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Frontiers in Cellular and Infection... 2024The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high...
BACKGROUND
The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection.
METHODS
This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients.
RESULTS
The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration.
CONCLUSION
Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.
Topics: Humans; Retrospective Studies; Invasive Pulmonary Aspergillosis; C-Reactive Protein; Biomarkers; Procalcitonin; Pulmonary Disease, Chronic Obstructive
PubMed: 38633749
DOI: 10.3389/fcimb.2024.1294971 -
Pathogens (Basel, Switzerland) Jul 2023, the causative agent of Lyme disease, has a highly reduced genome and relies heavily on glycolysis for carbon metabolism. As such, established inhibitors of lactate...
, the causative agent of Lyme disease, has a highly reduced genome and relies heavily on glycolysis for carbon metabolism. As such, established inhibitors of lactate dehydrogenase (LDH) were evaluated in cultures to determine the extent of their impacts on growth. Both racemic and enantiopure (AT-101) gossypol, as well as oxamate, galloflavin, and stiripentol, caused the dose-dependent suppression of growth in vitro. Racemic gossypol and AT-101 were shown to fully inhibit spirochetal growth at concentrations of 70.5 and 187.5 μM, respectively. Differences between racemic gossypol and AT-101 efficacy may indicate that the dextrorotatory enantiomer of gossypol is a more effective inhibitor of growth than the levorotatory enantiomer. As a whole, LDH inhibition appears to be a promising mechanism for suppressing growth, particularly with bulky LDH inhibitors like gossypol.
PubMed: 37513809
DOI: 10.3390/pathogens12070962 -
Applied Microbiology and Biotechnology Dec 2023Bacterial polyhydroxyalkanoates (PHAs) are promising bio-based biodegradable polyesters. It was recently reported that novel PHA block copolymers composed of...
Bacterial polyhydroxyalkanoates (PHAs) are promising bio-based biodegradable polyesters. It was recently reported that novel PHA block copolymers composed of (R)-3-hydroxybutyrate (3HB) and (R)-2-hydroxybutyrate (2HB) were synthesized by Escherichia coli expressing PhaC, a chimeric enzyme of PHA synthases derived from Aeromonas caviae and Ralstonia eutropha. In this study, the sequence-regulating PhaC was applied in the natural PHA-producing bacterium, R. eutropha. During the investigation, (R/S)-2HB was found to exhibit strong growth inhibitory effects on the cells of R. eutropha. This was probably due to formation of excess 2-ketobutyrate (2KB) from (R/S)-2HB and the consequent L-valine depletion caused by dominant L-isoleucine synthesis attributed to the excess 2KB. Deletion analyses for genes of lactate dehydrogenase homologs identified cytochrome-dependent D-lactate dehydrogenase (Dld) and [Fe-S] protein-dependent L-lactate dehydrogenase as the enzymes responsible for sensitivity to (R)-2HB and (S)-2HB, respectively. The engineered R. eutropha strain (phaC, ldhA-hadA encoding clostridial (R)-2-hydroxyisocaproate dehydrogenase and (R)-2-hydoroxyisocaproate CoA transferase, ∆dld) synthesized PHA containing 10 mol% of 2HB when cultivated on glucose with addition of sodium (RS)-2HB, and the 2HB composition in PHA increased up to 35 mol% by overexpression phaC. The solvent fractionation and NMR analyses showed that the resulting PHAs were most likely to be block polymers consisting of P(3HB-co-3HV) and P(2HB) segments, suggesting that PhaC functions as the sequence-regulating PHA synthase independently from genetic and metabolic backgrounds of the host cell. KEY POINTS: (R/S)-2-hydroxubutyrates (2HB) caused l-valine deletion in Ralstonia eutropha (R)- and (S)-lactate/2HB dehydrogenases functional in R. eutropha were identified The engineered R. eutropha synthesized block copolymers of 2HB-containing polyhydroxyalkanoates on glucose and 2HB.
Topics: Cupriavidus necator; L-Lactate Dehydrogenase; Lactate Dehydrogenases; Cadmium; Hydroxybutyrates; Polyhydroxyalkanoates; Polyesters; Escherichia coli; Valine; Lactates; Glucose
PubMed: 37773219
DOI: 10.1007/s00253-023-12797-6 -
Hormone Molecular Biology and Clinical... Sep 2023To determine whether inhibition of kinase signaling will suppress resistin-induced liver cancer progression. Resistin is located in monocytes and macrophages of adipose...
