Joint association of biological aging and lifestyle with risks of cancer incidence and mortality: A cohort study in the UK Biobank.

BACKGROUND: Aging is a risk factor for cancer incidence and mortality. Biological aging can reflect the aging degree of the body better than chronological age and can be aggravated by unhealthy lifestyle factors. We aimed to assess the joint effect of biological aging and lifestyle with risks of cancer incidence and mortality. METHODS: This study included a total of 281,889 participants aged 37 to 73 from the UK Biobank database. Biological age was derived from chronological age and 9 clinical blood indicators, and lifestyle score was constructed by body mass index, smoking status, alcohol consumption, physical activity, and diet. Multivariate Cox hazard proportional regression model was used to analyze the independent and joint association of biological aging and lifestyle with risks of cancer incidence and mortality, respectively. RESULTS: Over a median follow-up period of 12.3 years, we found that older biological age was associated with increased risks of overall cancer, digestive system cancers, lung, breast and renal cancers incidence and mortality (HRs: 1.12-2.25). In the joint analysis of biological aging and lifestyle with risks of cancer incidence and mortality, compared with unhealthy lifestyle and younger biological age, individuals with healthy lifestyle and older biological age had decreased risks of incidence (8% âˆ¼ 60%) and mortality (20% âˆ¼ 63%) for overall, esophageal, colorectal, pancreatic and lung cancers. CONCLUSIONS: Biological aging may be an important risk factor for cancer morbidity and mortality. A healthier lifestyle is more likely to mitigate the adverse effects of biological aging on overall cancer and some site-specific cancers.

First complete mitochondrial genome of the Alashan ground squirrel (Spermophilus alashanicus) (Rodentia: Sciuridae) from Ningxia, China.

The Alashan ground squirrel (Spermophilus alashanicus) is primarily distributed in the regions of Inner Mongolia and Ningxia, China. In this study, we present the first complete mitochondrial genome of S. alashanicus. The genome spans 16,464 base pairs and comprises 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a single control region with a marked AT bias. The overall GC content is 35.4%. Phylogenetic analyses indicate that S. alashanicus clusters are closely associated with S. dauricus. This comprehensive characterization of the S. alashanicus mitochondrial genome serves as a foundational resource for future studies on mitochondrial evolution, species identification, population genomics, and phylogenetics.

Association of total and different food-derived advanced glycation end-products with risks of all-cause and cause-specific mortality.

Background: advanced glycation end-products (AGEs), formed through a series of non-enzymatic reactions, can promote inflammation and oxidative stress. Their accumulation in the body has been linked to cardiovascular disease (CVD) and cancer. However, the association of total AGEs and AGEs from different food sources with risks of all-cause, CVD, and cancer mortality is still unknown. Methods: we conducted a prospective cohort study of a nationally representative sample of 22 124 participants from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2003-2006. A food frequency questionnaire (FFQ) was utilized to calculate total and different food-derived AGE intake. Associations between various dietary AGE scores and the risk of all-cause, CVD, and cancer mortality were assessed by weighted Cox proportional hazard regression models. Results: over a median follow-up period of 27.1 years, we found that in the general population, AGE scores of both baked foods and meat were risk factors for all-cause, CVD, and cancer mortality. Specially, higher AGE scores in total and those derived from 10 of the 13 food groups were statistically associated with an increased risk of CVD mortality. Egg-, fruit-, and vegetable-derived AGE scores were positively correlated with the risk of cancer mortality. Additionally, there were positive multiplicative and additive interactions between smoking and meat-derived AGE scores on all-cause mortality. Conclusions: high amounts of AGE consumption is associated with an increased risk of CVD mortality, and meat and baked food-derived AGEs were positively linked to all-cause, CVD, and cancer mortalities. Adherence to unhealthy lifestyles, such as smoking, may increase mortality from leading causes in individuals with AGE-enriched diet habits.

Spatial frequency shift super-resolution imaging based on quasiperiodic grating and deep learning.

