Variations in the morphological and chemical composition of the rhizomes of Polygonatum species based on a common garden experiment.

Polygonatum species have great potential in fighting chronic and hidden hunger. In this study, five Polygonatum species collected from different populations were cultivated in a common garden for 4 years. The species mainly differed in yield, saponin and polysaccharide contents, stem diameter, leaf width, inflorescence length, and floret inflorescence length. P. cyrtonema (PC) provides high-quality yield when planted in Zhejiang, with output as high as 7.5 tons per hectare and a promising breeding potential. Moreover, stem diameter can be used as an indicator of the harvest in the screening of varieties. In addition, the formation of plant genetic traits from different provenances is affected by the climatic factors of the origin. Furthermore, near-infrared spectroscopy combined with chemometrics for polysaccharide and saponin quantitation provides a rapid assessment of PC quality. Our findings provide a scientific basis for the development and sustainable utilization of PC as a high-yielding and high-quality forest crop.

Correction to: Re­fracture and correlated risk factors in patients with osteoporotic vertebral fractures.

In the Original publication of the article, the funding ID has been incorrectly published as (815602390) in the Acknowledgements.

Dietary ginger as a traditional therapy for blood sugar control in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Ancient medical practitioners used to encourage dietary supplements and herbal medicine for the treatment of type 2 diabetes mellitus (T2DM). Ginger (Zingiber officinale), is a nontoxic spice with negligible side effects, and is considered safe by the food and drug administration. In this analysis, we aimed to systematically compare fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) at baseline versus at follow-up in T2DM patients who consumed and who did not consume ginger. METHODS: A literature search was carried out through MEDLINE, Embase, the Cochrane Central, and www.ClinicalTrials.gov for English-published trials comparing glucose parameters in T2DM patients who were assigned to ginger consumption versus a control group. All the participants were patients with T2DM who were either assigned to ginger therapy (1600- 4000 mg daily) or to a control group. FBS and HbA1c were assessed in the ginger and control groups, respectively, from baseline to follow-up to observe any significant change. Weight mean difference (WMD) with 95% confidence intervals (CI) was calculated to represent the analysis which was carried out by the RevMan 5.3 software. RESULTS: Eight randomized trials consisting of a total number of 454 participants with T2DM were included in this analysis. At first, FBS was compared in patients with T2DM from baseline prior to ginger consumption until follow-up after ginger consumption. The results showed no significant difference in FBS (WMD: 1.38, 95% CI: [-0.53-3.30]; P = .16). For the T2DM patients who did not consume ginger, no significant difference in FBS was observed (WMD: -0.27, 95% CI: [-5.09-4.54]; P = .91). However, a significantly improved HbA1c from baseline to follow-up was observed in those participants with ginger consumption (WMD: 0.46, 95% CI: [0.09-0.84]; P = .02) whereas in the control group, no significant difference in HbA1c was observed (WMD: -0.23, 95% CI: [-0.60-0.14]; P = .22). CONCLUSION: This analysis involving patients with T2DM showed no significant difference in FBS with ginger consumption. However, dietary ginger significantly improved HbA1c from baseline to follow-up showing that this natural medicine might have an impact on glucose control over a longer period of time in patients with T2DM.

A novel peptide suppresses adipogenic differentiation through activation of the AMPK pathway.

Obesity rates have risen rapidly over the past several decades and obesity is now a global public health challenge. The reduction of excessive adipogenesis is thought to be an effective intervention for obesity and obesity-related metabolic diseases such as type 2 diabetes. In this study, a novel peptide PDBSN was identified that functions to suppress adipogenesis. In both human preadipocytes and mouse adipose-derived stem cells (ADSCs), PDBSN exhibited a suppressive effect on the accumulation of lipids and the expression of genes as well as their corresponding proteins (CCAAT/enhancer binding protein (C/EBP)ß, C/EBPα and nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ)) relevant to adipogenic cell differentiation. Although adipogenesis decreased, the preadipocyte number and proliferation were not influenced by the PDBSN treatment. Apoptosis and the cell cycle were also determined to not have a role in the action of PDBSN. Mechanistically, the activity of the AMPK (adenosine 5'-monophosphate-activated protein kinase) pathway was markedly increased upon PDBSN treatment. Moreover, treatment of preadipocytes with compound C, a selective AMPK inhibitor, abolished the effect of PDBSN in anti-adipogenesis, suggesting that the function of PDBSN relied on the AMPK pathway. These results suggest an effective role for PDBSN in suppressing adipogenesis and show potential for anti-obesity drug discovery.

Re-fracture and correlated risk factors in patients with osteoporotic vertebral fractures.

