Measuring Lactate Dehydrogenase Research Articles

A Study of Serum to Pleural Fluid Albumin Gradient in Differentiation of Exudative and Transudative Pleural Effusion in Comparison to Light’s Criteria

Pleural effusion is the accumulation of fluid between the parietal and visceral pleura called the pleural cavity. It can occur by itself or can be the result of surrounding parenchymal diseases like infection, malignancy or inflammatory conditions. Pleural effusion is one of the major causes of pulmonary mortality and morbidity. Both the visceral and the parietal pleura play an important role in fluid homeostasis in the pleural space. Pleural effusions develop when there is excess hydrostatic pressure in the pulmonary capillaries, when fluid removal is impaired by compromised lymphatic drainage or when protein and cell rich fluid enters the pleural space through leaky capillary and pleural membranes. Pleural fluid is classified as a transudate or exudate based on modified Light’s criteria, proposed by Light et al., in 1972 which has been the standard differentiation method. It is considered an exudative effusion if at least one of the criteria is met:  Pleural fluid protein/serum protein ratio of more than 0.5  Pleural fluid lactate dehydrogenase (LDH)/serum LDH ratio of more than 0.6  Pleural fluid LDH is more than two-thirds of the upper limits of normal laboratory value for serum LDH. Commonly performed tests on the pleural fluid to determine etiology are a measurement of fluid pH, fluid protein, albumin and LDH, fluid glucose, fluid triglyceride, fluid cell count differential, fluid gram stain and culture and fluid cytology.

Protective Effects of Tunisian Orange Co-Product Extract and Oleuropein-Hesperidin Combination on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers' levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

Shedding light on the next pandemic path, from outpatient to ICU, the effect of vitamin D deficiency in the SARS-CoV-2 pandemic.

Vitamin D insufficiency is named "the pandemic of our era" by some experts. World Health Organization warns against a "deadlier outbreak" than the COVID-19 pandemic. Critical evidence is hereby for future pandemic prevention, with special emphasis on Vitamin D. A cross-sectional study was conducted with 172 unvaccinated adult participants, who presented to the emergency department. Blood measurements, radiological findings, and demographic features were evaluated in the four categories of "healthy adults, COVID-19 outpatients, hospitalized inpatients on the wards, and in the ICU." Results were statistically significant in association with age, gender, weight, Vitamin D, glucose, urea, creatinine, leucocyte, aspartate transaminase, hemoglobin, C-reactive protein, troponin, platelet/thrombocyte, ferritin, D-dimer, triglycerate, glycated haemoglobin, lactate dehydrogenase measurements, and chest computed tomography features (each p < 0.050). This article presents evidence to support the importance of Vitamin D for global public health. Patients with adequate levels of Vitamin D, glucose, urea, creatinine, leucocyte, aspartate transaminase, hemoglobin, C-reactive protein, troponin, platelet/thrombocyte, ferritin, D-dimer, triglycerate, glycated haemoglobin, lactate dehydrogenase are less likely to be admitted to ICU versus being outpatients. Factors include gender, age, weight, comorbidities, and computed tomography findings. The ultimate goal is to globally minimize preventable burdens of disease and death.

Glycyrrhizic acid alleviated MI/R-induced injuries by inhibiting Hippo/YAP signaling pathways

