The Efficacy of Dietary Intake, Supplementation, and Blood Concentrations of Carotenoids in Cancer Prevention: Insights from an Umbrella Meta-Analysis.

Previous meta-analyses of multiple studies have suggested that dietary intake and blood concentrations of carotenoids, as well as dietary supplement of certain carotenoids, play a role in reducing the risk of cancer. However, the conclusions of these studies have been subject to controversy. We conducted an umbrella review of meta-analyses to comprehensively analyze and evaluate the evidence pertaining the association between carotenoids and cancer outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases of meta-analyses and systematic reviews up to June 2023. Our selection criteria encompassed meta-analyses of cohort and case-control studies, as well as randomized controlled clinical trials, which investigated the associations between carotenoids and cancer risk. We also determined the levels of evidence for these associations with AMSTAR 2 criteria. We included 51 eligible articles, including 198 meta-analyses for qualitative synthesis in the umbrella review. Despite the presence of moderate to high heterogeneity among the studies, dietary intake, supplementation, and blood concentrations of carotenoids were inversely associated with the risk of total cancer, and certain specific cancers of lung, digestive system, prostate, breast, head and neck, and others. Subgroup analysis also showed that individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene) offer certain protection against specific types of cancers. However, high doses of carotenoid supplements, especially ß-carotene, significantly increased the risk of total cancer, lung cancer, and bladder cancer. Our umbrella meta-analysis supported that high intake of dietary carotenoids as a whole food approach could be more beneficial in reducing cancer risk. Concurrently, the findings suggest that the efficacy of single-carotenoid supplementation in cancer prevention remains a subject of controversy.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Development and application of machine learning models for prediction of soil available cadmium based on soil properties and climate features.

Identifying the key influencing factors in soil available cadmium (Cd) is crucial for preventing the Cd accumulation in the food chain. However, current experimental methods and traditional prediction models for assessing available Cd are time-consuming and ineffective. In this study, machine learning (ML) models were developed to investigate the intricate interactions among soil properties, climate features, and available Cd, aiming to identify the key influencing factors. The optimal model was obtained through a combination of stratified sampling, Bayesian optimization, and 10-fold cross-validation. It was further explained through the utilization of permutation feature importance, 2D partial dependence plot, and 3D interaction plot. The findings revealed that pH, surface pressure, sensible heat net flux and organic matter content significantly influenced the Cd accumulation in the soil. By utilizing historical soil surveys and climate change data from China, this study predicted the spatial distribution trend of available Cd in the Chinese region, highlighting the primary areas with heightened Cd activity. These areas were primarily located in the eastern, southern, central, and northeastern China. This study introduces a novel methodology for comprehending the process of available Cd accumulation in soil. Furthermore, it provides recommendations and directions for the remediation and control of soil Cd pollution.

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting ß-catenin/TGF-ß1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.

Chinese surgical robot-assisted surgery for parotid tumor: a case report.

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.

Comparison of the clinical effects of dual-modality endoscopy and traditional laparotomy for the treatment of intra- and extrahepatic bile duct stones.

