Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK signaling pathways

BACKGROUND: Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function. METHOD: Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting. RESULTS: Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19. CONCLUSIONS: The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy

Life-Threatening Hypocalcemia following Subtotal Parathyroidectomy in a Patient with Renal Failure and Previous Roux-en-Y Gastric Bypass Surgery

Background. Roux-en-Y gastric bypass (RYGB) can result in calcium and vitamin D deficiency. Parathyroid surgery carries the risk of immediate and long-term hypocalcemia. Methods and Results. We describe a 54-year-old woman with history of end-stage renal disease and gastric bypass surgery who developed calciphylaxis requiring a 3.5-gland parathyroidectomy. Seven weeks later, she presented with weakness, perioral numbness, leg cramps, a positive Chvostek's sign, hypotension, prolonged QT-interval, and serum calcium of 5.4 mg/dL. Oral and intravenous calcium, calcitriol, and high calcium bath hemodialysis were given. She required 18 days of intravenous calcium and an outpatient maintenance regimen of calcitriol 6 mcg/day, calcium carbonate 8 grams/day, calcium citrate 1.2 grams/day, and ergocalciferol 50,000 IU/week. Conclusion. The patient's life-threatening prolonged hypocalcemia and large requirements of calcium and calcitriol were due to a combination of malabsorption, hypoparathyroidism, and renal failure. Special considerations should be given to bariatric surgery patients undergoing neck exploration

Is physiological glucocorticoid replacement important in children?

Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics

The Relationship Among Morningness-Eveningness, Sleep Duration, Social Jetlag, and Body Mass Index in Asian Patients With Prediabetes

Background: Circadian system is known to influence energy metabolism. Recent evidence suggested that evening preference could be associated with higher body mass index (BMI). Moreover, evening preference is known to be associated with insufficient sleep duration and greater social jetlag, both described to be associated with obesity. This study aimed to explore whether morningness-eveningness was directly associated with BMI or its effect was transmitted through sleep duration or social jetlag in patients with prediabetes.Methods: A total 2,133 patients with prediabetes were enrolled. Morningness-eveningness was assessed using a Composite Scale of Morningness (CSM). Average weekly sleep duration and sleep timing were obtained, and social jetlag was calculated. BMI was calculated by weight (kg)/height2 (m2). A mediation analysis was performed based on two pathways, i.e. CSM→sleep→duration→BMI and CSM→social jetlag→BMI. A sequential equation model was used to estimate the direct and indirect effects of CSM on BMI.Results: Mean (SD) age and BMI were 63.6 (9.2) years and 25.8 (4.0) kg/m2. For CSM→sleep duration→BMI pathway, every one point decrease in CSM (more evening preference) was associated with a decrease in sleep duration by 0.054 h (95% CI 0.043–0.066), whereas sleep duration was negatively associated with BMI (coefficient = −0.156, 95%CI −0.288, −0.024). Mediation analysis indicated that a change in CSM (from 90th to 10th percentile, more evening preference) was associated with a decrease in sleep duration and an increase in BMI by 0.102 kg/m2 (95% CI 0.015, 0.207). In addition, this change in CSM was directly associated with an increase in BMI by 0.511 kg/m2 (95%CI 0.030, 0.952). The CSM→social jetlag→BMI pathway analysis revealed that social jetlag was not significantly associated with BMI. A subgroup analysis in those aged ≤60 years (n = 784) revealed that each hour increase in social jetlag was associated with an increase in BMI by 0.56 kg/m2 (p = 0.026) while CSM and sleep duration were not.Conclusion: In patients with prediabetes, more evening preference was directly associated with higher BMI and indirectly through insufficient sleep duration, while social jetlag did not mediate the relationship between CSM and BMI. In those ≤60 years, only greater social jetlag was associated with higher BMI. These data could inform further interventional studies to reduce BMI in this high risk group

Sodium quercetin-8-sulfonate trihydrate

The organic anion of the title compound, {[Na(C15H9O10S)(H2O)2]·H2O}n {systematic name: poly[[diaqua­[μ-2-(3,4-dihy­droxy­phen­yl)-3,5,7-trihy­droxy-4-oxo-4H-chromene-8-sulfon­ato]­sodium] monohydrate]}, has a nearly planar structure. The Na atom is six-coordinated by O atoms, two from water mol­ecules and four from the anion. The dihedral angle between the ring systems in the anion is 10.1 (1)°. Intra­molecular O—H⋯S and O—H⋯O inter­actions occur. In the crystal structure, an extensive network of classical inter­molecular O—H⋯S and O—H⋯O hydrogen bonds forms layers along the c axis

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures.

Circadian (∼ 24 hour) timing systems pervade all kingdoms of life, and temporally optimize behaviour and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behaviour and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these too are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally-driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioural and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important

UPLC-ESI-MRM/MS for Absolute Quantification and MS/MS Structural Elucidation of Six Specialized Pyranonaphthoquinone Metabolites From Ventilago harmandiana

Pyranonaphthoquinones (PNQs) are important structural scaffolds found in numerous natural products. Research interest in these specialized metabolites lies in their natural occurrence and therapeutic activities. Nonetheless, research progress has thus far been hindered by the lack of analytical standards and analytical methods for both qualitative and quantitative analysis. We report here that various parts of Ventilago harmandiana are rich sources of PNQs. We developed an ultraperformance liquid chromatography-electrospray ionization multiple reaction monitoring/mass spectrometry method to quantitatively determine six PNQs from leaves, root, bark, wood, and heartwood. The addition of standards in combination with a stable isotope of salicylic acid-D-6 was used to overcome the matrix effect with average recovery of 82% +/- 1% (n = 15). The highest concentration of the total PNQs was found in the root (11,902 mu g/g dry weight), whereas the lowest concentration was found in the leaves (28 mu g/g dry weight). Except for the root, PNQ-332 was found to be the major compound in all parts of V. harmandiana, accounting for similar to 48% of the total PNQs quantified in this study. However, PNQ-318A was the most abundant PNQ in the root sample, accounting for 27% of the total PNQs. Finally, we provide novel MS/MS spectra of the PNQs at different collision induction energies: 10, 20, and 40 eV (POS and NEG). For structural elucidation purposes, we propose complete MS/MS fragmentation pathways of PNQs using MS/MS spectra at collision energies of 20 and 40 eV. The MS/MS spectra along with our discussion on structural elucidation of these PNQs should be very useful to the natural products community to further exploring PNQs in V. harmandiana and various other sources