BackgroundPrevious research has demonstrated that glycyrrhizic acid (GA) exhibits antioxidant, anti-inflammatory, and antiapoptotic characteristics. Using myocardial ischemia/reperfusion injury as a case study, this study aims to clarify the functional significance of GA and to elucidate the mechanisms involved. Materials and methodsIn this study, an MI/R injury model was established both in vivo and in vitro to investigate the impact of GA on MI/R injury. The viability of H9c2 cells was evaluated using the Cell Counting Kit-8. Myocardial damage was assessed through the measurement of creatine kinase myocardial band (CK-MB) levels and lactate dehydrogenase (LDH), HE staining, and MASSON staining. Inflammatory cytokine levels (IL-6, IL-1β, IL-10, and TNF-α) were measured to determine the presence of inflammation. Cellular oxidative stress was evaluated by measuring ROS and MMP levels, while cardiac function was assessed using cardiac color Doppler ultrasound. Immunofluorescence staining to determine the nuclear translocation of YAP, TUNEL to determine apoptosis, and western blotting to determine gene expression. ResultsGA treatment effectively alleviated myocardial injury induced by MI/R, as evidenced by reduced levels of inflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) and cardiac biomarkers (CK-MB, LDH) in MI/R rats. Moreover, There was a significant increase in cell viability in vitro after GA treatment and inhibited reactive oxygen species (ROS) during oxidative stress, while also increasing mitochondrial membrane potential (MMP) in vitro. The Western blot findings indicate that GA treatment effectively suppressed apoptosis in both in vivo and in vitro settings. Additionally, GA demonstrated inhibitory effects on the activation of the Hippo/YAP signaling pathway triggered by MI/R and facilitated YAP nuclear translocation both in vitro and in vivo. It has been found, however, in vitro, that silencing the YAP gene negates GA's protective effect against hypoxia/reoxygenation-induced myocardial injury. ConclusionThis study suggests that GA regulates YAP nuclear translocation by inhibiting the Hippo/YAP signaling pathway, which protects ists against MI/R injury. This finding may present a novel therapeutic approach for the treatment of MI/R.

Protective Effect of Dihydromyricetin Against ExerciseInduced Muscle Damage and Its Mechanism

Objective To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.Methods Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight ·d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.Conclusion DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Cardiac endothelial ischemia/reperfusion injury-derived protein damage-associated molecular patterns disrupt the integrity of the endothelial barrier

Human cardiac microvascular endothelial cells (HCMECs) are sensitive to ischemia and vulnerable to damage during reperfusion. The release of damage-associated molecular patterns (DAMPs) during reperfusion induces additional tissue damage. The current study aimed to identify early protein DAMPs in human cardiac microvascular endothelial cells subjected to ischemia-reperfusion injury (IRI) using a proteomic approach and their effect on endothelial cell injury. HCMECs were subjected to 60 min of simulated ischemia and 6 h of reperfusion, which can cause lethal damage. DAMPs in the culture media were subjected to liquid chromatography-tandem mass spectrometry proteomic analysis. The cells were treated with endothelial IRI-derived DAMP medium for 24 h. Endothelial injury was assessed by measuring lactate dehydrogenase activity, morphological features, and the expression of endothelial cadherin, nitric oxide synthase (eNOS), and caveolin-1. The top two upregulated proteins, DNAJ homolog subfamily B member 11 and pyrroline-5-carboxylate reductase 2, are promising and sensitive predictors of cardiac microvascular endothelial damage. HCMECs expose to endothelial IRI-derived DAMP, the lactate dehydrogenase activity was significantly increased compared with the control group (10.15 ± 1.03 vs 17.67 ± 1.19, respectively). Following treatment with endothelial IRI-derived DAMPs, actin-filament dysregulation, and downregulation of vascular endothelial cadherin, caveolin-1, and eNOS expressions were observed, along with cell death. In conclusion, the early protein DAMPs released during cardiac microvascular endothelial IRI could serve as novel candidate biomarkers for acute myocardial IRI. Distinct features of impaired plasma membrane integrity can help identify therapeutic targets to mitigate the detrimental consequences mediated of endothelial IRI-derived DAMPs.

Hyperpolarized [1-13 C] pyruvate MRSI to detect metabolic changes in liver in a methionine and choline-deficient diet rat model of fatty liver disease.