BACKGROUND: Bile duct stones (BDSs) may cause patients to develop liver cirrhosis or even liver cancer. Currently, the success rate of surgical treatment for intrahepatic and extrahepatic BDSs is not satisfactory, and there is a risk of postoperative complications. AIM: To compare the clinical effects of dual-modality endoscopy (duodenoscopy and laparoscopy) with those of traditional laparotomy in the treatment of intra- and extrahepatic BDSs. METHODS: Ninety-five patients with intra- and extrahepatic BDSs who sought medical services at Wuhan No.1 Hospital between August 2019 and May 2023 were selected; 45 patients in the control group were treated by traditional laparotomy, and 50 patients in the research group were treated by dual-modality endoscopy. The following factors were collected for analysis: curative effects, safety (incision infection, biliary fistula, lung infection, hemobilia), surgical factors [surgery time, intraoperative blood loss (IBL) volume, gastrointestinal function recovery time, and length of hospital stay], serum inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8], and oxidative stress [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced protein oxidation products (AOPPs)]. RESULTS: The analysis revealed markedly better efficacy (an obviously higher total effective rate) in the research group than in the control group. In addition, an evidently lower postoperative complication rate, shorter surgical duration, gastrointestinal function recovery time and hospital stay, and lower IBL volume were observed in the research group. Furthermore, the posttreatment serum inflammatory marker (TNF-α, IL-6, and IL-8) levels were significantly lower in the research group than in the control group. Compared with those in the control group, the posttreatment GSH-Px, SOD, MDA and AOPPs in the research group were equivalent to the pretreatment levels; for example, the GSH-Px and SOD levels were significantly higher, while the MDA and AOPP levels were lower. CONCLUSION: Dual-modality endoscopy therapy (duodenoscopy and laparoscopy) is more effective than traditional laparotomy in the treatment of intra- and extrahepatic BDSs and has a lower risk of postoperative complications; significantly shortened surgical time; shorter gastrointestinal function recovery time; shorter hospital stay; and lower intraoperative bleeding volume, while having a significant inhibitory effect on excessive serum inflammation and causing little postoperative oxidative stress.

Clinical application and nursing experience of the plan-do-check-act cycle in daytime varicocelectomy.

BACKGROUND: Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy. METHODS: Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction. RESULTS: The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P < 0.05).No significant difference was observed in the incidence of postoperative complications between the two groups during hospitalization (P > 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy. CONCLUSION: In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches. TRIAL REGISTRATION: The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.

A potential role for inflammatory cytokines in a rare late-onset capsular block syndrome: a case report.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

Intratumoural microbiota: a new frontier in cancer development and therapy.

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

Association between socio-demographic factors, lifestyle, eating habits and hypertension risk among middle-aged and older rural Chinese adults.

BACKGROUND AND AIMS: Hypertension is a global health issue with increasing prevalence. This study aimed to understand the epidemiological characteristics and influencing factors of hypertension in rural Chinese populations and help develop effective prevention and control strategies. METHODS AND RESULTS: This cross-sectional study used database from the Early Diagnosis and Early Treatment Project of Esophageal Cancer conducted in a rural population from September 2012 to December 2017. A total of 10,111 subjects aged 35-75 years residing in Huai'an District, Huai'an City, Jiangsu Province for at least three years were included. Unconditional univariate and multivariate logistic regression models were performed to evaluate the association between socio-demographic information, lifestyle habits, dietary characteristics and the risk of hypertension. The prevalence of hypertension was 34.32 % in this rural population. Men and older individuals are more likely to have hypertension when compared with women and young individuals, respectively. Factors associated with an increased risk of hypertension included: fast eating speed, a high-salt diet (both currently and ten years ago), a high-spicy diet ten years ago, high BMI, poor educational attainment, preference for fatty meats, hot diet, green tea drinking, intake of pickled potherb mustard and corn flour, family smoking and alcohol consumption. Light smoking in males, consumption of fruits, adzuki bean, and pork liver were associated with reduced risk of hypertension. CONCLUSIONS: The study identified some factors, including eat habits and lifestyle, associated with hypertension risk, and highlighted the need for targeted policies and interventions in rural China to address potential risk factors for hypertension.

Methylation of AcGST1 Is Associated with Anthocyanin Accumulation in the Kiwifruit Outer Pericarp.

