-
Journal of Investigative Surgery : the... Dec 2023Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an...
PURPOSE
Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer.
METHODS
We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model.
RESULTS
A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding.
CONCLUSIONS
Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.
Topics: Humans; Stomach Neoplasms; Propensity Score; Patient Readmission; Retrospective Studies; Postoperative Complications; Gastrectomy; Lactate Dehydrogenases
PubMed: 36775654
DOI: 10.1080/08941939.2023.2172488 -
International Journal of Molecular... Jul 2023is the most widespread cause of malaria, especially in subtropical and temperate regions such as Asia-Pacific and America. lactate dehydrogenase (PvLDH), an essential...
is the most widespread cause of malaria, especially in subtropical and temperate regions such as Asia-Pacific and America. lactate dehydrogenase (PvLDH), an essential enzyme in the glycolytic pathway, is required for the development and reproduction of the parasite. Thus, LDH from these parasites has garnered attention as a diagnostic biomarker for malaria and as a potential molecular target for developing antimalarial drugs. In this study, we prepared a transformed strain for the overexpression of PvLDH without codon optimization. We introduced this recombinant plasmid DNA prepared by insertion of the gene in the pET-21a(+) expression vector, into the Rosetta(DE3), an strain suitable for eukaryotic protein expression. The time, temperature, and inducer concentration for PvLDH expression from this Rosetta(DE3), containing the original gene, were optimized. We obtained PvLDH with a 31.0 mg/L yield and high purity (>95%) from this Rosetta(DE3) strain. The purified protein was characterized structurally and functionally. The PvLDH expressed and purified from transformed bacteria without codon optimization was successfully demonstrated to exhibit its potential tetramer structure and enzyme activity. These findings are expected to provide valuable insights for research on infectious diseases, metabolism, diagnostics, and therapeutics for malaria caused by .
Topics: Humans; Plasmodium vivax; L-Lactate Dehydrogenase; Escherichia coli; Malaria, Vivax; Malaria; Codon
PubMed: 37446261
DOI: 10.3390/ijms241311083 -
European Review For Medical and... Jul 2023In 1930, Otto Warburg reported that "aerobic glycolysis" is the intrinsic property of all tumor cells' fermentation of glucose to L-Lactate by lactate dehydrogenase A...
OBJECTIVE
In 1930, Otto Warburg reported that "aerobic glycolysis" is the intrinsic property of all tumor cells' fermentation of glucose to L-Lactate by lactate dehydrogenase A (LDHA) activity. This only produces per mole of glucose two moles of adenosine triphosphate (ATP), compared with 32 moles of ATP in a normal cell. Thus, tumor cells have to uptake 30 folds more glucose, the resulting accumulated lactate are then transported by a monocarboxylate transporter (MCT) with the participation of a CD147 molecule. Inhibition of MCT1 by RNA interference (RNAi) disrupted the unique metabolism of the tumor and caused tumor cell death. However, the effectiveness of the strategies depends on the targeted delivery of the therapeutics.
MATERIALS AND METHODS
In this study, a synergistic approach was used to target LDHA and MCT1 with small molecule inhibitors FX11 and AR-C155858, respectively. Cell cytotoxicity assays (AlamarBlue assay), and Mitochondria Membrane Potential (JC-1) dye assays were performed on human breast cancer cells MCF-7 and colorectal cancer cells HCT116. To achieve this aim, the following objectives were proposed: the effect of metabolic inhibitors on tumor glycolytic metabolite environment, and the efficacy of metabolite inhibitors on human breast and colorectal cancer cells in vitro. Then, gene expression analysis was performed using Qiagen RT2 Profiler PCR array for apoptosis. All these assays were performed on human breast cancer cells MCF-7 and colorectal cancer cells HCT116. Normal human fibroblasts were used as control cells under normal and hypoxic culture conditions.
RESULTS
In this study, the use of FX-11 inhibitors under normoxia or hypoxia in two or more cancer and normal cell lines has a direct effect on LDHA, whereby it inhibits its production, and this reduces the growth and cell proliferation of tumors. One of the more significant findings to emerge from this study is that using AR-C155858 inhibitor alone has increased the cell proliferation and showed no significant changes compared with the control. The other major finding was that combination of the two inhibitors, FX-11 and AR-C155858, under normoxia or hypoxia in two different cell lines MCF-7 and HCT-116 measured a decrease in the cells proliferative and red/green ratio.