Nonalcoholic fatty liver disease is an important cause of chronic liver disease. There are limited methods for monitoring metabolic changes during progression to steatohepatitis. Hyperpolarized 13 C MRSI (HP 13 C MRSI) was used to measure metabolic changes in a rodent model of fatty liver disease. Fifteen Wistar rats were placed on a methionine- and choline-deficient (MCD) diet for 1-18 weeks. HP 13 C MRSI, T2 -weighted imaging, and fat-fraction measurements were obtained at 3 T. Serum aspartate aminotransaminase, alanine aminotransaminase, and triglycerides were measured. Animals were sacrificed for histology and measurement of tissue lactate dehydrogenase (LDH) activity. Animals lost significant weight (13.6% ± 2.34%), an expected characteristic of the MCD diet. Steatosis, inflammation, and mild fibrosis were observed. Liver fat fraction was 31.7% ± 4.5% after 4 weeks and 22.2% ± 4.3% after 9 weeks. Lactate-to-pyruvate and alanine-to-pyruvate ratios decreased significantly over the study course; were negatively correlated with aspartate aminotransaminase and alanine aminotransaminase (r = -[0.39-0.61]); and were positively correlated with triglycerides (r = 0.59-0.60). Despite observed decreases in hyperpolarized lactate signal, LDH activity increased by a factor of 3 in MCD diet-fed animals. Observed decreases in lactate and alanine hyperpolarized signals on the MCD diet stand in contrast to other studies of liver injury, where lactate and alanine increased. Observed hyperpolarized metabolite changes were not explained by alterations in LDH activity, suggesting that changes may reflect co-factor depletion known to occur as a result of oxidative stress in the MCD diet. HP 13 C MRSI can noninvasively measure metabolic changes in the MCD model of chronic liver disease.

Drainage fluid LDH and neutrophil to lymphocyte ratio as biomarkers for early detecting anastomotic leakage in patients undergoing colorectal surgery.

In this study, we investigated the role of several circulating and drainage fluid biomarkers for detecting postoperative complications (PCs) and anastomotic leakage (AL) in patients undergoing colorectal surgery. All consecutive patients undergoing colorectal surgery between June 2018 and April 2020 were prospectively considered. On postoperative days (POD) 1, 3, and 5, we measured lactate dehydrogenase (LDH) in drainage fluid, C-reactive protein (CRP) in serum and drainage fluid, and neutrophil to lymphocyte ratio (NLR). We enrolled 187 patients. POD1 patients with AL had higher serum CRP levels, while on POD3 and on POD5 higher NLR and serum CRP. LDH and CRP in drainage fluid were also significantly higher at both time points. The area under the curves (AUCs) of serum and drainage fluid CRP were 0.752 (0.629-0.875) and 0.752 (0.565-0.939), respectively. The best cut-off for serum and drainage fluid CRP was 185.23 and 76 mg/dL, respectively. The AUC of NLR on POD3 was 0.762 (0.662-0.882) with a sensitivity and specificity of 84 and 63 %, respectively, at a cut-off of 6,6. Finally, drainage fluid LDH showed the best diagnostic performance for AL, with an AUC, sensitivity, and specificity of 0.921 (0.849-0.993), 82 %, and 90 % at a cut-off of 2,186 U/L. Trends in serum parameters between patients with or without PCs or AL were also evaluated. Interestingly, we found that NLR decreased faster in patients without PCs than in patients with PCs and patients with AL. Drainage fluid LDH and NLR could be promising biomarkers of PCs and AL.

Abstract 176: The Pathological Role of Aldose Reductase in Isolated Cardiomyocytes Undergoing Hypoxia / Reoxygenation After Prior Exposure to High Glucose Concentrations

Hyperglycemia increases the vulnerability of the cardiovascular system to ischemia/reperfusion (IR) injury. There are currently no effective therapeutic strategies. We hypothesized that hyperglycemia would increase glucose flux through the polyol pathway. Aldose reductase (AR) catalyzes the first step of this pathway by converting glucose to sorbitol. This reaction generates more oxidative stress due to the depletion of NADPH and osmotic stress caused by sorbitol accumulation, making the heart more susceptible to IR injury. This study aimed to better understand the injury mechanism in cardiomyocytes after high glucose exposure and IR injury. Confluent cardiomyocytes were exposed for 24 hours to 25, 50, or 100 mM glucose or 25 mM glucose with 25 or 75 mM sucrose concentrations added. The non-metabolizable sugar sucrose was used as an osmolarity control. Epalrestat, an AR inhibitor, was added at 0, 1, or 10 μM per well (n = 18 per group) during glucose or sucrose exposure. Cells were then subjected to 24 hours of hypoxic conditions (glucose-, sucrose- and serum-free media; 0.01% O 2 , 37 °C; hypoxic chamber) or normoxic conditions (complete media; 21% O 2 , 37 °C), followed by a 2-hour reoxygenation period in normoxic conditions. Cell injury was quantified by measurement of lactate dehydrogenase (LDH) release. Data were normalized to 25 mM glucose after control/normoxic conditions without AR inhibitor. A three-way ANOVA was conducted to compare groups, followed by the Holm-Šidák test. Increasing glucose concentrations lead to increased cell damage after hypoxia/reoxygenation. Adding the AR inhibitor during the glucose exposure period reduced LDH release after hypoxia/reoxygenation in a dose-dependent manner. The addition of sucrose did not increase cell injury. The AR inhibitor did not affect cells exposed to sucrose. The polyol pathway may play a dominant role in increased cell injury by hyperglycemia after hypoxia/reoxygenation.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest

BackgroundThe mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PurposeThis study explored the role and mechanism of CuB in the suppression of liver cancer progression. MethodsCell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. ResultsCuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. ConclusionThis study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Predictors of rapidly progressive interstitial lung disease and prognosis in Chinese patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

Rapidly progressive interstitial lung disease (RP-ILD) is the most serious complication of anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5+ DM). This study was performed to assess the prognostic factors of patients with anti-MDA5+ DM and the clinical characteristics and predictors of anti-MDA5+ DM in combination with RP-ILD. In total, 73 MDA5+ DM patients were enrolled in this study from March 2017 to December 2021. They were divided into survival and non-survival subgroups and non-RP-ILD and RP-ILD subgroups. The lactate dehydrogenase (LDH) concentration and prognostic nutritional index (PNI) were independent prognostic factors in patients with anti-MDA5+ DM: the elevated LDH was associated with increased mortality (p = 0.01), whereas the elevated PNI was associated with reduced mortality (p < 0.001). The elevated LDH was independent risk prognostic factor for patients with anti-MDA5+ DM (HR 2.42, 95% CI: 1.02-4.83, p = 0.039), and the elevated PNI was independent protective prognostic factor (HR, 0.27; 95% CI, 0.08 - 0.94; p = 0.039). Patients who had anti-MDA5+ DM with RP-ILD had a significantly higher white blood cell count and LDH concentration than those without RP-ILD (p = 0.007 and p = 0.019, respectively). In contrast, PNI was significantly lower in patients with RP-ILD than those without RP-ILD (p < 0.001). The white blood cell count and elevated LDH were independent and significant risk factors for RP-ILD (OR 1.54, 95% CI: 1.12 - 2.13, p = 0.009 and OR 8.68, 95% CI: 1.28 - 58.83, p = 0.027, respectively), whereas the lymphocyte was an independent protective factor (OR, 0.11; 95% CI, 0.01 - 0.81; p = 0.03). The elevated LDH and elevated PNI were independent prognostic factors for patients with anti-MDA5+ DM. The elevated LDH was independent risk factor for RP-ILD. Patients with anti-MDA5+ DM could benefit from the measurement of LDH and PNI, which are inexpensive and simple parameters that could be used for diagnosis as well as prediction of the extent of lung involvement and prognosis.

The novel cyclophilin inhibitor C105SR reduces hepatic ischaemia–reperfusion injury via mitoprotection

Mitochondrial permeability transition pore (mPTP) opening is critical for mediating cell death during hepatic ischaemia-reperfusion injury (IRI). Blocking mPTP opening by inhibiting cyclophilin D (CypD) is a promising pharmacological approach for the treatment of IRI. Here, we show that diastereoisomers of a new class of small-molecule cyclophilin inhibitors (SMCypIs) have properties that make them attractive candidates for the development of therapeutic agents against liver IRI. Derivatives of the parent SMCypI were synthesised and evaluated for their ability to inhibit CypD peptidyl-prolyl cis-trans isomerase (PPIase) activity and for their mitoprotective properties, evaluated by measuring mitochondrial swelling and calcium retention capacity in liver mitochondria. The ability of the selected compounds to inhibit mPTP opening was evaluated in cells subjected to hypoxia/reoxygenation using a calcein/cobalt assay. Their ability to inhibit cell death was evaluated in cells subjected to hypoxia/reoxygenation by measuring lactate dehydrogenase (LDH) release, propidium iodide staining, and cell viability. The compound performing best invitro was selected for invivo efficacy evaluation in a mouse model of hepatic IRI. The two compounds that showed the strongest inhibition of CypD PPIase activity and mPTP opening, C105 and C110, were selected. Their SR diastereoisomers carried the activity of the racemic mixture and exhibited mitoprotective properties superior to those of the known macrocyclic cyclophilin inhibitors cyclosporin A and alisporivir. C105SR was more potent than C110SR in inhibiting mPTP opening and prevented cell death in a model of hypoxia/reoxygenation. Finally, C105SR substantially protected against hepatic IRI invivo by reducing hepatocyte necrosis and apoptosis. We identified a novel cyclophilin inhibitor with strong mitoprotective properties both invitro and invivo that represents a promising candidate for cellular protection in hepatic IRI. Hepatic ischaemia-reperfusion injury (IRI) is one of the main causes of morbidity and mortality during or after liver surgery. However, no effective therapies are available to prevent or treat this devastating syndrome. An attractive strategy to prevent hepatic IRI aims at reducing cell death by targeting mitochondrial permeability transition pore opening, a phenomenon regulated by cyclophilin D. Here, we identified a new small-molecule cyclophilin inhibitor, and demonstrated the enhanced mitoprotective and hepatoprotective properties of one of its diastereoisomers both invitro and invivo, making it an attractive lead compound for subsequent clinical development.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 μM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity.

