Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of autophagy-related genes and modulators in colorectal carcinogenesis, and to develop potential beneficial agents for the prognosis and treatment of CRC.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Osteoarthritis (OA) is a multifactorial disease characterized by low‑grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case‑control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL‑4R ‑3223C>T (rs2057768), IL‑8 ‑251T>A (rs4073), IL‑10 ‑1082A>G (rs1800896) and TNF ‑A‑308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL‑4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21‑3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17‑3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL‑4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL‑4/IL‑4R pair in the pathogenesis of OA.

Background & Aims: MicroRNAs (miRNAs) play an important role in the occurrence and progression of human cancers, including gastric cancer. Our hospital-based case-control study aimed to investigate whether four commonly studied single nucleotide polymorphisms (SNPs) have effects on susceptibility to gastric cancer in a Romanian population.Method: We genotyped the miR-27a rs895819, miR-146a rs2910164, miR-196a2 rs11614913 and miR-499 rs3746444 SNPs by real-time PCR using predesignated TaqMan assays in 430 individuals (142 gastric cancer patients and 288 age and gender matched cancer-free controls). The associations between the investigated miRNA SNPs and gastric cancer risk were assessed by odds ratio (OR) with 95% confidence interval (CI) using logistic regression analysis.Results: A higher frequency of the miR-27a rs895819 CC genotype (OR 1.98, 95% CI: 1.05-3.73, p=0.036) was found in the patients with gastric cancer compared with the controls. Similar results were observed in a recessive model, the CC genotype was correlated with gastric cancer susceptibility (OR 1.95, 95% CI: 1.07-3.55, p=0.032). In the stratified analysis, the association between miR-27a rs895819 SNP and gastric cancer risk was limited to noncardia (OR 2.08, 95% CI: 1.10-3.94, p=0.027) and intestinal (OR 2.27, 95% CI: 1.05-4.92, p=0.042) subgroups. However, after Bonferroni correction, all associations described above lost statistical significance. No correlation was observed for the remaining SNPs and risk of gastric cancer in any genetic model studied.Conclusion: This study showed no association of the investigated miRNA SNPs with the risk of gastric cancer in a Romanian population.Key words: – – – .Abbreviations: GC: gastric cancer; miRNA: microRNA; SNP: single nucleotide polymorphism.