The relationship between vitamin D deficiency and oxidative stress can be independent of age and gender.

PMID: 

Int J Vitam Nutr Res. 2019 Nov 12:1-16. Epub 2019 Nov 12. PMID: 31711376

Abstract Title: 

The relationship between vitamin D deficiency and oxidative stress can be independent of age and gender.

Abstract: 

The active vitamin D (1,25(OH)D) acts through a nuclear receptor to perform several functions in cellular metabolism. 1,25(OH)D participates directly in calcium homeostasis, regulates the immune system, nervous system, blood pressure, insulin secretion, among others. Vitamin D deficiency could also be associated with several diseases and increased cellular oxidative damage. The present study aimed to investigate whether lipid peroxidation and/or protein oxidation are affected by vitamin D deficiency and whether sunlight exposure/diet, gender, and age might influence this relationship. Vitamin D concentrations were obtained from the Heart Hospital database and a questionnaire was applied among the 212 participants. We used the inactive vitamin D (25(OH)) in the analyses since 1,25(OH)D has a short half-life and a low blood concentration. Lipid peroxidation and protein oxidation analyses were performed using spectrophotometry. Multivariate analyses suggested the participation of vitamin D deficiency (

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Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an updated meta-analysis.

PMID: 

BMC Neurol. 2019 Nov 13 ;19(1):284. Epub 2019 Nov 13. PMID: 31722673

Abstract Title: 

Vitamin D deficiency as a risk factor for dementia and Alzheimer's disease: an updated meta-analysis.

Abstract: 

BACKGROUND: We aimed to comprehensively explore the associations between serum 25(OH)D deficiency and risk of dementia and Alzheimer's disease(AD).METHODS: We systematically searched Pubmed, the Cochrane Library, Embase and the reference lists of pertinent review articles for relevant articles published from database inception up until January 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with random effects models using the Stata 12.0 statistical software package.RESULTS: Twelve prospective cohort studies and four cross-sectional studies were included in this meta-analysis. The pooled HRs of dementia and AD, respectively, were 1.32 (95%CI: 1.16, 1.52) and 1.34 (95%CI: 1.13, 1.60) for vitamin D deficiency (

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The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma

PMID: 

Sci Rep. 2019 Nov 13 ;9(1):16719. Epub 2019 Nov 13. PMID: 31723229

Abstract Title: 

The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma.

Abstract: 

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (

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Sudden sensory-neural hearing loss patients with deficient vitamin D had the highest percentage of no response to treatment.

PMID: 

Am J Otolaryngol. 2019 Nov 12:102327. Epub 2019 Nov 12. PMID: 31735446

Abstract Title: 

Investigation of vitamin D levels in patients with Sudden Sensory-Neural Hearing Loss and its effect on treatment.

Abstract: 

BACKGROUND: Due to high prevalence of vitamin D deficiency and the possible association with Sudden Sensory-Neural Hearing Loss (SSNHL) finding the main causes and appropriate treatments are highly essential. This study aimed to investigate vitamin D levels in patients suffering SSNHL and its effect on response to treatment.MATERIALS AND METHODS: This cross-sectional study was performed on two groups of case (34 SSNHL patients) and control (34 healthy subjects without risk of hearing loss). All patient information such as age, sex, audiogram illustration of hearing frequency and the level of vitamin D were recorded at baseline. Patients with SSNHL received routine treatments such as 10 days of 1 mg/kg/day steroid and the response or lack of complete response to treatment was recorded and analyzed according to the audiometry.RESULTS: Vitamin D level in SSNHL group with a mean of 19.28 ± 9.56 ng/ml was significantly less than the control group (25.71 ± 11.21 ng/ml; P value 

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Vitamin D deficiency has a significant impact in heart failure patients.