Associations between self-reported sleep duration and cardiometabolic risk factors in young African-origin adults from the five-country Modeling the Epidemiologic Transition Study (METS)

To investigate associations between self-reported sleep duration and cardiometabolic (CM) risk factors in African-origin adults residing in five countries spanning the epidemiologic transition. Cross-sectional. Ghanaian (n = 491), South African (n = 503), Jamaican (n = 508), Seychellois (n = 501) and American (n = 480) men and women. Self-reported sleep duration was obtained using questionnaires. Sex- and site-stratified logistic regression analyses investigated relationships between sleep duration, individual CM risk factors and a binary CM risk variable (presence of ≥3 CM risk factors), adjusting for age, physical activity and education. Sleep duration distributions varied by cohort: 44.5%, 41.4%, 35.9%, 16.8% and 2.5% of American, Jamaican, Seychellois, Ghanaian and South African men reported <7 h sleep per night respectively (p < 0.001). Similarly, 42.6%, 28.6%, 25.2%, 12.8% and 1.5% of American, Jamaican, Seychellois, Ghanaian and South African women reported <7 h sleep respectively (p < 0.001). American men reporting ≤6 h sleep were more likely to be in the elevated CM risk group (OR: 2.52, 95%CI: 1.02, 6.22, p = 0.045) and to have a high waist circumference (OR: 2.44, 95%CI: 1.07, 5.57, p = 0.034) compared to those reporting 8 h sleep. Jamaican women reporting ≤6 h sleep (OR: 2.53, 95%CI: 1.19, 5.36, p = 0.016) and American women reporting 7 h sleep (OR: 2.71, 95%CI: 1.17, 6.26, p = 0.002) were more likely to be obese than those reporting 8 h sleep. Associations between short sleep and CM risk factors were only evident in the American men and women and Jamaican women. Future interventions to address CM risk and sleep health may need to be country-specific when targeting high-risk populations

Sex-specific associations between self-reported sleep characteristics and 10-year cardiovascular disease risk in men and women of African descent living in a low socioeconomic status environment

BackgroundRisk factors for cardiovascular disease (CVD) and sleep health are well-known to be sex- and race-specific. To build on the established relationship between sleep duration and CVD risk, this cross-sectional study aimed to describe sex-specific associations between CVD risk and other sleep characteristics (sleep quality, sleep timing and sleep onset latency) in low-income adults of African descent.MethodsSelf-reported sleep (Pittsburgh Sleep Quality Index [PSQI], Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]), demographic and lifestyle data were collected in 412 adults (56% women, 35.0±7.6y, 40% employed) living in an informal settlement in South Africa. CVD risk was determined using the BMI-modified Framingham 10-year CVD risk formula.ResultsLogistic regression analyses, adjusted for employment, alcohol use and physical activity, indicated that men reporting poor sleep quality (OR: 1.9[95%CI: 1.1-3.5],p=0.025) and earlier bedtimes (0.54[0.39-0.74],p&lt;0.001) were more likely to belong to a higher 10-year CVD risk score quintile. Women reporting earlier bedtimes (0.72[0.55-0.95],p=0.020) and wake-up times (0.30[0.1-0.7],p=0.007), longer sleep-onset latency (1.5[1.4-1.9],p=0.003), shorter total sleep times (0.84[0.7-0.9],p=0.029), higher PSQI global scores (1.9[1.3-2.9],p=0.001) and more moderate to severe symptoms of insomnia (ISI≥15)(3.24[1.04-10.04],p=0.016) were more likely to belong to higher 10-year CVD risk score quintile.ConclusionIn addition to sleep duration, we found that sleep quality, sleep timing and sleep onset latency are additional risk factors for CVD in adults of African descent. Sex-specific differences in the sleep-CVD-risk relationship observed suggests that future studies and recommendations about sleep health in relation to CVD should take sex into account.<br/

ACTIVE COMPOUND OF ZINGIBER CASSUMUNAR ROXB. DOWN-REGULATES THE EXPRESSION OF GENES INVOLVED IN JOINT EROSION IN A HUMAN SYNOVIAL FIBROBLAST CELL LINE

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovium. It is involved in up-regulation of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), resulting in joint inflammation and erosion. Zingiber cassumunar Roxb. has long been used to reduce joint pain and inflammation. This study aimed to investigate the inhibitory activities of an active compound of Z. cassumunar, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D), against cytokine-induced up-regulation of catabolic genes involved in cartilage degradation in RA. Synovial fibroblast cell line, SW982, was cultured in media containing interleukin-1ß (IL-1ß), in the presence or absence of compound D at the concentration range of 1 to 100 µM. After 24 hours, the cells were analyzed for the expressions of MMPs, IL-1ß and interleukin-1ß-converting enzyme (ICE) by RT-PCR. MMPs activities in the culture media were analyzed by zymographic techniques. Dexamethasone was used as the positive control. It was found that compound D at the concentration of 10 - 100 M significantly decreased the mRNA expressions of MMP-1, -2, -3, and -13 which was induced by IL-1ß (