OBJECTIVES
To determine whether inhibition of kinase signaling will suppress resistin-induced liver cancer progression. Resistin is located in monocytes and macrophages of adipose tissue. This adipocytokine is an important link between obesity, inflammation, insulin resistance, and cancer risk. Pathways that resistin is known to be involved include but are not limited to mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases (ERK). The ERK pathway promotes cellular proliferation, migration, survival of cancer cells, and tumor progression. The Akt pathway is known to be up-regulated in many cancers including liver cancer.
METHODS
Using an model, HepG2 and SNU-449 liver cancer cells were exposed to resistin ± ERK, Akt, or both inhibitors. The following physiological parameters were assessed: cellular proliferation, ROS, lipogenesis, invasion, MMP, and lactate dehydrogenase activity.
RESULTS
The inhibition of kinase signaling suppressed resistin-induced invasion and lactate dehydrogenase in both cell lines. In addition, in SNU-449 cells, resistin increased proliferation, ROS, and MMP-9 activity. Inhibition of PI3K and ERK decreased phosphorylated Akt and ERK, and pyruvate dehydrogenase.
CONCLUSIONS
In this study, we describe the effect of Akt and ERK inhibitors to determine if inhibition suppresses resistin-induced liver cancer progression. Resistin promotes cellular proliferation, ROS, MMP, invasion and LDH activity in SNU-449 liver cancer cells which is differentially mediated by Akt and ERK signaling pathways.
Topics: Humans; Cell Line; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Lactate Dehydrogenases; Liver Neoplasms; MAP Kinase Signaling System; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Resistin
PubMed: 36867542
DOI: 10.1515/hmbci-2022-0063 -
Global Medical Genetics Jun 2024This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with...
Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.
This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.
PubMed: 38606422
DOI: 10.1055/s-0044-1786005 -
Frontiers in Endocrinology 2024This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).
OBJECTIVE
This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).
METHODS
The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result.
RESULTS
A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings.
CONCLUSIONS
LDH can serve as a valuable biomarker for screening DKD in patients with T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Risk Factors; Nutrition Surveys; L-Lactate Dehydrogenase
PubMed: 38567310
DOI: 10.3389/fendo.2024.1369968 -
Frontiers in Oncology 2023The prognostic significance of lactate dehydrogenase (LDH) and its impact on the outcomes of gastric cancer (GC) is still unclear. We assessed the link between the...
BACKGROUND
The prognostic significance of lactate dehydrogenase (LDH) and its impact on the outcomes of gastric cancer (GC) is still unclear. We assessed the link between the levels of LDH and the overall survival (OS) and disease-free survival (DFS) in GC patients.
METHODS
A comprehensive search (both electronic and manual) was carried out in PubMed MEDLINE, Web of Science (WoS), Experta Medical Database (Embase), and CENTRAL (Cochrane Library) databases for citations that evaluated the strength of association between LDH cut-off levels and OS and/or DFS in GC. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was assessed.
RESULTS
Eighteen studies with 5328 patients were included in our review. The overall pooled HR for OS was 1.48 (95% CI: 1.22-1.80) with high heterogeneity (I2 = 86%). Subgroup analyses showed that the link between LDH and OS was more prominent in Caucasian (HR 1.50 95% CI [0.80, 2.81], p=0.21) than in Asian cohorts (HR, 1.51 95% CI [1.21, 1.87], p=0.002). No significant overall association between LDH and OS (HR = 1.12, 95% CI: 0.76-1.65, p = 0.58) was found. Similar subgroup analyses results were reported for the association between LDH and DFS.
CONCLUSION
In patients with GC, elevated LDH levels may correlate with worse OS and DFS, but the association is not significant. LDH is a significant predictor of OS but not of DFS. Further studies with larger sample sizes and more standardized criteria for defining elevated LDH levels are needed to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42023412449.
PubMed: 37727205
DOI: 10.3389/fonc.2023.1247444 -
Italian Journal of Pediatrics Sep 2023Early identification of intravenous immunoglobulin (IVIG) resistance contributes to better management of Kawasaki disease (KD). This study aims to establish an effective...
BACKGROUND
Early identification of intravenous immunoglobulin (IVIG) resistance contributes to better management of Kawasaki disease (KD). This study aims to establish an effective prediction model for IVIG resistance in the Chinese population.