PMID: 

Dis Markers. 2019 ;2019:4145821. Epub 2019 Oct 13. PMID: 31737126

Abstract Title: 

Vitamin D Deficiency Predicts Poor Clinical Outcomes in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

Abstract: 

Background and Aims: Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT.Methods and Results: We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (= 0.045) and poor clinical response (= 0.03) after adjusting to all significant baseline predictors.Conclusion: Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.

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Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy.

PMID: 

J Microencapsul. 2018 May ;35(3):301-311. Epub 2018 Jun 6. PMID: 29781344

Abstract Title: 

Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy.

Abstract: 

Vitamin C, as an antioxidant additive in pharmaceutical and food products, is susceptible to environmental conditions, and new design strategies are needed to enhance its stability. The aim of this study is to prepare vitamin C proliposome using film deposition on the carrier by applying different factors, and optimise the characteristics of the obtained powder using the design expertsoftware. The optimised formulation demonstrated acceptable flowability with 20% vitamin C loading. This formulation released about 90% vitamin C within 2 h and showed higher (1.7-fold) in-vitro antioxidant activity. Ex-vivo antioxidant activity was 1.9 and 1.6 times higher in brain and liver cells, respectively. A 27% reduction in malondialdehyde (MDA) level of liver cell was obtained comparing free vitamin C. Therefore, this study results suggestthat the vitamin C-encapsulated proliposome powder might be an appropriate carrier for oral drug delivery of vitamin C with better antioxidant efficacy.

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Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy.

PMID: 

Colloids Surf B Biointerfaces. 2015 Apr 1 ;128:419-426. Epub 2015 Mar 7. PMID: 25797481

Abstract Title: 

Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy.

Abstract: 

Paclitaxel (PTX) and curcumin (CUR) are potent chemotherapeutic agents used in the treatment of cancer. In the present study, hybrid polymer-lipid nanoparticles co-loaded with PTX and CUR were developed to investigate the therapeutic potential of a combination drug regimen. For this purpose, PTX-loaded albumin nanoparticles (APN) were prepared and encapsulated in PEGylated hybrid liposomes containing CUR (CL-APN) via a thin-film hydration technique. CL-APN was nanosized with a uniform spherical morphology. PTX and CUR release was sustained and occurred in a sequential manner, wherein CUR was expected to downregulate the nuclear factor NF-κB and Akt pathways and increase the therapeutic efficacy of PTX. The ratiometric combination of PTX and CUR was significantly more cytotoxic than the individual drugs. Importantly, dual-drug-loaded nanocarriers exhibited a superior cytotoxic effect than a cocktail combination at a lower dose. CL-APN induced significantly higher early and late apoptosis, induced a stronger G2/M arrest, and significantly increased the subG1 cell population. By combining CUR, an effective NF-κB inhibitor, with PTX, a powerful anticancer drug, in a polymer-lipid hybrid nanoparticle system, we could improve thetherapeutic efficacy in cancer treatments. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against various malignancies.

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Liposomal curcumin inhibits hypoxia-induced angiogenesis.

PMID: 

Onco Targets Ther. 2015 ;8:2601-11. Epub 2015 Sep 15. PMID: 26451117

Abstract Title: 

Liposomal curcumin inhibits hypoxia-induced angiogenesis after transcatheter arterial embolization in VX2 rabbit liver tumors.

Abstract: 

PURPOSE: The purpose of the study is to investigate the inhibition of hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors by liposomal curcumin.MATERIALS AND METHODS: A total of 54 VX2 rabbits were divided into three groups, and each group had three subgroups according to the sacrifice time. The animals in the control group (n=18) underwent sham embolization. Transcatheter arterial embolization (TAE)-treated group (n=18) animals underwent embolization with lipiodol (0.1 mL/kg body weight) and 90-180µm polyvinyl alcohol (PVA) particles. Liposomal curcumin TAE-treated group (n=18) animals underwent embolization with liposomal curcumin (20 mg/kg body weight) mixed with lipiodol (0.1 mL/kg body weight) and 90-180 µm PVA particles. After embolization, the animals in each subgroup were sacrificedat 6 hours, 24 hours, and 3 days, and the tumor samples were collected. Immunohistochemical staining was performed to evaluate expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins, and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels.RESULTS: The levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P0.05). The HIF-1α protein correlated considerably with VEGF mRNA (r=0.705, P=0.001) and protein (r=0.655, P=0.003), and MVD (r=0.521, P=0.027). A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).CONCLUSION: Liposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.

