Lactate Dehydrogenase Research Articles

Sevoflurane Activates PI3K/AKT Signaling Pathway by Upregulating GDF11 Expression to Attenuate Ischemia/Reperfusion Injury in Cardiomyocytes.

Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective effect on ischemic heart injury. However, the specific mechanism by which it exerts the protective effect remains unclear. This study was designed to investigate the role of SEVO in myocardial I/R injury and its potential molecular mechanisms. Blood samples were collected from patients with acute myocardial infarction (AMI) (n = 20) and healthy volunteers (n = 20). The human cardiomyocytes AC16 models of I/R injury were induced by hypoxia/reoxygenation. The mRNA expression levels of growth differentiation factor 11 (GDF11) in the cells and blood were determined by reverse transcription quantitative real-time PCR (RT-qPCR). The cell proliferation was detected by Cell Counting Kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to detect the levels of inflammatory factors interleukin (IL)-8, IL-1β and IL-6 in the cells. And biochemical assay kits were applied for the measurement of the activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the malondialdehyde (MDA) level in the cells. Moreover, western blot was employed to evaluate the levels of the p-serine-threonine protein kinase (AKT), AKT, and phosphatidylinositol 3-kinase (PI3K), protein expression in the cells. The GDF11 expression was decreased in the blood of AMI patients and cardiomyocytes induced by I/R (p < 0.01). Besides, 1% SEVO was presented to promote cardiomyocyte proliferation, inhibit apoptosis, oxidative stress and inflammation, and activate the PI3K/AKT signaling pathway through up-regulation of GDF11 expression (p < 0.01). SEVO promotes proliferation and inhibits inflammatory response, apoptosis, and oxidative stress of I/R-treated cardiomyocytes by elevating GDF11 expression, thereby reducing myocardial I/R injury. Notably, the mechanism underlying the alleviation of the I/R injury may involve the activation of PI3K/AKT signaling pathway.

Pharmacological efficacy study of the cardio-cerebral stasis transforming medicines on cerebral ischemia and myocardial infarction in rats

The purpose of this study was to investigate the efficacy and mechanisms of cardio-cerebral stasis transforming medicines (CCSTM) against cerebral infarction (CI) and myocardial infarction (MI). CI modeling was conducted using the refined Longa suture-occluded technique, while MI modeling was accomplished through the occlusion of the anterior descending branch of the left coronary artery. We found that compared with the model groups, CCSTM decreased the infarct size in models of CI and MI in a dose-dependent manner. After brain ischemia, CCSTM decreased the level of myeloperoxidase (MPO) and malondialdehyde (MDA), and increased the level of superoxide dismutase (SOD). Besides, CCSTM reduced the concentrations of lactate dehydrogenase (LDH), malondialdehyde MDA, and endothelin (ET) in the plasma of rats injured with MI. Histological examination of brain sections revealed that CCSTM alleviated cerebral damage after ischemia compared with the model group. CCSTM can reduce myocardial and cerebral infarction injury, and the oxidation level after myocardial and cerebral infarction in rats.

Prevalence and risk factors of low bone mineral density in Chinese Han male patients with alcohol dependence.

To investigate the prevalence of low bone mineral density (BMD) along with its possible risk factors in male Han Chinese patients with alcohol dependence (AD). This retrospective, cross-sectional study included male patients with AD, classified into normal and low BMD groups according to bone densitometry T scores. Demographic and alcohol-related data, and routine laboratory parameters were compared between the two groups. Binary logistic regression analysis was employed to evaluate risk factors associated with low BMD, and correlations between the T-score and demographic, alcohol-related, and routine laboratory data were evaluated. Among a total of 107 patients with AD included in the study, the prevalence of low BMD was 70.09% (75/107). Patients with low BMD were older, consumed more alcohol daily, and had higher lactate dehydrogenase (LDH) and lower Ca2+ levels than patients with normal BMD. Regression analysis revealed that increased daily alcohol intake, low serum Ca2+ levels, high serum LDH levels, and comorbid hypertension was related to low BMD in patients with AD. Further correlation analysis revealed a positive association between T-score and serum Ca2+ levels. Increased daily alcohol intake, low serum Ca2+ levels, high serum LDH levels, and comorbid hypertension may be risk factors for low BMD.

