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Disease Markers 2023Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing...
Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the role and mechanisms of ALDOA in CRC are still unclear. In the current study, high expression levels and enzymatic activity of ALDOA were detected in CRC tissues and cell lines, indicating the clinical significance of ALDOA in human CRC. In addition, silencing ALDOA significantly impaired the proliferation and metastasis of CRC cells and . Mechanistically, immunoprecipitation assays and mass spectrometry analysis identified the binding protein COPS6 of ALDOA. Furthermore, the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by COPS6 depletion, demonstrating COPS6 was required for ALDOA in mediating CRC progress. Moreover, the epithelial-mesenchymal transition (EMT) program and MAPK signaling pathway were found to be activated by ALDOA overexpression as well. In summary, our findings suggested that ALDOA facilitated the proliferation and metastasis of CRC by binding and regulating COPS6, inducing EMT, and activating the mitogen-activated protein kinase (MAPK) signaling pathway. The present study provided evidence for ALDOA as a promising potential biomarker for CRC.
Topics: Humans; Mitogen-Activated Protein Kinases; Fructose-Bisphosphate Aldolase; Cell Line, Tumor; Cell Movement; Signal Transduction; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; COP9 Signalosome Complex; Adaptor Proteins, Signal Transducing
PubMed: 37457886
DOI: 10.1155/2023/1702125 -
Advanced Science (Weinheim,... Sep 2023Aldolase A (ALDOA), a crucial glycolytic enzyme, is often aberrantly expressed in various types of cancer. Although ALDOA has been reported to play additional roles...
Aldolase A (ALDOA), a crucial glycolytic enzyme, is often aberrantly expressed in various types of cancer. Although ALDOA has been reported to play additional roles beyond its conventional enzymatic role, its nonmetabolic function and underlying mechanism in cancer progression remain elusive. Here, it is shown that ALDOA promotes liver cancer growth and metastasis by accelerating mRNA translation independent of its catalytic activity. Mechanistically, ALDOA interacted with insulin- like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to facilitate its binding to m A-modified eIF4G mRNA, thereby increasing eIF4G protein levels and subsequently enhancing overall protein biosynthesis in cells. Importantly, administration of GalNAc-conjugated siRNA targeting ALDOA effectively slows the tumor growth of orthotopic xenografts. Collectively, these findings uncover a previously unappreciated nonmetabolic function of ALDOA in modulating mRNA translation and highlight the potential of specifically targeting ALDOA as a prospective therapeutic strategy in liver cancer.
Topics: Humans; Fructose-Bisphosphate Aldolase; Eukaryotic Initiation Factor-4G; Cell Line, Tumor; Liver Neoplasms; RNA, Small Interfering
PubMed: 37431681
DOI: 10.1002/advs.202302425 -
Biology Direct Jul 2023LncRNA PSMA3-AS1 functions as an oncogene in several cancers, including ovarian cancer, lung cancer, and colorectal cancer. However, its role in gastric cancer (GC)...
LncRNA PSMA3-AS1 functions as an oncogene in several cancers, including ovarian cancer, lung cancer, and colorectal cancer. However, its role in gastric cancer (GC) progression remains unclear. In this study, the levels of PSMA3-AS1, miR-329-3p, and aldolase A (ALDOA) in 20 paired human GC tissues and adjacent nontumorous tissues were measured by real-time PCR. GC cells were transfected with recombinant plasmid carrying full-length PSMA3-AS1 or shRNA targeting PSMA3-AS1. The stable transfectants were selected by G418. Then, the effects of PSMA3-AS1 knockdown or overexpression on GC progression in vitro and in vivo were evaluated. The results showed that PSMA3-AS1 was highly expressed in human GC tissues. Stable knockdown of PSMA3-AS1 significantly restrained proliferation/migration/invasion, enhanced cell apoptosis, and induced oxidative stress in vitro. Tumor growth and matrix metalloproteinase expression in tumor tissues were markedly inhibited, while oxidative stress was enhanced in nude mice after stable PSMA3-AS1 knockdown. Additionally, PSMA3-AS1 negatively regulated miR-329-3p while positively regulated ALDOA expression. MiR-329-3p directly targeted ALDOA-3'UTR. Interestingly, miR-329-3p knockdown or ALDOA overexpression partially attenuated the tumor-suppressive effects of PSMA3-AS1 knockdown. Conversely, PSMA3-AS1 overexpression exhibited the opposite effects. PSMA3-AS1 promoted GC progression by regulating the miR-329-3p/ALDOA axis. PSMA3-AS1 might serve as a promising and effective target for GC treatment.
