No abstract

Background: Statins are widely utilized antidyslipidemics with a proven track record of safety and efficacy. However, the efficacy of these therapeutic agents hinges on patients' adherence to their prescribed statins. Objective: The primary objectives of this study were to examine the relationship between adherence to prescribed statins and its impact on the low-density lipoprotein (LDL) level, and to explore the factors that influence patient adherence to statins among patients with diabetes and dyslipidemia. Methods: This was a retrospective, cross-sectional study using the electronic health records data of adults (≥18 years) with type 2 diabetes and dyslipidemia visiting outpatient clinics at a university-affiliated tertiary care center. Adherence to statin therapy was estimated using the proportion of days covered (PDC). Patients with diabetes were considered adherent to statins if they had a PDC of ≥80%. Treatment success was considered if the LDL level of < 2.6 mmol/L. Results: Out of 10,226 of patients with diabetes, 1532 met the inclusion criteria and were included in the study. Seventy-nine percent of the patients with diabetes were on atorvastatin and 21% were on simvastatin. The vast majority of the patients with diabetes (77%) were considered adherent and about 42% achieved LDL-cholesterol goal < 2.6 mmol/L. No association between adherence to statin therapy and LDL goal attainment was observed. Women had lower odds of being adherent to statin therapy (AOR=0.66, 95% CI: 0.49-0.87) compared to men. Further, young adults (18-44 years) had lower odds of being adherent to statin therapy (AOR=0.58, 95% CI: 0.32-0.97) compared to older adults (age>65 years). Conclusion: The findings of this study highlight the need to examine the impact of adherence to statins on healthcare services utilization due to different complications of uncontrolled dyslipidemia.

Background The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer’s onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11–7082. Results The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381–452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range −9.99±0.8 to −34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Drug uptake and distribution through cell–receptor interactions are of prime interest in reducing the adverse effects and increasing the therapeutic effectiveness of delivered formulations. This study aimed to formulate silver nanoparticles (AgNPs) conjugated to somatostatin analogs for specific delivery through somatostatin receptors (SSTRs) expressed on cells and by nebulizing the prepared AgNPs formulations into lung cells for in vivo application. AgNPs were prepared using the citrate reduction method, yielding AgNPs–CTT, which was further chemically conjugated to octreotide (OCT) to form AgNPs–OCT through an amide linkage. The AgNPs–OCT formulation was coated using alginate to yield a carrier, AgNPs–OCT–Alg, feasible for drug delivery through nebulization. AgNPs were uniform in size with an acceptable range of zeta potential. Furthermore, the concentrations of AgNP formulations were found safe for the model cell lines used, and cell proliferation was significantly reduced in a dose-dependent manner (p < 0.05). In the healthy lung tissues, AgNPs–OCT–Alg accumulated at a concentration of 0.416 ± 5.7 mg/kgtissue, as determined via inductively coupled plasma optical emission spectrometry. This study established the accumulation of AgNPs, specifically the AgNPs–OCT–Alg, in lung tissues, and substantiated the active, specific, and selective targeting of SSTRs at pulmonary sites. The anticancer efficacy of the formulations was in vitro tested and confirmed in the MCF-7 cell lines. Owing to the delivery suitability and cytotoxic effects of the AgNPs–OCT–Alg formulation, it is a potential drug delivery formulation for lung cancer therapy in the future.

No abstract