ALDH2 variance in disease and populations

Disease Models & Mechanisms, Год журнала: 2022, Номер 15(6)

Опубликована: Июнь 1, 2022

The ALDH2*2 missense variant that commonly causes alcohol flushing reactions is the single genetic polymorphism associated with largest number of traits in humans. dysfunctional ALDH2 affects nearly 8% world population and highly concentrated among East Asians. Carriers present alterations a blood biomarkers, clinical measurements, biometrics, drug prescriptions, dietary habits lifestyle behaviors, they are also more susceptible to aldehyde-associated diseases, such as cancer cardiovascular disease. However, interaction between ALDH2-related pathology not clearly delineated. Furthermore, evidence indicates has been favorably selected for past 2000-3000 years. It therefore necessary consider disease risk mechanism deficiency, understand possible beneficial or protective effect conferred by deficiency whether pleiotropic effects variance all mediated use.

Язык: Английский

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Nitric Oxide‐Based Nanomedicines for Conquering TME Fortress: Say “NO” to Insufficient Tumor Treatment

Advanced Functional Materials, Год журнала: 2023, Номер 34(13)

Опубликована: Дек. 21, 2023

Abstract Almost all cancer treatments are significantly limited by the strong tumor microenvironment (TME) fortress formed abnormal vasculature, dense extracellular matrix (ECM), multidrug resistance (MDR) system, and immune “cold” environment. In huge efforts of dismantling TME fortress, nitric oxide (NO)‐based nanomedicines increasingly occupying a central position have already been identified as super “strong polygonal warriors” to dismantle for efficient treatment, benefiting from NO's unique physicochemical properties extremely fascinating biological effects. However, there is paucity systematic review elaborate on progress fundamental mechanism NO‐based in oncology this aspect. Herein, key characteristics potential NO reprogramming delineated highlighted. The evolution donors advantages discussed subsequently. Moreover, latest solid tumors comprehensively reviewed, including normalizing overcoming ECM barrier, reversing MDR, reactivating immunosuppression TME. Lastly, prospects, limitations, future directions manipulation provide new insights into construction more applicable anticancer nanomedicines.

Язык: Английский

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The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 24, 2024

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has highest incidence malignant tumors system. We performed two-sample Mendelian randomization analysis to explore associations between 19 metabolism-related lifestyle clinical risk DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, pancreatic cancer. The causal association was explored for all combinations each factor DSC. gathered information on instrumental variables (IVs) from various sources retrieved outcome Biobank Japan (BBJ). data were studies east Asian populations. Finally, 17,572 DSCs cases 195,745 controls included. Our found that genetically predicted alcohol drinking strong indicator gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) hepatocellular carcinoma (OR 1.11; CI: 1.05-1.18), whereas coffee consumption had potential protective effect 0.69; 0.53-0.90). Triglyceride potentially associated with decreased tract 0.53; 0.34-0.81), uric acid 0.59; 0.37-0.96). syndrome (MetS) esophageal Additionally, there no evidence other factors, body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total glycine, creatinine, gout, Graves' disease, DSCs. leave-one-out revealed single nucleotide polymorphism (SNP) rs671 ALDH2 gene disproportionately high contribution carcinoma, as well carcinoma. present study multiple valuable SNP highlighting significance metabolic both prevention treatment

Язык: Английский

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Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

Infectious Agents and Cancer, Год журнала: 2024, Номер 19(1)

Опубликована: Июль 2, 2024

Abstract The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability DNA damage, contributing tumorigenesis. stress-induced especially double-strand breaks, aids in integration into host promotes overexpression two viral proteins, E6 E7. Lifestyle factors, including diet, smoking, alcohol, psychological stress, along with genetic epigenetic modifications, oncoproteins may influence impacting progression HPV-related cancers. This review highlights various mechanisms oxidative-induced HPV-mediated carcinogenesis, altered mitochondrial morphology function leading elevated ROS levels, modulation antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), Peroxidase (GPx), induction chronic inflammatory environments, activation specific cell signaling pathways Phosphoinositide 3-kinase, Protein kinase B, Mammalian target rapamycin (PI3K/AKT/mTOR) Extracellular signal-regulated (ERK) pathway. study significance comprehending controlling preventing treating cancer. We suggested that incorporating dietary antioxidants targeting cells through involving could be potential interventions mitigate impact on malignancies.