In this study, we propose a pioneering spatially frequency-shifted super-resolution microscopy technique that utilizes the synergy of quasiperiodic gratings and deep learning. First, a quasiperiodic grating capable of converting evanescent waves into propagating waves is designed. The grating is positioned between the object under investigation and the objective lens, and the high-frequency information carried by the evanescent waves in the near-field region of the object is shifted into the detection window and becomes accessible in the far field for imaging. Subsequently, we provide two deep learning models for image and video reconstructions to achieve the reconstruction of static and dynamic samples respectively. Simulation results demonstrate the high feasibility of the proposed method, and both static and dynamic objects with sub-wavelength features can be resolved. The developed method paves the way to the realization of super-resolution imaging by using a traditional bright-field microscope without the need for an extensive optical system design.

Preparation of COPs Mixed Matrix Membrane for Sensitive Determination of Six Sulfonamides in Human Urine.

In this study, TpDMB-COPs, a specific class of covalent organic polymers (COPs), was synthesized using Schiff-base chemistry and incorporated into a polyvinylidene fluoride (PVDF) polymer for the first time to prepare COPs mixed matrix membranes (TpDMB-COPs-MMM). A membrane solid-phase extraction (ME) method based on the TpDMB-COPs-MMM was developed to extract trace levels of six sulfonamides from human urine identified by high-performance liquid chromatography (HPLC). The key factors affecting the extraction efficiency were investigated. Under the optimum conditions, the proposed method demonstrated an excellent linear relationship in the range of 3.5-25 ng/mL (r2 ≥ 0.9991), with the low limits of detection (LOD) between 1.25 ng/mL and 2.50 ng/mL and the limit of quantification (LOQ) between 3.50 ng/mL and 7.00 ng/mL. Intra-day and inter-day accuracies were below 5.0%. The method's accuracy was assessed by recovery experiments using human urine spiked at three levels (7-14 ng/mL, 10-15 ng/mL, and 16-20 ng/mL). The recoveries ranged from 87.4 to 112.2% with relative standard deviations (RSD) ≤ 8.7%, confirming the applicability of the proposed method. The developed ME method based on TpDMB-COPs-MMM offered advantages, including simple operation, superior extraction affinity, excellent recycling performance, and easy removal and separation from the solution. The prepared TpDMB-COPs-MMM was demonstrated to be a promising adsorbent for ME in the pre-concentration of trace organic compounds from complex matrices, expanding the application of COPs and providing references for other porous materials in sample pre-treatment.

Associations of physical frailty with incidence and mortality of overall and site-specific cancers: A prospective cohort study from UK biobank.

OBJECTIVE: Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. METHODS: This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. RESULTS: A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. CONCLUSIONS: Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking.

Association between diabetes at different diagnostic ages and risk of cancer incidence and mortality: a cohort study.

Background: Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37-73 years. Methods: Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41-50, 51-60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses. Results: Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41-50, 51-60, and >60 years, especially at 51-60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51-60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088-2.416, HR for mortality: 1.276-3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51-60 years. Conclusion: Our findings highlighted that the age at diagnosis of diabetes, especially 51-60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer.

Does inclusion of bioactive n-3 PUFAs in parenteral nutrition benefit postoperative patients undergoing liver surgery? A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs. DATA EXTRACTION AND SYNTHESIS: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively. RESULTS: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups. CONCLUSIONS: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration.

Preparation of a Multifunctional and Multipurpose Chitosan/Cyclodextrin/MIL-68(Al) Foam Column and Examining Its Adsorption Properties for Anionic and Cationic Dyes and Sulfonamides.

