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Animals : An Open Access Journal From... Nov 2023The plerocercoid of can parasitize both human and animals, resulting in sparganosis. Lactate dehydrogenase (LDH) is an important enzyme in parasites. However, our...
The plerocercoid of can parasitize both human and animals, resulting in sparganosis. Lactate dehydrogenase (LDH) is an important enzyme in parasites. However, our knowledge of the LDH family in is still inadequate. This work identified 19 new LDH members in . Clustering analysis demonstrated that all LDHs were divided into two main groups, which is consistent with the patterns of conserved motif organization. According to RT-qPCR, 2 LDHs were highly expressed in the plerocercoid stage and 17 LDHs were highly expressed in the adult stage. The evolutionary tree showed a high level of diversity of both cestode and trematode LDHs. LDHs contained both conserved family members and members in the process of further diversification. rLDH has a NAD-binding domain and a substrate-binding domain. The protein was immunolocalized in the epidermis of the pleroceroid and in the tegument, uterus and egg shell of adult worms. The optimum activity for rLDH in the pyruvate reduction reaction was found to be pH 4.5 and 37 °C. In the oxidation reaction, optimal values for pH and temperature were 9.0 and 30 °C, respectively. Gossypol was found to be the most powerful inhibitor in both reduction and oxidation reactions. The results provide a basis for the further study of the biological roles of LDHs in and other LDH-containing taxa.
PubMed: 38066993
DOI: 10.3390/ani13233642 -
Bioanalysis 2024Enzymes have been used for disease diagnosis for many decades; however, advancements in technology like ELISA and flow cytometry-based detection... (Review)
Review
Enzymes have been used for disease diagnosis for many decades; however, advancements in technology like ELISA and flow cytometry-based detection have significantly increased their use and have increased the sensitivity of detection. Technological advancements in recombinant enzyme production have increased enzymatic stability, and the use of colorimetric-based and florescence-based assays has led to their increased use as biomarkers for disease detection. Enzymes like acid phosphatase, cathepsin, lactate dehydrogenase, thymidine kinase and creatine kinase are indispensable markers for diagnosing cancer, cardiovascular diseases and others. This minireview summarizes various enzymes used in disease diagnosis, their metabolic role, market value and potential as disease markers across various metabolic and other disorders.
Topics: Humans; Biomarkers; Enzymes; Neoplasms; Cardiovascular Diseases
PubMed: 38530222
DOI: 10.4155/bio-2023-0207 -
Device Jul 2023We report a simple droplet fluidic point-of-care test (POCT) that uses gravity to manipulate the sequence, timing, and motion of droplets on a surface. To fabricate this...
We report a simple droplet fluidic point-of-care test (POCT) that uses gravity to manipulate the sequence, timing, and motion of droplets on a surface. To fabricate this POCT, we first developed a surface coating toolbox of nine different coatings with three levels of wettability and three levels of slipperiness that can be independently tailored. We then fabricated a device that has interconnected fluidic elements-pumps, flow resistors and flow guides-on a highly slippery solid surface to precisely control the timing and sequence of motion of multiple droplets and their interactions on the surface. We then used this device to carry out a multi-step enzymatic assay of a clinically relevant analyte-lactate dehydrogenase (LDH)-to demonstrate the application of this technology for point-of-care diagnosis.
PubMed: 37872891
DOI: 10.1016/j.device.2023.100009 -
Rheumatology (Oxford, England) Dec 2023To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout.
OBJECTIVES
To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout.
METHODS
We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA.
RESULTS
We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)].
CONCLUSION
Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.
Topics: Male; Humans; Gout; Hyperuricemia; Homozygote; Lactic Acid; Lactate Dehydrogenases
PubMed: 37021930
DOI: 10.1093/rheumatology/kead118 -
Cancer Research Oct 2023Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer could help identify strategies to improve the treatment and prevention of...
UNLABELLED
Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer could help identify strategies to improve the treatment and prevention of metastatic disease. Here, we used a systems biology approach to compare metabolic fluxes used by parental breast cancer cells and their brain- and lung-homing derivatives. Divergent lineages had distinct, heritable metabolic fluxes. Lung-homing cells maintained high glycolytic flux despite low levels of glycolytic intermediates, constitutively activating a pathway sink into lactate. This strong Warburg effect was associated with a high ratio of lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) expression, which correlated with lung metastasis in patients with breast cancer. Although feature classification models trained on clinical characteristics alone were unable to predict tropism, the LDH/PDH ratio was a significant predictor of metastasis to the lung but not to other organs, independent of other transcriptomic signatures. High lactate efflux was also a trait in lung-homing metastatic pancreatic cancer cells, suggesting that lactate production may be a convergent phenotype in lung metastasis. Together, these analyses highlight the essential role that metabolism plays in organ-specific cancer metastasis and identify a putative biomarker for predicting lung metastasis in patients with breast cancer.