Topics: Animals; Mice; Humans; Stomach Neoplasms; MicroRNAs; RNA, Long Noncoding; Fructose-Bisphosphate Aldolase; Mice, Nude; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Movement; Proteasome Endopeptidase Complex
PubMed: 37403106
DOI: 10.1186/s13062-023-00392-8 -
Frontiers in Immunology 2023Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in , comprising a multisystemic disease characterized by steroid... (Review)
Review
BACKGROUND
Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in , comprising a multisystemic disease characterized by steroid resistant nephrotic syndrome, primary adrenal insufficiency, neurological problems, skin abnormalities and immunodeficiency in described cases. Signal transducer and activator of transcription 1 (STAT1) plays an important role in orchestrating an appropriate immune response through JAK-STAT pathway. Biallelic loss of function (LOF) variants lead to STAT1 deficiency with a severe phenotype of immunodeficiency with increased frequency of infections and poor outcome if untreated.
CASE PRESENTATION
We report novel homozygous SGPL and variants in a newborn of Gambian ethnicity with clinical features of SPLIS and severe combined immunodeficiency. The patient presented early in life with nephrotic syndrome, severe respiratory infection requiring ventilation, ichthyosis, and hearing loss, with T-cell lymphopenia. The combination of these two conditions led to severe combined immunodeficiency with inability to clear respiratory tract infections of viral, fungal, and bacterial nature, as well as severe nephrotic syndrome. The child sadly died at 6 weeks of age despite targeted treatments.
CONCLUSION
We report the finding of two novel, homozygous variants in and in a patient with a severe clinical phenotype and fatal outcome early in life. This case highlights the importance of completing the primary immunodeficiency genetic panel in full to avoid missing a second diagnosis in other patients presenting with similar severe clinical phenotype early in life. For SPLIS no curative treatment is available and more research is needed to investigate different treatment modalities. Hematopoietic stem cell transplantation (HSCT) shows promising results in patients with autosomal recessive STAT1 deficiency. For this patient's family, identification of the dual diagnosis has important implications for future family planning. In addition, future siblings with the familial variant can be offered curative treatment with HSCT.
Topics: Humans; Aldehyde-Lyases; Immunologic Deficiency Syndromes; Janus Kinases; Nephrotic Syndrome; Severe Combined Immunodeficiency; Signal Transduction; STAT Transcription Factors; STAT1 Transcription Factor; Infant, Newborn
PubMed: 37377976
DOI: 10.3389/fimmu.2023.1186575 -
Parasites & Vectors May 2023Ticks are obligate hematophagous ectoparasites that transmit a variety of pathogens to humans, wildlife and domestic animals. Vaccination is an effective and...
BACKGROUND
Ticks are obligate hematophagous ectoparasites that transmit a variety of pathogens to humans, wildlife and domestic animals. Vaccination is an effective and environmentally friendly method for tick control. Fructose-1,6-bisphosphate aldolase (FBA) is an important glycometabolism enzyme that is a candidate vaccine against parasites. However, the immune protection of FBA in ticks is unclear. METHODS AND RESULTS: The 1092-bp open reading frame (ORF) of FBA from Haemaphysalis longicornis (HlFBA), encoding a 363-amino acid protein, was cloned using PCR methodology. The prokaryotic expression vector pET32a(+)-HlFBA was constructed and transformed into cells of Escherichia coli BL21(DE3) strain for protein expression. The recombinant HlFBA protein (rHlFBA) was purified by affinity chromatography, and the western blot results suggested that the rHlFBA protein was immunogenic.
RESULTS
Results of the enzyme-linked immunosorbent assay showed that rabbits immunized with rHlFBA produced a humoral immune response specific to rHlFBA. A tick infestation trial indicated that, compared to the ticks in the histidine-tagged thioredoxin (Trx) group, the engorged tick weight and oviposition of female ticks and egg hatching rate of those in the rHlFBA group was reduced by 22.6%, 45.6% and 24.1%, respectively. Based on the cumulative effect of the these three parameters, the overall immune efficacy of rHlFBA was estimated to be 68.4%.
