Cathepsins and cancer risk: a Mendelian randomization study.

Background: Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis. Methods: We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis. Results: After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027-1.114, P = 0.001, PFDR = 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919-0.975, P = 0.0002, P FDR = 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001-1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001-1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012-1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949-0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902-0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938-0.990, P = 0.006). Conclusion: Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer.

Association of composite dietary antioxidant index with depression and all-cause mortality in middle-aged and elderly population.

Current research has shown an increasing acceptance of interventions for depression through dietary modifications. However, whether composite dietary antioxidant index (CDAI) is associated with depression and all-cause mortality in middle-aged and elderly population remains unknown. This study aimed to explore those associations in American middle-aged and elderly population. Weighted logistic regression models and weighted Cox proportional hazard regression models were used to assess the association of CDAI, covariates, depression, and all-cause mortality, respectively. The stability of the results was also determined by a linear trend test based on CDAI quintiles. Restricted cubic spline curves were employed to test for non-linear relationships. In the model adjusted for all covariates, significant associations were found with the ORs (95% CI) for CDAI and depression [0.77 (0.67, 0.89)] and the HRs (95% CI) for CDAI with all-cause mortality[0.91 (0.83, 1.00)]. Upon conducting restricted cubic spline curves, we found that the association between CDAI and depression was linear, whereas the association between CDAI and all-cause mortality was non-linear with an inflection point of -0.19. Statistical significance was only found before the inflection point. In this study of middle-aged and elderly Americans, CDAI was linearly negatively associated with depression and non-linearly negatively associated with all-cause mortality.

Pharmacological and mechanistic aspects of quercetin in osteoporosis.

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/ß-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

Effect of Dietary Puerarin Supplementation on Growth Performance, Immune Response, Antioxidant Capacity, and Intestinal Morphology in Domestic Pigeons (Columba livia).

Puerarin is an isoflavone extracted from Gegen (Pueraria lobata) and has been widely utilized to treat various human diseases; however, information regarding its benefits in animal production is limited. In this study, we aimed to investigate the influence of dietary puerarin supplementation on growth performance, immune organ index, immunoglobulin profile, antioxidant capacity, and intestinal morphology in pigeons. In total, 375 healthy 28-day-old White King pigeons were randomly divided into five groups, each consisting of five replicates and 15 pigeons per replicate. Each group was administered one of five dietary treatments: the basal diet, or the basal diet supplemented with 40, 80, 120, or 160 mg/kg puerarin. Treatment duration was 30 days following a 7-day acclimation period. Puerarin treatment did not significantly alter the growth performance of pigeons but afforded a significant linear enhancement in the thymus index (P < 0.05). Additionally, puerarin supplementation significantly increased serum immunoglobulin A and immunoglobulin M levels in pigeons in a linear manner (P < 0.05). Similarly, puerarin significantly and linearly increased the activities of total antioxidant capacity, superoxide dismutase, glutathione, and catalase in the serum and liver, and decreased the malondialdehyde content (P < 0.05). Moreover, the villus height (VH), crypt depth (CD), and VH/CD ratio of the small intestine (including the duodenum, jejunum, and ileum) increased linearly upon puerarin supplementation (P < 0.05). Collectively, these results indicate that puerarin supplementation could improve the immune response, antioxidant capacity, and intestinal morphology of pigeons.

Association between selenium intake and migraine: a nationwide cross-sectional study.

Background: Dietary interventions for migraine are receiving increasing attention. However, it remains unclear whether there is any relationship between migraine and selenium intake. The aim of this study was to investigate the association between selenium intake and migraine. Methods: We used multivariate logistic regression equations to explore the association between selenium intake and migraine. Restricted cubic splines were used to examine the presence of non-linear relationships. Upon finding a non-linear relationship, a recursive algorithm was used to calculate the inflection point. Population differences were also explored through stratified analysis. Results: In the model adjusted for all covariates, the ORs (95% CI) for the association between selenium intake and migraine were 0.96 (0.88, 1.04), which was no statistical significance. However, the result of the linear trend test with quadrilles of selenium intake indicated the association between selenium intake and migraine may be non-linear. The restricted cubic splines confirmed this non-linear relationship, finding an inflection point (93.1 mcg/day), where the odds of migraine decreased with increasing selenium intake before the inflection point, and no statistically significant relationship was found after the inflection point. The association between selenium intake and migraine was non-linear in all strata except the obese. Conclusion: We found a non-linear association between selenium intake and migraine in the general American population.