Язык: Английский

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Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression

Cell Death and Disease, Год журнала: 2021, Номер 12(12)

Опубликована: Дек. 14, 2021

Aldehyde dehydrogenases (ALDHs) play an essential role in regulating malignant tumor progression; however, their cholangiocarcinoma (CCA) has not been elucidated. We analyzed the expression of ALDHs 8 paired and peritumor perihilar (pCCA) tissues found that ALDH3B1 ALDH3B2 were upregulated tissues. Further survival analysis intrahepatic (iCCA, n = 27), pCCA (n 87) distal (dCCA, 80) cohorts have revealed was a prognostic factor CCA independent iCCA pCCA. associated with serum CEA dCCA, T stage, M neural invasion CA19-9 In two cell lines, overexpression promoted proliferation clone formation by promoting G1/S phase transition. Knockdown inhibited migration, invasion, EMT vitro, restrained metastasis vivo. Patients high also ITGB1 iCCA, pCCA, dCCA at both mRNA protein levels. downregulated phosphorylation level c-Jun, p38, ERK. Meanwhile, knockdown effect on proliferation, invasion. is double-positive exhibits better performance predicting patient prognosis. conclusion, promotes upregulating its downstream signaling pathway. The serves as biomarker CCA.

Язык: Английский

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Proteomic Profiling of Fallopian Tube-Derived Extracellular Vesicles Using a Microfluidic Tissue-on-Chip System

Bioengineering, Год журнала: 2023, Номер 10(4), С. 423 - 423

Опубликована: Март 27, 2023

The human fallopian tube epithelium (hFTE) is the site of fertilization, early embryo development, and origin most high-grade serous ovarian cancers (HGSOCs). Little known about content functions hFTE-derived small extracellular vesicles (sEVs) due to limitations biomaterials proper culture methods. We have established a microfluidic platform hFTE for EV collection with adequate yield mass spectrometry-based proteomic profiling, reported 295 common sEV proteins first time. These are associated exocytosis, neutrophil degranulation, wound healing, some crucial fertilization processes. In addition, by correlating protein profiles tissue transcripts characterized using GeoMx® Cancer Transcriptome Atlas, spatial transcriptomics analysis revealed cell-type-specific that encode sEVs proteins, among which, FLNA, TUBB, JUP, FLNC were differentially expressed in secretory cells, precursor cells HGSOC. Our study provides insights into establishment baseline profile derived from tissue, its correlation lineage-specific transcripts, which can be used evaluate whether shifts cargo during cancer carcinogenesis role reproductive functions.

Язык: Английский

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Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(12), С. e007487 - e007487

Опубликована: Дек. 1, 2023

Background Aldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme involved in endogenous aldehyde detoxification and has been implicated tumor progression. However, its role immune evasion remains unclear. Methods Here, we analyzed the relationship between ALDH2 expression antitumor features multiple cancers. knockout cells were then established using CRISPR/Cas9 system. In immunocompetent breast cancer EMT6 melanoma B16-F10 mouse models, investigated impact of blockade on cytotoxic T lymphocyte function microenvironment by flow cytometry, mass Luminex liquid suspension chip detection, immunohistochemistry. Furthermore, RNA sequencing, western blot, chromatin immunoprecipitation assay, luciferase reporter assays employed to explore detailed mechanism evasion. Lastly, synergistic therapeutic efficacy blocking genetic depletion or inhibitor disulfiram combination with checkpoint (ICB) was models. Results our study, uncovered positive correlation level T-cell dysfunction significantly suppressed growth enhancing activity CD8 + reshaping landscape cytokine milieu tumors vivo . Mechanistically, inhibiting ALDH2-mediated metabolism downregulated V-domain Ig suppressor activation (VISTA) via inactivating nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. As result, revitalized. Importantly, markedly reinforced ICB treatment. Conclusions Our data delineate that drives activating NOD/NF-κB/VISTA axis. Targeting provides an effective combinatorial strategy for immunotherapy.