SIGNIFICANCE
Lung-homing metastatic breast cancer cells express an elevated ratio of lactate dehydrogenase to pyruvate dehydrogenase, indicating that ratios of specific metabolic gene transcripts have potential as metabolic biomarkers for predicting organ-specific metastasis.
Topics: Humans; Female; Breast Neoplasms; L-Lactate Dehydrogenase; Lung Neoplasms; Biomarkers; Neoplasms, Second Primary; Lung; Lactates; Pyruvates; Melanoma, Cutaneous Malignant
PubMed: 37526524
DOI: 10.1158/0008-5472.CAN-23-0153 -
Chinese Journal of Integrative Medicine Dec 2023To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats.
OBJECTIVE
To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats.
METHODS
Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1β (IL-1β) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3).
RESULTS
Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1β (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01).
CONCLUSIONS
HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.
Topics: Humans; Rats; Animals; NF-kappa B; Myocardial Reperfusion Injury; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; C-Reactive Protein; Toll-Like Receptor 4; Phosphatidylinositol 3-Kinases; Molecular Docking Simulation; Signal Transduction; Myocardial Infarction; Creatine Kinase; L-Lactate Dehydrogenase; Superoxide Dismutase
PubMed: 37608040
DOI: 10.1007/s11655-023-3640-1 -
Nature Communications Sep 2023Mycobacterium tuberculosis (Mtb) disrupts glycolytic flux in infected myeloid cells through an unclear mechanism. Flux through the glycolytic pathway in myeloid cells is...
Mycobacterium tuberculosis (Mtb) disrupts glycolytic flux in infected myeloid cells through an unclear mechanism. Flux through the glycolytic pathway in myeloid cells is inextricably linked to the availability of NAD, which is maintained by NAD salvage and lactate metabolism. Using lung tissue from tuberculosis (TB) patients and myeloid deficient LDHA (Ldha) mice, we demonstrate that glycolysis in myeloid cells is essential for protective immunity in TB. Glycolytic myeloid cells are essential for the early recruitment of multiple classes of immune cells and IFNγ-mediated protection. We identify NAD depletion as central to the glycolytic inhibition caused by Mtb. Lastly, we show that the NAD precursor nicotinamide exerts a host-dependent, antimycobacterial effect, and that nicotinamide prophylaxis and treatment reduce Mtb lung burden in mice. These findings provide insight into how Mtb alters host metabolism through perturbation of NAD(H) homeostasis and reprogramming of glycolysis, highlighting this pathway as a potential therapeutic target.
Topics: Animals; Mice; NAD; Homeostasis; Myeloid Cells; Tuberculosis; Niacinamide; Glycolysis; Lactate Dehydrogenase 5
PubMed: 37673914
DOI: 10.1038/s41467-023-40545-x -
Cancer Letters Apr 2024Lactate dehydrogenase A (LDHA) serves as a key regulator of the Warburg Effect by catalyzing the conversion of pyruvate to lactate in the final step of glycolysis. Both...
Lactate dehydrogenase A (LDHA) serves as a key regulator of the Warburg Effect by catalyzing the conversion of pyruvate to lactate in the final step of glycolysis. Both the expression level and enzyme activity of LDHA are upregulated in cancers, however, the underlying mechanism remains incompletely understood. Here, we show that LDHA is post-translationally palmitoylated by ZDHHC9 at cysteine 163, which promotes its enzyme activity, lactate production, and reduces reactive oxygen species (ROS) generation. Replacement of endogenous LDHA with a palmitoylation-deficient mutant leads to reduced pancreatic cancer cell proliferation, increased T-cell infiltration, and limited tumor growth; it also affects pancreatic cancer cell response to chemotherapy. Moreover, LDHA palmitoylation is upregulated in gemcitabine resistant pancreatic cancer cells. Clinically, ZDHHC9 is upregulated in pancreatic cancer and correlated with poor prognoses for patients. Overall, our findings identify ZDHHC9-mediated palmitoylation as a positive regulator of LDHA, with potentially significant implications for cancer etiology and targeted therapy for pancreatic cancer.
