Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study.

BACKGROUND: Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. METHODS: We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67-0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44-0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. CONCLUSIONS: Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Integrated small RNA, mRNA and protein omics reveal a miRNA network orchestrating metabolic maturation of the developing human heart.

BACKGROUND: As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases in a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such as microRNAs (miRNAs), contribute to the establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics and genome-wide miRNA regulatory networks controlling maturation of the human fetal heart remain poorly understood. RESULTS: Transcriptome profiling of small RNAs revealed the temporal expression patterns of miRNA, piRNA, circRNA, snoRNA, snRNA and tRNA in the developing human heart between 8 and 19 weeks of gestation. Our analysis demonstrated that miRNAs were the most dynamically expressed small RNA species throughout mid-gestation. Cross-referencing differentially expressed miRNAs and mRNAs predicted 6200 mRNA targets, 2134 of which were upregulated and 4066 downregulated as gestation progressed. Moreover, we found that downregulated targets of upregulated miRNAs, including hsa-let-7b, miR-1-3p, miR-133a-3p, miR-143-3p, miR-499a-5p, and miR-30a-5p predominantly control cell cycle progression. In contrast, upregulated targets of downregulated miRNAs, including hsa-miR-1276, miR-183-5p, miR-1229-3p, miR-615-3p, miR-421, miR-200b-3p and miR-18a-3p, are linked to energy sensing and oxidative metabolism. Furthermore, integrating miRNA and mRNA profiles with proteomes and reporter metabolites revealed that proteins encoded in mRNA targets and their associated metabolites mediate fatty acid oxidation and are enriched as the heart develops. CONCLUSIONS: This study presents the first comprehensive analysis of the small RNAome of the maturing human fetal heart. Our findings suggest that coordinated activation and repression of miRNA expression throughout mid-gestation is essential to establish a dynamic miRNA-mRNA-protein network that decreases cardiomyocyte proliferation potential while increasing the oxidative capacity of the maturing human fetal heart. Our results provide novel insights into the molecular control of metabolic maturation of the human fetal heart.

Association between adherence to Eat-Lancet diet and incidence and mortality of lung cancer: A prospective cohort study.

Previous research has shown that adhering to the Eat-Lancet diet (ELD) is associated with a lower risk of chronic diseases and mortality. However, the associations between ELD and lung cancer incidence and mortality are unclear. To address this gap, we conducted a prospective cohort study involving 101,755 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial in the USA. The ELD score was utilized to assess compliance with the ELD, with higher scores indicating greater compliance. We employed Cox regression analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ELD score with the incidence and mortality of lung cancer and its subtypes. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In total, 1706 cases of lung cancer and 1217 lung cancer-associated deaths were recorded during the study period. Our analysis revealed that higher ELD scores were significantly associated with a reduced incidence (HRQuartile 4 vs. Quartile 1 : 0.73; 95% CI: 0.60, 0.89; ptrend = 0.001) and mortality (HRQuartile 4 vs. Quartile 1 : 0.74; 95% CI: 0.59, 0.93; ptrend = 0.005) of lung cancer in a dose-response manner (all pnonlinearity > 0.05). The reliability of these results was supported by sensitivity analyses. Notably, these associations were primarily observed in non-small-cell lung cancer. In conclusion, our findings suggest that adherence to the ELD may be associated with a reduced risk of lung cancer incidence and mortality.

Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study.

BACKGROUND: The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined. METHODS: A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61-0.95, Ptrend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55-0.97, Ptrend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51-0.81, Ptrend < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46-0.83, Ptrend = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48-0.98, Ptrend = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53-0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68-1.67) (Pinteraction = 0.02). CONCLUSIONS: Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk.

Association of diabetes risk reduction diet with renal cancer risk in 101,755 participants: a prospective study.

BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Predictive factors on postoperative venous thromboembolism after minimally invasive colorectal cancer surgery: a retrospective observational study.

