In this study, we have identified the growth factors supporting myeloma self-renewal in eight myeloma cell lines. All cell lines able to form self-colonies displayed constitutive P-AKT and P-ERK1,2 but not P-STAT3 and did not express CD45, suggesting the presence of an insulin-like growth factor 1 (IGF1) loop. We showed that a blocking anti-insulin-like growth factor 1 receptor (IGF1R) monoclonal antibody (mAb) inhibited colony formation in correlation with IGF1R expression and decreased P-AKT. Imatinib or a blocking anti-stem cell factor (SCF) mAb also inhibited colony formation of two cell lines expressing C-KIT and SCF, and decreased P-AKT. Moreover, the PI3K/AKT pathway inhibitor wortmannin inhibited colony formation. Blocking interleukin (IL)6R did not inhibit colony formation in good agreement with a lack of constitutive P-STAT3. We showed that primary cells frequently co-expressed IGF1R/IGF1 but not C-KIT/SCF or IL6R/IL6, suggesting that in vivo autonomous growth could be possible via IGF1R. Despite their similar role in clonogenic growth and shared signaling pathway, IGF1R and C-KIT had opposite prognostic values, suggesting that they were surrogate markers. Indeed, we showed that both C-KIT and IGF1R prognostic values were not independent of MMSET expression. This study highlights the autocrine role of IGF1 in myeloma cells and reinforces the interest in targeting IGF1R in IGFR1+ CD45+/− patients, such as MMSET+ patients.

Increasing energy expenditure by activating thermogenesis in brown and beige adipocytes is a critical approach to protect against obesity. Here, we investigated the action and mechanism of a natural polymethoxyflavone on adaptive thermogenesis in high-fat diet-induced obesity mouse model. Nobiletin treatment significantly ameliorated obesity, alleviated the whitening of brown adipose tissue, and promoted browning of white adipose tissue in mice fed a high-fat diet. Gut microbiota analysis and metabolomic profiling revealed that nobiletin treatment resulted in a composition shift in the gut microbiota thereby altering fermentation products acetate levels in the host feces and serum. Further, transplantation of the microbiota from nobiletin-treated mice to microbiota-depleted mice activated brown adipose tissue activity, promoted beige adipocytes formation, and improved high-fat diet-induced obesity. Our results indicate that nobiletin could be used as a dietary therapy to prevent HFD-induced obesity, and provide a potential target-specific gut microbial species-driven mechanism for activating thermogenesis in brown and beige adipocytes.

Background: Preeclampsia is one form of hypertensive disorders, responsible for severe morbidity, long-term disability and maternal and newborn mortality worldwide. Studies have assessed the role of diet on the risk of preeclampsia using various dietary patterns, however, the association between dietary pattern and the risk of preeclampsia is not entirely clear. This study aimed to determine the association between maternal dietary patterns and the risk of preeclampsia through a meta-analysis of observational studies. Methods: Electronic literature was searched in 3 databases, including PubMed, Cochrane Library, and Web of Science, for articles published up to November 2020 that examined the association between dietary patterns and preeclampsia. Only studies considered observational were included. Two authors independently performed study selection and data extraction. Pooled effect sizes of eligible studies were estimated by using randomeffects models for healthy diet patterns and fixed-effects models for western diet patterns. Results: A total of 12 articles reporting 25 studies were selected for this study. Results from 11 articles reporting 22 studies were pooled. Healthy dietary patterns (16 studies) and western dietary pattern (6 studies) were identified. Higher adherence to a healthy dietary pattern was significantly associated with a reduced risk of preeclampsia (OR (95% CI): 0.79 (0.73e0.85), I 2 ¼ 57.2%, P ¼ 0.009),

Naringin, a natural flavonoid mainly found in citrus fruit, has been reported to exert a positive effect on improving skeletal muscle health. However, the effects and potential mechanisms of naringin on skeletal muscle fiber switching is still unclear. Here, we discovered that oral administration of naringin increased the low-speed running time, four-limb hanging time, body oxygen consumption in mice, enhanced aerobic enzyme activity, MyHC I expression, and slow-twitch fiber percentage in mice skeletal muscle. By contrast, naringin decreased α-GPDH enzyme activity, MyHC IIb expression, and fast-twitch fiber percentage. Moreover, naringin increased the concentration of serum adiponectin and activated the expression of AdipoR1, APPL1, AMPK, and PGC-1α. Furthermore, by the in vitro experiment and AdipoR1 knockdown, we found that inhibition of the AdipoR1 signaling pathway significantly reduced the effect of naringin on slow-twitch fiber-/fast-twitch fiber-related gene and protein expression. In conclusion, our results indicated that naringin could induce skeletal muscle fiber transition from fast twitch to slow twitch via the AdipoR1 signaling pathway. This study may provide new strategy for improving exercise endurance and slow muscle fiber deficiency-related diseases.

Sesamin, a major lignin mainly found in sesame (Sesamum indicum) oil and sesame seeds, has been demonstrated to possess lipoclasis-promoting, antiobesity, and antidiabetic effects. Irisin is a newly discovered myokine that has attracted great interest as a key target to prevent/treat obesity and its related metabolic diseases. However, the effect and potential mechanism of sesamin on FNDC5/irisin are still vacant. In this study, we showed that sesamin treatment increased FNDC5/irisin activation and regulated SIRT1, PGC-1α, and p-SMAD3/SMAD3 expression in C2C12 cells. By using specific inhibitors and lentivirus in C2C12 cells, we found that the SIRT1/SMAD3 axis plays an important role in sesamin regulated FNDC5/irisin activation. We also found that sesamin treatment activated FNDC5 expression and regulated the SIRT1/SMAD3 signaling axis in mice's skeletal muscle. What is more, by the high-fat diet induced obese model, we further showed that sesamin improved the high-fat diet induced decrease in irisin production and secretion, which results in an improvement of body weight gain and skeletal muscle dysfunction. Our results suggested that sesamin could activate FNDC5 expression and stimulate irisin secretion through the SIRT1 pathway both in vitro and in vivo, which may provide a new strategy for preventing and improving irisin deficiency related diseases.