Topics: Humans; L-Lactate Dehydrogenase; Lipoylation; Cell Line, Tumor; Lactate Dehydrogenase 5; Pancreatic Neoplasms; Glycolysis; Cell Proliferation; Lactates
PubMed: 38331089
DOI: 10.1016/j.canlet.2024.216696 -
Hematology (Amsterdam, Netherlands) Dec 2024To investigate the prognostic value of lactate dehydrogenase (LDH), serum albumin (ALB) and the lactate dehydrogenase/albumin ratio (LAR) in diffuse large B-cell...
OBJECTIVE
To investigate the prognostic value of lactate dehydrogenase (LDH), serum albumin (ALB) and the lactate dehydrogenase/albumin ratio (LAR) in diffuse large B-cell lymphoma (DLBCL) before primary treatment.
METHODS
The clinical data of 212 primary adult DLBCL patients admitted to the First People's Hospital of Lianyungang from January 2017 to December 2022 were analyzed retrospectively. The optimal cutoff values of LDH, ALB, and LAR were determined using ROC curves. Survival curves of LDH, ALB, and LAR were plotted and analyzed using the Cox regression model and Kaplan-Meier method with the log-rank test.
RESULTS
Among the 212 patients admitted, the study derived the optimal cutoff values for ALB, LDH, and LAR as 38, 301, and 6, respectively. The Kaplan-Meier method and log-rank test analysis indicated a significant association between lower ALB levels, elevated LDH levels, elevated LAR levels, and shorter overall survival (OS) and progression-free survival (PFS) (< 0.05). Additionally, the critical values of ALB and LDH were grouped into three categories. The differences in OS and PFS among these three groups were statistically significant (< 0.05). Cox multifactorial analysis revealed that the LAR was an independent factor influencing the prognosis of OS and PFS, with a higher prognostic value than LDH and ALB alone.
CONCLUSION
Decreased ALB levels and elevated LDH and LAR levels at the time of initial diagnosis are indicative of a poor prognosis in DLBCL patients. Furthermore, the study highlighted that the LAR has a higher prognostic value than LDH and ALB alone.
Topics: Adult; Humans; Serum Albumin; Prognosis; L-Lactate Dehydrogenase; Retrospective Studies; Lymphoma, Large B-Cell, Diffuse
PubMed: 38108323
DOI: 10.1080/16078454.2023.2293514 -
Translational Lung Cancer Research Jul 2023Not all non-small cell lung cancer (NSCLC) patients will benefit from immune checkpoint therapy and use of these medications carry serious autoimmune adverse effects....
Prognostic value of baseline and early treatment response of neutrophil-lymphocyte ratio, C-reactive protein, and lactate dehydrogenase in non-small cell lung cancer patients undergoing immunotherapy.
BACKGROUND
Not all non-small cell lung cancer (NSCLC) patients will benefit from immune checkpoint therapy and use of these medications carry serious autoimmune adverse effects. Therefore, biomarkers are needed to better identify patients who will benefit from its use. Here, the correlation of overall survival (OS) with baseline and early treatment period serum biomarker responses was evaluated in patients with NSCLC undergoing immunotherapy.
METHODS
Patients diagnosed with NSCLC undergoing immunotherapy (n=597) at a tertiary academic medical center in South Korea were identified between January 2010 and November 2021. The neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels in the survival and non-survival groups were examined at baseline and early treatment periods. Additionally, aberrant laboratory parameters at each period were used to stratify survival curves and examine their correlation with one-year OS.
RESULTS
In the non-survival group, the NLR, CRP, and LDH levels at the early treatment period were higher than those at the baseline (P<0.001). The survival curves stratified based on aberrant laboratory findings in each period varied (log-rank test P<0.001). Multivariate Cox regression analysis revealed that having prescribed more than 3rd line of chemotherapy [hazard ratio (HR) =3.19, 95% confidence interval (CI): 1.04-9.82; P=0.043] and early treatment period CRP (HR =3.88; 95% CI: 1.55-9.72; P=0.004) and LDH (HR =4.04; 95% CI: 2.01-8.12; P<0.001) levels were significant predictors of one-year OS.
CONCLUSIONS
Early treatment period CRP and LDH levels were significant predictors of OS in patients with NSCLC undergoing immunotherapy.
PubMed: 37577328
DOI: 10.21037/tlcr-23-7