Most red-fleshed kiwifruit cultivars, such as Hongyang, only accumulate anthocyanins in the inner pericarp; the trait of full red flesh becomes the goal pursued by breeders. In this study, we identified a mutant "H-16" showing a red color in both the inner and outer pericarps, and the underlying mechanism was explored. Through transcriptome analysis, a key differentially expressed gene AcGST1 was screened out, which was positively correlated with anthocyanin accumulation in the outer pericarp. The result of McrBC-PCR and bisulfite sequencing revealed that the SG3 region (-292 to -597 bp) of AcGST1 promoter in "H-16" had a significantly lower CHH cytosine methylation level than that in Hongyang, accompanied by low expression of methyltransferase genes (MET1 and CMT2) and high expression of demethylase genes (ROS1 and DML1). Transient calli transformation confirmed that demethylase gene DML1 can activate transcription of AcGST1 to enhance its expression. Overexpression of AcGST1 enhanced the anthocyanin accumulation in the fruit flesh and leaves of the transgenic lines. These results suggested that a decrease in the methylation level of the AcGST1 promoter may contribute to accumulation of anthocyanin in the outer pericarp of "H-16".

MXene/PPy@PDMS sponge-based flexible pressure sensor for human posture recognition with the assistance of a convolutional neural network in deep learning.

The combination of flexible sensors and deep learning has attracted much attention as an efficient method for the recognition of human postures. In this paper, an in situ polymerized MXene/polypyrrole (PPy) composite is dip-coated on a polydimethylsiloxane (PDMS) sponge to fabricate an MXene/PPy@PDMS (MPP) piezoresistive sensor. The sponge sensor achieves ultrahigh sensitivity (6.8925 kPa-1) at 0-15 kPa, a short response/recovery time (100/110 ms), excellent stability (5000 cycles) and wash resistance. The synergistic effect of PPy and MXene improves the performance of the composite materials and facilitates the transfer of electrons, making the MPP sponge at least five times more sensitive than sponges based on each of the individual single materials. The large-area conductive network allows the MPP sensor to maintain excellent electrical performance over a large-scale pressure range. The MPP sensor can detect a variety of human body activity signals, such as radial artery pulse and different joint movements. The detection and analysis of human motion data, which is assisted by convolutional neural network (CNN) deep learning algorithms, enable the recognition and judgment of 16 types of human postures. The MXene/PPy flexible pressure sensor based on a PDMS sponge has broad application prospects in human motion detection, intelligent sensing and wearable devices.

Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice.

Nonalcoholic steatohepatitis (NASH) is epidemiologically associated with obesity and diabetes and can lead to liver cirrhosis and hepatocellular carcinoma if left untreated. The intricate signaling pathways that orchestrate hepatocyte energy metabolism and cellular stress, intrahepatic cell crosstalk, as well as interplay between peripheral tissues remain elusive and are crucial for the development of anti-NASH therapies. Herein, we reveal E3 ligase FBXW7 as a key factor regulating hepatic catabolism, stress responses, systemic energy homeostasis, and NASH pathogenesis with attenuated FBXW7 expression as a feature of advanced NASH. Multiomics and pharmacological intervention showed that FBXW7 loss-of-function in hepatocytes disrupts a metabolic transcriptional axis conjointly controlled by the nutrient-sensing nuclear receptors ERRα and PPARα, resulting in suppression of fatty acid oxidation, elevated ER stress, apoptosis, immune infiltration, fibrogenesis, and ultimately NASH progression in male mice. These results provide the foundation for developing alternative strategies co-targeting ERRα and PPARα for the treatment of NASH.

Melatonin Promotes Iron Reactivation and Reutilization in Peach Plants under Iron Deficiency.

The yellowing of leaves due to iron deficiency is a prevalent issue in peach production. Although the capacity of exogenous melatonin (MT) to promote iron uptake in peach plants has been demonstrated, its underlying mechanism remains ambiguous. This investigation was carried out to further study the effects of exogenous MT on the iron absorption and transport mechanisms of peach (Prunus persica) plants under iron-deficient conditions through transcriptome sequencing. Under both iron-deficient and iron-supplied conditions, MT increased the content of photosynthetic pigments in peach leaves and decreased the concentrations of pectin, hemicellulose, cell wall iron, pectin iron, and hemicellulose iron in peach plants to a certain extent. These effects stemmed from the inhibitory effect of MT on the polygalacturonase (PG), cellulase (Cx), phenylalanine ammonia-lyase (PAL), and cinnamoyl-coenzyme A reductase (CCR) activities, as well as the promotional effect of MT on the cinnamic acid-4-hydroxylase (C4H) activity, facilitating the reactivation of cell wall component iron. Additionally, MT increased the ferric-chelate reductase (FCR) activity and the contents of total and active iron in various organs of peach plants under iron-deficient and iron-supplied conditions. Transcriptome analysis revealed that the differentially expressed genes (DEGs) linked to iron metabolism in MT-treated peach plants were primarily enriched in the aminoacyl-tRNA biosynthesis pathway under iron-deficient conditions. Furthermore, MT influenced the expression levels of these DEGs, regulating cell wall metabolism, lignin metabolism, and iron translocation within peach plants. Overall, the application of exogenous MT promotes the reactivation and reutilization of iron in peach plants.