BACKGROUND: Venous thromboembolism (VTE) is a serious and preventable postoperative complication. However, the predictive significance of perioperative biochemical parameters for VTE after minimally invasive colorectal cancer surgery remains unclear. METHODS: A total of 149 patients undergoing minimally invasive colorectal cancer surgery were collected between October 2021 and October 2022. Biochemical parameters related to preoperative and postoperative day 1, day 3, and day 5 were collected, including D-Dimer, mean platelet volume (MPV), and maximum amplitude (MA) of thromboelastography (TEG). Receiver operating characteristic (ROC) curves were used to explore the predictive powers of meaningful biochemical parameters for postoperative VTE, and calibration curves were used to assess predictive accuracy. RESULTS: The overall cumulative incidence of VTE was 8.1% (12/149). The preoperative and postoperative day 3 D-Dimer, postoperative day 3, and day 5 MPV, and postoperative day 1, day 3, and day 5 TEG-MA was significantly higher in the VTE group than in the non-VTE group (P < 0.05). The results of both the ROC curve and the calibration curve indicated that these meaningful D-Dimer, MPV, and TEG-MA had moderate discrimination and consistency for postoperative VTE. CONCLUSIONS: D-Dimer, MPV, and TEG-MA may predict postoperative VTE in patients undergoing minimally invasive surgery for colorectal cancer at specific times in the perioperative period.

Influencing factors associated with quality of life and depression among COVID-19 survivors during convalescence.

This study aims to investigate influencing factors of quality of life (QoL) and depression among COVID-19 survivors during convalescence. A cross-sectional study was conducted in November 2020 in Wuhan, China. Information on social support, physical activity, QoL and depressive symptoms were assessed using self-administered questionnaires. Multivariate linear regression and multivariate logistic regression were used to assess the risk factors of subdomains of QoL (physical component score (PCS) and mental component score (MCS)) and depression, respectively. A total of 151 COVID-19 survivors (68 males) aged 53.21 (SD: 12.70) years participated in the study. Multivariate linear regression showed that age (ß=-0.241), history of chronic disease (ß=-0.4.774), physical activity (ß = 2.47) and social support (ß = 0.147) were significantly associated with PCS, while having a spouse (ß = 9.571), monthly income (ß = 0.043) and social support (ß = 0.337) were significantly associated with MCS. Logistic regression suggested that participants aged 40-60 years (OR = 10.20, 95%CI: 1.41-73.82) or above 60 years (OR = 15.63, 95%CI: 1.87-131.00), with high school or above education (OR = 5.81, 95%CI: 1.24-27.20), with low/moderate physical activity (low, OR = 2.97, 95%CI: 1.14-7.77; moderate, OR = 3.42, 95%CI: 1.07-10.91) and low/medium social support (low, OR = 4.81, 95% CI: 2.02-11.43; medium, OR = 9.70, 95%CI: 1.17-80.10) were more likely to be depressed, while higher monthly income (≥3000 Yuan RMB/month) was associated with lower risk for depression (OR = 0.27, 95%CI: 0.09-0.82). These findings indicate COVID-19 survivors with older age, having chronic conditions, without a spouse, low monthly income, low level of physical activity and social support had significantly increased risks for poor QoL and depression, and more attention should be given to this population.

Maternal obesity induces liver lipid accumulation of offspring through the lncRNA Lockd/mTOR autophagy pathway.

