-
Molecules (Basel, Switzerland) May 2024Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer...
Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer a potential strategy to mitigate oxidative damage by free radicals. We investigated the protective effects of mulberry leaf flavonoids (MLF) against HO-induced oxidative damage in HepG2 cells. It assessed the inhibitory effect of MLF (62.5-500 μg/mL) on HO-induced oxidative damage by analyzing cellular morphology and oxidative stress markers, including ROS production, mitochondrial membrane potential, antioxidant enzyme levels, MDA, and apoptosis-related proteins. The results demonstrated that MLF prevented spiny cell formation triggered by 750 μM HO and significantly reduced ROS levels, restored mitochondrial membrane potential, decreased lactate dehydrogenase and alanine transaminase leakage, and reduced MDA content induced by HO. MLF also modulated antioxidant enzymes and attenuated oxidative damage to HepG2 cell DNA, as confirmed by staining techniques. These findings indicate the potential of MLF as a hepatoprotective agent against oxidative damage in HepG2 cells.
Topics: Humans; Morus; Oxidative Stress; Hep G2 Cells; Flavonoids; Plant Leaves; Hydrogen Peroxide; Antioxidants; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Plant Extracts; Protective Agents; Apoptosis; Cell Survival
PubMed: 38893475
DOI: 10.3390/molecules29112597 -
International Journal of Molecular... Jun 2024The aim of this study was to explore how the total flavonoids from leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by...
The aim of this study was to explore how the total flavonoids from leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group ( < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress ( < 0.01). The mRNA expression level of increased ( < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of and increased ( < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via -related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.
Topics: Animals; Rats; Flavonoids; Eucommiaceae; Plant Leaves; PC12 Cells; Ischemic Stroke; Oxidative Stress; Neuroprotective Agents; Male; Reactive Oxygen Species; Plant Extracts; Vascular Endothelial Growth Factor A; Cell Survival; Reperfusion Injury; Rats, Sprague-Dawley; Malondialdehyde
PubMed: 38892459
DOI: 10.3390/ijms25116271 -
International Journal of Molecular... May 2024is the only that causes zoonotic disease among the that cause infection in humans. It is fatal due to its short asexual growth cycle within 24 h. Lactate...
is the only that causes zoonotic disease among the that cause infection in humans. It is fatal due to its short asexual growth cycle within 24 h. Lactate dehydrogenase (LDH), an enzyme that catalyzes the final step of glycolysis, is a biomarker for diagnosing infection by spp. parasite. Therefore, this study aimed to efficiently produce the soluble form of LDH (PkLDH) using a bacterial expression system for studying malaria caused by . Recombinant pET-21a(+)- plasmid was constructed by inserting the gene into a pET-21a(+) expression vector. Subsequently, the recombinant plasmid was inserted into the protein-expressing Rosetta(DE3) strain, and the optimal conditions for overexpression of the PkLDH protein were established using this strain. We obtained a yield of 52.0 mg/L PkLDH from the Rosetta(DE3) strain and confirmed an activity of 483.9 U/mg through experiments. This methodology for high-efficiency PkLDH production can be utilized for the development of diagnostic methods and drug candidates for distinguishing malaria caused by .
Topics: Plasmodium knowlesi; L-Lactate Dehydrogenase; Cloning, Molecular; Malaria; Recombinant Proteins; Escherichia coli; Animals; Humans; Gene Expression; Protozoan Proteins
PubMed: 38891805
DOI: 10.3390/ijms25115615 -
The Journal of Extra-corporeal... Jun 2024The usage of cardiopulmonary bypass (CPB) in cardiothoracic surgery contributes to the activation of the inflammatory response. In certain cases, the systemic...
The usage of cardiopulmonary bypass (CPB) in cardiothoracic surgery contributes to the activation of the inflammatory response. In certain cases, the systemic inflammatory response may be immoderate, leading to organ dysfunction, such as acute renal failure or multiorgan dysfunction. This study aimed to examine the effect of haemoadsorption (HA) therapy on inflammatory markers and renal damage indices during cardiopulmonary bypass and in the early postoperative period. We conducted a retrospective analysis of prospectively collected data in a single tertiary care center on patients operated between January 2021 and May 2022. The levels of inflammatory markers and renal parameters in blood samples (Interleukin (IL) 6, C-reactive protein (CRP), white blood cells, lactate, procalcitonin (PCT), and NT-proBNP, urea, creatinine, glomerular filtration rate (GFR), mechanical ventilation days and intensive care unit (ICU) days) were compared between the three groups. Data from the Jafron HA 330 (n = 20) and CytoSorb300 (n = 20) groups were compared with those from the control group (n = 20). All patients underwent cardiopulmonary bypass for more than 120 min. Baseline patient characteristics were similar in all three groups. Acute kidney injury (AKI) was diagnosed in 17 patients (28.3%); seven patients were in the Jafron HA 330, two in the CytoSorb300, and eight in the control group. We found that IL1α, IL 6, IL8, Lactate dehydrogenase, PCT, NT-proBNP, CRP, Leukocyte, and TNFα had no significant or clinical difference between the CytoSorb 300 and Jafron HA 330 adsorber groups. Our results indicate that haemoadsorption therapy does not significantly reduce the risk of AKI after prolonged CPB, but decreases the need for renal replacement therapy.
