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The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years).This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old.This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (20 years).Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis.This work was supported by Wenzhou Medical University grant [89219029].Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

Objective With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied. Methods High-fat diet-induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied. Results Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes. Conclusions Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway.

// Ling Qi 1,* , Lijuan Ding 2,* , Shuran Wang 3 , Yue Zhong 3 , Donghai Zhao 3 , Ling Gao 2 , Weiyao Wang 1 , Peng Lv 1 , Ye Xu 1 and Shudong Wang 4 1 Basic Medical College, Jilin Medical University, Jilin, China 2 Department of Radiation Oncology, First Hospital of Jilin University, Changchun, China 3 Department of Science and Technology, Jilin Medical University, Jilin, China 4 Center of Cardiovascular Diseases, First Hospital of Jilin University, Changchun, China * These authors have contributed equally to this work Correspondence to: Ye Xu, email: // Shudong Wang, email: // Keywords : chemotherapy, radiotherapy, glioma, network meta-analysis, temozolomide Received : April 05, 2016 Accepted : July 10, 2016 Published : July 21, 2016 Abstract Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely been compared with each other and the optimum drug still remains to be proved. In this research, medical databases were consulted, PubMed, Embase and Cochrane Library included. As primary outcomes, hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with their corresponding 95% credential intervals ( CrI ) were reported. A network meta-analysis was conducted; the surface under the cumulative ranking curve (SUCRA) was utilized for treatment rank and a cluster analysis based on SUCRA values was performed. This research includes 14 trials with 3,681 subjects and eight interventions. In terms of network meta-analysis, placebo was proved to be inferior to the combination of temozolomide (TMZ), nimustine (ACNU) and cisplatin (CDDP). Also, bevacizumab (BEV) in conjunction with TMZ were significantly more effective than placebo with an HR of 0.40. The estimated probabilities from SUCRA verified the above outcomes, confirming that the combination of TMZ, ACNU and CDDP exhibited the highest ranking probability of 0.889 with respect to OS, while BEV in combination with TMZ - with a probability of 0.772 - ranked the first place with respect to PFS. According to the results of this network meta-analysis, the combination of (1) TMZ, ACNU and CDDP; (2) BEV in combination with TMZ and (3) cilengitide in combination with TMZ, are considered as the preferable choices of chemotherapy drugs for glioma treatment.

To investigate the association between pathological myopia (PM) and immunological/inflammatory markers and to identify the possible risk factors for the formation of myopic choroidal neovascularization (mCNV).One hundred fourteen unrelated subjects were recruited: 63 PM patients (PM group) with spherical equivalent of at least -8.00 diopters (range, -8.00 to -25.00) and axial length exceeding 26.5 mm, accompanied by characteristic pathologic changes, and 51 emmetropic age- and sex-matched individuals (control group) with spherical equivalent within ±1.0 diopter in both eyes. In the PM group, patients were assigned to two subgroups, mCNV group and no CNV group, according to the results of fluorescein angiography. Serum high-sensitivity C-reactive protein (hs-CRP) and complement profile (C3, C4, and CH50) were assayed. Statistical analysis was performed between the two groups. Binary logistic regression analysis was used to analyze the relative risk factors that were associated with the development of mCNV in the PM group patients.The range of axial length was 26.50 to 37.08 mm in the PM group and 22.32 to 24.56 mm in the control group. There were 24 patients in the mCNV group and 39 patients in the no CNV group. The PM group patients had significantly higher serum hs-CRP (p = 0.033), C3 (p = 0.004), and CH50 (p0.001) compared with the control group patients. There were no significant differences between the two groups for C4 level (p = 0.071). Binary logistic regression analysis, which included hs-CRP, C3, C4, CH50, age, and sex as covariates, showed that C3 (p = 0.03) and age (p = 0.01) were risk factors for mCNV, whereas serum hs-CRP, C4, CH50, and sex were not statistically significant predictors of mCNV in the PM group patients (p0.05).Our data support the hypothesis that immunological/inflammatory markers, namely hs-CRP, C3, and CH50 may play an important role in the development of PM, and that C3 level may be a predictive risk factor for mCNV formation.

