Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/Caspase-1 pathway.

BACKGROUND: Previous studies found Propionibacterium acnes (P. acnes) has a strong association with acne inflammation and cell pyroptosis. Because of the various side effects of current acne medicines, it is important to explore alternative drugs with anti-inflammatory activity against P. acnes. we explored the effect of Lutein on P. acnes-induced cell pyroptosis and accelerated the recovery of acne inflammation in vitro and vivo. METHODS: Lutein was utilized to expose HaCaT keratinocytes, then we reassessed the effect of Lutein on the cell apoptosis, pyroptotic-associated inflammatory factors and catabolic enzymes in heat-killed P. acnes-treated HaCaT cells. Next, living P. acnes was intradermally injected into the right ears of ICR mice to induce mice with acne inflammation, and the effect of Lutein on living P. acnes-induced inflammation was investigated. Moreover, we explored the mechanism of Lutein on TLR4/NLRP3/Caspase-1 pathways by ELISA, immunofluorescence microscopy, and western blot assay. RESULTS: Heat-killed P. acnes triggered remarkable cell pyroptosis, pyroptotic inflammatory factors and catabolic enzymes in HaCaT cells, including up-regulating interleukin (IL)-1ß, IL-18, TNF-α, MMP3, MMP13, ADAMTS4, and ADAMTS5, TLR4, NLRP3, caspase-1, and the ratio of gasdermin D to cleaved gasdermin D, whereas these effects were suppressed by Lutein. In addition, Lutein effectively improved ear redness, swelling, and the expression of TLR4, IL-1ß and TNF-α in vivo. Finally, NLRP3 activator (nigericin) increased caspase-1, IL-1ß and IL-18 level, while TLR4 inhibitor (TAK-242) significantly blocked this effect in heat-killed P. acnes-treated cells. CONCLUSIONS: Lutein attenuated P. acnes-caused pyroptosis of HaCaTs and the subsequent acne inflammation via the TLR4/NLRP3/Caspase-1 pathway.

Association between early life adversity and allostatic load in girls with precocious puberty.

CONTEXT: The mechanisms underlying the elevated long-term health risk in girls with precocious puberty remain unclear, but might result from physiological wear and tear associated with greater exposure to early life adversity. OBJECTIVE: This study aims to explore early life adversity in girls with precocious puberty and its association with allostatic load. METHODS: Early life adversity and hair cortisol concentration were measured among 213 girls with precocious puberty (8.21 ± 1.07). Allostatic load score is constructed by using 13 physiological biomarkers representing four systems and hair cortisol concentration. Multivariate linear regression models have estimated the associations between cumulative early life adversity exposure with total and system-specific allostatic load scores. Associations between cumulative early life adversity and the risk of high allostatic load (3 + high-risk biomarkers) were tested using binary logistics regression. RESULTS: More than two-thirds (67.6%) of girls with central precocious puberty reported two or more early life adversity exposure. Compared to those with no early life adversity exposure, girls who reported early life adversity score ≥ 2 had significantly higher total allostatic load score (ß: 1.20-1.64, P < 0.001). Metabolic system was more sensitive to cumulative early life adversity exposure, each form of early life adversity exposure was associated with 0.48-unit increases in metabolic allostatic load score (95%CI: 0.06, 0.90, P = 0.026). Girls reported early life adversity score ≥ 3 were three times more likely to have a high allostatic load compared with those without early life adversity exposure in both unadjusted and adjusted models (ORadjusted=3.83, 95%CI: 1.17, 12.55, P = 0.001). CONCLUSION: Multisystem physiological dysregulation is observed in girls with central precocious puberty, which might result from cumulative wear-and-tear associated with early life adversity.

Alginate oligosaccharide ameliorates azithromycin-induced gut microbiota disorder via Bacteroides acidifaciens-FAHFAs and Bacteroides-TCA cycle axes.

