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BMC Nephrology Jun 2024There is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury...
BACKGROUND
There is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury (SAKI). We aimed to investigate the predictive impact of LAR for SAKI in patients with sepsis.
METHODS
A total of 4,087 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were included. Logistic regression analysis was used to identify the association between LAR and the risk of developing SAKI, and the relationship was visualized using restricted cubic spline (RCS). The clinical predictive value of LAR was evaluated by ROC curve analysis. Subgroup analysis was used to search for interactive factors.
RESULTS
The LAR level was markedly increased in the SAKI group (p < 0.001). There was a positive linear association between LAR and the risk of developing SAKI (p for nonlinearity = 0.867). Logistic regression analysis showed an independent predictive value of LAR for developing SAKI. The LAR had moderate clinical value, with an AUC of 0.644. Chronic kidney disease (CKD) was identified as an independent interactive factor. The predictive value of LAR for the development of SAKI disappeared in those with a history of CKD but remained in those without CKD.
CONCLUSIONS
Elevated LAR 12 h before and after the diagnosis of sepsis is an independent risk factor for the development of SAKI in patients with sepsis. Chronic comorbidities, especially the history of CKD, should be taken into account when using LAR to predict the development of AKI in patients with sepsis.
Topics: Humans; Acute Kidney Injury; Sepsis; Male; Female; Retrospective Studies; Risk Factors; Aged; Middle Aged; L-Lactate Dehydrogenase; Serum Albumin; Predictive Value of Tests; Biomarkers
PubMed: 38898431
DOI: 10.1186/s12882-024-03636-5 -
Zhen Ci Yan Jiu = Acupuncture Research Jun 2024To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial...
OBJECTIVES
To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA.
METHODS
A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot.
RESULTS
After intervention, compared with the normal group, the knee circumference was significantly enlarged (<0.05), the pain threshold was significantly decreased (<0.05);the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased (<0.05);positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all <0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased (<0.05), the pain threshold was significantly increased (<0.05);in synovial tissue, the pathological score was decreased (<0.05);the positive expressions of TNF-α, IL-1β, IL-6 and IL-17 in synovial tissue were decreased (<0.05), the lactic acid content in synovial tissue was decreased (<0.05);the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased (<0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased (<0.05), positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all <0.05) in HRN group.
CONCLUSIONS
HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.
Topics: Animals; Rabbits; Hypoxia-Inducible Factor 1, alpha Subunit; Glycolysis; Humans; Arthritis, Rheumatoid; Male; Acupuncture Therapy; Female; Tumor Necrosis Factor-alpha; Acupuncture Points; Interleukin-6
PubMed: 38897802
DOI: 10.13702/j.1000-0607.20230487 -
Life Sciences Aug 2024This investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis...
BACKGROUND AND OBJECTIVES
This investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis of primary nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) quantification is a crucial prognostic indicator in NPC cases, but not all patients with NPC test positive for EBV. Furthermore, widespread adoption of EBV-DNA quantification remains challenging due to its high cost. Consequently, it is imperative to incorporate additional convenient and cost-effective prognostic markers to comprehensively evaluate patient outcomes.
METHODS
This retrospective analysis included 203 newly diagnosed NPC cases treated at the Affiliated Qingyuan Hospital of Guangzhou Medical University between January 2018 and March 2022. The dataset included personal information and clinical data, and the treatment protocols followed the CSCO guidelines. Efficacy assessments were based on the RECIST 1.1 criteria and were conducted after induction chemotherapy and one week and three months after radiotherapy.
RESULTS
A noteworthy correlation emerged between baseline serum LDH levels and treatment efficacy at one week after radiotherapy (P = 0.03) and at three months after radiotherapy (P < 0.01). Additionally, a prognostic model that incorporates age (P = 0.010), LDH (P < 0.001), C-reactive protein (P = 0.010), and alkaline phosphatase (P = 0.005) demonstrated robust predictive accuracy and clinical applicability.
CONCLUSION
This investigation substantiates the significant correlation between baseline serum LDH levels and NPC outcomes. Furthermore, we introduce a refined prognostic model that holds promise for informing personalized treatment strategies, thereby contributing to the advancement of the diagnosis of NPC.
Topics: Humans; Female; Male; Nasopharyngeal Carcinoma; L-Lactate Dehydrogenase; Middle Aged; Retrospective Studies; Nasopharyngeal Neoplasms; Prognosis; Adult; Aged; Biomarkers, Tumor; Herpesvirus 4, Human; Treatment Outcome; Young Adult; Multivariate Analysis; Epstein-Barr Virus Infections; Clinical Relevance
PubMed: 38897348
DOI: 10.1016/j.lfs.2024.122856 -
Applied Microbiology and Biotechnology Jun 2024Bacteriocins have the potential to effectively improve food-borne infections or gastrointestinal diseases and hold promise as viable alternatives to antibiotics. This...