A multifunctional cylindrical hybrid foam column, referred to as the chitosan/cyclodextrin/MIL-68(Al) (CS/CD/MIL-68(Al)) foam column, was prepared for the first time. The prepared foam column could be used for the adsorption/removal of hydrophilic and hydrophobic contaminants by different forms. Here, it was placed in hydrophilic dye solutions to investigate the adsorption behavior of methylene blue and trypan blue. The adsorption process followed the pseudo-second-order kinetic model with R2 ranging from 0.9983 to 0.9998 for methylene blue and from 0.9993 to 1.0000 for trypan blue, and the adsorption process was consistent with the Langmuir isothermal model with R2 greater than 0.96. The RL values for methylene blue and trypan blue were 0.8871 and 0.5366, respectively, which were present between 0 and 1, indicating that the adsorption behaviors of the two dyes onto the CS/CD/MIL-68(Al) foam column were favorable. The maximum adsorption capacities (Qm) of methylene blue and trypan blue were 60.61 and 454.55 mg/g at 298 K, respectively. Also, the CS/CD/MIL-68(Al) foam column was spun into a syringe and used to adsorb trace hydrophobic sulfonamides from water in the form of filtration. The porous structure impeded the need for any external force and equipment, allowing the water sample to pass through the foam column smoothly. The conditions of the CS/CD/MIL-68(Al) foam column were optimized. The adsorption was carried out under the condition of pH = 4, the amount of the adsorbent was two foam columns, and no salt was added. It was found that the removal rate of the CS/CD/MIL-68(Al) foam column for six sulfonamides was 100%, and it could be reused at least five times. Therefore, this CS/CD/MIL-68(Al) foam column had a simple preparation method, offered a flexible and diverse form of use, was nonpolluting, biodegradable, and reusable, and could have a wider application in the field of environmental pollutant removal and adsorption.

Plant-based dietary patterns, genetic predisposition and risk of colorectal cancer: a prospective study from the UK Biobank.

BACKGROUND: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. METHODS: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. RESULTS: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. CONCLUSIONS: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

An enzyme-based system for extraction of small extracellular vesicles from plants.

Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.

Plasma One-Carbon Metabolism-Related Micronutrients and the Risk of Breast Cancer: Involvement of DNA Methylation.

Findings of epidemiologic studies focusing on the association between one-carbon metabolism-related micronutrients and breast cancer risk, along with the involvement of DNA methylation, have been inconsistent and incomprehensive. We conducted a case-control study in China including 107 paired participants and comprehensively detected 12 plasma one-carbon metabolism-related micronutrients. Genomic DNA methylation was measured using an 850 K chip and differential methylation probes (DMPs) were identified. Multivariate logistic regression was performed to estimate the associations between plasma micronutrients and the odds of breast cancer. The mediation of selected DMPs in micronutrient breast cancer associations was examined using mediation analyses. An inverse association of plasma folate, methionine cycling-related micronutrients (methionine, S-adenosylmethionine, and S-adenosylhomocysteine), and all micronutrients in the choline metabolism and enzymatic factor groups, and a positive association of methionine cycling-related cysteine with breast cancer risk were observed. Nine micronutrients (methionine, cysteine, SAM, folate, choline, betaine, P5P, vitamins B2, and B12) were related to global or probe-specific methylation levels (p < 0.05). The selected DMPs mediated the micronutrient breast cancer associations with an average mediation proportion of 36.43%. This study depicted comprehensive associations between circulating one-carbon metabolism-related micronutrients and breast cancer risk mediated by DNA methylation.

The state of female hepato-pancreato-biliary (HPB) surgeons in China: see us in operation theater with great prospects.

OBJECTIVE: This study aims to investigate the proportion and distribution of female HPB surgeons in China, describe their current status, and analyze the possible barriers and challenges in their careers. METHOD: Tertiary hospitals with the division of HPB in mainland China in 2021 were enrolled and surgeon demographic information was collected through the review of official websites and/or telephone interviews. RESULTS: The majority of female HPB surgeons (72.92%) were located in the first or second-tier cities in mainland China, with an increasing number of new female HPB surgeons entering the field annually, particularly after 2005 (from 27 to 52 per 5 years). Despite no significant difference in academic backgrounds, female HPB surgeons initiated their careers at an earlier age and took a longer time to obtain chief titles (P < 0.05). Interestingly, female HPB surgeons performed laparoscopic complex HPB cases at a similar rate (95.42%) to their male counterparts and were more likely to specialize in endoscopic surgery (P = 0.021), with a similar ratio of obtaining administrative positions. CONCLUSION: Minimally invasive surgery may provide females with unprecedented opportunities in the HPB surgery field. However, despite the increasing numbers of female HPB surgeons, the proportion remains low in China.