Alginate oligosaccharide is a kind of prebiotic with broad application prospects. However, little attention is paid to the recovery effect of alginate oligosaccharide on disordered intestinal microecology caused by azithromycin. Therefore, we evaluated the regulatory effect of alginate oligosaccharide and its compound on azithromycin-disturbed gut microbiota in mice via microbiome-metabolomics analysis. The gut microbiota analysis revealed that alginate oligosaccharide and its compound significantly increased the richness and diversity of the gut microbiota which were reduced by azithromycin, with an obvious enrichment of beneficial bacteria such as the Akkermansia genus and Bacteroides acidifaciens, and a remarkable decrease of pathogenic bacteria such as the Staphylococcus genus, which indicated its impact on the gut microbiota dysbiosis. Additionally, the effect of the alginate oligosaccharide compound on regulating the gut microbiota disorder is more significant than that of alginate oligosaccharide. The favorable effects of alginate oligosaccharide were confirmed by beneficial alterations in metabolic effector molecules, which indicated that alginate oligosaccharide and its compound improved metabolic homeostasis via the Bacteroides acidifaciens-fatty acid esters of hydroxy fatty acids (FAHFAs) axis and increasing the levels of the intermediate products of the tricarboxylic acid cycle (TCA cycle), such as citric acid, fumaric acid and α-ketoglutaric acid. Spearman correlation analysis showed that the contents of these three metabolites were also positively related to Bacteroides acidifaciens and Bacteroides sartorii populations, suggesting the potential regulatory role of the Bacteroides genus in energy balance through the TCA cycle. This study may provide an innovative dietary strategy for the regulation of intestinal microecological disorders caused by antibiotics, and reveal the prospect of alginate oligosaccharide as an intestinal microecological regulator.

C-phycocyanin alleviated cisplatin-induced oxidative stress and inflammation via gut microbiota-metabolites axis in mice.

C-phycocyanin is a natural protein extracted from Spirulina platensis. We aim to investigate the preventive effect of C-phycocyanin on cisplatin chemotherapy-induced oxidative damage and inflammation. The result showed that C-phycocyanin treatment reduced cisplatin-induced mortality and inflammation including decreased levels of serum IL6, kidney MCP1, and liver IL1ß. Furthermore, C-phycocyanin also exerted antioxidant effects on mice, including increased GSH-Px, GGT, and GSH levels in the liver and increased CAT and SOD levels in the kidney. HepG2 cells experiments showed that C-phycocyanin exhibited none of the prevention effects on cisplatin injury. Faecalibaculum showed the greatest reduction among genera after cisplatin treatment, which was related to the enrichment of Romboutsia and Lactobacillus genera. C-phycocyanin treatment reduced the populations of harmful bacteria of Enterococcus faecalis, which was positively correlated with inflammation induced by cisplatin. C-phycocyanin increased the contents of 23-nordeoxycholic acid and ß-muricholic acid. Moreover, C-phycocyanin increased amino acid-related metabolites, Nα-acetyl-arginine and trimethyl-lysine contents, and decreased fatty acid esters of hydroxy fatty acids (FAHFAs) contents. In conclusion, C-phycocyanin inhibited inflammation via the 23-nordeoxycholic acid-Enterococcus faecalis-inflammation axis, and enhanced the antioxidant capacity of kidney via Lactobacillus-NRF2 pathway. C-phycocyanin alleviated cisplatin injury via the modulation of gut microbiota, especially Lactobacillus and Enterococcus, as well as regulation of metabolites, especially bile acid and FAHFAs, which highlight the effect of C-phycocyanin and provide a new strategy to prevent cisplatin injury.

Gui Shao Tea Extracts Inhibit Gastric Cancer Growth in Vitro and in Vivo and Prolong Survival in Nude Mice.

BACKGROUND: Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota. METHODS: GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes. RESULTS: The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, Camellia sinensis, picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation (p = 0.037), induced G0/G1 arrest (p < 0.001) and promoted early apoptosis (p = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 (p = 0.042), and that in the MTF group was 55.21% on Day 14 (p = 0.002) and 61.6% on Day 28 (p = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% (p = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells (p = 0.016) and tissues (p = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth. CONCLUSIONS: We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.

Restoration of cefixime-induced gut microbiota changes by a prebiotic blend in a mouse model.