Topics: Humans; Acute Kidney Injury; Cardiopulmonary Bypass; Male; Female; Middle Aged; Retrospective Studies; Aged; Incidence; Biomarkers
PubMed: 38888547
DOI: 10.1051/ject/2024004 -
Comparative Biochemistry and... Jun 2024The current research investigates individual and combined toxicity effects of nickel (Ni) and imidacloprid (IMI) on earthworm species Eisenia fetida fetida. Employing...
The current research investigates individual and combined toxicity effects of nickel (Ni) and imidacloprid (IMI) on earthworm species Eisenia fetida fetida. Employing standardized toxicity parameters, we assessed the impact of environmentally relevant concentrations (ERC) of Ni, IMI, and their mixtures on key biomarkers and reproductive fitness of earthworms. Our findings reveal concentration-dependent responses with discernible adverse effects on physiological parameters. The ERC obtained for Ni was 0.095 ppm, and for imidacloprid was 0.01 ppm. Two concentrations (ERC and 1/5th) of both toxicants (individually and in combinations) were further given for 14 days, and parameters like avoidance behaviour, antioxidants, histology, and metabolomic profile were observed. The behaviour of earthworms was noted, where at 24-48 h, it was found to be in control soil, while later, at 72-96 h, they migrated to toxicants-treated soil. Levels of antioxidants (superoxide dismutase, catalase, reduced glutathione, ascorbic acid), lipid peroxidation, and lactate dehydrogenase were elevated in the testis, spermatheca, ovary, and prostate gland in a high concentration of Ni + IMI. Histological studies showed more vacuolization and disruption of epithelium that was increased in the prostate gland of the Ni + IMI high group, decreased number of spermatids, and damaged cell architecture was noted in testis and spermatheca of the Ni + IMI high group. The highest number of metabolites was found in Ni exposed group (181), followed by IMI (131) and Control (125). Thus, this study sheds light on the ecotoxicological effects of combinational exposure of these contaminants on an essential soil-dwelling organism, where IMI was more toxic than Ni, and both toxicants decreased earthworm reproductive fecundity.
PubMed: 38885748
DOI: 10.1016/j.cbpc.2024.109964 -
European Review For Medical and... Jun 2024Carbon monoxide (CO), a toxic gas, poses a significant threat to human health. Children, pregnant women, and elderly individuals are particularly vulnerable to this...
OBJECTIVE
Carbon monoxide (CO), a toxic gas, poses a significant threat to human health. Children, pregnant women, and elderly individuals are particularly vulnerable to this toxicity. This study aims to evaluate the demographic and clinical characteristics of pediatric, pregnant, and geriatric patients.
PATIENTS AND METHODS
The study included pediatric, pregnant, and geriatric patients with a confirmed diagnosis of CO poisoning, excluding those with complete file data and those with carboxyhemoglobin (COHb) levels below 5% (for children and pregnant patients) and 10% (for elderly patients). Patients aged < 18 years, > 65 years, and pregnant patients admitted to the adult and pediatric emergency departments were included in the study; statistical analyses were conducted using SPSS Inc., with a p-value of < 0.05 considered statistically significant.
RESULTS
For pediatric patients, a statistically significant difference was observed between the two groups in terms of their main complaints, which were primarily attributed to neurological and general symptoms. A positive correlation was found between follow-up time and several factors, including white blood cell (WBC) count and troponin, lactate, lactate dehydrogenase (LDH), and COHb levels. For pregnant patients, no in-hospital mortality was observed in the patients included in this study. A significant negative correlation was identified between age and both COHb and hemoglobin (Hb) levels. A strong positive correlation was found between the COHb levels and hospital follow-up time. For elderly patients, no significant differences were found between the two treatment modalities. Notably, higher COHb levels on admission were associated with a more fatal in-hospital course, with COHb levels > 40% of all patients requiring intubation.
CONCLUSIONS
Vulnerable populations are at increased risk of exposure to CO, and the study results emphasize the necessity of heightened awareness and preventive measures to safeguard these individuals from CO poisoning.
Topics: Humans; Carbon Monoxide Poisoning; Female; Pregnancy; Child; Aged; Male; Carboxyhemoglobin; Adolescent; Child, Preschool
PubMed: 38884506
DOI: 10.26355/eurrev_202406_36376 -
American Journal of Hematology Jun 2024Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE...
Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.
PubMed: 38884175
DOI: 10.1002/ajh.27412 -
Journal of Thoracic Disease May 2024Lactate dehydrogenase (LDH), total protein (TP) and glucose (Glu) in pleural hydrothorax and ascites can be used in the diagnosis of exudate, and adenosine deaminase...