Association between niacin intake and depression: A nationwide cross-sectional study.

BACKGROUND: The association between dietary intake and depression is receiving increasing attention. However, the relationship between depressive symptoms and niacin intake is still unclear. The purpose of this study was to explore the association between niacin intake and depressive symptoms. METHODS: We used univariate analysis and multivariate logistic regression equations to explore the association between covariates or niacin intake and depression. Generalized additive models and smoothing fitted curves were used to examine the presence of nonlinear relationships. Upon finding a nonlinear relationship, a recursive algorithm was used to calculate the inflection point . Population differences were also explored through stratified analysis. RESULTS: In the model adjusted for all covariates，the ORs (95 % CI) for the association between niacin intake and depression were 0.94 (0.87, 1.01), which was no statistical significance. However, the result of the linear trend test with quartiles of niacin intake indicated the association between niacin intake and depression may be U-shaped. The generalized additive model confirmed this U-shaped relationship, finding an inflection point (26.6 mg/d). An opposite relationship was observed before and after the inflection point, with ORs (95 % CI) of 0.77 (0.68, 0.87) before the inflection point and 1.13 (1.01, 1.28) after the inflection point. The association in men, Mexican American, White, adults aged<40, and BMI <30 was consistent with the overall tendency. CONCLUSION: We found a U-shaped association between niacin intake and depression in the general American population, and the same association was observed in men, Mexican American, White, adults aged < 40, and BMI < 30.

Causal association between atopic eczema and inflammatory bowel disease: A two-sample bidirectional Mendelian randomization study of the East Asian population.

Observation studies have postulated that atopic eczema is associated with a risk of inflammatory bowel disease in the East Asian population; however, this association does not obviate the biases resulting from confounding effects and reverse causation. This study aimed to determine whether this association is causal in the East Asian population using a bidirectional two-sample Mendelian randomization design. Independent genetic variants obtained from public genome-wide association studies for atopic eczema (4296 cases, 163 807 controls) were extracted to estimate the causal effects on inflammatory bowel disease (2824 cases, 3719 controls) and its two main conditions: Crohn's disease (1690 cases, 3719 controls) and ulcerative colitis (1134 cases, 3719 controls). Atopic eczema was found to be strongly associated with inflammatory bowel disease (odds ratio [95% confidence interval]: 1.520 [1.179, 1.959]; p = 0.001), but not vice versa. Subtype analyses revealed that atopic eczema is significantly associated with Crohn's disease (1.650 [1.293, 2.106]; p = 0.000) but not with ulcerative colitis. Both Crohn's disease and ulcerative colitis were found to be causally related to atopic eczema; Crohn's disease could reduce the risk of atopic eczema (0.866 [0.807, 0.930]; p = 0.000) while ulcerative colitis could increase the risk of atopic eczema (1.112 [1.021, 1.212]; p = 0.015). In conclusion, this study revealed that statistically causal relationships are present between atopic eczema and inflammatory bowel disease in the East Asian population. These findings are significant for guiding the treatment of atopic eczema and inflammatory bowel disease in clinical practice.

Withdrawn: MiR-101-3p inhibits MTX-mediated HMGB1 release and reduces recruitment and M1-like polarization of macrophages through the UBE2D1/KAT2B pathway.

The above article, published online on 5 December 2022, on Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/htj.22448), has been withdrawn by agreement between the journal Editor in Chief, Hari Bhat, and Wiley Periodicals, LLC. The withdrawal has been agreed due to a technical error at the publisher that caused the article to be mistakenly published online although publication had been canceled because the authors did not approve their proof.