Pre-implantation embryo metabolism identified by PEMA reveals endogenous lactate insufficiency contributes to pre-implantation development arrest

Metabolism is a major regulator of pre-implantation embryonic development, but pre-implantation development arrest (PIDA) due to abnormal metabolisms remains ambiguous. By estimating a weight for each metabolic reaction using the translatome data, we developed a computational tool to perform pre-implantation embryos metabolic analysis (PEMA), and uncovered that the embryos exist in high activities of lactate dehydrogenase (LDH) and lactate synthesis when major zygotic genome activation (ZGA) occurs in humans and mice. The insufficiency of endogenous lactate was predicted by PEMA in human 8-cell PIDA and corrected human tripronuclear (ch3PN) embryos, which was coordinated with failed H3K18lac and major ZGA. In transcriptomes, the human PIDA embryos resembled endogenous lactate-deprived mouse embryos. Lac-CoA addition could promote H3K18lac, major ZGA, and ch3PN pre-implantation development. Collectively, our study decodes the metabolic abnormalities in human PIDA embryos. The experimental validation suggests that PEMA offers an opportunity to study metabolic heterogeneity in early embryos.

Can some inflammatory parameters predict the survival of patients with malignant pleural effusion?

Background: This study aimed to investigate whether there is a correlation between some serum inflammatory markers and the survival of patients with malignant pleural effusions (MPEs). Methods: The prospective study included 125 patients (67 males, 58 females; median age: 62 years; range, 40 to 92 years) who underwent thoracentesis for pleural effusion between January 2020 and December 2021. An overall survival analysis was performed, and survival differences between the groups were investigated. The cutoff value of the inflammatory parameters associated with mortality was determined by receiver operating characteristic analysis. Results: Median survival after detection of MPE was six months, and three- and five-year overall survivals were 16% and 4%, respectively. There was a significant correlation between the ECOG (Eastern Cooperative Oncology Group) score of the patients and the median survival. Serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), fluid albumin, and serum lactate dehydrogenase (LDH)-to-pleural LDH ratio and survival had a statistically significant relationship in receiver operating characteristic analysis. Threshold values were determined accordingly. Poor prognostic factors that were found to be statistically significant were high CRP (p=0.001), high NLR (p=0.001), high PLR (p=0.02), and high serum LDH-to-pleural LDH ratio (p=0.04). Conclusion: Some serum inflammatory markers, including high CRP, high NLR, high PLR, and high serum LDH-to-pleural LDH ratio, can be a simple and inexpensive method in predicting prognosis in patients with MPE.

Effects of different microplastics levels combined with NaClO on activated sludge in MBRs: toxicity, key enzymes, extracellular polymers, and communities

NaClO, as a common membrane cleaning agent were introduced from the permeate side across membrane, which could diffuse into MBR membrane pool. Microplastics would also accumulate in MBR membrane pool during wastewater treatment, thus, NaClO and MPs are co-exposed to activated sludge. This study investigated the effects of PET-MPs (0, 50, 100 and 300 μg/g-ss) on activated sludge with or without NaClO stress. The presence of PET-MPs had no significant impact on nitrification and denitrification rates, but when exposed to NaClO, the increasing level of PET-MPs (i.e., from 0 to 300 μg/g-ss) inhibited the nitrification (94.85 % to 65.90 %) and denitrification (88.68 % to 60.09 %) rates. For microbial metabolism (key enzymes) evaluated, the key enzymes related to organic matter biodegradation, nitrification as well as denitrification were both inhibited with PET-MPs level rise under NaClO stress. The generation of reactive oxygen species (ROS) and the release of lactate dehydrogenase (LDH) increased significantly indicating NaClO caused the toxicity of MPs to activated sludge by enhancing the oxidative stress level. Correspondingly, a variation in abundance related to membrane pollution, nitrification, and denitrification after exposure to PET-MPs with NaClO stress accompanied these adverse effects.