Recent studies have provided compelling evidence linking the composition of the gut microbiota, host diet, and host physiology. Prebiotics are substrates that are selectively utilized by host microorganisms, conferring health benefits. Prebiotics, such as prebiotic blends (PB), are commonly used worldwide in food processing. Here, microbiome-metabolomics was used to evaluate how PB affect gut microbes and metabolic functions in C57BL/6 J mice administered cefixime. We found favorable effects of PB on obesity outcomes. PB supplementation significantly increased the abundance of Bifidobacterium, Parabacteroides, Alloprevotella, Alistipes, and Dubosiella, and decreased that of Robinsoniella, Blautia, Lachnoclostridium, Coprobacillus, Hungatella, Erysipelatoclostridium, Helicobacter, Clostridium sensu stricto 1, Enterococcus, and Akkermansia compared to that in the cefixime administration (CEF) group. In particular, PB increased the abundance of Parabacteroides goldsteinii and suppressed that of Robinsoniella peoriensis and Akkermansia muciniphila. In addition, it regulated the levels of microbial metabolites such as unsaturated fatty acids and bile acids. Thus, PB can alleviate metabolic disorders induced by antibiotic intervention, indicating a potential dietary strategy for populations with antibiotic-associated diarrhea. KEY POINTS: • Prebiotic blends significantly increased the Parabacteroides goldsteinii colony. • Prebiotic blends selectivity reversed this increase of Akkermansia muciniphila by antibiotic intervention. • Prebiotic blends relieve cefixime-induced alteration of intestinal flora by regulating metabolites, such as fatty acids and bile acids.

Alginate Oligosaccharide Alleviated Cisplatin-Induced Kidney Oxidative Stress via Lactobacillus Genus-FAHFAs-Nrf2 Axis in Mice.

Alginate oligosaccharide is the depolymerized product of alginate, a natural extract of brown algae, which is associated with beneficial health effects. Here, we aimed to investigate the mechanism via which alginate oligosaccharides improve kidney oxidative damage and liver inflammation induced by cisplatin chemotherapy via the gut microbiota. C57BL/6J mice were treated with cisplatin were administered alginate oligosaccharide via gavage for 3 weeks. Compared to that observed in the cisplatin chemotherapy group without intragastric administration of alginate oligosaccharide, liver inflammation improved in the alginate oligosaccharide group, indicated by reduction in lipopolysaccharide and interleukin-1ß (IL-1ß) levels. This was accompanied by improvement in the oxidative stress of mice kidneys, indicated by the increase in the levels of superoxide dismutase (SOD), catalase (CAT) and nuclear NF-E2-related factor 2 (Nrf2) in renal tissue, and reduction in the levels of malondialdehyde (MDA) in renal tissue and serum creatinine (Cr) to the levels of the normal control group. Alginate oligosaccharide intervention increased the concentration of fatty acid esters of hydroxy fatty acids (FAHFAs). Alginate oligosaccharide regulated the composition of the intestinal microbial community and promoted Lactobacillus stains, such as Lactobacillus johnsonii and Lactobacillus reuteri. Spearman analysis showed that 5 members of FAHFAs concentrations were positively correlated with Lactobacillus johnsonii and Lactobacillus reuteri abundance. We observed that alginate oligosaccharide increased FAHFAs producing-related bacterial abundance and FAHFAs levels, enhanced the levels of SOD and CAT in kidney tissue, and reduced the levels of MDA via activating Nrf2, thereby ameliorating the renal redox injury caused by cisplatin chemotherapy.

Casual Associations and Shape Between Prepuberty Body Mass Index and Early Onset of Puberty: A Mendelian Randomization and Dose-Response Relationship Analysis.

Background: There is an ongoing controversial issue regarding whether onset of puberty is related to childhood BMI. Objectives: This study aims at investigating the causal association and its shape between prepuberty BMI and early puberty onset. Methods: Breast development and testicular volume were assessed annually from a population-based prospective cohort of 997 children for consecutive years by professional endocrinologists. Seventeen puberty- and BMI-related SNPs were selected to calculate the polygenic risk score. The two-stage least square method was used to assess and confirm causal effects. A dose-response association between prepuberty BMI and early puberty onset was conducted by using restricted cubic spline Cox regression. Results: After adjusting for covariates, prepuberty BMI was positively associated with early thelarche among girls (coefficients = 0.18, 95% CI: 0.01, 0.29). A non-linear model suggested an inverted U-shaped relationship between prepuberty BMI and risk for early thelarche (χ2 = 276.3, p < 0.001). The risk for early thelarche increased rapidly from prepuberty BMI at 15.70 kg/m2 (P25) to 20.75 kg/m2 (P85) and gradually decreased afterward. Compared with the P25 of prepuberty BMI, the HRs (95% CI) for early thelarche were 5.08 (1.15, 8.55), 4.48 (1.02, 7.74), 10.15 (3.93, 17.50), and 8.43 (1.91, 13.71) for percentiles P25-P50, P50-P75, P75-P85, and ≥P85 of BMI categories, respectively. In boys, compared with the P25 of prepuberty BMI, boys with BMI between P25 and P50 showed an increased risk of early puberty (HR: 3.94, 95% CI: 1.44, 6.80). Conclusions: Prepuberty BMI may serve the purpose of identifying the girls at higher risk of early thelarche, which could assist in the adaptation of prevention and intervention strategies targeting childhood obesity. The findings emphasize a non-linear correlation between prepuberty BMI and early puberty onset.

