OBJECTIVE: Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) ₂D ₃ and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) ₂D ₃ and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. METHODS: In vitro, HaCaT cells were treated with 1,25(OH) ₂D ₃ or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm ², then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. RESULTS: Compared with the HaCaT cells treated with 1,25(OH) ₂D ₃ or TAK-242, the cells treated with both 1,25(OH) ₂D ₃ and TAK-242 showed, 1) significantly lower production of ROS ( P < 0.05); 2) significantly less apoptosis of HaCaT cells ( P < 0.05); 3) significantly lower expression of NF- κB, Caspase-8, Cyto-C, Caspase-3 ( P < 0.05). CONCLUSION The combination of 1,25(OH) ₂D ₃ and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) ₂D ₃ or TAK-242 alone.
Humans ; HaCaT Cells ; NF-kappa B ; Reactive Oxygen Species ; Toll-Like Receptor 4 ; Ultraviolet Rays/adverse effects* ; Cholecalciferol/analogs & derivatives*

OBJECTIVETo study the effect of 1,25-(OH)2D3 supplementation during gestation and lactation on TGF-β1 and Smad3 expression in lungs of rat offspring with asthma.

METHODSThirty-two female Wistar rats were randomly divided into four groups: low-, medium- and high-dose 1,25-(OH)2D3 supplementation and control groups (n=8 each). From the 7th day of gestation, the three 1,25-(OH)2D3 supplementation groups were administered with 2,10 and 20 μg/mL of 1,25-(OH)2D3 respectively every other day until weaning (rat offspring: 21 days old). The control group received normal saline instead. Then, bronchial asthma was induced in rat offspring from the 4 groups. The protein and mRNA expression of TGF-β1 and Smad3 in the lung tissue was measured by immunochemistry and RT-PCR.

RESULTSEosinophil cell infiltration and airway inflammation decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups, but increased in rat offspring of the high-dose 1,25-(OH)2D3 group compared with the control group. Immunohistochemistry of lung tissues showed that the expression of TGF-β1 protein and pSmad3 decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups (P<0.05), but increased significantly in rat offspring from the high-dose 1,25-(OH)2D3 group compared with the control group (P<0.05). PCR showed that the expression of TGF-β1 and Smad3 mRNA in the lung tissue decreased in rat offspring from the low- and medium-dose 1,25-(OH)2D3 groups (P<0.05), but increased significantly in rat offspring from the high-dose 1,25-(OH)2D3 group compared with the control group (P<0.05).

CONCLUSIONS1,25-(OH)2D3 supplementation plays a role in regulating the immune system in asthmatic rats. Its mechanism may be associated with regulation of the expression of TGF-β/Smad signal pathway-related proteins through the vitamin D receptor signal pathway.

Animals ; Asthma ; metabolism ; Cholecalciferol ; administration & dosage ; analogs & derivatives ; Dietary Supplements ; Female ; Lactation ; metabolism ; Lung ; metabolism ; pathology ; Male ; Pregnancy ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Signal Transduction ; Smad3 Protein ; genetics ; physiology ; Transforming Growth Factor beta1 ; genetics ; physiology

BACKGROUND/AIMS: Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness. METHODS: We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention. RESULTS: The baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group (35.4 +/- 8.5 ng/mL vs. 18.4 +/- 7.3 ng/mL, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups. CONCLUSIONS: Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.
Calcium, Dietary/administration & dosage ; Cholecalciferol/*administration & dosage ; Diabetes Mellitus, Type 2/complications/*drug therapy/physiopathology ; Double-Blind Method ; Female ; Humans ; *Insulin Resistance ; Male ; Middle Aged ; Prospective Studies ; Vascular Stiffness/*drug effects ; Vitamin D/analogs & derivatives/blood ; Vitamin D Deficiency/blood/complications/drug therapy

Vitamin D deficiency is common and may contribute to osteopenia, osteoporosis and falls risk in the elderly. Screening for vitamin D deficiency is important in high-risk patients, especially for patients who suffered minimal trauma fractures. Vitamin D deficiency should be treated according to the severity of the deficiency. In high-risk adults, follow-up serum 25-hydroxyvitamin D concentration should be measured 3-4 months after initiating maintenance therapy to confirm that the target level has been achieved. All patients should maintain a calcium intake of at least 1,000 mg for women aged ≤ 50 years and men ≤ 70 years, and 1,300 mg for women > 50 years and men > 70 years.
Aged ; Bone Density ; Bone Diseases, Metabolic ; prevention & control ; Calcium, Dietary ; therapeutic use ; Cholecalciferol ; administration & dosage ; Female ; Hip Fractures ; complications ; epidemiology ; Humans ; Male ; Middle Aged ; Osteoporosis ; prevention & control ; Practice Guidelines as Topic ; Prevalence ; Primary Health Care ; methods ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; diagnosis ; epidemiology

OBJECTIVETo investigate the effects of Chinese kidney-tonifying drugs on bone mineral density, biomechanics, 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 of ovariectomized osteoporosis rats, and explore the mechanism of treating osteoporosis with the drugs.

METHODSThirty-six female SD rats (four months) were randomly divided into model group, sham group and treatment group. All the rats had been ovariectomied except those in sham group. Selecting 4, 8, 12 weeks in the experiment, the value of bone mineral density (BMD) was measure by dual energy X-ray absorptiometry (DEXA) of femoral head, while the biomechanics machine was applied to analysis femoral head biomechanics index and ELISA method was used to detect the content of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 discern in blood-serum, liver and kidney.

RESULTSTreatment group rats' BMD of femoral head was enhance compared with model group, significant differences were absent (P<0.05), and the maximal load and maximal stress measurement were improved, significant differences were absent (P<0.05). As the content of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 discern in blood-serum, liver and kidney were elevate, furthmore there were significant differences in group comparison, all significant differences were absent (P<0.05). But those compared with sham group, there was no significant difference (P>0.05).

CONCLUSIONIn the early period in absence of estrogenic hormone, the Chinese kidney-tonifying drugs could activate bone metabolism to raise BMD and reinforce quality of bone through up-regulating expression of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 at protein level.

Animals ; Biomechanical Phenomena ; drug effects ; Bone Density ; drug effects ; Cholecalciferol ; analogs & derivatives ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Femur Head ; drug effects ; metabolism ; Humans ; Osteoporosis ; drug therapy ; metabolism ; physiopathology ; Ovariectomy ; adverse effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Renal Agents ; pharmacology