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The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals.

PMID: 

Int J Nanomedicine. 2017 ;12:1369-1384. Epub 2017 Feb 17. PMID: 28260885

Abstract Title: 

The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals.

Abstract: 

Glioblastoma is a kind of malignant gliomas that is almost impossible to cure due to the poor drug transportation across the blood-brain barrier and the existence of glioma stem cells. We prepared a new kind of targeted liposomes in order to improve the drug delivery system onto the glioma cells and induce the apoptosis of glioma stem cells afterward. In this experiment, curcumin was chosen to kill gliomas, while quinacrine was used to induce apoptosis of the glioma stem cells. Also,-aminophenyl-α-D-mannopyranoside could facilitate the transport of liposomes across the blood-brain barrier and finally target the brain glioma cells. The cell experiments in vitro indicated that the targeted liposomes could significantly improve the anti-tumor effects of the drugs, while enhancing the uptake effects, apoptosis effects, and endocytic effects of C6 glioma cells and C6 glioma stem cells. Given the animal experiments in vivo, we discovered that the targeted liposomes could obviously increase the survival period of brain glioma-bearing mice and inhibit the growth of gliomas. In summary, curcumin and quinacrine liposomes modified with-aminophenyl-α-D-mannopyranoside is a potential preparation to treat brain glioma cells and brain glioma stem cells.

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Liposomal curcumin could rescue part of adriamycin resistance in breast cancer.

PMID: 

Gene. 2017 Jul 30 ;622:1-12. Epub 2017 Apr 18. PMID: 28431975

Abstract Title: 

Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression.

Abstract: 

BACKGROUND: Emerging evidence suggests that curcumin can overcome drug resistance to classical chemotherapies, but poor bioavailability and low absorption have limited its clinical use and the mechanisms remain unclear. Also, Adriamycin (Adr) is one of the most active cytotoxic agents in breast cancer; however, the high resistant rate of Adr leads to a poor prognosis.METHODS: We utilized encapsulation in liposomes as a strategy to improve the bioavailability of curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr-resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay. The miRNA and mRNA expression profiles of MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr cells were analyzed by microarray and further confirmed by real-time PCR. We focused on differentially expressed miR-29b-1-5p to explore the involvement of miR-29b-1-5p in the resistance of Adr. Candidate genes of dysregulated miRNAs were identified by prediction algorithms based on gene expression profiles. Networks of KEGG pathways were organized by the selected dysregulated miRNAs. Moreover, protein-protein interaction (PPI) was utilized to map protein interaction networks of curcumin regulated proteins.RESULTS: We first demonstrated liposomal curcumin could rescue part of Adriamycin resistance in breast cancer and further identified 67 differentially expressed microRNAs among MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr. The results showed that lower expressed miR-29b-1-5p decreased the IC50 of MCF-7/Adr cells and higher expressed miR-29b-1-5p, weaken the effects of liposomal curcumin to Adr-resistance. Besides, we found that 20 target genes (mRNAs) of each dysregulated miRNA were not only predicted by prediction algorithms, but also differentially expressed in the microarray. The results showed that MAPK, mTOR, PI3K-Akt, AMPK, TNF, Ras signaling pathways and several target genes such as PPARG, RRM2, SRSF1and EPAS1, may associate with drug resistance of breast cancer cells to Adr.CONCLUSIONS: We determined that an altered miRNA expression pattern is involved in acquiring resistance to Adr, and that liposomal curcumin could change the resistance to Adr through miRNA signaling pathways in breast cancer MCF-7 cells.

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