Associations between distinct dimensions of early life adversity and accelerated reproductive strategy among middle-aged women in China.

BACKGROUND: Life history theory argues that unpredictable and harsh conditions such as early life adversity tends to produce a fast life history strategy, characterized by early sexual maturation and less parenting of offspring. It remains unclear whether all forms of early life adversity are associated with accelerated reproductive strategy, and most previous studies predominantly focused on single form of reproductive strategy indicators. OBJECTIVE: To examine the associations between 2 distinct dimensions of early life adversity (ie, threat and deprivation) and reproductive strategies across global metrics. STUDY DESIGN: We used data from 9674 middle-aged women of the China Health and Retirement Longitudinal Study. The experiences of threat and deprivation were assessed using the Life History Survey Questionnaire in 2014. Reproductive strategy information was assessed via self-report from the follow-up of 2013, 2015 and 2018, including age at menarche, age at natural menopause, age at first birth, total number of children, and number of abortions. Multivariate linear regression analyses were performed to assess the associations between distinct dimensions of early life adversity and multiple reproductive strategy indicators, adjusting for age, Hukou location, family socioeconomic status in adulthood and body mass index. RESULTS: Of the 9674 women (mean [standard deviation] age at baseline, 55.89 [10.23] years), 4084 (42.20%) reported exposure to threat-related early life adversity and 7332 (75.79%) reported exposure to deprivation-related early life adversity. Early life adversity characterized by threat was associated with accelerated reproductive strategy. Compared with women who have no experiences of threat-related early life adversity, ≥3 threat-related early life adversity was associated with 3.7-month earlier age at menarche (ß=-0.31, 95% confidence interval, -0.53 to -0.08; P=.007), 8.6-month earlier age at natural menopause (ß=-0.72, 95% confidence interval, -1.29 to -0.15; P=.013), >1-year earlier age at first birth (ß=-1.14, 95% confidence interval, -1.58 to -0.71; P<.0001), and an increased total number of children (ß=0.25, 95% confidence interval, 0.10-0.41; P=.002). In contrast, experiences of deprivation were associated with delayed age at natural menopause (ß=.50, 95% confidence interval, 0.06-0.94; P=.025) and increased number of abortions (ß=.17, 95% confidence interval, 0.01-0.34, P=.037), in models adjusting for co-occurring threat exposures. CONCLUSION: This study suggests that early life adversity characterized by threat was associated with accelerated reproductive strategy, whereas deprivation was associated with slower reproduction strategy. Future research should clarify the biological pathways between different dimensions of early life adversity and reproductive strategies and further determine whether accelerated reproduction is an adaptive response to early life adversity in humans.

Speech depression recognition based on attentional residual network.