Re-fracture risk is higher following osteoporotic fracture. However, there is no accurately reported rate of re-fracture incidence in southwest China. The purpose of this study was to describe the osteoporotic vertebral fracture (OVF) survival for re-fracture state and analyze the risk of re-fracture. This historical cohort study was conducted in four hospitals in southwest China. Patients aged ≥ 50 years (n = 586) with OVF who were supposed to receive anti-osteoporosis drugs after the fracture were included (2012-2017). Telephone follow-up and referring case files were used to estimate the survival for re-fracture and identify the determinants of re-fracture. A total of 555 patients completed the follow-up investigation. Overall, 285 patients experienced a re-fracture, and the longest follow-up investigation time was 72 months. The survival rates for re-fracture at 12 months, 24 months, 36 months, and 48 months were 82.0%, 71.5%, 61.7%, and 34.0%, respectively. The factors correlated with re-fracture hazard were advanced age [hazard ratio (HR) = 1.996], being female (HR = 1.342), smoking (HR = 1.435), history of hypertension (HR = 1.219) and diabetes (HR = 3.271), and persistence of taking anti-osteoporosis drugs after fracture [0-3 months, 4-6 months, 7-12 months, and more than 12 months (HR = 0.703)]. OVF patients with advanced age, who were female, smoked, had fracture with hypertension or diabetes, and who complied poorly with anti-osteoporosis drug treatment presented higher prevalence of re-fracture and low anti-osteoporosis adherence in southwest China. The management of anti-osteoporosis after fracture is necessary in this area.

miR-199a-3p regulates brown adipocyte differentiation through mTOR signaling pathway.

Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes' metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders.

PID1 in adipocytes modulates whole-body glucose homeostasis.

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes.

Identification and characterization of metformin on peptidomic profiling in human visceral adipocytes.

To gain insight into the effect of metformin on losing weight from peptidomic perspective and to screen potential active peptides for reducing fat lipid deposition. After determining the proper concentration of metformin on human primary visceral adipocytes, we constructed a comparative peptidomic profiling between control and metformin treatment group (n = 3) using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by liquid chromatography tandem mass spectrometry. We identified and quantified 3065 non-redundant peptides, 304 of which were differentially expressed after metformin treatment, 206 peptides were up regulated and 98 peptides were down regulated significantly. Gene ontology (GO) enrichment and pathway analysis were performed to study differentially peptides though their precursor proteins. We concluded three peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for obesity. On one hand, these results confirmed the versatile effects of metformin on adipocyte and advance our current understanding of metformin, on the other hand, these identified peptides might play putative roles in treatment of obesity.

Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds.

Molecular hybridization is considered as an effective tactic to develop drugs for the treatment of cancer. A series of novel hybrid compounds of isatin and Michael acceptor were designed and synthesized on the basis of association principle. These hybrid compounds were tested for cytotoxic potential against human cancer cell lines namely, BGC-823, SGC-7901 and NCI-H460 by MTT assay. Most compounds showed good anti-growth activities in all tested human cancer cells. SAR and QSAR analysis may provide vital information for the future development of novel anti-cancer inhibitors. Notably, compound 6a showed potent growth inhibition on BGC-823, SGC-7901 and NCI-H460 with the IC50 values of 3.6 ±â€¯0.6, 5.7 ±â€¯1.2, 3.2 ±â€¯0.7 µM, respectively. Besides, colony formation assays, wound healing assays and flow cytometry analysis indicated 6a exhibited a potent anti-growth and anti-migration ability in a concentration-dependence manner through arrested cells in the G2/M phase of cell cycle. Moreover, 6a significantly repressed tumor growth in a NCI-H460 xenograft mouse model. Overall, our findings suggested isatin analogues inspired Michael acceptor may provide promising lead compounds for the development of cancer chemotherapeutics.

Obesity­associated miR­148a is regulated by cytokines and adipokines via a transcriptional mechanism.

Our previous study revealed that miR­148a, a cyclic adenosine monophosphate­response element binding protein­modulated microRNA that promotes adipocyte differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects and a mouse model. The present study investigated the expression of miR­148a in human adipose tissue­derived mesenchymal stem cells (hMSCs­Ad) in response to inflammatory cytokines and adipokines to clarify its underlying mechanism. miR­148a expression was detected using reverse transcription­quantitative polymerase chain reaction analysis and its promoter activity was detected with a luciferase assay. miR­148a expression levels decreased when differentiated hMSCs­Ad were exposed to inflammatory cytokines or adipokines, which suggested that miR­148a may be important in adipocyte metabolism and inflammation. Furthermore, the promoter activity of miR­148a decreased following treatment of cells with inflammatory cytokines or adipokines. The results of the present study indicated a novel role of miR­148a in adipocyte inflammation; therefore, miR­148a may be involved in obesity complications via its own underlying transcriptional mechanism.

Food intolerance prevalence in active ulcerative colitis in southwest China.