BACKGROUND
Lactate dehydrogenase (LDH), total protein (TP) and glucose (Glu) in pleural hydrothorax and ascites can be used in the diagnosis of exudate, and adenosine deaminase (ADA) can be used in the diagnosis of tuberculous effusion. However, the manufacturers do not claim that their biochemical reagents can be used to detect hydrothorax and ascites samples. Therefore, medical laboratories must conduct suitability studies on biochemical reagents for hydrothorax and ascites samples to comply with regulatory requirements for humor detection. This study aimed to verify the analytical performance and clinical diagnostic accuracy of the Mindray biochemical reagents, including LDH, TP, Glu and ADA, for hydrothorax and ascites.
METHODS
The repeatability, detection limits and reference intervals of Mindray biochemical reagents (LDH, TP, Glu, ADA) in detecting hydrothorax and ascites were determined. The comparison of different measurement procedures was performed. Meanwhile, the diagnostic accuracy of LDH, TP, Glu and ADA were assessed.
RESULTS
The quality control results of LDH, TP, Glu, and ADA were all under control. The repeatability coefficient of variation (%) of LDH, TP, Glu, and ADA were all less than 1%. The limits of blank of LDH, TP, Glu, and ADA were 0.33 U/L, 0.45 g/L, 0.00 mmol/L, and 0.04 U/L, respectively; the limits of detection were 1.57 U/L, 1.85 g/L, 0.05 mmol/L, and 0.12 U/L, respectively. Compared with the reference measurement program, the correlation coefficients of LDH, TP, Glu and ADA were 0.9931, 0.9983, 0.9996 and 0.9966, respectively; the regression equations were y=1.0082x-10.06, y=0.9965x-0.4732, y=0.9903x+0.0522 and y=1.0051x-0.0232, respectively. The reference intervals of LDH, TP, Glu, and ADA in hydrothorax and ascites were ≤198.39 U/L, ≤32.97 g/L, ≥5.03 mmol/L. and ≤11.00 U/L respectively. For differentiating between exudates and transudates, the area under the curve (AUC) of LDH, TP, and Glu were 0.913, 0.875, and 0.767, respectively; the AUC of ADA for the differential diagnosis of tuberculous and nontuberculous effusions was 0.876.
CONCLUSIONS
The LDH, TP, Glu, and ADA assays were validated for use with the Mindray BS-2800 analyzer for hydrothorax and ascites evaluation. LDH, TP, and Glu in hydrothorax and ascites are applicable to the differential diagnosis of exudates and transudates; ADA in hydrothorax and ascites can be employed to differentiate and diagnose tuberculous and nontuberculous effusions.
PubMed: 38883656
DOI: 10.21037/jtd-24-345 -
Biochemia Medica Jun 2024Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia... (Review)
Review
Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of β-rapidly accelerated fibrosarcoma () proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and β-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.
Topics: Humans; Male; Diagnosis, Differential; Leukemia, Hairy Cell; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Sex Factors
PubMed: 38882583
DOI: 10.11613/BM.2024.020502 -
Translational Cancer Research May 2024Non-small cell lung cancer (NSCLC) is a common malignant tumor worldwide, remaining resistant to chemotherapy drugs. Lanatoside C can inhibit the growth of cancer cell...
BACKGROUND
Non-small cell lung cancer (NSCLC) is a common malignant tumor worldwide, remaining resistant to chemotherapy drugs. Lanatoside C can inhibit the growth of cancer cell lines. In this study we aimed to investigate the relationship between lanatoside C and ferroptosis, exploring the possible mechanism in NSCLC.
METHODS
Experiments and were conducted. A549 cells were used for in vitro, including cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release, western blotting, flow cytometry, transmission electron microscopy (TEM), and confocal microscopy. , a subcutaneous tumor model in nude mice using A549 cells was built and body size of the mice was observed. Ki67 immunohistochemistry, hematoxylin-eosin (HE) staining, and western blotting were conducted respectively.
RESULTS
The results showed that lanatoside C had an inhibitory effect on the growth of A549 cells, and the dose of lanatoside C used in this experiment was set at 0.4 µM for 24 hours. When A549 cells were treated with lanatoside C, the cell viability was decreased observably (P<0.001) and LDH release was significantly enhanced (P<0.01) compared with the control group. However, when A549 cells were treated together with lanatoside C and five different inhibitors, containing ferroptosis inhibitors, necroptosis inhibitors, apoptosis inhibitors, pyroptosis inhibitors, and autophagy inhibitors, the results showed that the viability of A549 cells with lanatoside C and ferrostatin-1 (Fer-1) was reduced (P>0.05) and the LDH release was significantly enhanced (P<0.05). Besides, TEM and confocal microscopy showed that the mitochondria of A549 cells in the lanatoside C group disappeared and the mitochondrial membrane potential decreased. , lanatoside C efficiently enhanced the sensitivity of the xenograft tumors, as well as reducing the size and weight of the tumor. Moreover, immunohistochemical staining analysis revealed that the SLC7A11 and GPX4 levels significantly decreased in the lanatoside C group. In addition, the expression of GPX4 and SLC7A11 by western blotting was decreased in lanatoside C group.
CONCLUSIONS
Collectively, lanatoside C could inhibit the proliferation and induce ferroptosis, and have a biological effect on inducing ferroptosis in NSCLC.
PubMed: 38881941
DOI: 10.21037/tcr-23-2285