BACKGROUND: Depressive disorder is a common affective disorder, also known as depression, which is characterized by sadness, loss of interest, feelings of guilt or low self-worth and poor concentration. As speech is easy to obtain non-offensively with low-cost, many researchers explore the possibility of depression prediction through speech. Adopting speech signals to recognize depression has important practical significance. Aiming at the problem of the complex structure of the deep neural network method used in the recognition of speech depression and the traditional machine learning methods need to manually extract the features and the low recognition rate. METHODS: This paper proposes a model that combines residual thinking and attention mechanism. First, depression corpus is designed based on the classic psychological experimental paradigm self-reference effect (SRE), and the speech dataset is labeled; then the attention module is introduced into the residual, and the channel attention is used to learn the features of the channel dimension, the spatial attention feedback the features of the spatial dimension, and the combination of the two to obtain the attention residual unit; finally the stacking unit constructs a speech depression recognition model based on the attention residual network. RESULTS: Experimental results show that compared with traditional machine learning methods, this model obtains better results in the recognition of depression, which can meet the need for actual recognition application of depression. CONCLUSIONS: In this study, we not only predict whether person is depressed, but also estimate the severity of depression. In the designed corpus, the depression binary classification of an individual is given based on the severity of depression which is measured using BDI-II scores. Experimental results show that spontaneous speech can obtain better results than automatic speech, and the classification of speech features corresponding to negative questions is better than other tasks under negative emotions. Besides, the recognition accuracy rate of both male and female subjects is higher than that under other emotions.

Pubertal recalibration of cortisol reactivity following early life parent-child separation.

BACKGROUND: The hypothalamic-pituitary-adrenocortical (HPA) axis had been proved to calibrate to early-life adversity and puberty may reverse the calibration. This study examines the consequences of prolonged parent-child separation on HPA axis reactivity and the pubertal recalibration hypothesis. METHODS: Totally of 144 participants aged 8.75 to 15.25 (mean age 12.50 years, SD: 1.32) were enrolled from rural areas of Chizhou city, Anhui Province of China in 2019. Data on parent-child separation was collected from parents. Self-reported Peterson Pubertal Development Scale was used to assess pubertal maturation and HPA axis stress reactivity was measured using the Trier Social Stress Test for Children. RESULTS: For children at early stage of puberty, childhood parent-child separation experiences were associated with blunted HPA axis reactivity (B = -1.888, p = 0.034); while for those at later stage of puberty, HPA axis reactivity was similar between children experienced early childhood separation and those without separation (AUCi: B = -0.426, p = 0.878). In contrast, for children experienced persistent parent-child separation, blunted HPA axis reactivity was observed (all p < 0.05). LIMITATIONS: Due to the cross-sectional nature of this study, conclusions about causality remain speculative. CONCLUSIONS: The effect of parent-child separation on dysregulation of HPA axis acts in a time-dependent manner. This finding provides support for the pubertal recalibration hypothesis suggesting that a focus of improving environment in adolescence would help those individuals reared initially in non-supportive conditions.

Association between dietary patterns and central precocious puberty in girls / 中国学校卫生

Objective@#To explore the relationship between dietary patterns and central precocious puberty in children, and to provide a scientific basis for dietary prevention of precocious puberty.@*Methods@#A case-control study was conducted, among 35 newly diagnosed central precocious puberty girls from May to December 2019 as the case group, and 70 healthy girls with normal development as the control group. Physical development examination, parent questionnaire survey and child interview were carried out. Dietary information was assessed using a simplified food frequency questionnaire(FFQ). Principal component analysis was used to identify children s dietary patterns, and multiple Logistic regression was used to assess the association between dietary patterns and precocious puberty.@*Results@#Three different dietary patterns have been established, namely "snack and processed food type", "animal protein type" and "nutritional tonic type" dietary patterns, respectively. After adjusting for covariates such as age and BMI, Logistic regression analysis showed that the "snack and processed food type" dietary pattern was positively correlated with precocious puberty(OR=10.81, 95%CI=2.59-45.15, P<0.01). There was a negative correlation between "animal protein type" and precocious puberty(OR=0.24, 95%CI=0.06-0.91, P=0.04), while the association between "nutritive tonic" and precocious puberty was not statistically significant(OR=0.28, 95%CI=0.07-1.05, P=0.06).@*Conclusion@#Children s dietary patterns were related to precocious puberty." Snack and processed food "dietary pattern with a high intake of fried foods, puffed foods, foods containing preservatives or pigments, western fast foods, chocolate and products, was closely related to central precocious puberty.

Undaria pinnatifida improves obesity-related outcomes in association with gut microbiota and metabolomics modulation in high-fat diet-fed mice.