Maternal obesity increases the risk of obesity and metabolic diseases in the offspring in early life, but the underlying mechanism has not been elucidated. The aim of this study is to explore whether lncRNA and autophagy are involved in the regulation of maternal obesity on the liver lipid metabolism of the offspring. C57BL/6 mice were fed high-fat diet (HFD) or standard chow diet (CD) for 12 weeks before the start of mating and continued until the end of the lactation period. The lipid metabolism indexes of the three-week-old offspring were detected. The RNA sequencing (RNA-seq) and western blot analysis for autophagy-related protein were performed on the offspring's liver to determine the comprehensive expression profile of lncRNA and autophagy level. In addition, AML12 cells were treated with small interfering RNA (siRNA) and rapamycin. Western blot, qRT-PCR and Oil Red O staining were used to detect protein expression, mRNA expression and lipid accumulation levels. As a result, maternal obesity leads to low expression of lncRNA Lockd and autophagy inhibition in the offspring's liver. Knockdown of lncRNA Lockd could further inhibit autophagy and aggravate lipid accumulation. Rapamycin treatment could improve lipid accumulation in AML12 cells. Our study revealed that maternal obesity caused low expression of lncRNA Lockd in the offspring's liver, and lncRNA Lockd positively regulates autophagy through the mTOR signaling pathway. This study provides new insights into the occurrence of lipid accumulation in the liver of offspring.

MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes.

BACKGROUND: Type 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction. METHODS: The microRNA (miRNA) content of circulating extracellular vesicles (EVs) was assessed in T2D models to identify biomarkers of coronary microvascular dysfunction/rarefaction. The potential source of circulating EV-encapsulated miRNAs was determined, and the mechanisms of induction and the function of candidate miRNAs were assessed in endothelial cells (ECs). RESULTS: We found an increase in miR-30d-5p and miR-30e-5p in circulating EVs that coincided with indices of coronary microvascular EC dysfunction (i.e., markers of oxidative stress, DNA damage/senescence) and rarefaction, and preceded echocardiographic evidence of diastolic dysfunction. These miRNAs may serve as biomarkers of coronary microvascular dysfunction as they are upregulated in ECs of the left ventricle of the heart, but not other organs, in db/db mice. Furthermore, the miR-30 family is secreted in EVs from senescent ECs in culture, and ECs with senescent-like characteristics are present in the db/db heart. Assessment of miR-30 target pathways revealed a network of genes involved in fatty acid biosynthesis and metabolism. Over-expression of miR-30e in cultured ECs increased fatty acid ß-oxidation and the production of reactive oxygen species and lipid peroxidation, while inhibiting the miR-30 family decreased fatty acid ß-oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to down-regulate the expression of eNOS, a key regulator of microvascular and cardiomyocyte function. Finally, knock-down of the miR-30 family in db/db mice decreased markers of oxidative stress and DNA damage/senescence in the microvascular endothelium. CONCLUSIONS: MiR-30d/e represent early biomarkers and potential therapeutic targets that are indicative of the development of diastolic dysfunction and may reflect altered EC fatty acid metabolism and microvascular dysfunction in the diabetic heart.

Image restoration for real-world under-display imaging.

Under-display imaging technique was recently proposed to enlarge the screen-to-body ratio for full-screen devices. However, existing image restoration algorithms have difficulty generalizing to real-world under-display (UD) images, especially to images containing strong light sources. To address this issue, we propose a novel method for building a synthetic dataset (CalibPSF dataset) and introduce a two-stage neural network to solve the under-display imaging degradation problem. The CalibPSF dataset is generated using the calibrated high dynamic range point spread function (PSF) of the under-display optical system and contains various simulated light sources. The two-stage network solves the color distortion and diffraction degradation in order. We evaluate the performance of our algorithm on our captured real-world test set. Comprehensive experiments demonstrate the superiority of our method in different dynamic range scenes.

An immune-related model based on INHBA, JAG2 and CCL19 to predict the prognoses of colon cancer patients.