Association between the Finnish Diabetes Risk Score and cancer in middle-aged and older adults: Involvement of inflammation.

BACKGROUND: Diabetes is associated with increased risk of common cancers. However, evidence of cancer risk in individuals with different diabetes risk is still scarce, and the underlying mechanism remains unknown. Therefore, we aimed to evaluate the relationship between the Finnish Diabetes Risk Score (FINDRISC) and risks of cancer incidence and mortality in a prospective study, and to explore whether low-grade inflammation partially mediated the association. METHODS: A total of 330,384 participants aged 37 to 73 at baseline from the UK Biobank database was included in this study. The Cox proportional hazards model was used to examine the relationship of the FINDRISC and low-grade inflammation with risks of cancer incidence and mortality. Then, we estimated the contribution of higher FINDRISC to risks of overall and site-specific cancers. In addition, the role of low-grade inflammation in the association between FINDRISC and cancer risks was investigated through mediation analysis. RESULTS: The increased FINDRISC was dose-dependently associated with higher incidence and mortality risks of overall cancer and an overwhelming majority of site-specific cancers. The higher FINDRISC was a strong contributor to incidence of eighteen site-specific cancers and mortality of fourteen site-specific cancers, with a population-attributable risk of 8.1 %-39.1 %, 14.2 %-39.7 %, respectively. Additionally, low-grade inflammation mainly mediated the association between the FINDRISC and risks of incidence and mortality of overall cancer, colorectal cancer, etc. CONCLUSIONS: Our findings highlighted the higher FINDRISC as critical risk factors of cancer incidence and mortality, partially mediated by low-grade inflammation. Individuals with increased risk of diabetes are also needed to be concerned about cancer prevention.

Pharmacological network analysis of the functions and mechanism of kaempferol from Du Zhong in intervertebral disc degeneration (IDD).

Background: Senescence and apoptosis of the nucleus pulposus cells (NPCs) are essential components of the intervertebral disc degeneration (IDD) process. Senescence and anti-apoptosis treatments could be effective ways to delay or even stop disc degeneration. IDD has been treated with Eucommia ulmoides Oliver (Du Zhong, DZ) and its active ingredients. However, the roles and mechanisms of DZ in NPC apoptosis and senescence remain unclear. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to select the main active ingredients of DZ with the threshold of oral bioavailability (OB) â€‹≥ â€‹30% and drug-likeness (DL) â€‹≥ â€‹0.2. GSE34095 contained expression profile of degenerative intervertebral disc tissues and non-degenerative intervertebral disc tissues were downloaded for different expression genes analysis. The disease targets genes of IDD were retrieved from GeneCards. The online tool Metascape was used for functional enrichment annotation analysis. The specific effects of the ingredient on IL-1ß treated NPC cell proliferation, cell senescence, reactive oxygen species (ROS) accumulation and cell apoptosis were determined by CCK-8, SA-ß-gal staining, flowcytometry and western blot assays. Results: A total of 8 active compounds of DZ were found to meet the threshold of OB â€‹≥ â€‹30% and DL â€‹≥ â€‹0.2 with 4151 drug targets. After the intersection of 879 IDD disease targets obtained from GeneCards and 230 DEGs obtained from the IDD-related GSE dataset, a total of 13 hub genes overlapped. According to functional enrichment annotation analysis by Metascape, these genes showed to be dramatically enriched in AGE-RAGE signaling, proteoglycans in cancer, wound healing, transmembrane receptor protein tyrosine kinase signaling, MAPK cascades, ERK1/2 cascades, PI3K/Akt signaling pathway, skeletal system, etc. Disease association analysis by DisGeNET indicated that these genes were significantly associated with IDD, intervertebral disc disease, skeletal dysplasia, and other diseases. Active ingredients-targets-signaling pathway networks were constructed by Cytoscape, and kaempferol was identified as the hub active compound of DZ. In the IL-1ß-induced IDD in vitro model, kaempferol treatment significantly improved IL-1ß-induced NPC cell viability suppression and senescence. In addition, kaempferol treatment significantly attenuated IL-1ß-induced ROS accumulation and apoptosis. Furthermore, kaempferol treatment partially eliminated IL-1ß-induced decreases in aggrecan, collagen II, SOX9, and FN1 levels and increases in MMP3, MMP13, ADAMTS-4, and ADAMTS-5. Moreover, kaempferol treatment significantly relieved the promotive effects of IL-1ß stimulation upon p38, JNK, and ERK1/2 phosphorylation. ERK1/2 inhibitor PD0325901 further enhanced the effect of kaempferol on the inhibition of ERK1/2 phosphorylation, downregulation of MMP3 and ADAMTS-4 expression, and upregulation of aggrecan and collagen II expressions. Conclusion: Kaempferol has been regarded as the major active compound of DZ, protecting NPCs from IL-1ß-induced damages through promoting cell viability, inhibiting cell senescence and apoptosis, increasing ECM production, and decreasing ECM degradation. MAPK signaling pathway may be involved. The translational poteintial of this article: This study provides in vitro experimental data support for the pharmacological effects of kaempferol in treating IDD, and lays a solid experimental foundation for its future clinical application in IDD treatment.