CONCLUSIONS
FBA is a candidate anti-tick vaccine that can significantly reduce the engorged tick weight, oviposition, and egg hatching rate. The use of enzymes involved in glucose metabolism is a new strategy in the development of anti-tick vaccines.
Topics: Humans; Animals; Female; Rabbits; Ixodidae; Fructose-Bisphosphate Aldolase; Vaccines; Recombinant Proteins; Tick Infestations; Aldehyde-Lyases
PubMed: 37231514
DOI: 10.1186/s13071-023-05794-1 -
Malaria Journal May 2023Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned...
BACKGROUND
Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned travellers has become important. The accurate and timely diagnosis of malaria is the key in preventing re-establishment, and malaria rapid diagnostic tests (RDTs) are frequently used due to their convenience. However, the RDT performance in Plasmodium malariae (P. malariae) infection diagnosis remains unknown.
METHODS
This study analysed epidemiological features and diagnosis patterns of imported P. malariae cases from 2013 to 2020 in Jiangsu Province and evaluated the sensitivity of four parasite enzyme lactate dehydrogenase (pLDH)-targeting RDTs (Wondfo, SD BIONLINE, CareStart and BioPerfectus) and one aldolase-targeting RDT(BinaxNOW) for P. malariae detection. Furthermore, influential factors were investigated, including parasitaemia load, pLDH concentration and target gene polymorphisms.
RESULTS
The median duration from symptom onset to diagnosis among patients with P. malariae infection was 3 days, which was longer than that with Plasmodium falciparum (P. falciparum) infection. The RDTs had a low detection rate (39/69, 56.5%) among P. malariae cases. All tested RDT brands had poor performance in P. malariae detection. All the brands except the worst-performing SD BIOLINE, achieved 75% sensitivity only when the parasite density was higher than 5000 parasites/μL. Both pLDH and aldolase showed relatively conserved and low gene polymorphism rates.
CONCLUSIONS
The diagnosis of imported P. malariae cases was delayed. The RDTs had poor performance in P. malariae diagnosis and may threaten the prevention of malaria re-establishment from returned travellers. The improved RDTs or nucleic acid tests for P. malariae cases are urgently needed for the detection of imported cases in the future.
Topics: Humans; Plasmodium malariae; Rapid Diagnostic Tests; Malaria; Malaria, Falciparum; China; Fructose-Bisphosphate Aldolase; Aldehyde-Lyases; L-Lactate Dehydrogenase
PubMed: 37226272
DOI: 10.1186/s12936-023-04596-1 -
Angewandte Chemie (International Ed. in... Sep 2023We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a...
We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.
Topics: Fructose-Bisphosphate Aldolase; Models, Molecular; Peptides; Amino Acids; Aldehyde-Lyases; Hydrogen Bonding
PubMed: 37218617
DOI: 10.1002/anie.202305326 -
Microbial Biotechnology Jan 2024Mycobacterial mutants blocked in ring degradation constructed to achieve C19 synthons production, also accumulate by-products such as C22 intermediates throughout an...
Mycobacterial mutants blocked in ring degradation constructed to achieve C19 synthons production, also accumulate by-products such as C22 intermediates throughout an alternative pathway reducing the production yields and complicating the downstream purification processing of final products. In this work, we have identified the MSMEG_6561 gene, encoding an aldolase responsible for the transformation of 22-hydroxy-3-oxo-cholest-4-ene-24-carboxyl-CoA (22-OH-BCN-CoA) into the 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) precursor (20S)-3-oxopregn-4-ene-20-carboxaldehyde (3-OPA). The deletion of this gene increases the production yield of the C-19 steroidal synthon 4-androstene-3,17-dione (AD) from natural sterols, avoiding the production of 4-HBC as by-product and the drawbacks in the AD purification. The molar yield of AD production using the MS6039-5941-6561 triple mutant strain was checked in flasks and bioreactor improving very significantly compared with the previously described MS6039-5941 strain.