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer deaths and most common malignant tumors worldwide. Immune-related genes (IRGs) can predict prognoses of patients and the effects of immunotherapy. A series of colon cancer (CCa) samples from The Cancer Genome Atlas (TCGA) were analyzed to provide a new perspective into this field. METHODS: Differential IRGs and IRGs with significant clinical outcomes (sIRGs) were calculated by the limma algorithm and univariate COX regression analysis. The potential molecular mechanisms of IRGs were detected by PPI, KEGG and GO analysis. Immune-related risk score model (IRRSM) was established based on multivariate COX regression analysis. Based on the median risk score of IRRSM, the high-risk group and low-risk group were distinguished. The expression levels of IHNBA and JAG2 and relationships between IHNBA and clinical features were verified by RT-qPCR. RESULTS: 6 differential sIRGs of patients with CCa were selected by univariate COX regression analysis. Based on the sIRGs (INHBA, JAG2 and CCL19), the IRRSM was established to predict survival probability of CCa patients and to explore the potential correlations with clinical features. Furthermore, IRRSM reflected the infiltration status of 22 types of immune cells. The expression levels of IHNBA and JAG2 were higher in CCa tissues than that in adjacent normal tissues. The expression levels of IHNBA and JAG2 were increased in advanced T stages. CONCLUSION: Our results illustrated that some sIRGs showed the latent value of predicting the prognoses of CCa patients and the clinical features. This study could provide a new insight for immune research and treatment strategies in CCa patients.

Genome-wide identification and evolution of HECT genes in soybean.

Proteins containing domains homologous to the E6-associated protein (E6-AP) carboxyl terminus (HECT) are an important class of E3 ubiquitin ligases involved in the ubiquitin proteasome pathway. HECT-type E3s play crucial roles in plant growth and development. However, current understanding of plant HECT genes and their evolution is very limited. In this study, we performed a genome-wide analysis of the HECT domain-containing genes in soybean. Using high-quality genome sequences, we identified 19 soybean HECT genes. The predicted HECT genes were distributed unevenly across 15 of 20 chromosomes. Nineteen of these genes were inferred to be segmentally duplicated gene pairs, suggesting that in soybean, segmental duplications have made a significant contribution to the expansion of the HECT gene family. Phylogenetic analysis showed that these HECT genes can be divided into seven groups, among which gene structure and domain architecture was relatively well-conserved. The Ka/Ks ratios show that after the duplication events, duplicated HECT genes underwent purifying selection. Moreover, expression analysis reveals that 15 of the HECT genes in soybean are differentially expressed in 14 tissues, and are often highly expressed in the flowers and roots. In summary, this work provides useful information on which further functional studies of soybean HECT genes can be based.

[Effects of adenosine on hMLH1 methylation of human colorectal cancer cells].

OBJECTIVE: To explore the effects of adenosine on hMLH1 methylation of human colorectal cancer cells. METHODS: The SW480 cells were treated with adenosine at the concentrations of 0, 1.5, 3.0, 4.5 mmol/L for 72 h. The hMLH1 methylation levels of CpG islands were detected by bisulfite sequencing polymerase chain reaction (BSP), hMLH1 mRNA expression levels by reverse transcription-polymerase chain reaction (RT-PCR), the expression levels of hMLH1 protein by Western blot and the apoptotic rates by flow cytometry (FCM). The cells were treated with adenosine at the concentrations of 0, 1.5, 3.0, 4.5 mmol/L for 24, 48, 72, 96 h. And their proliferation rates were detected by methyl thiazolyl tetrazolium (MTT). RESULTS: After a 72 h treatment of adenosine, the hMLH1 promoter methylation levels of 1.5, 3.0 and 4.5 mmol/L groups were 65% ± 4%, 45% ± 11% and 16% ± 4% respectively and were all significantly lower than that of the control group (80% ± 4%, all P < 0.01). The mRNA expression levels, hMLH1 protein expression levels and apoptotic rates were all significantly higher than that of the control group (0.230 ± 0.032, 0.359 ± 0.029 and 0.570 ± 0.019 vs 0.079 ± 0.010; 0.353 ± 0.016, 0.654 ± 0.018 and 0.854 ± 0.014 vs 0.126 ± 0.016; 11.9% ± 0.6%, 20.0% ± 1.8% and 35.8% ± 1.8% vs 3.9% ± 1.4%, all P < 0.01). MTT showed that the proliferation rates of SW480 cells were lower than that of the control group and a time-dosage dependence existed (all P < 0.05). CONCLUSION: Adenosine can reverse the abnormal methylation of hMLH1 CpG island and promote the expression of hMLH1 so as to restrain the proliferation and promote the apoptosis of colocectal cancer cells.