Association of serum Klotho levels with cancer and cancer mortality: Evidence from National Health and Nutrition Examination Survey.

BACKGROUND: Klotho has both anticancer and hormone-like functions. But the research on Klotho and cancer is mainly based on animal experiments and small-scale clinical research, thus we explored the association between serum Klotho and cancer and cancer mortality based on the National Health and Nutrition Survey (NHANES). METHODS: Participants were employed from the NHANES 2007-2016, excluding pregnant, chronic renal insufficiency, and incomplete data of cancer questionnaire and serum Klotho level. The association of serum Klotho with cancer and mortality was analyzed by weighted Logistic regression, weighted Cox regression and competitive risk model, respectively. Correlations between serum Klotho and testosterone and estradiol levels were analyzed by Spearman correlation and restricted cubic spline respectively. RESULTS: We found Klotho had an inverse effect with risk of pan-cancer (all p < 0.02), with each unit increase in Klotho (1ug/g creatinine) associated with a 0.9%-2.2% reduction in the risk of cancer, and higher levels showing a stronger negative association (all p-trend <= 0.0005). Whereas, we did not observe any association between serum Klotho level with all-cause mortality and cancer-specific mortality (all p > 0.05). Then, stratified analysis found that people aged 60-79, female, overweight and non-Hispanic whites or Mexican Americans were less likely to develop cancer. In addition, there was a strong nonlinear and linear positive correlation of Klotho with estradiol (p-nonlinear = 0.0178) and testosterone only among male participants (ß = -0.513, p = 0.0137), respectively. CONCLUSIONS: We found an inverse association between serum Klotho and cancer, but without cancer mortality. And this effect may be partially mediated by estradiol and testosterone. Further prospective studies are needed to prove these findings.

Association of urinary phytoestrogens with hormone-related cancers and cancer biomarkers: NHANES 1999-2010.