Ranking age-specific modifiable risk factors for cardiovascular disease and mortality: evidence from a population-based longitudinal study.

Background: Cardiovascular disease (CVD) remains a paramount contemporary health challenge. This study examined age-specific effects of 14 risk factors on CVD and mortality in different age groups. Methods: We analyzed data from 226,759 CVD-free participants aged 40 years and older in the UK Biobank during the period from baseline time (2006-2010) to September 30, 2021. The primary CVD outcome was a composite of incident coronary artery disease, heart failure, and stroke. We calculated age-specific hazard ratios (HRs) and population-attributable fractions (PAF) for CVD and mortality associated with 14 potentially modifiable risk factors. Findings: During 12.17-year follow-up, 23,838 incident CVD cases and 11,949 deaths occurred. Age-specific disparities were observed in the risk factors contributing to CVD, and the overall PAF declined with age (PAF of 56.53% in middle-age; 49.78% in quinquagenarian; 42.45% in the elderly). Metabolic factors had the highest PAF in each age group, with hypertension (14.04% of the PAF) and abdominal obesity (9.58% of the PAF) being prominent. Behavioral factors had the highest PAF in the middle-aged group (10.68% of the PAF), and smoking was the leading behavioral factor in all age groups. In socioeconomic and psychosocial risk clusters, low income contributed most among middle-aged (3.74% of the PAF) and elderly groups (3.66% of the PAF), while less education accounted more PAF for quinquagenarian group (4.46% of the PAF). Similar age-specific patterns were observed for cardiovascular subtypes and mortality. Interpretation: A large fraction of CVD cases and deaths were associated with modifiable risk factors in all age groups. Targeted efforts should focus on the most impactful risk factors, as well as age-specific modifiable risk factors. These findings may inform the development of more precise medical strategies to prevent and manage CVD and related mortality. Funding: The work was supported by the Bill & Melinda Gates Foundation (grant number: INV-016826 to Hualiang Lin) and the National Natural Science Foundation of China (grant number: 82373534 to Hualiang Lin).

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Egg white protein hydrolysate decreased blood pressure via the competing endogenous RNA regulatory networks in female spontaneously hypertensive rats.

Despite numerous studies having reported the effects and mechanisms of antihypertensive peptides including peptides derived from egg white proteins, the role of peptides in a female hypertensive animal model is unknown. On the other hand, the role of epigenetic modulation by peptide treatment has rarely been investigated. This study sought to investigate the effect of egg white protein hydrolysate (EWH) in female spontaneously hypertensive rats (SHRs) as well as to explore the underlying mechanisms from the perspectives of the transcriptome and the profiles of non-coding RNAs. Young (12-14-week-old) female SHRs were orally administered 250 mg per kg body weight (low-dose) or 1000 mg per kg body weight (high-dose) EWH daily for 10 weeks. The blood pressure of the rats was monitored weekly. The mRNA and non-coding RNAs (miRNA, lncRNA, and circRNA) in the aorta were profiled by the high-throughput RNA-seq technique. Differentially expressed (DE) RNAs in the aorta were identified for the construction of the competing endogenous RNA (ceRNA) networks and key molecules were validated by qRT-PCR. The treatment of the high-dose EWH showed a significant effect on reducing blood pressure in female SHRs. Bioinformatic analyses revealed 813, 90, 347 and 869 DE-mRNAs, DE-miRNAs, DE-lncRNAs and DE-circRNAs, respectively. The CNTN5-LncRNA-XR_001835895.1-miR-384-5p was identified as the central network which was validated in the aorta and circulation of female SHRs. The results from this study demonstrated that the treatment with EWH reduced blood pressure via regulating the ceRNA networks in female SHRs, which provided novel insights into the mechanisms of food protein-derived antihypertensive peptides.