Association between Dietary Anthocyanidins and Biliary Cancer Risk in 98,458 Participants: Results from a Prospective Study.

BACKGROUND: Previous studies have suggested anthocyanidins or anthocyanidin-rich foods and extracts exhibit protective effects against various cancers. However, the relationship between dietary anthocyanidins and the risk of biliary cancer remains uncertain. METHODS: This study used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate the relationship between total anthocyanidins intake and biliary cancer incidence. Cox regression analysis was conducted to estimate HRs and corresponding 95% confidence intervals (CI) for the incidence of biliary cancer, with adjustments made for confounding factors. A restricted cubic spline model was employed to examine the dose-response relationship. In addition, subgroup and sensitivity analyses were conducted to evaluate potential interactions and test the model's robustness. RESULTS: During 8.9 years and 872,645.3 person-years of follow-up, 95 cases of biliary cancer were observed. The incidence rate of biliary cancer in this study was 11 cases per 100,000 person-years. Using the fully adjusted Cox regression model, the inverse association was observed between total anthocyanidins intake and the risk of biliary cancer (HR Q4 vs..Q1: 0.52; 95% CI: 0.29-0.91; Ptrend = 0.043). This association remained significant in sensitivity analyses. A linear dose-response relationship (Pnonlinearity = 0.118) and potential interaction with drinking status (Pinteraction = 0.033) were identified. CONCLUSIONS: This study provides evidence of an inverse association between total anthocyanidins intake and biliary cancer incidence. IMPACT: Our study found a total anthocyanidin-rich diet was associated with a reduced risk of biliary cancer in Americans ages 55 to 74 years.

Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study.

OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

13-oxyingenol dodecanoate derivatives induce mitophagy and ferroptosis through targeting TMBIM6 as potential anti-NSCLC agents.

Ingenol diterpenoids continue to attract the attention for their extensive biological activity and novel structural features. To further explore this type of compound as anti-tumor agent, 13-oxyingenol dodecanoate (13-OD) was prepared by a standard chemical transformation from an Euphorbia kansui extract, and 29 derivatives were synthesized through parent 13-OD. Their inhibition activities against different types of cancer were screened and some derivatives showed superior anti-non-small cell lung cancer (NSCLC) cells cytotoxic potencies than oxaliplatin. In addition, TMBIM6 was identified as a crucial cellular target of 13-OD using ABPP target angling technique, and subsequently was verified by pull down, siRNA interference, BLI and CETSA assays. With modulating the function of TMBIM6 protein by 13-OD and its derivatives, Ca2+ release function was affected, causing mitochondrial Ca2+ overload, depolarisation of membrane potential. Remarkably, 13-OD, B6, A2, and A10-2 induced mitophagy and ferroptosis. In summary, our results reveal that 13-OD, B6, A2, and A10-2 holds great potential in developing anti-tumor agents for targeting TMBIM6.

[Effects and mechanisms of phosphatidylinositol 3 kinase B signal pathway on colon cancer cell SW480].

