Fasting is known to have many health benefits such as prolonging lifespan and suppression of tumorigenesis. [1][2][3] In the present study, we systematically evaluated the effects of water-only fasting on metabolic-syndrome and age-related risk markers in 45 normal-weight individuals.As shown, a 4.59 kg reduction in body weight, 9.85 cm reduction in waist circumference, and 1.64 kg/m 2 reduction in body mass index (BMI) were observed during a 5-day water-only fast (Figures 1A-1C). After refeeding for 1 month (day 38), body weight, waist circumference, and BMI were still lower than the baseline level . Blood pressure (BP) significantly declined during water-only fasting with diastolic BP declining more than systolic BP and gradually both increased to the baseline level by 98 d (Figures 1D and 1E). Considering many fasting studies showed diastolic BP reduction did not exceed systolic BP reduction, future studies are needed on water-only fasting and BP reduction. Insulin dropped approximately 2.8-fold lower than the baseline level during water-only fasting (Figure 1F). Insulin-like growth factor 1 (IGF-1) decreased by a total of 26% during water-only fasting and decreased more in females than males (Figure 1G and Table S1). Future studies will address the sexual disparity of IGF-1 reduction during water-only fasting. The number of pan T cells, CD4+T cells, CD8+T cells, and B cells decreased during water-only fasting . In contrast, the frequency of Treg cells significantly increased during fasting and still exceeded the baseline level 3 months after refeeding (Figures 1L and 1M). This is an important benefit, since Treg cells have anti-inflammation effects. 4 With regard to thyroid hormones, T4 increased rapidly during fasting, whereas T3 and TSH decreased (Figures 1N-1P). The decreased level of T3 during water-only fasting is of particularly importance since a low T3 level, without impairing thyroid function, is strongly associated with longevity. 5,6 The present studyThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Recently, numerous genome wide association studies (GWAS) and other case-control association studies examining the relationship between interleukin-7 receptor α chain (IL7RA) gene rs3194051, rs987107, rs11567686, and rs11567685 variants and multiple sclerosis (MS) risk have been conducted, but the conclusions have been inconsistent. The main objective of this meta-analysis was to more precisely explore the association of these four IL7RA variants with MS development. Twenty-seven eligible studies involving 9734 cases and 10436 controls were included in the present meta-analysis. Power calculation, publication bias, sensitivity analysis and cumulative meta-analysis were performed to derive a reliable conclusion. Our study indicated three IL7RA loci were significantly associated with increasing MS risk (rs3194051: recessive model: OR = 1.22, 95% CI 1.08–1.38; rs987107: recessive model: OR = 1.44, 95% CI 1.22–1.69; and rs11567686: dominant model: OR = 1.18, 95% CI 1.01–1.37). Additionally, IL7RA rs11567685 variants might not be related to MS development. In all, IL7RA locus polymorphisms could play an important role in the predisposition to MS, which could contribute to a better understanding the pathogenesis of multiple sclerosis.

Estrogen receptor (ER)-positive breast cancer is the main subtype of breast cancer (BRCA) with high incidence and mortality. Andrographolide (AD), a major active component derived from the traditional Chinese medicine Andrographis paniculate, has substantial anti-cancer effect in various tumors. However, the antitumor efficacy and the underlying molecular mechanisms of AD on ER-positive breast cancer are poorly understood. In the present study, we demonstrated that andrographolide (AD) significantly inhibited the growth of ER-positive breast cancer cells. Mechanistically, AD suppressed estrogen receptor 1 (ESR1, encodes ER-α) transcription to inhibit tumor growth. Further studies revealed that AD induced ROS production to down-regulate FOXM1-ER-α axis. Conversely, inhibiting ROS production with N-acetylcysteine (NAC) elevated AD-decreased ER-α expression, which could be alleviated by FOXM1 knockdown. In addition, AD in combination with fulvestrant (FUL) synergistically down-regulated ER-α expression to inhibit ER-positive breast cancer both in vitro and in vivo. These findings collectively indicate that AD suppresses ESR1 transcription through ROS-FOXM1 axis to inhibit ER-positive breast cancer growth and suggest that AD might be a potential therapeutic agent and fulvestrant sensitizer for ER-positive breast cancer treatment.

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