Background: The key enzyme of methylenetetrahydrofolate reductase (MTHFR) is involved in DNA biosynthesis and repair. Objectives: The role of MTHFR C677T polymorphism in susceptibility to breast cancer is controversial. Methods: In the present case-control investigation, 297 individuals consisted of 100 patients with breast cancer and 197 healthy women were studied for MTHFR C677T genotypes, using PCR-RFLP method. Results: The frequency of MTHFR TT genotype was 10% in patients and 3% in controls (P = 0.008). The presence of TT genotype was associated with susceptibility to breast cancer [OR = 1.97, 95%CI: 1.16-3.36, P = 0.012]. The T allele of MTHFR was found in 30% of the patients compared to 27.6% healthy controls (P = 0.024) that enhanced the risk of breast cancer by 1.56 times (95% CI: 1.06-2.3, P = 0.024). There were 71 individuals (71%) with the age of breast cancer diagnosis ≤ 51 years old. Comparing patients with the age of cancer diagnosis ≤ 50 years old with those > 51 years old group indicated a higher frequency of MTHFR TT genotype in the latter (20.7%) compared to the first group (5.6%, P = 0.05). Conclusions: Our study demonstrated an association between the MTHFR C677T polymorphism with the risk of breast cancer among population of Western Iran. Also, our study suggests that the MTHFR TT genotype could be a risk factor for breast cancer in postmenopausal women.

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Herein, the authors synthesised chitosan nanoparticles (Cs NPs) as a resveratrol (RSV) carrier and evaluated their efficacy in stimulating apoptosis in MDA‐MB 231 cells. Blank (Cs NPs) and RSV‐ Cs NPs (RSV‐Cs NPs) were synthesised via ionic gelation and characterised by using fourier‐transform infrared spectroscopy (FTIR), Scanning electron microscope, dynamic light scattering/Zeta potential and RSV release. MDA‐MB 231 cells were treated with RSV, Cs NPs and RSV‐Cs NPs (24, 48, and 72 h), followed by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay. Cell toxicity was evaluated using lactate dehydrogenase assay, and real‐time polymerase chain reaction was performed to explore apoptosis induction. FTIR spectra confirmed the NPs via the formation of cross‐linking bonds. Cs and RSV‐Cs NPs sizes were about 75 and 198 nm with 14 and 24 mV zeta potentials. The RSV entrapment efficiency was 52.34 ± 0.16%, with an early rapid release followed by a sustained manner. Cs and RSV‐Cs NPs inhibited cell proliferation at lower concentrations and IC50 values. RSV‐Cs NPs had the most cytotoxic effect and stimulated intrinsic apoptotic pathway, indicated by increased Bcl‐2‐associated x (BAX), BAX/Bcl‐2 ratio, P53 expressions, reduced Bcl‐2 and upregulated caspases 3, 8 and 9. RSV‐Cs NPs have a great potential to suppress invasive breast cancer cell proliferation by targeting mitochondrial metabolism and inducing the intrinsic apoptotic pathway.

Fabricating degradable polymer-based membranes has attracted much attention for guided bone regeneration. Chitosan/gelatin (Cs/Gel) composites are among the most known scaffolds with structural similarity to bone matrix and a high potential to support cell attachment and proliferation. Recently, plant-derived phenolic compound apigenin has been identified to direct the osteogenic differentiation of mesenchymal stem cells and retain osteoblast metabolic functions. We incorporated apigenin into Cs/Gel membranes to improve apigenin bioavailability and get proper concentrations for efficient biological activities. Apigenin-loaded Cs/Gel membranes were prepared using a solution casting method with various apigenin contents (0, 10, 25, 50, and 100 µM). Chemical composition, morphological characteristics, swelling behavior, degradation rate, and apigenin release from membranes were evaluated. Saos-2 osteoblasts were cultured on membranes to investigate cell-membrane interaction, proliferation, viability, and mineralization under the osteogenic culture condition. The results showed that membranes had homogeneous and moderate rough surfaces, facilitating osteoblast attachment and expansion. Swelling ratios exceeded 200%, reaching a stable rate in 24 h. Apigenin-loaded membranes degraded slower in vitro. Membranes containing lower apigenin concentrations exhibited a higher cargo release profile over 21 days. Apigenin improved osteoblast proliferation and viability, but the mineralization depended on apigenin dose, with optimized values at low concentrations. These data suggested that Cs/Gel membranes loaded with low apigenin contents improved osteoblast survival, proliferation, and mineralization.

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