Phytoestrogens may have potential effects on hormone-related cancers (HRC) and cancer biomarkers, but the findings have been inconsistent so far. Participants from the National Health and Nutrition Examination Survey 1999-2010 with information on the levels of urinary phytoestrogens, serum cancer biomarkers and cancer history were included. Sampling-weighted logistic regression models examined the association between urinary phytoestrogens concentrations (creatinine-standardised and log-transformed) and HRC, followed by stratified analyses by race/ethnicity, age and menopausal status for different gender. Correlation analyses between phytoestrogens and cancer biomarkers were performed. Of the total 8844 participants, there were 373 with HRC. We observed total isoflavone and enterodiol excretion were positively associated with HRC, especially in non-Hispanic white female subpopulations (Ptrend < 0·05). Similar association also existed in the total isoflavones and enterodiol levels with breast cancer. Whereas the highest concentration of total isoflavones was significantly linked to a reduced prevalence of HRC (OR = 0·40, 95 % CI: 0·19, 0·84) in white males and of prostate cancer (OR = 0·40, 95 % CI: 0·18, 0·86). Among twenty-four participants with HRC, urinary equol concentration was positively correlated with CA15.3. Also, an inverse correlation of total prostate-specific antigens (PSA) and positive correlation of the PSA ratio with urinary enterolactone were detected in thirteen prostate cancer patients. Our findings indicated that higher concentrations of total isoflavones and enterodiol were positively associated with HRC. Urinary certain phytoestrogen excretion may affect serum cancer biomarker levels in cancer patients. But further prospective studies are needed to provide stronger evidence.

The Number of Positive Tumor Markers (NPTM) Achieves Higher Value in the Prognosis Prediction of Gastric Cancer.

Purpose: The clinical application of combined tumor markers is still limited. We aim to explore the value of the combination of multiple tumor markers in gastric cancer (GC) prognosis. Methods: The prognostic significance was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The estimated area under the curve (AUC) was compared to evaluate the discriminatory ability of different indicators. A nomogram was constructed based on the results of multivariable cox regression, and its performance was evaluated by Harrell's concordance index and calibration curve. Results: NPTM (number of positive tumor markers) displayed independent prognostic significance whether in the whole cohort or in patients with different stages. Patients with the all-negative tumor markers had a worse prognosis after postoperative chemotherapy in all cohort (P = 0.023) or in age ≤60 subgroup (P = 0.012), while patients with positive tumor markers had a better prognosis after postoperative chemotherapy in stage III (P = 0.012). The AUC value of NPTM is higher than any individual tumor marker. The 1-, 3-, and 5-year AUC values of the CTNM (combination of NPTM and pTNM) increased by 5%, 4.8%, and 3.6%, respectively, compared with TNM staging system. The nomogram constructed including NPTM showed its high accuracy (C - index = 0.706) versus TNM staging system (C - index = 0.646) and CTNM (C - index = 0.681). Conclusions: NPTM was an independent predictor of gastric cancer prognosis, showing more accurate prognostic performance than individual tumor markers. Especially its significance in guiding postoperative adjuvant chemotherapy regimens and predicting prognosis by combination with TNM staging system may have a better clinical application value.

Genetically Modified Circulating Levels of Advanced Glycation End-Products and Their Soluble Receptor (AGEs-RAGE Axis) with Risk and Mortality of Breast Cancer.

The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer.

Drug Value of Drynariae Rhizoma Root-Derived Extracellular Vesicles for Neurodegenerative Diseases Based on Proteomics and Bioinformatics.

Extracellular vesicles (EVs) are nano-sized membrane vesicles released by various cell types. Mammalian EVs have been studied in-depth, but the role of plant EVs has rarely been explored. For the first time, EVs from Drynariae Rhizoma roots were isolated and identified using transmission electron microscopy and a flow nano analyzer. Proteomics and bioinformatics were applied to determine the protein composition and complete the functional analysis of the EVs. Seventy-seven proteins were identified from Drynariae Rhizoma root-derived EVs, with enzymes accounting for 47% of the proteins. All of the enzymes were involved in important biological processes in plants. Most of them, including NAD(P)H-quinone oxidoreductase, were enriched in the oxidative phosphorylation pathway in plants and humans, and Alzheimer's disease, Huntington's disease, and Parkinson's disease, which are associated with oxidative stress in humans. These findings suggested that EVs from Drynariae Rhizoma roots could alleviate such neurological diseases and that enzymes, especially NAD(P)H-quinone oxidoreductase, might play an important role in the process.