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Cureus Dec 2023This systematic review and meta-analysis was planned with the objective of evaluating the level of Lactate Dehydrogenase (LDH) in oral submucous fibrosis patients and in... (Review)
Review
This systematic review and meta-analysis was planned with the objective of evaluating the level of Lactate Dehydrogenase (LDH) in oral submucous fibrosis patients and in controls and comparing them. For this meta-analysis, we searched Google Scholar, PubMed, Scopus, and Directory of Open Access Journals (DOAJ) databases using a search methodology that included combinations of MeSH terms and keywords and included cross-sectional studies to evaluate the levels of LDH in patients with Oral Submucous Fibrosis (OSMF), Oral Squamous Cell Carcinoma (OSCC) and compared it with the controls. The total number of records identified through database searching was 4161 (n). Analysis of the quality of the studies was done using the National Heart, Lungs and Blood Institute (NHLBI) tool for case-control studies. Twelve case-control studies which matched the inclusion criteria were included after the literature search. The meta-analysis was carried out using R Studio (version 4.1.3, 2022; The R Foundation for Statistical Computing, Vienna, Austria). The pooled estimate that has been calculated from the salivary LDH course for OSMF was 15.35% and from the serum LDH course for OSMF was 6.82%. There was a visual observation of the funnel's plot asymmetry suggesting publication bias. After adjusting the publication bias, the t values for salivary and serum LDH were 41% and 14.71%, respectively, which was less than 50%, indicating that the meta-analysis was statistically significant. The evaluation of salivary and serum LDH can be a useful method for early diagnosis of OSMF as well as OSCC. To infer that individuals may have OPMD or OSCC, specific values for salivary and serum LDH must be found in further investigations.
PubMed: 38264399
DOI: 10.7759/cureus.51008 -
American Family Physician Nov 2023Pleural effusion affects 1.5 million patients in the United States each year. New effusions require expedited investigation because treatments range from common medical...
Pleural effusion affects 1.5 million patients in the United States each year. New effusions require expedited investigation because treatments range from common medical therapies to invasive surgical procedures. The leading causes of pleural effusion in adults are heart failure, infection, malignancy, and pulmonary embolism. The patient's history and physical examination should guide evaluation. Small bilateral effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis. In contrast, pleural effusion in the setting of pneumonia (parapneumonic effusion) may require additional testing. Multiple guidelines recommend early use of point-of-care ultrasound in addition to chest radiography to evaluate the pleural space. Chest radiography is helpful in determining laterality and detecting moderate to large pleural effusions, whereas ultrasonography can detect small effusions and features that could indicate complicated effusion (i.e., infection of the pleural space) and malignancy. Point-of-care ultrasound should also guide thoracentesis because it reduces complications. Computed tomography of the chest can exclude other causes of dyspnea and suggest complicated parapneumonic or malignant effusion. When diagnostic thoracentesis is indicated, Light's criteria can help differentiate exudates from transudates. Pleural aspirate should routinely be evaluated using Gram stain, cell count with differential, culture, cytology, protein, l-lactate dehydrogenase, and pH levels. Additional assessments should be individualized, such as tuberculosis testing in high-prevalence regions. Parapneumonic effusions are the most common cause of exudates. A pH level less than 7.2 is indicative of complicated parapneumonic effusion and warrants prompt consultation for catheter or chest tube drainage, possible tissue plasminogen activator/deoxyribonuclease therapy, or thoracoscopy. Malignant effusions are another common cause of exudative effusions, with recurrent effusions having a poor prognosis.
Topics: Humans; Adult; Tissue Plasminogen Activator; Pleural Effusion; Exudates and Transudates; Neoplasms; Heart Failure
PubMed: 37983698
DOI: No ID Found -
Journal of Cancer Research and Clinical... Dec 2023This research aimed to evaluate the prognostic significance of baseline prognostic nutritional index (PNI) and lactate dehydrogenase (LDH) for the outcome of individuals...
Prognostic nutritional index and serum lactate dehydrogenase predict the prognosis of nasopharyngeal carcinoma patients who received intensity-modulated radiation therapy.
PURPOSE
This research aimed to evaluate the prognostic significance of baseline prognostic nutritional index (PNI) and lactate dehydrogenase (LDH) for the outcome of individuals diagnosed with non-metastatic nasopharyngeal carcinoma (NPC).
METHODS
A retrospective analysis was conducted on data from 810 patients with non-metastatic NPC who underwent intensity-modulated radiation therapy (IMRT) with or without chemotherapy. The best cut-offs for PNI and LDH were identified by X-tile software to be 48.5 and 150, respectively. To find the independent prognostic factors for survival outcomes, univariate and multivariate regression analyses were conducted, and AUCs were used to compare their prognostic values.
