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Identification of key ferroptosis-related genes associated with the development of gastric cancer: Prognostic models, molecular mechanisms and potential treatment strategies.

Ferroptosis is a novel iron-dependent form of cell death that influences the development and progression of gastric cancer (GC), affecting its growth, invasion and metastasis. However, molecular regulatory mechanisms of ferroptosis in GC remain unclear. The present study aimed to identify key ferroptosis-related genes associated with GC development. Ferroptosis-related genes were collected from FerrDb, a database that collects data on genes and substances that regulate ferroptosis, and the top survival-related genes (including progression-free and overall survival), and differentially expresse

Effect of dietary n-3 polyunsaturated fatty acid supplementation and post-insemination plane of nutrition on systemic concentrations of metabolic analytes, progesterone, hepatic gene expression and embryo development and survival in beef heifers.

Nutrition, and particularly dietary energy intake, plays a fundamental role in reproductive function in cattle. There is some evidence that supplemental omega-3 dietary polyunsaturated fatty acids (n-3 PUFA) can exert positive effects on fertility. The objectives of this study were to evaluate the effect of dietary n-3 PUFA supplementation, post-insemination energy plane of nutrition and their interaction on embryo survival in cattle. Crossbred beef heifers (n = 185) were individually offered barley straw ad libitum and 6 kg DM of concentrate supplemented with either a rumen-protected source o

AKR1C3-PKM2-oxidative phosphorylation axis drives prostate cancer radioresistance via UBE2T upregulation.

Radioresistance is one of the primary causes of prostate cancer treatment failure and post-radiotherapy progression. However, there is currently a lack of effective targets to increase radiotherapy sensitivity and inhibit malignant progression. We identified AKR1C3 as a potential key target associated with radioresistance and malignant progression through integrated bioinformatic analysis of RNA sequencing (RNA-seq) data from prostate cancer clinical samples in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The promotion of radioresistance by AKR1C3 in both AR-posi

Polymorphisms of the HSD17B6 and HSD17B5 genes in Chinese women with polycystic ovary syndrome.

OBJECTIVES: To investigate the polymorphisms of the 17β-hydroxysteroid dehydrogenase type 5 and type 6 (HSD17B5 and HSD17B6) genes in Chinese women with polycystic ovary syndrome (PCOS). METHODS: Two hundred twenty-two PCOS patients and 283 controls were studied. Menarche age was recorded. Body mass indices (BMI) were calculated. Blood samples were obtained for single nucleotide polymorphism (SNP) analyses and hormone measurements. Genotyping of HSD17B6 and HSD17B5 in cases and controls was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

The role of ferroptosis-related genes for overall survival prediction in breast cancer.

BACKGROUND: Ferroptosis is a novel iron-dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis-related genes on the prognosis of breast cancer remains unclear. METHODS: RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis-related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis w

A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures.

Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic

A Mansonone Derivative Coupled with Monoclonal Antibody 4D5-Modified Chitosan Inhibit AKR1C3 to Treat Castration-Resistant Prostate Cancer.

PURPOSE: Aldo-ketoreductase (AKR) 1C3 is crucial for testosterone synthesis. Abnormally high expression/activity of AKR1C3 can promote castration-resistant prostate cancer (CRPC). A mansonone derivative and AKR1C3 inhibitor, 6e, was combined with 4D5 (extracellular fragment of the monoclonal antibody of human epidermal growth factor receptor-2)-modified chitosan to achieve a nanodrug-delivery system (CS-4D5/6e) to treat CRPC. MATERIALS AND METHODS: Morphologies/properties of CS-4D5/6e were characterized by atomic force microscopy, zeta-potential analysis, and Fourier transform-infrared spectr

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. METHODS: We performed a human deep metabolic in vivo phenotyping study examining the systemic and intra-adipos

Exploration and validation of a novel reactive oxygen species-related signature for predicting the prognosis and chemotherapy response of patients with bladder cancer.

BACKGROUND: Reactive Oxygen Species (ROS), a hallmark of cancer, is related to prognosis, tumor progression, and treatment response. Nevertheless, the correlation of ROS-based molecular signature with clinical outcome and immune cell infiltration has not been thoroughly studied in bladder cancer (BLCA). Accordingly, we aimed to thoroughly examine the role and prognostic value of ROS-related genes in BLCA. METHODS: We obtained RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) for bladder cancer (BLCA) patients and identified ROS-associated genes using the GeneCards and Molec

The molecular architecture of human labor at term during the execution phase: changes across cervical dilatation.

OBJECTIVE: Human parturition includes a preparatory phase that precedes the clinical onset of labor and an execution phase represented by clinically established labor. We sought to define the molecular architecture of the execution phase by characterizing the changes in the amniotic fluid proteome associated with increasing cervical dilatation during human labor at term. STUDY DESIGN: This retrospective cross-sectional study included 98 women who delivered at term by cesarean delivery with intact membranes. Amniotic fluid was obtained from 61 women not in labor and 37 women in spontaneous lab

17-Hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) and treatment with oral contraceptive pills in PCOS women without metabolic comorbidities.

We studied (1) the effects of oral contraceptive pills (OCPs) on hirsutism, hormonal and metabolic variables in 49 polycystic ovary syndrome patients without metabolic comorbidities and (2) the effect of 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) on the response to OCP treatment. Mean age was 21.9 ± 6.5 years. Patients received monophasic OCP (20 μg ethinyl estradiol plus 75 μg gestodene), 21/28 days per cycle, during 6 months; 32 patients with severe hirsutism also received spironolactone 100 mg. The frequencies of HSD17B5 genotypes were: AA = 0.49 (55.1%),

Estrogen and progesterone metabolism in the cervix during pregnancy and parturition.