Serial measurements of lymphocytes, D-dimer, LDH, and CRP do not improve the ability to predict COVID-19 adverse outcomes

We evaluated the discriminatory ability of variations in lymphocyte, D-dimer, C-reactive protein (CRP), and lactate dehydrogenase (LDH) serum levels at 48 to 72 hours of hospitalization compared with baseline measurements to predict unfavorable clinical outcomes in patients with COVID-19. We analyzed diagnostic test results based on a retrospective cohort to determine the ability of variations (gradients or ratios) in patients' lymphocyte, D-dimer, CRP, and LDH serum levels taken 48 to 72 hours after hospital admission to predict adverse outcomes such as death, mechanical ventilation, or intensive care unit (ICU) admission developing. Among 810 patients (56.1% men, age 61.6 ± 16.2 years), 37.5% had at least one adverse outcome; 28.2% required ICU admission, 26.5% required mechanical ventilation, and 19.4% died during hospitalization. In comparing baseline measurements with measurements at 48 to 72 hours, D-dimer, lymphocyte delta, LDH, and CRP had similar discriminatory ability (area under the receiver operating characteristic curve [AUC] 0.57 vs. 0.56, 0.53 vs. 0.57, 0.64 vs. 0.66, and 0.62 vs. 0.65, respectively). Measuring serum risk markers upon hospital admission can be used to evaluate risk of adverse outcomes in hospitalized patients with COVID-19. Repeating these measurements at 48 to 72 hours does not improve discriminatory ability.

Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway

AimTo examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action. MethodsMice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury. ResultsWe found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury. ConclusionHigh doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

Pengaruh Ekstrak Etanol Daun Asam Jawa (Tamarindus indica L.) terhadap Jantung Tikus Putih (Rattus norvegicus L.) yang Diinduksi Minyak Jelantah

This study aims to determine the effect of ethanol tamarind leaves (Tamarindus indica L.) om histology and levels of the enzyme lactate dehydrogenase (LDH) in rat hearts induced by used cooking oil.This study used a completely randomized design with 25 male white rats devided into 5 groups: negetive control, positive control, 1, 2 and 3 doses treatment (150 mg/kg BW, 200 mg/kg BW, and 250 mg/kg BW), where each group consisted of 5 replications. The stages of this research were phytochemical screening, total flavonoid test, antioxidant test, oil quality test, measurement of lactate dehydrogenase (LDH) enzyme levels and cardiac histological observations. The data analysis used was one way ANOVA followed by Duncan’s test. The results showed that the dose of ethanol extract of tamarind leaves (Tamarindus indica L.) 250 mg/kg BW was the most optimal dose to reduce histological damage in the form of pycnotic percentage with an average of 30.40% and thickness of the myocardium of the heart with an average of 852.8 um and decreased cardiac lactate dehydrogenase (LDH) levels by an average of 152 U/L. The ethanol extract of tamarind leaves (Tamarindus indica L.) had an effect on the hearts of white rats (Rattus norvegicus L.) induced by used cooking oil.

Antiamoebic properties of Methyltrioctylammonium chloride based deep eutectic solvents.