OBJECTIVE: To explore the effects of phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signal pathway on the proliferation, apoptosis and invasiveness of colon cancer cell line SW480 and explore its possible mechanisms. METHODS: SW480 cells were cultured with various concentrations (0, 5, 10, 20 and 40 µmol/L) of LY294002 and methyl thiazolyl tetrazolium (MTT) assay was conducted after 24, 48 and 72 hours. SW480 cells were cultured for 24 hours with various concentrations (0, 10, 20 and 40 µmol/L) of LY294002. The apoptotic rate was measured by flow cytometry (FCM). The difference of invasiveness was examined by Transwell invasion test. Western blotting was used to examine the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). One-way ANOVA was used for statistical analysis. RESULTS: MTT assay showed that the proliferation rate of all SW480 cells except for the lowest concentration group (5 µmol/L) was lower than the control group (0 µmol/L) and a time-dosage dependence existed (all P < 0.05). The results of FCM demonstrated that the apoptotic rates of 10, 20 and 40 µmol/L groups were 13.3% ± 0.9%, 30.9% ± 2.5% and 41.2% ± 4.1% respectively, and were all significantly higher than control group (5.2% ± 1.8%, all P < 0.05). The number of cells penetrating through the membrane of 10, 20 and 40 µmol/L groups were 87 ± 6, 65 ± 7 and 46 ± 11 respectively. All invasiveness groups were all lower than control group (100 ± 10, all P < 0.05) except the 10 µmol/L concentration group (P = 0.096). Western blotting showed that the expressions of VEGF and MMP-9 were all lower than control group (all P < 0.05). CONCLUSIONS: PI3K-AKT signal pathway plays an important role in the proliferation, apoptosis and inhibition of colonic cancer cells. Its mechanism is probably related with the inhibitions of VEGF and MMP-9. PI3K-AKT signal pathway may become a potential target for the treatment of colon cancer.

ANXA10 is a prognostic biomarker and suppressor of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

Liver hepatocellular carcinoma (LIHC) is one of the main cancers worldwide and has high morbidity and mortality rates. Although previous studies have shown that ANXA10 is expressed at low levels in LIHC tumor tissues, the biological function of ANXA10 in LIHC is still unclear. Therefore, we utilized TCGA, TIMER, GEPIA2, TISIDB, LinkedOmics, ssGSEA algorithms and CIBERSORT methodology to preliminarily evaluate the potential mechanism of ANXA10 in LIHC. In vitro experiments were used to further verify some functions of ANXA10. Consequently, we found that ANXA10 mRNA/protein expression was downregulated in LIHC tissue compared to normal tissue. ANXA10 was significantly linked with clinicopathological features, immunocytes, multiple cancer-related pathways, m6A modification and a ceRNA network. A three-gene prognostic signature rooted in ANXA10-related immunomodulators was determined and found to be an independent prognostic predictor. A nomogram was constructed to predict survival with good accuracy. Additionally, in vitro trials revealed that ANXA10 upregulation inhibited LIHC cell proliferation and migration. This study reveals that ANXA10 may serve as a prognostic marker and promising therapeutic target in LIHC clinical practice through various biologic functions.

Corrigendum: Adenosine kinase on deoxyribonucleic acid methylation: Adenosine receptor-independent pathway in cancer therapy.

[This corrects the article DOI: 10.3389/fphar.2022.908882.].

Low-fat dairy consumption and the risk of lung cancer: A large prospective cohort study.

BACKGROUND: Despite the possible contribution of dairy products to the development or prevention of cancers, there is a lack of epidemiological evidence linking low-fat dairy consumption to the risk of developing lung cancer. This research was conducted to fill this knowledge gap. METHODS: The data for this research were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The Cox proportional risk model was employed to evaluate the link between low-fat dairy consumption and the risk of developing lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were measured in both unadjusted and adjusted models. A series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: The study included data from 98,459 individuals. During a total of 869,807.9 follow-up person-years, 1642 cases of lung cancer were observed, with an incidence of 0.189 cases for every 100 person-years. In the fully adjusted model, participants in the highest quartile of low-fat dairy consumption had a significantly decreased risk of lung cancer compared to the ones in the lowest quartile (HRquartile 4 vs. 1 : 0.769, 95% CI: 0.664, 0.891, ptrend = 0.005). The restricted cubic spline plot revealed an inverse nonlinear dose-response relationship between low-fat dairy consumption and lung cancer risk (pnonlinearity = 0.008). Subgroup analyses demonstrated that the inverse association was stronger among participants with higher daily caloric intake (pinteraction = 0.031). Various sensitivity analyses produced consistent results. CONCLUSION: Consuming more low-fat dairy products is significantly linked to a reduced risk of developing lung cancer, indicating that an appropriate increase in the use of low-fat dairy products may help prevent lung cancer.