RESULTS
Multivariate analysis revealed that patients with PNI > 48.5 had better overall survival (OS) (HR: 0.502, P < 0.001), progression-free survival (PFS) (HR: 0.618, P < 0.001), and distant metastasis-free survival (DMFS) (HR: 0.637, P = 0.005). Higher LDH was associated with poorer OS (HR: 1.798, P < 0.001), PFS (HR: 1.671, P < 0.001), and DMFS (HR: 1.756, P < 0.001). The combination of low PNI and high LDH in non-metastatic NPC patients was correlated with poor OS (P < 0.001), PFS (P < 0.001), and DMFS (P < 0.001). The combination of PNI and LDH had the highest AUCs for predicting OS, PFS, and DMFS.
CONCLUSIONS
PNI and LDH might become valuable predictors of the prognosis of non-metastatic NPC patients undergoing IMRT with or without chemotherapy. Prognostic accuracy can be enhanced by combining PNI and LDH.
Topics: Humans; Nasopharyngeal Carcinoma; Prognosis; Nutrition Assessment; Carcinoma; Radiotherapy, Intensity-Modulated; Retrospective Studies; Nasopharyngeal Neoplasms; Disease-Free Survival; Lactate Dehydrogenases
PubMed: 37934254
DOI: 10.1007/s00432-023-05485-5 -
International Journal of Molecular... Jun 2023Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative...
Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue.
Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.
Topics: Rats; Animals; Lactate Dehydrogenase 5; Nociception; Osteoarthritis; Chondrocytes; Cartilage, Articular; Cartilage Diseases; Disease Models, Animal
PubMed: 37445948
DOI: 10.3390/ijms241310770 -
Biomedicine & Pharmacotherapy =... Oct 2023Hepatocellular carcinoma (HCC) is the most common primary malignant tumor. Although sorafenib and regorafenib have been approved for first-line and second-line...
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor. Although sorafenib and regorafenib have been approved for first-line and second-line treatment, respectively, of patients with advanced HCC, long-term treatment often results in acquired resistance. Given that glycolysis-mediated lactate production can contribute to drug resistance and impair HCC treatment efficacy, we investigated the effects of ketone body treatment on the metabolic shift in sorafenib-resistant HCC cells. We discovered differential expression of 3-hydroxymethyl glutaryl-CoA synthase 2 (HMGCS2) and the ketone body D-β-hydroxybutyrate (β-HB) in four sorafenib-resistant HCC cell lines. In sorafenib-resistant HCC cells, lower HMGCS2 and β-HB levels were correlated with more glycolytic alterations and higher lactate production. β-HB treatment enhanced pyruvate dehydrogenase (PDH) expression and decreased lactate dehydrogenase (LDHA) expression and lactate production in sorafenib-resistant HCC cells. Additionally, β-HB combined with sorafenib or regorafenib promoted the antiproliferative and antimigratory abilities of sorafenib-resistant HCC cells by inhibiting the B-raf/mitogen-activated protein kinase pathway and mesenchymal N-cadherin-vimentin axis. Although the in vivo β-HB administration did not affect tumor growth, the expression of proliferative and glycolytic proteins was inhibited in subcutaneous sorafenib-resistant tumors. In conclusion, exogenous β-HB treatment can reduce lactate production and reverse sorafenib resistance by inducing a glycolytic shift; it can also synergize with regorafenib for treating sorafenib-resistant HCC.
Topics: Humans; Sorafenib; Carcinoma, Hepatocellular; 3-Hydroxybutyric Acid; Liver Neoplasms; Drug Resistance, Neoplasm; Glycolysis; Lactates; Cell Line, Tumor; Antineoplastic Agents
PubMed: 37567069
DOI: 10.1016/j.biopha.2023.115293 -
Oncology Letters Nov 2023The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International...
The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International Federation of Gynecology and Obstetrics (FIGO) 2009 cervical cancer (CC) stages IB1-IIA2. All patient medical records with FIGO 2009 stage IB1-IIA2 CC between January 2012 and January 2022 were analyzed retrospectively. The association between serum LDH and LNM was assessed using uni- and multivariate logistic regression analyses, subgroup analyses and P-splines. The present study included 586 patients, 91 (15.5%) of whom had LNM. Patients with an elevated LDH level were more likely to have a deep stromal invasion, lymph-vascular space invasion, LNM and to be of an older age. Multivariate logistic regression revealed a significant association between LNM and LDH levels. After adjusting for age, FIGO stage, tumor markers and risk factors according to the Sedlis criteria, patients in the highest LDH quartile had an increased risk of LNM compared with those in the lowest LDH quartile (odds ratio, 3.5; 95% CI, 1.57-7.81). Furthermore, P-spline regression revealed a dependence of LNM on LDH. The predictive value of LDH level remained significant in the subgroup analysis. The present study suggested that a higher LDH level was independently associated with CC and LNM, and that LDH level may serve as a potential tumor marker and treatment-related indicator.
PubMed: 37818132
DOI: 10.3892/ol.2023.14069 -
Diabetes Research and Clinical Practice Sep 2023This study aimed to investigate the role of the lactate dehydrogenase (LDH) in the development of end-stage renal disease (ESRD) and the cardiovascular mortality in...
OBJECTIVE
This study aimed to investigate the role of the lactate dehydrogenase (LDH) in the development of end-stage renal disease (ESRD) and the cardiovascular mortality in individuals with diabetic kidney disease (DKD).