Background and aims Chronic inflammation plays pivotal roles in both cancer and cardiovascular diseases. A large body of evidence suggests that high intake of cruciferous vegetables is closely related with low risk of these disorders. However, the underlying mechanisms of protection are not fully understood. The aim of this study is to test the protective effects of an isothiocyanate sulphoraphane on inflammatory injury and related regulation pathways in cultured endothelial cells. Methods and results The expressions of adhesion molecules were determined by TaqMan real-time polymerase chain reaction (PCR) and Western blot analysis. Nuclear factor-kappa B (NF-кB) translocation was detected by immunofluorescent hybridisation. Other proteins were measured by Western blot analysis. The results demonstrated that sulphoraphane significantly suppresses the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 stimulated by lipopolysaccharide (LPS) both at the transcriptional and translational levels. In addition, sulphoraphane inhibited the translocation of NF-кB into the nucleus. Sulphoraphane decreased the phosphorylation of extra-cellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), while further blockade and activation using individually specific agents confirm that p38 MAPK and JNK are mainly involved. Interestingly, sulphoraphane down-regulated Toll-like receptor (TLR)-4, a receptor of LPS located on the membrane. In addition, MyD88, an effector downstream TLR-4 signal pathway was subsequently attenuated. Conclusion Taken all together, adhesion molecules are confirmed to be the novel targets of sulphoraphane in preventing inflammatory insult to endothelial cells. Sulphoraphane suppressed TLR-4 followed by MyD88 and downstream factors such as p38 MAPK and JNK, ultimately blocking NF-кB translocation and the subsequent expression of adhesion molecules. These data suggested a novel inflammatory pathway mediated by sulphoraphane.

The isothiocyanate, sulforaphane and the flavonoid, apigenin modulate gene expression including phase II detoxifying enzymes, such as glutathione S-transferases (GST) and UDP-glucuronosyltransferases (UGT). Using undifferentiated CaCo-2 cells, we have examined the interactions between sulforaphane and apigenin in the regulation of UGT and GST expression. We show that apigenin induces UGT1A1 transcription (4-fold) but not GSTA1, and that sulforaphane induces both UGT1A1 (3.7-fold) and GSTA1 (2.8-fold) transcription in both dose- and time-dependent manners. The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1 mRNA up to 12-fold, although this interaction was not seen for GSTA1. Nuclear factor kappa B (NF-kappaB) mRNA was induced by apigenin and sulforaphane (2.5- and 2-fold, respectively). NF-kappaB translocation inhibitor SN50 and phosphatidylinositol 3-kinase (PI3) inhibitor LY294002 decreased the induction of GSTA1 by sulforaphane almost to baseline level. However, the MEK inhibitor PD98059 enhanced significantly the induction of GSTA1 by sulforaphane. This suggests that NF-kappaB and PI3-kinase signaling pathways play a role in GSTA1 gene expression. Conversely, the induction of UGT1A1 transcription by sulforaphane was totally abolished by PD98059, although PD98059 slightly enhanced (20%) the induction of UGT1A1 by apigenin implying that the induction of UGT1A1 by sulforaphane is mediated by MAPK/extracellular signal-regulated kinase kinase, whereas UGT1A1 induction by apigenin may be associated with NF-kappaB translocation since the NF-kappaB translocation inhibitor, SN50 enhanced the induction of UGT by apigenin. The results show that UGT1A1 and GSTA1 are regulated by sulforaphane through different signal transduction pathways and the differences in the mechanisms of modulation of UGT1A1 transcription by sulforaphane and apigenin resulted in a synergistic effect between these two compounds in the induction of UGT1A1.

In the present study, we investigated the potential efficacy of cruciferous vegetable-derived sulforaphane (SFN) in improving homocysteine (HCY)-stressed cells. After human hepatocyte line HHL-5 was preincubated with SFN and subsequently with 10 mmol/L HCY, SFN improved the pathologic changes which are caused by HCY, including cell morphological abnormality, endoplasmic reticulum (ER) swelling, excessive generation of reactive oxygen species (ROS), the increased malondialdehyde (MDA) levels, as well as the increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Phase II enzymes, thioredoxin reductase-1 (TrxR-1) andquinone oxidoreductase 1 (NQO1), were involved in the protective effect of SFN against injury by HCY. The ER stress-specific proteins, such as glucose-regulated protein-78 (GRP78) and protein kinase RNA (PKR)-like ER kinase (PERK), were strikingly abolished by SFN. Furthermore, Nrf-2 translocation was enhanced by SFN, which lead to the induction of TrxR-1and NQO1.

Background: Body energy homeostasis is largely regulated by the interactions between appetite-related brain regions and gut hormones. Objective: We hypothesized that the sensitivity of appetite-related brain regions [eg, hypothalamus, insula, thalamus, parahippocampal/ hippocampal cortex, caudate, putamen, amygdala, and orbitofrontal cortex (OFC)] varies for each macronutrient, and the differential sensitivity is associated with gut hormone concentrations in humans. Design: Brain activation responses to ingested fat, glucose, protein, and water in the above-mentioned 8 brain regions of 14 healthy men were investigated by using functional magnetic resonance imaging. Fasting and postprandial plasma glucose, insulin, ghrelin, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1) concentrations were measured. The relation of the blood oxygen level–dependent (BOLD) signal with plasma glucose and hormone concentrations was assessed by using Pearson’s correlation analysis. Results: Ingested macronutrients similarly reduced the BOLD signal in the middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC. Protein ingestion reduced the BOLD signal in the amygdala more effectively than did fat and glucose ingestion. BOLD signal changes were positively correlated with circulating ghrelin concentrations and were negatively correlated with circulating insulin, CCK, and GLP-1 concentrations. The findings indicate variations in the correlation between brain activation and plasma hormone concentrations after ingestion of different macronutrients. Conclusions: The middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC, but not the amygdala, have sensitivities similar to those of isocaloric and isovolumetric macronutrient solutions. Differential correlations exist between BOLD signal changes in activated brain regions and postprandial changes in plasma concentrations of different gut hormones in response to the ingestion of different macronutrients. This trial was registered at chictr.org as ChiCTR-TRC-12001945. Am J Clin Nutr 2012; 96:275–82.

