Gadolinium Enhancement May Indicate a Condition at Risk of Developing Necrosis in Marchiafava–Bignami Disease: A Case Report and Literature Review

Marchiafava–Bignami disease (MBD) is a rare condition characterized by demyelination, necrosis and atrophy of the corpus callosum (CC), and mainly associated with alcoholism. MBD may present with various clinical manifestations. Brain magnetic resonance imaging (MRI) scan is important in prompt diagnosis and treatment of MBD. Here we reported a case of MBD and reviewed literature about the usage of gadolinium-enhanced MRI in MBD. Gadolinium enhancement may indicate a condition at risk of developing necrosis. We therefore recommend a contrast-enhanced MRI study in severe alcoholics with suspected diagnosis of MBD

Gauss-Bonnet-Chern theorem on moduli space

In this paper, we proved the Gauss-Bonnet-Chern theorem on moduli space of polarized Kahler manifolds. Using our results, we proved the rationality of the Chern-Weil forms (with respect to the Weil-Petersson metric) on CY moduli. As an application in physics, by the Ashok-Douglas theory, counting the number of flux compactifications of the type IIb string on a Calabi-Yau threefold is related to the integrations of various Chern-Weil forms. We proved that all these integrals are finite (and also rational).Comment: Final version, Journal ref adde

Age of onset correlates with clinical characteristics and prognostic outcomes in neuromyelitis optica spectrum disorder

ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes.MethodWe retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (<50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (≥50 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (≥70 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated.ResultsCompared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%, p = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%, p = 0.031) and brainstem/cerebral attacks (7.50% vs. 18.30%, p = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus.ConclusionAge of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD

Modulatory Effect of Fermented Papaya Extracts on Mammary Gland Hyperplasia Induced by Estrogen and Progestin in Female Rats

Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and yeasts. In this study, we investigated the protective effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen. Rats were randomly divided into 6 groups, including a control group, an FPE-alone group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5 ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate and progestin administration. FPEs could improve the pathological features of the animal model and reduce estrogen levels in the serum. Analysis of oxidant indices revealed that FPEs could increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the mammary glands and serum of the animal models, and decrease the proportion of cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary glands. Additionally, estradiol benzoate and progestin altered the levels of serum biochemical compounds such as aspartate transaminase (AST), total bilirubin (TBIL), and alanine transaminase (ALT), as well as hepatic oxidant indices such as SOD, GSH-Px, MDA, and 8-oxo-2′-deoxyguanosine (8-oxo-dG). These indices reverted to normal levels upon oral administration of a high dose of FPEs. Taken together, our results indicate that FPEs can protect the mammary glands and other visceral organs from oxidative damage

CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents

Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound

Depletion of G9A attenuates imiquimod-induced psoriatic dermatitis via targeting EDAR-NF-κB signaling in keratinocyte

Abstract Psoriasis is a common and recurrent inflammatory skin disease characterized by inflammatory cells infiltration of the dermis and excessive proliferation, reduced apoptosis, and abnormal keratosis of the epidermis. In this study, we found that G9A, an important methyltransferase that mainly mediates the mono-methylation (me1) and di-methylation (me2) of histone 3 lysine 9 (H3K9), is highly expressed in lesions of patients with psoriasis and imiquimod (IMQ)-induced psoriasis-like mouse model. Previous studies have shown that G9A is involved in the pathogenesis of various tumors by regulating apoptosis, proliferation, differentiation, and invasion. However, the role of G9A in skin inflammatory diseases such as psoriasis remains unclear. Our data so far suggest that topical administration of G9A inhibitor BIX01294 as well as keratinocyte-specific deletion of G9A greatly alleviated IMQ-induced psoriatic alterations in mice for the first time. Mechanistically, the loss function of G9A causes the downregulation of Ectodysplasin A receptor (EDAR), consequently inhibiting the activation of NF-κB pathway, resulting in impaired proliferation and increased apoptosis of keratinocytes, therefore ameliorating the psoriatic dermatitis induced by IMQ. In total, we show that inhibition of G9A improves psoriatic-like dermatitis mainly by regulating cell proliferation and apoptosis rather than inflammatory processes, and that this molecule may be considered as a potential therapeutic target for keratinocyte hyperproliferative diseases such as psoriasis