Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.

[Malnutrition in early life and cardiovascular disease in adulthood].

Epidemiological and experimental studies have demonstrated that the risk of cardiovascular disease (CVD) in adulthood is influenced by the environment in early life. Intrauterine and early postnatal malnutrition and the following catch-up growth have a long-term effect on blood pressure and endothelial function in adulthood. Well-established prenatal or/and postnatal animal models are used to study the impact of different nutritional intervention on CVD in adulthood. This article reviews the early original cause of chronic CVD in adulthood with the hypothesis of DOHaD (the developmental origins of health and disease), and proposes possible preventions in early life on the basis of this theory.

Epigenetics of Notch1 regulation in pulmonary microvascular rarefaction following extrauterine growth restriction.

BACKGROUND: Extrauterine growth restriction (EUGR) plays an important role in the developmental origin of adult cardiovascular diseases. In an EUGR rat model, we reported an elevated pulmonary arterial pressure in adults and genome-wide epigenetic modifications in pulmonary vascular endothelial cells (PVECs). However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular consequences later in life remains unclear. METHODS: A rat model was used to investigate the physiological and structural effect of EUGR on early pulmonary vasculature by evaluating right ventricular systolic pressure and pulmonary vascular density in male rats. Epigenetic modifications of the Notch1 gene in PVECs were evaluated. RESULTS: EUGR decreased pulmonary vascular density with no significant impact on right ventricular systolic pressure at 3 weeks. Decreased transcription of Notch1 was observed both at 3 and 9 weeks, in association with decreased downstream target gene, Hes-1. Chromatin immunoprecipitation and bisulfite sequencing were performed to analyze the epigenetic modifications of the Notch1 gene promoter in PVECs. EUGR caused a significantly increased H3K27me3 in the proximal Notch1 gene promoter, and increased methylation of single CpG sites in the distal Notch1 gene promoter, both at 3 and 9 weeks. CONCLUSIONS: We conclude that EUGR results in decreased pulmonary vascular growth in association with decreased Notch1 in PVECs. This may be mediated by increased CpG methylation and H3K27me3 in the Notch1 gene promoter region.

Apocrine carcinoma of the vulva in a band-like arrangement with inflammatory and telangiectatic metastasis via local lymphatic channels.

BACKGROUND: Primary adenocarcinomas of the vulva have been classified as sweat gland carcinomas, extramammary Paget's disease, and primary breast carcinomas of the vulva. They share some common histopathologic features. METHODS: We describe a 72-year-old Japanese woman with apocrine carcinoma of the vulva and local lymphatic metastasis. RESULTS: The patient presented with a bruise on her inguinal area. Physical examination revealed a 4 cm x 7 cm, dark-red, irregularly elevated tumor on the left labium majora. Dome-shaped, flesh-colored, small papulovesicles were scattered on the abdomen, accompanied by erythema and induration. The lesion showed a band-like arrangement. General examination revealed multiple bone metastases, particularly in the spine. Microscopic examination revealed a moderately differentiated adenocarcinoma with signet ring cells. A few pagetoid clear cells were present in the hypertrophic epidermis. The peripheral papulovesicles demonstrated the same histopathologic view as in inflammatory and telangiectatic, metastatic breast carcinoma. Tumor cells were positive for various ductal and glandular markers. Estrogen and progesterone receptors were not expressed. Ultrastructural findings suggested differentiation towards apocrine or mammary glands because of the presence of an apocrine process and electron-dense mucous granules. The patient died in spite of combination chemotherapy and irradiation therapy. CONCLUSIONS: We report a rare case of apocrine carcinoma of the vulva in a band-like arrangement with local lymphatic metastasis which showed the clinical and histopathologic characteristics of inflammatory and telangiectatic carcinoma.