abnormalities than patients without GI symptoms. There was no significant difference in chest CT findings or stool SARS-CoV-2 test positive percentages between the two groups. The number of patients admitted with GI symptoms showed an overall downward trend with time. At the time of writing, 242 patients were discharged, one died, and one critically ill patient was still in the intensive care unit. ConclusionCOVID-19 infected children with GI symptoms are prone to presenting with more clinical and laboratory abnormalities than patients without GI symptoms. More attention and timely hospital admission are needed for these patients. Significance of this studyO_LSTWhat is already known on this subject?C_LSTO_LICOVID-19 is now a pandemic with more than 1.6 million people infected worldwide C_LIO_LIAlthough attacking the respiratory tract mostly, both adult and children infected with COVID-19 can present with GI symptoms C_LI O_LSTWhat are the new findings?C_LSTO_LIInfants younger than two years old and presence of fever are the two risk factors of presenting with GI symptoms C_LIO_LIA high proportion of patients without GI symptoms and asymptomatic patients will have positive RT-PCR for the virus in stool C_LIO_LIEarlier testing through contact screening of family members means more COVID-19 infected children are diagnosed when completely asymptomatic C_LI O_LSTHow might it impact on clinical practice in the foreseeable future?C_LSTO_LIThe presence of COVID-19 in stool in infected children will have a major implication for parents and carers of young infants C_LIO_LIIncreasing number of asymptomatic COVID-19 patients who are detected through screening could provide a useful lesson for other countries still experiencing the rise and peak of the pandemic C_LI