ERRα fosters running endurance by driving myofiber aerobic transformation and fuel efficiency.

OBJECTIVE: Estrogen related receptor α (ERRα) occupies a central node in the transcriptional control of energy metabolism, including in skeletal muscle, but whether modulation of its activity can directly contribute to extend endurance to exercise remains to be investigated. The goal of this study was to characterize the benefit of mice engineered to express a physiologically relevant activated form of ERRα on skeletal muscle exercise metabolism and performance. METHODS: We recently shown that mutational inactivation of three regulated phosphosites in the amino terminal domain of the nuclear receptor ERRα impedes its degradation, leading to an accumulation of ERRα proteins and perturbation of metabolic homeostasis in ERRα3SA mutant mice. Herein, we used a multi-omics approach in combination with physical endurance tests to ascertain the consequences of expressing the constitutively active phospho-deficient ERRα3SA form on muscle exercise performance and energy metabolism. RESULTS: Genetic heightening of ERRα activity enhanced exercise capacity, fatigue-resistance, and endurance. This phenotype resulted from extensive reprogramming of ERRα global DNA occupancy and transcriptome in muscle leading to an increase in oxidative fibers, mitochondrial biogenesis, fatty acid oxidation, and lactate homeostasis. CONCLUSION: Our findings support the potential to enhance physical performance and exercise-induced health benefits by targeting molecular pathways regulating ERRα transcriptional activity.

Beneficial Effects of Dietary Flaxseed Oil through Inflammation Pathways and Gut Microbiota in Streptozotocin-Induced Diabetic Mice.

Flaxseed oil (FO) has displayed potential anti-diabetes properties by providing a high content of α-linolenic acid. However, the effects and mechanisms of FO on type 1 diabetes are still unclear. The present study aims to explore the effects of different doses of FO feeding on hepatic inflammation and gut microbiota in streptozotocin-induced diabetic mice. Forty-eight six-week-old C57BL/6J male mice were divided into a control group (CON), a diabetic group (MOD), a diabetes with 7.0% w/w FO feeding group (FO-L), and a diabetes with 10.5% w/w FO feeding group (FO-H) for six weeks. The 7.0% w/w and 10.5% w/w FO feeding groups exhibited potential recovery of the number and size of pancreas tissues. The fasting blood glucose level was significantly decreased only after 4 weeks of feeding with 10.5% w/w FO in diabetic mice. The 10.5% w/w FO feeding group significantly decreased the postprandial blood glucose level of mice in the OGTT test. Hepatic glycogen levels were dramatically upregulated in the mice fed with both 7.0% w/w and 10.5% w/w FO. FO feeding significantly attenuated hepatic LPS, TNF-α, and IL-1ß levels. In addition, we observed that 7.0% w/w and 10.5% w/w FO feedings notably downregulated hepatic gene and protein expressions of TLR4, MyD88, and P65. Furthermore, only 10.5% FO regulated fecal microbiota by increasing the relative abundance of the Bacteroidetes phylum, Lactococcus family, and Muribaculaceae and Streptococcaceae family and genus in streptozotocin-induced diabetic mice. Therefore, we conclude that FO feeding plays a role in anti-inflammation via the regulation of hepatic LPS/TLR4/MyD88 pathways and gut microbiota. In addition, different doses of FO supplementation may exhibit varying mechanisms in streptozotocin-induced mice.