METHODS
Two cohorts were recruited in this study. We explored the correlation between LDH and renal injury in individuals with DKD in using a Cohort 1. Additionally, we validated this correlation in the NHANES database and further investigated its association with the risk of cardiovascular mortality in Cohort 2 which also comprised individuals with DKD.
RESULTS
In cohort 1, multivariate Cox regression analysis demonstrated that individuals in DKD with higher LDH were independently associated with an increased risk of ESRD compared to those with lower LDH (HR = 2.11; 95 % CI, 1.07-4.16). In cohort 2, linear regression models showed that LDH affects the level of albumin-creatinine ratio (ACR) (β = 2.95, P = 0.001). Additionally, multivariate Cox regression analysis results showed that an increase in LDH per 1-standard deviation (SD) was associated with a 27 % increased risk of cardiovascular mortality (HR = 1.27; 95 % CI, 1.09-1.48).
CONCLUSIONS
LDH levels are associated with renal injury and progression to ESRD, as well as being an independent risk factor for cardiovascular in individuals with DKD.
Topics: Humans; Diabetic Nephropathies; Nutrition Surveys; Diabetes Mellitus, Type 2; Kidney; Kidney Failure, Chronic; Cardiovascular Diseases; Lactate Dehydrogenases
PubMed: 37478980
DOI: 10.1016/j.diabres.2023.110838 -
Annals of Neurosciences Oct 2023Epilepsy is a chronic neurological disorder that affects approximately 50-70 million people worldwide. Epilepsy has a significant economic and social burden on patients... (Review)
Review
BACKGROUND
Epilepsy is a chronic neurological disorder that affects approximately 50-70 million people worldwide. Epilepsy has a significant economic and social burden on patients as well as on the country. The recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy. The current antiepileptic drugs provide symptomatic relief by restoring the balance of excitatory and inhibitory neurotransmitters. Besides, about 30% of epileptic patients do not achieve seizure control. The prevalence of adverse drug reactions, including aggression, agitation, irritability, and associated comorbidities, is also prevalent. Therefore, researchers should focus on developing more effective, safe, and disease-modifying agents based on new molecular targets and signaling cascades.
SUMMARY
This review overviews several clinical trials that help identify promising new targets like lactate dehydrogenase inhibitors, c-jun n-terminal kinases, high mobility group box-1 antibodies, astrocyte reactivity inhibitors, cholesterol 24-hydroxylase inhibitors, glycogen synthase kinase-3 beta inhibitors, and glycolytic inhibitors to develop a new antiepileptic drug.
KEY MESSAGES
Approximately 30% of epileptic patients do not achieve seizure control. The current anti-seizure drugs are not disease modifying, cure or prevent epilepsy. Lactate dehydrogenase inhibitor, cholesterol 24-hydroxylase inhibitor, glycogen synthase kinase-3 beta inhibitors, and mTOR inhibitors have a promising antiepileptogenic effect.
PubMed: 38020406
DOI: 10.1177/09727531231185991 -
Molecular Metabolism Sep 2023Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood....
Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.
Topics: Humans; NF-kappa B; Diabetes Mellitus, Type 2; Colorectal Neoplasms; Signal Transduction
PubMed: 37406987
DOI: 10.1016/j.molmet.2023.101766 -
Blood Advances Jul 2023The effect of aerobic glycolysis remains elusive in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Increasing evidence has revealed that dysregulation of...
The effect of aerobic glycolysis remains elusive in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Increasing evidence has revealed that dysregulation of deubiquitination is involved in glycolysis, by targeting glycolytic rate-limiting enzymes. Here, we demonstrated that upregulated deubiquitinase ubiquitin-specific peptidase 1 (USP1) expression correlated with poor prognosis in pediatric primary T-ALL samples. USP1 depletion abolished cellular proliferation and attenuated glycolytic metabolism. In vivo experiments showed that USP1 suppression decreased leukemia progression in nude mice. Inhibition of USP1 caused a decrease in both mRNA and protein levels in lactate dehydrogenase A (LDHA), a critical glycolytic enzyme. Moreover, USP1 interacted with and deubiquitinated polo-like kinase 1 (PLK1), a critical regulator of glycolysis. Overexpression of USP1 with upregulated PLK1 was observed in most samples of patients with T-ALL. In addition, PLK1 inhibition reduced LDHA expression and abrogated the USP1-mediated increase of cell proliferation and lactate level. Ectopic expression of LDHA can rescue the suppressive effect of USP1 silencing on cell growth and lactate production. Pharmacological inhibition of USP1 by ML323 exhibited cell cytotoxicity in human T-ALL cells. Taken together, our results demonstrated that USP1 may be a promising therapeutic target in pediatric T-ALL.
Topics: Animals; Child; Humans; Mice; Cell Line, Tumor; Disease Progression; Glycolysis; L-Lactate Dehydrogenase; Lactate Dehydrogenase 5; Lactates; Mice, Nude; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocytes; Ubiquitin-Specific Proteases; Polo-Like Kinase 1
PubMed: 36912760
DOI: 10.1182/bloodadvances.2022008284