Язык: Английский

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ALDH2 promotes cancer stemness and metastasis in colorectal cancer through activating β‐catenin signaling

Journal of Cellular Biochemistry, Год журнала: 2023, Номер 124(6), С. 907 - 920

Опубликована: Май 14, 2023

Abstract Colorectal cancer (CRC) is the primary cause of death from gastrointestinal cancers. Aldehyde dehydrogenase 2 (ALDH2), a crucial mitochondrial enzyme for oxidative pathway alcohol metabolism, plays dual role in progression. In some cancers, it tumor suppressive; others, drives However, whether targeting ALDH2 has any therapeutic implications or prognostic value CRC still unclear. Here, we investigated progression by its enzymatic activity rather than gene expression. We found that inhibiting CVT‐10216 and daidzein significantly decrease migration stemness properties both DLD‐1 HCT 116 cells, whereas activating Alda‐1 enhances rate. Concomitantly, inhibition downregulates mRNA levels fibronectin, snail, twist, MMP7, CD44, c‐Myc, SOX2, OCT‐4, which are oncogenic advanced stage CRC. Furthermore, Gene Set Enrichment Analysis (GSEA) on co‐expressed genes The Cancer Genome Atlas (TCGA) revealed MYC target sets upregulated. decreased nuclear protein pGSK3β serine 9 c‐Myc. This suggests probably targets β‐catenin signaling cells. Together, our results demonstrate as regulates migration. Our findings also propose plant‐derived isoflavone could be potential chemotherapeutic drug

Язык: Английский

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Superior cuproptotic efficacy of diethyldithiocarbamate-Cu4O3 nanoparticles over diethyldithiocarbamate-Cu2O nanoparticles in metastatic hepatocellular carcinoma

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 15, 2024

Metastatic hepatocellular carcinoma (HC) is a serious health concern. The stemness of cancer stem cells (CSCs) key driver for HC tumorigenesis, apoptotic resistance, and metastasis, functional mitochondria are critical its maintenance. Cuproptosis Cu-dependent non-apoptotic pathway (mitochondrial dysfunction) via inactivating mitochondrial enzymes (pyruvate dehydrogenase "PDH" succinate "SDH"). To effectively treat metastatic HC, it necessary to induce selective cuproptosis (for halting genes) with oxidative imbalance increasing cell susceptibility inducing non-CSCs death). Herein, two types Cu oxide nanoparticles (Cu

Язык: Английский

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Identification of senescence-related molecular subtypes and key genes for prostate cancer

Asian Journal of Andrology, Год журнала: 2022, Номер 25(2), С. 223 - 229

Опубликована: Сен. 8, 2022

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radiotherapy (RT). conducted all analyses using R software its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), androgen-regulated mucin-like 1 (PARM1), leucine zipper 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix (COMP), vestigial-like 3 (VGLL3), apolipoprotein E (APOE), aldehyde dehydrogenase (ALDH2), were eventually used to subtype PCa from The Cancer Genome Atlas (TCGA) database GSE116918, the showed good correlations clinical features. In terms tumor immune environment (TME) analysis, compared 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells lower in TCGA database. There was a statistically significant correlation between both CAFs biochemical recurrence (BCR)-free survival for RP. For GSE116918 database, had levels purity higher stromal, immune, Estimation STromal Immune MAlignant Tumor tissues Expression data (ESTIMATE) scores than 1; addition, high CAFs, stromal scores, ESTIMATE low tended suffer BCR. Based on median differentially expressed checkpoints, expression CD96, hepatitis virus cellular receptor (HAVCR2), neuropilin (NRP1) CD160 necrosis factor (ligand) superfamily 18 (TNFSF18) associated risk BCR their counterparts. conclusion, we first constructed RP RT fresh perspective senescence.

Язык: Английский

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