To investigate the effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival human leukocyte antigen II (HLA-DR) expression in dry eyes.Sixty patients with dry eyes were randomized to 2 groups. Patients in group 1 received topical pranoprofen 0.1% plus topical sodium hyaluronate 0.1%; and patients in group 2 received sodium hyaluronate without pranoprofen. Ocular surface disease index (OSDI), tearfilig;lm break-up time (TBUT), Schirmer I test, ocular surface staining (OSS), and conjunctival HLA-DR expression were evaluated before treatment and at 15 and 30 days after treatment.On day 15, patients in group 1 had significantly lower OSDI, OSS, and HLA-DR-positive cells compared with patients in group 2 (P0.01), and the TBUT was significantly longer in patients in group 1 than that of patients in group 2 (P0.01). On day 30, the difference between the 2 groups in OSS lost significance; however, there continued to be significant differences in the OSDI, TBUT, and HLA-DR expression between the 2 groups (P0.01). On days 15 and 30, the values in group 1 patients had significant improvement compared with their baseline values in terms of the above-mentioned parameters. The comparisons within group 2 did not reveal any significant differences. There was no significant effect in the Schirmer I test value in eyes of patients in group 1 or group 2 at days 15 or 30 (P0.05).Topical pranoprofen 0.1% has a beneficial effect in reducing the ocular signs and symptoms of dry eyes and decreasing the inflammatory markers of conjunctival epithelial cells.

Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer.

Sulforaphane (SFN), mainly derived from cruciferous vegetables, has received much attention for its cancer chemopreventive property. Though there have been a few epidemiological studies supporting its beneficial effect on cardiovascular diseases, much experimental evidence are still required to understand its mechanism. In this study, human vascular endothelial cell, a barrier of blood, was used as an in vitro model to investigate the protective effect of sulforaphane on inflammatory damage induced by lipopolysaccharide (LPS). The results showed that sulforaphane inhibited the expression of COX-2 and iNOS stimulated by lipopolysaccharide in a dose- and time-dependent manner. Moreover, sulforaphane suppressed the phosphorylation of ERK1/2, JNK, and p38 activated by lipopolysaccharide. Pretreatment with SB202190, the specific inhibitor of p38, abolished the expression of COX-2 induced by LPS. Likewise, SP600125, inhibitor of JNK, abrogated iNOS expression stimulated by LPS. Moreover, pretreatment with anisomycin (AM), an activator of p38 and JNK, instead of LPS, the expression of COX-2 and iNOS is still inhibited by sulforaphane. Interestingly, SFN significantly induced HO-1 and TR expression down-regulated by LPS. Taken together, these data indicated that sulforaphane exhibited the protective role against the inflammatory injury in vascular endothelia cells, through inactivating p38 MAPK and JNK, as well as inducing phase 2 enzymes.

Cyclooxygenase-2 (COX-2) overexpression has been associated with the grade, prognosis and recurrence of transitional cell carcinoma (TCC) of the bladder. In this study, sulforaphane, a dietary isothiocyanate, down-regulated COX-2 expression in human bladder transitional cancer T24 cells at both transcriptional- and translational levels. Sulforaphane (5-20 microM) induced nuclear translocation of NF-kappaB and reduced its binding to the COX-2 promoter, a key mechanism for suppressing COX-2 expression by sulforaphane. Moreover, sulforaphane increased expression of p38 and phosphorylated-p38 protein. A specific inhibitor of p38 MAPK, SB202190, was used to further investigate its pivotal role in sulforaphane-mediated down-regulation of COX-2. Exposure of T24 cells to SB202190 1 hour prior to sulforaphane treatment abolished the effect of sulforaphane on COX-2 mRNA down-regulation, but enhanced COX-2 transcription. Furthermore, SB202190 alone induced NF-kappaB translocation to the nucleus, promoted NF-kappaB binding to the COX-2 promoter and resulted in up-regulation of COX-2 expression. Taken together, these data suggest that p38 is essential in sulforaphane-mediated COX-2 suppression and provide new insights into the molecular mechanisms of sulforaphane in the chemoprevention of bladder cancer.