METHODS
A total of 658 eligible patients diagnosed with KD were enrolled in this study, with 461 in the training cohort and 197 in the validation cohort. The demographic characteristics and potential risk factors were compared between IVIG-responsive and resistant groups. Predictors were selected by the Akaike information criterion. The nomogram's performance was evaluated by calibration curve, decision curve analysis, and operating characteristic curve.
RESULTS
White blood cell counts (WBC), neutrophil-lymphocyte ratio (N/L ratio), hematocrit (HCT), albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and creatinine (Cr) were detected as predictors of IVIG resistance. A predictive nomogram incorporating these predictors was constructed using the training cohort. The calibration curve and decision curve analysis showed good discrimination and calibration of the proposed nomogram in both training and validation sets, and the area under the receiver operating characteristic curve (AUROC) in both sets was 75.8% and 74.2%, respectively.
CONCLUSION
This study identified WBC, N/L ratio, HCT, ALB, TBIL, LDH, and Cr as predictors for IVIG resistance in patients with KD. The proposed novel nomogram with a high level of accuracy and reliability may benefit clinical decision-making upon treatment initiation.
Topics: Humans; Asian People; Bilirubin; Creatinine; Immunoglobulins, Intravenous; L-Lactate Dehydrogenase; Leukocyte Count; Mucocutaneous Lymph Node Syndrome; Reproducibility of Results; Drug Resistance
PubMed: 37749617
DOI: 10.1186/s13052-023-01531-7 -
Journal of Medical Biochemistry Apr 2024To investigate the relationship between lactate dehydrogenase and apolipoprotein A1 levels and the condition and prognosis of patients with severe pneumonia.
BACKGROUND
To investigate the relationship between lactate dehydrogenase and apolipoprotein A1 levels and the condition and prognosis of patients with severe pneumonia.
METHODS
Data was collected from 204 patients with severe pneumonia who were hospitalized from January 1, 2019 to December 1, 2021 in Zhaotong First People's Hospital (respiratory intensive care unit (RICU)), and divided into survival group (160 patients) and death group (44 patients) according to their hospitalization outcome. The relationship between lactate dehydrogenase and apolipoprotein A1 levels and general information, disease, and treatment needs of patients with severe pneumonia was analyzed, and lactate dehydrogenase, apolipoprotein A1, neutrophil-to-lymphocyte ratio, hematocrit, C-reactive protein, calcitoninogen, D-dimer, Acute Physiology and Chronic Health Status Rating System II, and Pneumonia Severity Index scores were compared between the survival and death groups. The value of these indicators in determining the prognosis of patients was analyzed using subject operating characteristic (ROC) curves. Logistic regression was used to analyze the risk factors for death from severe pneumonia.
PubMed: 38699695
DOI: 10.5937/jomb0-45782 -
Toxicology Reports Dec 2023Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However,...
Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However, there is currently insufficient evidence regarding the role of lactate dehydrogenase (LDH) in COVID-19 and its prognostic implications. This retrospective cross-sectional study analyzed data from all patients hospitalized at Urmia Imam Khomeini Hospital between September 2021 and March 2023 with a diagnosis of COVID-19 involving the Delta and Omicron variants. Patient information, including age, sex, duration of hospitalization, admission to the intensive care unit (ICU), strain type, and outcomes, was extracted. Exclusion criteria encompassed myocardial infarction, lung, liver, blood, skeletal muscle diseases, injury, neoplasm, pancreatitis, pregnancy, poisoning, unwillingness to participate in the study, and the use of ascorbic acid. A total of 609 patients with an average age of 54.80 years were included in this study. Among these patients, 56.3% were female, and the mortality rate was 20.7%. The serum LDH levels were significantly higher in patients who succumbed to the disease (P < 0.001), those requiring ICU admission (P < 0.001), and female patients (P = 0.02) compared to other groups. Furthermore, the LDH serum levels exhibited a strong significant correlation with the duration of hospitalization (r = -0.11, P = 0.007). The results revealed that there is a difference in the mean serum LDH levels between deceased patients and discharged patients (P < 0.001). The findings indicate that elevated serum LDH levels are associated with increased mortality, prolonged hospitalization, ICU admission, and infection with the Delta variant of COVID-19.
PubMed: 37868806
DOI: 10.1016/j.toxrep.2023.10.003