Topics: Sterols; Fructose-Bisphosphate Aldolase; Cholestenones; Aldehyde-Lyases
PubMed: 37154793
DOI: 10.1111/1751-7915.14270 -
Microbial Cell Factories May 2023Aromatic α-hydroxy ketones, such as S-2-hydroxypropiophenone (2-HPP), are highly valuable chiral building blocks useful for the synthesis of various pharmaceuticals and...
BACKGROUND
Aromatic α-hydroxy ketones, such as S-2-hydroxypropiophenone (2-HPP), are highly valuable chiral building blocks useful for the synthesis of various pharmaceuticals and natural products. In the present study, enantioselective synthesis of 2-HPP was investigated by free and immobilized whole cells of Pseudomonas putida ATCC 12633 starting from readily-available aldehyde substrates. Whole resting cells of P. putida, previously grown in a culture medium containing ammonium mandelate, are a source of native benzoylformate decarboxylase (BFD) activity. BFD produced by induced P. putida resting cells is a highly active biocatalyst without any further treatment in comparison with partially purified enzyme preparations. These cells can convert benzaldehyde and acetaldehyde into the acyloin compound 2-HPP by BFD-catalyzed enantioselective cross-coupling reaction.
RESULTS
The reaction was carried out in the presence of exogenous benzaldehyde (20 mM) and acetaldehyde (600 mM) as substrates in 6 mL of 200 mM phosphate buffer (pH 7) for 3 h. The optimal biomass concentration was assessed to be 0.006 g dry cell weight (DCW) mL. 2-HPP titer, yield and productivity using the free cells were 1.2 g L, 0.56 g 2-HPP/g benzaldehyde (0.4 mol 2-HPP/mol benzaldehyde), 0.067 g 2-HPP g DCW h, respectively, under optimized biotransformation conditions (30 °C, 200 rpm). Calcium alginate (CA)-polyvinyl alcohol (PVA)-boric acid (BA)-beads were used for cell entrapment. Encapsulated whole-cells were successfully employed in four consecutive cycles for 2-HPP production under aerobic conditions without any noticeable beads degradation. Moreover, there was no production of benzyl alcohol as an unwanted by-product.
CONCLUSIONS
Bioconversion by whole P. putida resting cells is an efficient strategy for the production of 2-HPP and other α-hydroxyketones.
Topics: Pseudomonas putida; Carboxy-Lyases; Benzaldehydes; Hydroxypropiophenone; Stereoisomerism; Ketones; Acetaldehyde
PubMed: 37131175
DOI: 10.1186/s12934-023-02073-7 -
Medicine Apr 2023Aldolase B (ALDOB) gene is essential for the process of glycolysis and differentially expressed in cancers. The aims of this study were to explore the potential role of...
Aldolase B (ALDOB) gene is essential for the process of glycolysis and differentially expressed in cancers. The aims of this study were to explore the potential role of ALDOB in pan-cancer, in order to deepen the research on the pathological mechanism of cancer. Hence, we used several online tools (TIMER2, GEPIA2, UALCAN, cBioPortal, and MXPRESS) and R language to identify the correlation between the ALDOB expression and survival analysis, genetic alteration, DNA methylation, and immune cell infiltration based on The Cancer Genome Atlas project. The results showed that ALDOB was lowly expressed in pan-cancer. Survival analysis revealed that low expression of ALDOB was markedly related with poor clinical prognosis, while the genetic alteration within ALDOB changed along with the difference of overall survival (OS) and disease-free survival (DFS) prognosis in several cancers. A possible relationship between DNA methylation and ALDOB expression for several tumors was found. Besides, ALDOB expression was confirmed to be associated with tumor immune cell infiltration, especially in breast invasive carcinoma (BRCA), esophageal carcinoma (ESCA), and testicular germ cell tumors (TGCT) cases. Further, the enrichment analysis demonstrated that metabolic pathway was closely related to ALDOB expression. Our results provide a comprehensive pan-cancer analysis and suggest ALDOB could act as a promising tumor predictive biomarker for human cancer.
Topics: Humans; Male; Fructose-Bisphosphate Aldolase; Prognosis; Testicular Neoplasms; Breast Neoplasms; Carcinoma; Biomarkers, Tumor
PubMed: 37083815
DOI: 10.1097/MD.0000000000033577