CONCLUSIONS
We successfully demonstrated that a combination of MCT1 inhibitor and LDHA inhibitor led to better outcomes. Indeed, this makes LDHA an ideal metabolic therapeutic target.
Topics: Female; Humans; Adenosine Triphosphate; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Glucose; Glycolysis; Lactate Dehydrogenase 5; Lactates; Monocarboxylic Acid Transporters
PubMed: 37522672
DOI: 10.26355/eurrev_202307_33131 -
Cellular Signalling Aug 2024Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies. Lactate dehydrogenase family genes (LDHs) play a critical role in tumor metabolism,...
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies. Lactate dehydrogenase family genes (LDHs) play a critical role in tumor metabolism, but their functions in HNSCC have not been investigated thoroughly. Thus, we aimed to explore the value of LDHs in HNSCC.
METHODS
The association between LDHs expression and mutations, methylation, copy number variations (CNVs), alternative splicing (AS) and competing endogenous RNA (ceRNA) was investigated in The Cancer Genome Atlas (TCGA). The expression level of LDHs in OSCC tissues and adjacent normal tissues was verified by qPCR. Algorithms, such as ssGSEA, ESTIMATE, xCell and TIDE were utilized to analyze the characteristics of immune infiltration. Pathway alternations were enriched by GO, GSEA and KEGG analysis. The Mantel test was employed to elucidate the correlation between metabolism and the tumor microenvironment (TME). Subsequently, MTT and colony formation assays were utilized to assess the impact of LDHB knockdown on cellular proliferation. Additionally, ATP and lactate assays were performed to examine metabolic alterations. Co-culture experiments further investigated the effect of LDHB knockdown on T cell differentiation.
RESULTS
LDHs were completely analyzed in multiple databases, among which LDHB was differentially expressed in HNSCC and significantly associated with prognosis. Low LDHB expression had better clinicopathological characteristics. Downregulated LDHB expression was associated with enhanced immune cell infiltration and could influence tumor metabolism. Despite having worse cytotoxic T lymphocyte dysfunction, the LDHB group was predicted to respond more favorably to immune checkpoint inhibitors (ICIs) therapy. Moreover, the correlation between metabolism and TME was depicted. In vitro, LDHB knockdown resulted in inhibited cell proliferation, increased lactate levels and decreased ATP levels, while promoted the Th1 differentiation of T cells.
CONCLUSIONS
Our study provided a comprehensive analysis of the LDHs and illustrated low LDHB expression could inhibit tumor cell proliferation and ATP production by influencing metabolism, with improved immune cell infiltration and better response to immunotherapy.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; L-Lactate Dehydrogenase; Immunotherapy; Head and Neck Neoplasms; Tumor Microenvironment; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Cell Differentiation; Isoenzymes
PubMed: 38719019
DOI: 10.1016/j.cellsig.2024.111200 -
Reviews in Medical Virology Nov 2023There's critical need for risk predictors in long COVID. This meta-analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long... (Meta-Analysis)
Meta-Analysis Review
There's critical need for risk predictors in long COVID. This meta-analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long COVID and explores the contribution of LDH to symptoms persistent across the distinct post-acute sequelae of COVID-19 (PASC) domains. PubMed, EMBASE, Web of Science, and Google Scholar were searched for articles published up to 20 March 2023 for studies that reported data on LDH levels in COVID-19 survivors with and without PASC. Random-effect meta-analysis was employed to estimate the standardized mean difference (SMD) with corresponding 95% confidence interval of each outcome. There were a total of 8289 study participants (3338 PASC vs. 4951 controls) from 46 studies. Our meta-analysis compared to the controls showed a significant association between LDH elevation and Resp-PASC [SMD = 1.07, 95%CI = 0.72, 1.41, p = 0.01] but not Cardio-PASC [SMD = 1.79, 95%CI = -0.02, 3.61, p = 0.05], Neuro-PASC [SMD = 0.19, 95%CI = -0.24, 0.61, p = 0.40], and Gastrointestinal-PASC [SMD = 0.45, 95%CI = -1.08, 1.98, p = 0.56]. This meta-analysis suggests elevated LDH can be used for predicting Resp-PASC, but not Cardio-PASC, Neuro-PASC or gastrointestinal-PASC. Thus, elevated plasma LDH following COVID infection may be considered as a disease biomarker.