CONTEXT: Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood. OBJECTIVE: Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood. DESIGN:

Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation.

BACKGROUND: Elucidation of the biochemical pathways involved in activation of preterm and term human labour would facilitate the development of effective management and inform judgements regarding the necessity for preterm tocolysis and post-term induction. Prostaglandins act at all stages of human reproduction, and are potentially activators of labour. METHODS: Expression of 15 genes involved in prostaglandin synthesis, transport and degradation was measured by qPCR using tissue samples from human placenta, amnion and choriodecidua at preterm and full-term vaginal and caesarean delivery. Cel

Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization.

With the ongoing rise in the incidence of inflammatory bowel disease (IBD), its extraintestinal manifestations have garnered significant attention. IBD-related arthritis is notable for its insidious onset and unpredictability, presenting considerable challenges for clinical diagnosis and management. Factors such as gut microbiota, plasma proteins, inflammatory proteins, and biomarkers found in blood and urine may be closely associated with IBD-related arthritis. However, the mechanisms by which these factors influence this condition remain poorly understood and require urgent investigation. We

Fine mapping analysis confirms and strengthens linkage of four chromosomal regions in familial hypospadias.

Hypospadias is a common male genital malformation and is regarded as a complex disease affected by multiple genetic as well as environmental factors. In a previous genome-wide scan for familial hypospadias, we reported suggestive linkage in nine chromosomal regions. We have extended this analysis by including new families and additional markers using non-parametric linkage. The fine mapping analysis displayed an increased LOD score on chromosome 8q24.1 and 10p15 in altogether 82 families. On chromosome 10p15, with the highest LOD score, we further studied AKR1C2, AKR1C3 and AKR1C4 involved in

Expression of Concern.

The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the Special Issue titled "Omics sciences in the personalization of diagnosis and therapy" and, in particular, the following articles: ·      J. Kaftalli, K. Donato, G. Bonetti, K. Dhuli, A. Macchia, P.E. Maltese, K. Louise Herbst, S. Michelini, P. Chiurazzi, M. Hill, S. Michelini, S. Michelini, G. Marceddu, A. Bernini, M. Bertelli. Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as caus

Prevention of Anthracycline-Induced Cardiotoxicity: The Good and Bad of Current and Alternative Therapies.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) remains a serious health burden, especially in developing countries. Unfortunately, the high cost of current preventative strategies has marginalized numerous cancer patients because of socio-economic factors. In addition, the efficacy of these strategies, without reducing the chemotherapeutic properties of Dox, is frequently questioned. These limitations have widened the gap and necessity for alternative medicines, like flavonoids, to be investigated. However, new therapeutics may also present their own shortcomings, ruling out the idea of "natur

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… The two-electron reduction of Dox forms Doxol via several oxidoreductases namely, carbonyl reductase 1 (CBR1) and 3 (CBR3), and aldo-keto reductases family 1 member (AKR1C3) and AKR1A1, in the presence of nicotinamide adenine dinucleotide phosphate (NADPH). … Inactivation of the anticancer drugs doxorubicin and oracin by aldo–keto reductase (AKR) 1C3 . Toxicol Lett. ( 2008 ) 181 : 1 – 6 . 10.1016/j.toxlet.2008.06.858 18616992 103. Alshammari TM . Drug safety: The concept, inception and its importance in patients' health . …

Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.

New anticancer therapeutic strategies, including targeting of iron dysregulation in affected cancer types and stages, are urgently needed to decrease the associated annual cancer death rate of about 10 million worldwide. Many tumours evade treatment and support metastatic potential by effluxing iron and upregulating antioxidant systems, leading to suppression of lipid peroxidation and ferroptotic cell death. Similarly, many tumours manipulate the tumour microenvironment (TME) by ensuring the continuous supply of iron. This involves phenotypic modulation of immune cells, including macrophages,

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… For example, they increase the expression of aldo-keto reductases, which help detoxify lipid peroxidation products and protect against ferroptosis [ 114 ]. … To overcome this barrier, metastatic cells activate antioxidant defences (e.g., increased glutamine synthetase and upregulation of SLC7A11, GPX4, and FSP1), lipid metabolic adaptations (ApoE secretion, lipid remodelling, and increased aldo-keto reductases), and microenvironmental support mechanisms, …

A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy.

Background: Cancer has become a major disease endangering human health around the world. Conventional chemotherapy suffers from many side effects including pain, cardiotoxicity, hepatotoxicity, and renal toxicity. This review aims to describe a natural product of resveratrol as a chemoprotective and synergistic agent in the modulation of cancer chemotherapy. Methods: The publications were identified by comprehensive searching of SciFinder, PubMed, Web of Science, and our own reference library. Search terms included combinations of "resveratrol," "cancer," "natural products," "chemotherapy," an

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… Chem. 58 6494 – 6506 . 10.1021/acs.jmedchem.5b00536 26204233 Abbreviations 5-fluorouracil aldo-keto reductases protein kinase B anthracycline antibiotics promyelocytic leukemia carbonyl reductases cyclin-dependent kinases combination index cyclooxygenase a kind of aromatase a kind of cytochrome …

Keyword Index for Volume 110

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