The recent emergence of coronavirus disease 2019 (COVID-19) pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This

Aims/hypothesis Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This casecohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Methods Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prenticeweighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. Results A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n=778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m 2 and 102.7 cm in men, and 30.1 kg/m 2 and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. Conclusions/interpretation InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

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Urokinase-type plasminogen activator (uPA) is a serine protease that is involved in cancer progression, especially invasion and metastasis including prostate cancer. uPA activation is mediated by transactivation of uPAR and epidermal growth factor receptor (EGF-R) in prostate cancer progression. Prostate cancer (PC-3) cells have highly invasive capacity and they express uPA and uPAR gene. PC-3 cells are treated with quercetin, which inhibits invasion and migration of PC-3 cells. Quercetin downregulates uPA, uPAR and EGF, EGF-R mRNA expressions. Quercetin inhibits cell survival factor β-catenin, NF-κB and also proliferative signalling molecules such as p-EGF-R, N-Ras, Raf-1, c.Fos c.Jun and p-c.Jun protein expressions. But quercetin increased p38 mitogen-activated protein kinase protein expression. Our results suggest that quercetin inhibit migration and invasion of prostate cancer cells. It shows the value for treatment of invasive and metastasis type of prostate cancer.

Progression of prostate cancer is facilitated by growth factors that activate critical signaling cascades thereby promote prostate cancer cell growth, survival, and migration. To investigate the effect of quercetin on insulin-like growth factor signaling and apoptosis in androgen independent prostate cancer cells (PC-3), IGF-IR, PI-3K, p-Akt, Akt, cyclin D1, Bad, cytochrome c, PARP, caspases-9 and 10 protein levels were assessed by western blot analysis. Mitochondrial membrane potency was detected by rhodamine-123 staining. Quercetin induced caspase-3 activity assay was performed for activation of apoptosis. Further, RT-PCR was also performed for Bad, IGF-I, II, IR, and IGFBP-3 mRNA expression. Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells. IGF-IRβ, PI3K, p-Akt, and cyclin D1 protein expression and mRNA levels of IGF-I, II and IGF-IR were decreased significantly. Further, treatment with PI3K inhibitor (LY294002) and quercetin showed decreased p-Akt levels. Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells. This study suggests that quercetin decreases the survival of androgen independent prostate cancer cells by modulating the expression of insulin-like growth factors (IGF) system components, signaling molecules and induces apoptosis, which could be very useful for the androgen independent prostate cancer treatment.

Prostate cancer is responsible for major deaths globally after lung cancer. Nimbolide is an important constituent of neem, and it acts as a potent inhibitor for many cancer cells. The present study was designed to evaluate the effects of nimbolide on apoptosis and insulin-like growth factor (IGF) signalling molecules in androgen-independent prostate cancer (PC-3) cells line. Nimbolide (0.5-2 μM) treatment resulted in 50% inhibition at a dose of 2 μM in the PC-3 cell line. The mRNA expression of Fas ligand, Fas-associated death domain receptor (FADDR), Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter (Bad), phosphatidylinositide 3-kinases (PI3K), Akt, IGF1, IGF1 receptor (IGF1R) and IGF binding protein 3 were quantified by reverse transcription polymerase chain reaction and protein expression of Bax, cytochrome c, X-linked inhibitor of apoptosis protein (XIAP), B-Cell Lymphoma 2 (Bcl-2), caspases -8, -9, -10 and -3, poly(ADP-ribose) polymerase (PARP), cleaved PARP, IGF1R, PI3K, Akt, p-Akt was determined by western blot analysis, in nimbolide-treated PC-3 cell line. Nimbolide-induced apoptosis by activating DNA fragmentation in PC-3 cells. Nimbolide treatment increased the mRNA of Fas ligand, FADDR, Bax, Bad and IGF binding protein 3, decreased PI3K, Akt, IGF1 and IGF1R, increased protein expression of caspases 8, 3, 10, 9, Bax and cytochrome c and decreased the expression of XIAP, Bcl2, cleaved PARP, p-Akt and IGF1R. The results suggest that nimbolide acts as a potent anti-cancer agent by inducing apoptosis and inhibiting cell proliferation via PI3K/Akt pathway in PC-3 cells.

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