Topics: Humans; Post-Acute COVID-19 Syndrome; COVID-19; L-Lactate Dehydrogenase; Plasma; PubMed
PubMed: 37706263
DOI: 10.1002/rmv.2477 -
Scientific Reports Dec 2023Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder associated with chronic hemolysis. A major complication is vaso-occlusive crisis (VOC), associating...
Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder associated with chronic hemolysis. A major complication is vaso-occlusive crisis (VOC), associating frequent hospitalization, morbidity and mortality. The aim of this study was to investigate whether hemolysis biomarkers were able to predict VOC risk in adult patients with SCD requiring hospitalization within 1 year. This single-center prospective study included adult patients with SCD at steady state or during VOC. A total of 182 patients with SCD were included, 151 at steady state and 31 during VOC. Among the 151 patients at steady state 41 experienced VOC within 1 year (median: 3.0 months [2.0-6.5]). We observed an increase of lactate dehydrogenase (LDH) (p = 0.01) and hemolysis index (HI) (p = 0.0043) during VOC compared to steady state. Regarding patients with VOC requiring hospitalization, LDH (p = 0.0073) and HI (p = 0.04) were increased. In unadjusted logistic regression, LDH > median (> 260 U/L) (RR = 3.6 [1.29-10.88], p = 0.0098) and HI > median (> 8 UA/L) (RR = 3.13 [1.91-5.33]; p < 0.001) were associated with VOC. The association of LDH > 260 U/L and HI > 12 UA/L presented a sensitivity of 90%, and a specificity of 72.9% to predict VOC. The association of LDH and HI cut-off was able to predict VOC risk in SCD.
Topics: Adult; Humans; Hemolysis; L-Lactate Dehydrogenase; Prospective Studies; Volatile Organic Compounds; Anemia, Sickle Cell
PubMed: 38040880
DOI: 10.1038/s41598-023-48324-w -
Zoological Research Nov 2023Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I (PH1), the most common and...
Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I (PH1), the most common and life-threatening type of primary hyperoxaluria. The compact Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) from the and (Cpf1) protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus (AAV) delivery. We hypothesized that the multiplex capabilities of the Cpf1 system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1 ( ) and lactate dehydrogenase A ( ) genes. Study cohorts included treated PH1 rats ( rats injected with AAV-AsCpf1 at 7 days of age), phosphate-buffered saline (PBS)-injected PH1 rats, untreated PH1 rats, and age-matched wild-type (WT) rats. The most efficient and specific CRISPR RNA (crRNA) pairs targeting the rat and genes were initially screened . experiments demonstrated efficient genome editing of the and genes, primarily resulting in small deletions. This resulted in decreased transcription and translational expression of and . Treatment significantly reduced urine oxalate levels, reduced kidney damage, and alleviated nephrocalcinosis in rats with PH1. No liver toxicity, ex-liver genome editing, or obvious off-target effects were detected. We demonstrated the AAV-AsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1, serving as a proof-of-concept for the development of multiplex genome editing-based gene therapy.
Topics: Animals; Rats; Gene Editing; Hyperoxaluria, Primary; Liver; Oxalates
PubMed: 37759334
DOI: 10.24272/j.issn.2095-8137.2022.495 -
Wilderness & Environmental Medicine Mar 2024Scorpion stings are a significant public health problem in many parts of the world. Children are at a higher risk of developing severe complications from scorpion...
INTRODUCTION
Scorpion stings are a significant public health problem in many parts of the world. Children are at a higher risk of developing severe complications from scorpion envenoming, including cardiac, respiratory, and neurologic complications. In Turkey, members of the Buthidae family are the most common culprits in severe envenoming events.
METHODS
This retrospective-descriptive study was conducted in Turkey. Children aged 0 to 18 y admitted to the emergency department of Kahta State Hospital between December 2017 and December 2020 were included in the study. Patient information was reviewed, and 78 patients with complete demographic, laboratory, and clinical data were included in the study.