This aim of this study was to assess anti-parasitic properties of deep eutectic solvents against eye pathogen, Acanthamoeba, often associated with the use of contact lens. Assays were performed to investigate the effects of various Methyltrioctylammonium chloride-based deep eutectic solvents on Acanthamoeba castellanii, comprising amoebicidal assays, encystment assays, excystment assays, cytotoxicity assays by measuring lactate dehydrogenase release from human cells, and cytopathogenicity assays to determine parasite-mediated host cell death. In a 2h incubation period, DES-B, DES-C, DES-D, and DES-E exhibited up to 85% amoebicidal activity at micromolar doses, which was enhanced further following 24h incubation. When tested in encystment assays, selected deep eutectic solvents abolished cyst formation and were able to block excystment of A. castellanii. All solvents exhibited minimal human cell cytotoxicity except DES-D. Finally, all tested deep eutectic solvents inhibited amoeba-mediated cytopathogenicity, except DES-B. Deep eutectic solvents show potent antiamoebic effects. These findings are promising and could lead to the development of novel contact lens disinfectants, as well as opening several avenues to explore the molecular mechanisms, various doses and incubation periods, and use of different bases against Acanthamoeba castellanii.

Heparin interacts with candidalysin and neutralizes its cytotoxicity to oral epithelial cells

ObjectivesCandidalysin is a peptide toxin produced by Candida albicans that causes damage to epithelial cells by destabilizing the plasma membrane. This study aimed to evaluate heparin's ability to neutralize candidalysin and protect epithelial cells from lysis. MethodsThe study was conducted using a human oral epithelial cell line and synthetic candidalysin. Cell damage was assessed by measuring lactate dehydrogenase release. Enzyme-linked immunosorbent assay and immunoblotting were used to determine cytokine concentrations and assess activation of intracellular signaling molecules and transcription factors, respectively. Flow cytometry was used to measure cell-bound candidalysin. ResultsHeparin diminished the cell–lytic activity of candidalysin and subsequent epithelial responses. Additionally, heparin inhibited the interaction between candidalysin and epithelial cells. Furthermore, polyacrylic acid, a synthetic polymer, mimicked the neutralizing effects of candidalysin. ConclusionOur findings suggest that negatively charged polymers could be a potential therapeutic option for preventing the damage caused by candidalysin. Further research is needed to explore the effectiveness of other anionic polymers and their potential clinical applications.

Effects of Electronic Cigarette E-Liquids on the Adhesion and Growth of Osteoblast Cells

Electronic cigarettes (E-cigarettes) were designed to replace traditional cigarettes to decrease the harmful effects of smoking. The liquid in e-cigarettes contains different chemicals, such as Propylene Glycol (PG) and Vegetable Glycerin (VG), and may contain nicotine. To be more attractive, e-liquids are supplemented with flavorings. Because vaped e-liquids are shown to be damaging to oral tissues, similar effects could occur in the oral cavity with non-vaped e-liquids. We evaluated the effects of non-vaped e-liquid constituents on osteoblast behavior. For this purpose, human osteoblast cells (MG-63) were exposed to e-liquid containing 70% PG -30% VG with and without tobacco flavor and with or without nicotine at 12, 18 mg/mL, or no nicotine content. The e-liquids were used at various concentrations (0, 1, and 5%). To evaluate the effect of the e-liquids on osteoblast morphology and adhesion, optical microscope observations and viable cell counting using trypan blue exclusion were used. Cell growth was also analyzed using the Methyl Thiazol Tetrazolium (MTT) assay, while cytotoxicity was tested by measuring Lactate Dehydrogenase (LDH) levels after cell exposure for 24 h to the e-liquids. Our results show that e-liquids induced significant morphological changes evidenced by round cell forms, with no contact between cells. Adhesion was significantly reduced, particularly in the presence of nicotine. E-liquids at a concentration of 5% significantly reduced osteoblast growth. This effect was observed with both flavored and non-flavored e-liquid with or without nicotine. The decreased osteoblast adhesion and growth after exposure to e-liquid was confirmed by increased levels of LDH. Overall results indicate the potentially harmful effects of e-liquid non-vaped chemicals on bone cells, which could lead to the impairment of bone regeneration and tissue remodeling processes.