Bacteriocins have the potential to effectively improve food-borne infections or gastrointestinal diseases and hold promise as viable alternatives to antibiotics. This study aimed to explore the antibacterial activity of three bacteriocins (nisin, enterocin Gr17, and plantaricin RX-8) and their ability to attenuate intestinal barrier dysfunction and inflammatory responses induced by Listeria monocytogenes, respectively. Bacteriocins have shown excellent antibacterial activity against L. monocytogenes without causing any cytotoxicity. Bacteriocins inhibited the adhesion and invasion of L. monocytogenes on Caco-2 cells, lactate dehydrogenase (LDH), trans-epithelial electrical resistance (TEER), and cell migration showed that bacteriocin improved the permeability of Caco-2 cells. These results were attributed to the promotion of tight junction proteins (TJP) assembly, specifically zonula occludens-1 (ZO-1), occludin, and claudin-1. Furthermore, bacteriocins could alleviate inflammation by inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways and reducing the secretion of interleukin-6 (IL-6), interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α). Among three bacteriocins, plantaricin RX-8 showed the best antibacterial activity against L. monocytogenes and the most pronounced protective effect on the intestinal barrier due to its unique structure. Based on our findings, we hypothesized that bacteriocins may inhibit the adhesion and invasion of L. monocytogenes by competing adhesion sites. Moreover, they may further enhance intestinal barrier function by inhibiting the expression of L. monocytogenes virulence factors, increasing the expression of TJP and decreasing the secretion of inflammatory factors. Therefore, bacteriocins will hopefully be an effective alternative to antibiotics, and this study provides valuable insights into food safety concerns. KEY POINTS: • Bacteriocins show excellent antibacterial activity against L. monocytogenes • Bacteriocins improve intestinal barrier damage and inflammatory response • Plantaricin RX-8 has the best protective effect on Caco-2 cells damage.
Topics: Listeria monocytogenes; Bacteriocins; Humans; Caco-2 Cells; Anti-Bacterial Agents; Inflammation; NF-kappa B; Bacterial Adhesion; Tight Junction Proteins; Cytokines; Listeriosis; Cell Movement
PubMed: 38896287
DOI: 10.1007/s00253-024-13228-w -
Naunyn-Schmiedeberg's Archives of... Jun 2024Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation...
Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation (SD)-induced cardiac injury and the mechanisms are unknown. This study established SD mice model using a modified multiple platform water method and induced ferroptosis model in H9c2 cells using Erastin. The heart rate of mice was measured, and myocardial and mitochondrial structures were visualized using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Myocardial injury, oxidative stress indicators, and Fe levels were detected by the kit method. The reactive oxygen species (ROS) levels were detected by immunofluorescence, and SIRT6 and ferroptosis-associated protein expression levels were detected by Western blot. Reduced heart rate and abnormalities in myocardial tissue and mitochondrial structure were ameliorated in the SD group of mice after GAS treatment. GAS treatment reduced ROS levels in Erastin-induced H9c2 cells. GAS treatment reduced atrial natriuretic peptide (ANP), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MAD), and Fe levels, and increased superoxide dismutase (SOD) and glutathione (GSH) levels in the SD and Erastin groups. Western blot showed that GAS treatment increased the expression of sirtuin 6 (SIRT6), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) and decreased the expression of P53 in SD and Erastin groups. The SIRT6 inhibitor OSS_128167 (OSS) reversed GAS treatment of Erastin-induced ferroptosis in H9c2 cells. These observations propose that GAS prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6.
PubMed: 38896272
DOI: 10.1007/s00210-024-03230-4 -
BioRxiv : the Preprint Server For... Jun 2024larval growth requires efficient conversion of dietary nutrients into biomass. Lactate Dehydrogenase (Ldh) and Glycerol-3-phosphate dehydrogenase (Gpdh1) support larval...
larval growth requires efficient conversion of dietary nutrients into biomass. Lactate Dehydrogenase (Ldh) and Glycerol-3-phosphate dehydrogenase (Gpdh1) support larval biosynthetic metabolism by maintaining NAD/NADH redox balance and promoting glycolytic flux. Consistent with the cooperative functions of Ldh and Gpdh1, the loss of both enzymes, but neither single enzyme, induces a developmental arrest. However, Ldh and Gpdh1 exhibit complex and often mutually exclusive expression patterns, suggesting that the double mutant lethal phenotype could be mediated nonautonomously. Here we find that the developmental arrest displayed by the double mutants extends beyond simple metabolic disruption and instead stems, in part, from changes in systemic growth factor signaling. Specifically, we demonstrate that this synthetic lethality is linked to the upregulation of Upd3, a cytokine involved in the Jak/Stat signaling pathway. Moreover, we demonstrate that either loss of the Upd3 or dietary administration of the steroid hormone 20-hydroxyecdysone (20E) rescue the synthetic lethal phenotype of double mutants. Together, these findings demonstrate that metabolic disruptions within a single tissue can nonautonomously modulate interorgan signaling to ensure synchronous developmental growth.
PubMed: 38895259
DOI: 10.1101/2024.06.06.597835 -
Molecules (Basel, Switzerland) Jun 2024Understanding the optimal extraction methods for flavonoids from flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the...
Optimization of Flavonoid Extraction from Flowers Using Ultrasonic Techniques: Predictive Modeling through Response Surface Methodology and Deep Neural Network and Biological Activity Assessment.
Understanding the optimal extraction methods for flavonoids from flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors-solid-to-liquid ratio (1:10 to 1:50 g·mL), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)-were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD < 1%). Additionally, the inhibitory effects of the optimized extracts against () were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on , with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic . is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively.
Topics: Flavonoids; Abelmoschus; Flowers; Neural Networks, Computer; Plant Extracts; Antioxidants; Ultrasonic Waves
PubMed: 38893486
DOI: 10.3390/molecules29112610 -
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