BACKGROUND AND OBJECTIVES: Food intolerance is believed to be a source of frequent medical problems in ulcerative colitis (UC), which closely correlate with patients' dietary pattern. Living in an underdeveloped area of China, residents in southwestern region have diverse dietary habits. The objective of this study is to determine the prevalence of food intolerance in the UC patients in this area and to discuss some of the possible risk factors leading to the condition. METHODS AND STUDY DESIGN: Food antibodies in serum of 80 patients with active UC were determined by standard enzyme-linked immuno sorbent assay (ELISA). This study examined the risk factors contributing to high titers of food antibodies and the dietary patterns correlating with food intolerance in these demographics. RESULTS: 83.8% of patients (67/80) were found to be seropositive for food intolerance. Patients of female, aged between 20 to 40 and the one who tended to have a high fat diet were tested to be highly seropositive (p<0.05). Neither spicy food intake nor the course the disease manifested any relationship with the presence of food intolerance (p>0.05). CONCLUSION: Active UC patients in southwestern region of China have showed to be high seropositive in food intolerance, particularly in female and young patients. Dietary patterns with high in fat intake seem to have caused high prevalence of seropositivity in food intolerance. Although rice has been taken as staple food and the spicy food has been popular among citizen in this region, these foods have indicated to no effect on food intolerance in this study.

miR-1275 inhibits adipogenesis via ELK1 and its expression decreases in obese subjects.

Excessive adipocyte differentiation and proliferation are closely associated with the onset of obesity, which has been partially linked to microRNA expression. In previous studies, using miRNA microarray screening, we found that miR-1275 was significantly decreased in human mature adipocytes. In this study, we examined the role of miR-1275 in adipogenesis. Our results indicated that miR-1275 can inhibit the differentiation of human visceral preadipocytes without affecting their proliferation. ELK1, an E-twenty-six (ETS)-domain transcription factor associated with adipocyte differentiation, was strongly suppressed by miR-1275 in human visceral adipocytes. This was demonstrated via a dual-luciferase reporter assay and pointed to ELK1 as a direct target of miR-1275. Furthermore, miR-1275 expression was significantly diminished in the visceral adipose tissue of overweight and obese human subjects accompanied by a negative correlation with body mass index. These results suggest that miR-1275 could play a future role in the management of obesity, as a novel therapeutic target or biomarker.

Adipogenic miRNA and meta-signature miRNAs involved in human adipocyte differentiation and obesity.

MicroRNAs (miRNAs) have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism, adipocyte differentiation. To determine the role of adipogenic miRNAs in the adipocyte differentiation process, we used microarray technology to monitor miRNA levels in human adipose-derived mesenchymal stem cells (hMSCs-Ad), human stromal vascular cells (SVCs) and differentiated adipocytes. 79 miRNAs were found to be differentially expressed, most of which are located in obesity related chromosomal regions but have not been previously linked to adipocyte differentiation process. A systematic search was made for relevant studies in academic data bases, involving the Gene Expression Omnibus (GEO) ArrayExpress, Pubmed and Embase database. Eight studies on human adipocyte differentiation or obesity were included in the final analysis. After combining our microarray data with meta-analysis of published microarray data, we detected 42 differently expressed miRNAs (meta-signature miRNAs) in mature adipocytes compared to SVCs or hMSCs-Ad. Our study shows meta-signature miRNAs specific for adipogenesis, several of which are correlated with key gene targets demonstrating functional relationships to pathways in BMP signaling pathway, Cell differentiation, Wnt signaling, insulin receptor signaling pathway, MAPK signaling, Cell cycle and lipid metabolic process. Our study shows that the first evidence of hsa-let-7 family, hsa-miR-15a-5p, hsa-miR-27a-3p, hsa-miR-106b-5p, hsa-miR-148a-3p and hsa-miR-26b-5p got a great weight in adipogenesis. We concluded that meta-signature miRNAs involved in adipocyte differentiation and provided pathophysiological roles and novel insight into obesity and its related metabolic diseases.

MiR-146b is a regulator of human visceral preadipocyte proliferation and differentiation and its expression is altered in human obesity.

Visceral obesity is an independent risk factor for metabolic syndrome, and abnormal fat accumulation is linked to increases in the number and size of adipocytes. MiR-146b was a miRNA highly expressed in mature adipocytes while very lowly expressed in human mesenchymal stem cells (hMSCs) and human visceral preadipocytes (vHPA). In this paper, we mainly focused on the roles of miR-146b in adipogenesis. We found miR-146b could inhibit the proliferation of visceral preadipocytes and promote their differentiation. MiR-146b in human visceral adipocytes inhibited the expression of KLF7, a member of the Kruppel-like transcription factors, as demonstrated by a firefly luciferase reporter assay, indicating that KLF7 is a direct target of the endogenous miR-146b. MiR-146b expression was significantly altered in visceral and subcutaneous adipose tissues in human overweight and obese subjects, and in the epididymal fat tissues and brown fat tissues of diet-induced obese mice. Our data indicates that miR-146b may be a new therapeutic target against human visceral obesity and metabolic dysfunction.