RESULTS
Out of the 78 patients, 24.4% were six years old or younger while the 75.6% were older than six years. Alpha blocker was given to 12.8% of the patients, and antivenom was given to 43.6% of the patients. Of the 78 patients, 71.8% were followed up in the emergency department, 21.8% were followed up in the inpatient unit, and 6.4% were followed up in the intensive care unit. Two patients (2.6%) died within 1 month. There was a significant difference regarding lactate dehydrogenase value according to the sting site (=0.014). Lactate dehydrogenase values of patients stung on the head and neck and upper extremity were higher than those of patients bitten on lower extremities.
CONCLUSIONS
Elevated levels of specific laboratory parameters, such as leukocytes, aspartate transaminase, and lactate dehydrogenase, are linked to worse outcomes. Additionally, stings on the head, neck, and upper extremities are more strongly associated with severity. These findings guide tailored treatment strategies for scorpion stings, with the potential for further refinement through broader studies across diverse regions and populations.
Topics: Child; Humans; Scorpion Stings; Retrospective Studies; Antivenins; Death; Lactate Dehydrogenases
PubMed: 38379470
DOI: 10.1177/10806032231220393 -
Frontiers in Pediatrics 2023pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children...
BACKGROUND
pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children had greater MPP severity.
METHODS
Retrospective analysis was conducted on 539 (ages 3-14 years) patients who were hospitalized in the First Affiliated Hospital of Anhui Medical University for MPP between January 2018 and December 2021, 195 were atopic and 344 were nonatopic. Of them, 204 had refractory MPP, and 335 had general MPP. And of atopic children, 94 had refractory MPP, and 101 had general MPP. Data on demographic and clinical characteristics, laboratory findings, clinical treatments were analyzed.
RESULTS
Significantly more boys with MPP were atopic than nonatopic (< 0.05). More atopic (than nonatopic) children presented with prolonged fever and hospitalization, severe extra-pulmonary complications, asthma attaking, steroid and oxygen treatment, and increased IgE levels (all < 0.05). In atopic (vs. nonatopic) children with MPP, the incidence of sputum plugs under the fiberoptic bronchoscopy and lobar pneumonia was significantly increased and required bronchoscopy-assisted and steroid therapy. Compared with nonatopic children, more atopic children developed refractory MPP (< 0.05). Prolonged fever and hospitalization, severe extra-pulmonary complications, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and percentages of atopy were all significantly higher (< 0.05) among children with refractory MPP vs. general MPP. Moreover, Prolonged fever and hospitalization, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and the treantment of steroid were all significantly higher (< 0.05) among atopic children with refractory MPP vs. general MPP. Spearman correlation analysis showed strong associations between atopy and male sex, length of hospital stay, fever duration, IgE level, wheezing, lobar pneumonia, refractory MPP, and treatment with oxygen, hormones or bronchoscopy (< 0.05).
CONCLUSIONS
Atopy may be a risk factor for and was positively correlated with the severity of MPP in children.
PubMed: 38078330
DOI: 10.3389/fped.2023.1281479 -
Journal of Personalized Medicine Apr 2024(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case-control study conducted on...
(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case-control study conducted on neonates hospitalized at the Clinical Hospital "Louis Turcanu", Timisoara, Romania, from October 2018 to July 2023. Using a vacutainer collection device, venous blood was collected at admission for complete blood tests, including ferritin, hemoglobin, LDH, and blood culture analysis. Neonates were divided into two groups: sepsis-positive and sepsis-negative. The outcome of interest was a diagnosis of sepsis. (3) Results: Data from 86 neonates, 51 of whom had been confirmed to have sepsis, were analyzed. This study found no significant difference in gestational age, infant weight, fetal growth restriction, or APGAR score between neonates with and without sepsis. However, there was a higher incidence of sepsis among neonates delivered via cesarean section. Neonatal patients with sepsis showed significantly higher levels of neonatal serum ferritin and LDH compared to those without sepsis. Ferritin and LDH biomarkers demonstrated excellent discriminatory capabilities in diagnosing neonatal sepsis. Logistic regression analysis revealed a significant association between elevated ferritin and LDH levels and the likelihood of neonatal sepsis, while anemia did not show a significant association. (4) Conclusions: LDH and ferritin concentrations are found to be predictive biomarkers for neonatal sepsis, indicating a potential role in detecting susceptible neonates and implementing prompt interventions to improve patient outcomes.
PubMed: 38793057
DOI: 10.3390/jpm14050476