Reproductive effort affects cellular response in the mantle of Nodipecten subnodosus scallops exposed to acute hyperthermia

In marine ecosystems, temperature regulates the energy metabolism of animals. In the last decades, the temperature increase was related to mass mortality events of marine ectotherms, particularly during high-energy investment for reproduction. In scallops, the mantle has been poorly investigated while this tissue covers more than 40 % of the body mass, contributing to the perception of surrounding environmental stimuli. Our aim was to assess the cellular and molecular responses linked to energy metabolism in the mantle of adult N. subnodosus facing acute hyperthermia during reproductive effort. Scallops collected in spring (late gametogenesis) and summer (ripe gonads) were exposed to a control temperature (22 °C) or acute hyperthermia (30 °C) for 24 h. In spring, increased arginine kinase (AK) activity together with increased pyruvate kinase/citrate synthase ratio (PK/CS) suggested an enhanced carbohydrate, pyruvate, and arginine metabolism to maintain the adenylate energy charge (AEC) in the mantle of scallops coping with acute thermal increase. In summer, animals decreased their AEC (5 %) and arginine phosphate pool (40 %) and increased their anaerobic metabolism as shown by enhanced activities of lactate-dehydrogenase (LDH) and octopine dehydrogenase (ODH), respectively. The abundance of twenty proteins involved in energy metabolism (isocitrate dehydrogenase, ATP synthase subunit β), protein protection (cognates heat shock protein 70), and cytoskeleton (actins and tubulins) were affected only by season. These results underlie the role of the mantle of N. subnodosus in the seasonal responses of this tissue to thermal fluctuations during reproductive effort with possible implications for the physiological performance of scallops under heat waves in wild or harvest conditions.

Bioaccumulation, transformation and toxicity of imidacloprid and dinotefuran in Eisenia fetida under single and binary exposure scenarios

Earthworms (Eisenia fetida) were exposed to individual and binary mixture of imidacloprid (IMI) and dinotefuran (DIN) at 0.05 and 0.5 mg/kg for 28 days to investigate their bioaccumulation, transformation and toxicity. IMI was more easily absorbed by earthworms than DIN, and worms didn’t accumulate or generate toxic metabolites. The obvious accumulation of neonicotinoids during later period caused significant neural dysfunction, especially when exposed to high-concentration IMI. Meanwhile, oxidative stress indicated by decreased SOD/CAT activity (33.2 %-68.1 %) and increased MDA (38.4 %-55.0 %) was induced by binary exposure with high-concentration IMI. By contrast, coelomocytes responded earlier and more strongly than oxidative responses. Coelomocytes’ viability and mitochondrial membrane potential were inhibited (23.6 %-91.7 %) mainly by IMI and binary exposure. Coelomocytes’ lactate dehydrogenase activity exerted a fluctuating pattern, suggesting irregular disturbance on cellular functions. This study highlights the role of coelomocytes and the need to consider binary/multiple scenarios and transformation of neonicotinoids in their risk assessment to earthworms.

Performance verification of Mindray BS-2800M chemistry analyzer for detecting lactate dehydrogenase, albumin and adenosine deaminases in cerebrospinal fluid and evaluation of its diagnostic accuracy in central nervous system diseases

Performance verification of Mindray BS-2800M chemistry analyzer for detecting lactate dehydrogenase, albumin and adenosine deaminases in cerebrospinal fluid and evaluation of its diagnostic accuracy in central nervous system diseases

Near-infrared photoimmunotherapy for osteosarcoma targeting epidermal growth factor receptor

Osteosarcoma is the most common bone tumor, and it possesses high metastatic propensity. Although systemic chemotherapy has improved its prognosis, improvements in survival rates have stalled in recent years. Moreover, the prognosis of patients with metastatic osteosarcoma remains poor. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer therapy that induces immunogenic cell death (ICD), and the therapeutic effects spread to distant metastatic sites. Therefore, NIR-PIT could be useful in both primary and metastatic osteosarcoma treatment. In this study, we investigated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) in osteosarcoma. The cytotoxic effects of NIR-PIT in osteosarcoma cell lines with different EGFR expression levels (MG63; high, Saos-2; low) were evaluated. NIR-PIT–induced cell death was dependent on the EGFR expression level. After NIR-PIT, swelling and bleb formation, the characteristic morphological changes induced by NIR-PIT associated with necrosis caused by the influx of extracellular fluid, were observed. In addition, the release of the ICD markers lactate dehydrogenase and ATP was detected after NIT-PIT. NIR-PIT significantly suppressed tumor growth in tumor-bearing mice. This study revealed that NIR-PIT targeting EGFR has therapeutic effects and induces ICD in osteosarcoma; thus, it is potentially a novel therapeutic strategy for primary and metastatic osteosarcoma.