Dietary fiber has beneficial effects on obesity-related diseases and gut microbiota, contributing a key role in the interaction between dietary metabolism and host metabolism. Our objective was to investigate the cause of the improvement in multiple types of physiological states with seaweed Undaria pinnatifida treatment on high-fat diet-fed mice and to evaluate whether its consequent anti-adiposity and anti-hyperlipidemic effects are associated with gut microbiota and its metabolomics regulation. U. pinnatifida administration in our experiment was shown to significantly decrease high-fat diet-induced body weight gain, as well as epididymal and abdominal adiposity. U. pinnatifida intake also significantly reduced liver weight and serum triacylglycerol accumulation. We also found that improving effects of U. pinnatifida on high-fat diet-induced metabolic dysfunctions were associated with significant increase in specific bacteria, such as Bacteroides acidifaciens and Bacteroides ovatus, as well as metabolites, including short-chain fatty acids and tricarboxylic acid cycle intermediates. Our result provides a cheap dietary strategy to host metabolism improvement and obesity management. KEY POINTS: • U. pinnatifida improved adipose accumulation and lipid metabolism. • B. acidifaciens and B. ovatus contributed to the beneficial effects of U. pinnatifida. • SCFAs and TCA cycle intermediates were critical to the metabolic outcomes. • Our study provides a cheap dietary strategy for obesity management.

Alginate oligosaccharide improves lipid metabolism and inflammation by modulating gut microbiota in high-fat diet fed mice.

Alginate oligosaccharides are associated with some beneficial health effects. Gut microbiota is one of the most recently identified factors in the development of several metabolic diseases induced by high-fat diet. Our objective was to evaluate how alginate oligosaccharides impact on high-fat diet­induced features of metabolic disorders and whether this impact is related to modulations in the modulation of the gut microbiota. C57BL/6J mice were fed with chow diet, high-fat diet, or high-fat diet supplemented with alginate oligosaccharides for 10 weeks. Alginate oligosaccharide treatment improved lipid metabolism, such as reducing levels of TG and LDL-C and inhibiting expression of lipogenesis genes. Alginate oligosaccharide administration reduced the levels of fasting blood glucose and increased the levels of serum insulin. Alginate oligosaccharide treatment was found to lower the expression of markers of inflammation, including IL1ß and CD11c. Alginate oligosaccharide treatment modulated gut microbial communities and markedly prompted the growth of Akkermansia muciniphila, Lactobacillus reuteri, and Lactobacillus gasseri. Additionally, alginate oligosaccharide intervention significantly increased concentrations of short-chain fatty acids, such as acetic acid, propionic acid, and butyric acid, as well as decreased levels of endotoxin. Alginate oligosaccharides exert beneficial effects via alleviating metabolic metrics induced by high-fat diet, which is associated with increase in A. muciniphila, L. reuteri, and L. gasseri, as well as the release of microbiota-dependent short-chain fatty acids and inhibition of endotoxin levels.

Prospective association of childhood BMI trajectory and polygenic genetic risk with puberty timing / 中国学校卫生

Objective@#To examine pubertal timing across body mass index (BMI) trajectory under polygenic susceptibility in boys and girls,and to provide a reference basis for children’s adolescent development deviation form early intervention strategies.@*Methods@#All the participants were recruited from 1 to 3 grade in 2016 from 2 Bengbu primary school and were followed up for 3 consecutive years. The study comprised 997 children (418 boys) with available data for height, weight, BMI, breast Tanner stages and testicular volume annually. The polygenic risk score (PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Group-based trajectory model (GBTM) was used to identified BMI trajectory in children. Accelerated failure time model (AFT) was used to examine associations of different BMI trajectory and polygenic risk with pubertal development in boys and girls.@*Results@#Classes of BMI trajectory were persistently healthy weight, persistently overweight and persistently obesity. Adjusted concomitant variables, boys with persistently obesity exhibited 6.10-mo delay of testicular volume in low polygenic risk group (adjusted TR=1.05，P=0.04). Compared with the girls in persistently healthy weight group, the girls with low PRS were persistently overweight or obesity, which was associated with thelarche age 3.42 and 6.84-mo earlier, respectively (adjusted TR=0.97，0.94,P<0.01). Persistently overweight or obesity in girls with moderate PRS was associated with an earlier age of thelarche timing of 6.72 and 8.96-mo, respectively (adjusted TR=0.94，0.92, P<0.01). At high PRS groups, the persistently obese girls were found to have a more advanced age (10.80 and 12.96-mo, respectively) of thelarche (adjusted TR=0.90，0.88, P<0.01).@*Conclusion@#Persistently overweight and obesity is associated with early thelarche in girls, but persistently obesity may increase delayed puberty risk in boys with low polygenic risk.