BackgroundPrevious research has found that the prevalence of childhood overweight/obesity varies depending on household income, ethnicity, and sex. The goal of our research is to examine changes over time in socioeconomic inequality and the prevalence of overweight/obesity among American children under five by sex and ethnicity.MethodsThis cross-sectional analysis used data from the National Health and Nutrition Examination Surveys (NHANES) collected from 2001–02 to 2017–18. Overweight/obesity in children under five [Body Mass Index (BMI)-for-age z-score >2 standard deviations] was defined according to the World Health Organization (WHO) growth reference standard. The slope inequality index (SII) and the concentration index (CIX) were used to measure the socioeconomic inequality in overweight/obesity.ResultsBetween 2001–02 and 2011–12, childhood overweight/obesity in the United States decreased from 7.3% to 6.3%, and had increased to 8.1% by 2017–18. However, this pattern varied widely by ethnicity and sex. For both the 2015–16 and 2017–18 surveys, overweight/obesity was more concentrated in the poorest household quintile for overall Caucasian children ((SII = −11.83, IC 95% = −23.17, −0.49 and CIX = −7.368, IC 95% = −13.92, −0.82) and (SII = −11.52, IC 95% = −22.13, −0.91 and CIX = −7.24, IC 95% = −13.27, −1.21), respectively) and for males of other ethnicities [(SII = −13.93, IC 95% = −26.95, −0.92) and CIX = −8.55, IC 95% = −0.86, −16.25] and (SII = −21.19, IC 95% = −40.65, −1.74) and CIX = −13.11, IC 95% = −1.42, −24.80), respectively). In the last three surveys, overweight/obesity was also more concentrated in the poorest household quintile for the overall children of other ethnicities. With the exception of African American females in the 2013–14 survey, for whom overweight/obesity was significantly concentrated in a quintile of the richest households (SII = 12.60, 95% CI = 0.24, 24.97 and CIX = 7.86, 95% CI = 15.59, 0.12); overweight/obesity was found to be concentrated in the richest household quintile for overall African American children, but not significantly so.ConclusionsOur findings give an update and reinforce the notion that overweight/obesity in children under the age of five has increased and that related wealth inequalities are a public health problem in the United States.

Background In sub-Saharan Africa, infant anemia, stunting and low birth weight remains major public health problems. It is unclear whether prenatal iron supplementation and/or deworming can reduce the risk of infant stunting, anemia and low birth weight. The aim of this study was to investigate the relationship between iron supplementation and/or deworming and stunting, anemia, and low birth weight in infants under two years of age in sub-Saharan Africa. Methods Our studies examined pooled data from Demographic and Health Surveys (DHS) in twenty-three African countries collected between 2014 and 2020. childhood anemia and stunting in infants under the age of two were the primary outcomes. Iron supplementation and deworming during prenatal visits were the main exposure variables. A multivariate logistic regression model was used to investigate these relationships. Results The prevalence of stunting was 29.9%, severe stunting was 10.6%, childhood anemia was 74.3%, childhood severe anemia was 3.2%, and low birth weight was 16.4%, respectively. The use of prenatal iron supplementation alone was associated with a significant reduction of childhood anemia [aOR (95% CI) = 0.9 (0.8–1.0)]. Prenatal deworming alone was associated with a significantly reduced risk of stunting [aOR (95% CI) = 0.7 (0.8–1.0)], childhood anemia [aOR (95% CI) = 0.7 (0.8–0.9)], and low birth weight [aOR (95% CI) = 0.7 (0.8–1.0)]. Prenatal iron supplementation plus deworming or iron supplementation (with or without deworming) were not associated with childhood anemia, infant stunting and low birth weight. Conclusions In Sub-Saharan Africa, prenatal deworming alone has the potential to improve infants’ outcomes. Childhood anemia was improved with prenatal iron supplementation alone. Our recent findings indicate the necessity for prospective studies on the association between prenatal iron supplementation plus deworming and childhood anemia, stunting and low birth weight.

Objectives This article assessed trends in the prevalence of overweight and obesity over ten years among adult women. Methods A cross-sectional study was conducted using National Surveys Data from China, Mali and the United States between 2001–2002 and 2012–2013. The sample population consisted of all adult women: 140,022 (2002) and 157,850 (2012) adults aged 18 and above in China, 10,424 (2002) and 4502 (2012) women aged 15–49 in Mali, 4413 (2001) and 5181 (2012) adults aged 20 and above in the USA. The proportion test (Z test) was used to evaluate the 10-year prevalence differences in different countries. Results In ten-year period, overweight has significantly increased from 22.7% to 29.9% among Chinese women with a growth of 7.2% (P-value < 0.05) and, 11.2% to 12.9% in Malian women with a growth of 1.7% (P-value < 0.05). Among US women, overweight has increased from 28.2% to 29.7% with a non-significant growth of 1.5% (P-value >0.05). The prevalence of women's obesity in all three countries has significantly increased, more particularly in China. Conclusions Data from the National Survey over ten years showed an increase in the prevalence of overweight as well as obesity in Chinese, Malian and US women. Funding Sources This work was supported by the National Natural Science Foundation of China [Project number 81,673,165].