Scutellaria baicalensis ameliorates allergic airway inflammation through agonism and transcriptional regulation of TAS2Rs

Ethnopharmacological relevanceScutellaria baicalensis Georgi (SCB, Huangqin) is a traditional medicinal plant used to treat fever and respiratory diseases. SCB has a good therapeutic effect on asthma and anti-inflammation in traditional clinic use. However, the molecular mechanism and targets of SCB in treating asthma are still unclear. Aim of the studyCombining transcriptomic analysis and in vitro experimental validation, this study aimed to reveal the molecular mechanism and targets of SCB in treating asthma. Materials and methodsThe anti-asthmatic effects of SCB and its active components, scutellarin and oroxylin A, were evaluated in ovalbumin (OVA)-induced rats by analysis of pulmonary function and pathology. The signaling pathways in rat pulmonary tissue were analyzed using transcriptomics and protein interaction network analysis. Calcium mobilization assay and molecular docking were utilized to discover the active compounds from SCB with agonism activity of type 2 taste receptors (TAS2Rs). The anti-asthmatic effect and transcriptional regulation of TAS2Rs regulated by SCB and its active components were analyzed in vitro. ResultsExtracts of SCB (ESB), scutellarin, and oroxylin A ameliorated airway function and inflammation in OVA-induced rats. The anti-asthma mechanism of ESB, scutellarin and oroxylin A was highly related to immune and taste transduction pathways based on transcriptomic analysis, especially the TAS2Rs signaling pathway. ESB was the direct agonist of TAS2R4 and TAS2R14 with EC50 of 209.1 and 217.2 μg/mL based on calcium mobilization assay, respectively. Baicalein was the main active component for TAS2R4 agonism activity, and scutellarin and oroxylin A had weak agonism activity of TAS2R4 and TAS2R14 through calcium mobilization assay and molecular docking. However, scutellarin and oroxylin A significantly upregulated the gene expression of Tas2r108 (the mouse ortholog of the TAS2R4) in lung tissue. ESB, scutellarin, and oroxylin A inhibited LPS-induced lactate dehydrogenase release and gene expression of TNF through transcriptional regulation of TAS2R4 and TAS2R14 on bronchial epithelial cells. ESB and oroxylin A ameliorated IgE-induced β-hexosaminidase release and gene expression of Il4 and Tnf and upregulated gene expression of Tas2r108. ConclusionThese results provided new insight into the anti-asthmatic mechanism of SCB and active components, scutellarin and oroxylin A, through agonism and transcriptional regulation of TAS2Rs to ameliorate allergic airway inflammation.

85 (PB073): Exploring the therapeutic potential of cell-penetrating peptide-assisted siRNA delivery to target Lactate dehydrogenase C (LDHC) in triplenegative breast Cancer

85 (PB073): Exploring the therapeutic potential of cell-penetrating peptide-assisted siRNA delivery to target Lactate dehydrogenase C (LDHC) in triplenegative breast Cancer

Metabolic modulation of melanoma enhances the therapeutic potential of immune checkpoint inhibitors.