TWSG1 Is a Novel Tumor Suppressor in Gastric Cancer.

Gastric cancer has a high incidence and mortality in the world, especially in China. The pathogenesis leading to the high heterogeneity of gastric cancer remains unclear. It is believed that TWSG1 is associated with a variety of tumors, but there are few studies related to gastric cancer. To investigate the biological significance of TWSG1, we evaluated the TWSG1 expression of the clinical samples and gastric cancer cell lines (BGC-823, MGC-803, and SGC-790) via stomach cancer tissue array, real-time PCR, and western blotting. Then, we used CCK-8 and flow cytometry to detect the function and mechanism of TWSG1 in gastric cell lines. The analysis showed that TWSG1 showed decreased expression in clinical samples and BGC-823, MGC-803, and SGC-7901 cells. And, overexpressed TWSG1 inhibited the cell cycle and proliferation, TWSG1 might influence the proliferation of SGC-7901 and MGC-803 by regulating the BMP signaling. However, the influence of TWSG1 on BGC-823 cell is not associated with the BMP signaling. In conclusion, all of our findings revealed that TWSG1 maybe serves as a tumor suppressor gene in gastric cancer and potential biomarker or therapeutic target for the diagnosis and treatment of gastric cancer.

Effects of siRNA interfering TWSG1 expression on proliferation and apoptosis of gastric cancer MGC-803 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To study the effects of twisted gastrulation protein homolog 1 (TWSG1) gene on proliferation and apoptosis of gastric cancer MGC-803 cells. Methods: Three siRNAs for TWSG1 gene were designed.The MGC-803 cells at logarithmic phase were divided into blank control group, negative control group (siRNA-NC), siRNA1 interference group, siRNA2 interference group and siRNA3 interference group by transfecting with relevant vectors. The mRNAand protein expressions of TWSG1 in each group were identified by qPCR and Western blotting, respectively; and the stable cell line with highest interference efficiency was screened.The proliferation of cells in each group was detected by CCK-8 assay, and the apoptosis of three groups was detected by flow cytometry. Results: The results of qPCR and Western blotting showed siRNA1 exhibited highest interference efficiency. Compared with the blank control group and the negative control group, the expression of TWSG1 in siRNAinterference cell group was lower (P<0.05), the cell proliferation significantly increased (P<0.05), and apoptosis significantly reduced (P<0.05). Conclusion: siRNA interfering TWSG1 expression in MGC-803 cells can promote cell proliferation, inhibit cell apoptosis.

Genetic profile characterization and population study of 21 autosomal STR in Chinese Kazak ethnic minority group.

Short tandem repeat loci have been recognized as useful tools in the routine forensic application and in recent decades, more and more new short tandem repeat (STR) loci have been constantly discovered, studied, and applied in forensic caseworks. In this study, we investigated the genetic polymorphisms of 21 STR loci in the Kazak ethnic minority as well as the genetic relationships between the Kazak ethnic minority and other populations. Allelic frequencies of 21 STR loci were obtained from 114 unrelated healthy Kazak individuals in the Ili Kazak Autonomous Prefecture, Xinjiang Uigur Autonomous Region of China. We observed a total of 159 alleles in the group with the allelic diversity values ranging from 0.0044 to 0.5088. The highest polymorphism was found at D19S433 locus and the lowest was found at D1S1627. Statistical analysis of the generated data indicated no deviation from Hardy-Weinberg equilibriums at all 21 STR loci. In order to estimate the population differentiation, allelic frequencies of all STR loci of the Kazak were compared with those of other neighboring populations using analysis of molecular variance method. Statistically significant differences were found between the studied population and other populations at 2-7 STR loci. A neighbor-joining tree was constructed based on allelic frequencies of the 21 STR loci and phylogenetic analysis indicates that the Kazak has a close genetic relationship with the Uigur ethnic group. The present results may provide useful information for forensic sciences and population genetics studies, and can also increase our understanding of the genetic background of this group. The present findings showed that all the 21 STR loci are highly genetically polymorphic in the Kazak group, which provided valuable population genetic data for the genetic information study, forensic human individual identification, and paternity tests.