Lactate is a pivotal molecule with diverse functions in the metabolic reprogramming of cancer cells. Beyond its role in metabolism, lactate exerts a modulatory effect within the tumor microenvironment; it is utilized by stromal cells and has been implicated in the suppression of the immune response against the tumor. Using in vitro assays (including flow cytometry, live-cell imaging and metabolic analyses), the impact of lactate dehydrogenase inhibitors (LDHIs) on melanoma cells were assessed. The therapeutic potential of LDHIs with immune checkpoint inhibitors (ICIs) were tested in vivo in murine models of melanoma tumors. A potent anti-proliferative effect (via both cell cycle alterations and enhanced apoptosis) of LDHIs, Oxamate (Oxa) and methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (NHI-2), was found upon treatment of melanoma cell lines. Using a combination of Oxa and NHI-2, a synergistic effect to inhibit proliferation, glycolysis, and ATP production was observed. Metabolic analysis revealed significant alteration in glycolysis and oxidative phosphorylation, while metabolite profiling emphasized consequential effects on lactate metabolism and induced energy depletion by LDHIs. Detection of increased RANTES and MCP-1, with Oxa and NHI-2 treatment, prompted the consideration of combining LDHIs with ICIs. In vivo studies using a murine B78 melanoma tumor model revealed a significant improvement in treatment efficacy when LDHIs were combined with ICIs. These findings propose the potential of targeting lactate metabolism to enhance the efficacy of ICI treatments in patients with melanoma.

Coumarin-chalcone derivatives as dual NLRP1 and NLRP3 inflammasome inhibitors targeting oxidative stress and inflammation in neurotoxin-induced HMC3 and BE(2)-M17 cell models of Parkinson's disease.

In Parkinson's disease (PD) brains, microglia are activated to release inflammatory factors to induce the production of reactive oxygen species (ROS) in neuron, and vice versa. Moreover, neuroinflammation and its synergistic interaction with oxidative stress contribute to the pathogenesis of PD. In this study, we investigated whether in-house synthetic coumarin-chalcone derivatives protect human microglia HMC3 and neuroblastoma BE(2)-M17 cells against 1-methyl-4-phenyl pyridinium (MPP+)-induced neuroinflammation and associated neuronal damage. Treatment with MPP+ decreased cell viability as well as increased the release of inflammatory mediators including cytokines and nitric oxide in culture medium, and enhanced expression of microglial activation markers CD68 and MHCII in HMC3 cells. The protein levels of NLRP3, CASP1, iNOS, IL-1β, IL-6, and TNF-α were also increased in MPP+-stimulated HMC3 cells. Among the four tested compounds, LM-016, LM-021, and LM-036 at 10 μM counteracted the inflammatory action of MPP+ in HMC3 cells. In addition, LM-021 and LM-036 increased cell viability, reduced lactate dehydrogenase release, ameliorated cellular ROS production, decreased caspase-1, caspase-3 and caspase-6 activities, and promoted neurite outgrowth in MPP+-treated BE(2)-M17 cells. These protective effects were mediated by down-regulating inflammatory NLRP1, IL-1β, IL-6, and TNF-α, as well as up-regulating antioxidative NRF2, NQO1, GCLC, and PGC-1α, and neuroprotective CREB, BDNF, and BCL2. The study results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanisms, and indicate the potential use of LM-021 and LM-036 as dual inflammasome inhibitors in treating both NLRP1- and NLRP3-associated PD.

Differential interaction modes of As(III)/As(V) with microbial cell membrane induces opposite effects on organic contaminant biodegradation in groundwater

Arsenic, a widespread toxic metalloid in groundwater, derives both from natural geological environment and industrial discharge, is extensively detected to be coexisting with organic contaminants, such as 2,4,6-trichlorophenol (TCP), a prior concerned pollutant. During biological remediation of groundwater, arsenic potentially intervenes microbial behaviors. This study found an opposite interference of arsenic in its two different valences (III and V) on the degradation of TCP by the functional bacteria, Sphingomonas fennica K101. As(III) inhibited TCP degradation in a concentration-dependent manner (from 0.1-10 mg/L), with a maximum inhibition rate of 35.5 %, whereas As(V) exhibited promoting effects by 13.8 % and 33.2 % at 1 mg/L and 10 mg/L, respectively. Employing field emission transmission electron microscopy, quantum chemical calculation, fourier-transform ion cyclotron resonance mass spectrometry and metabolomic analysis, we unveil distinct interactions between cell membranes and arsenic in two valence states. Exposure to As(III) led to significant accumulation of As(III) in the cytoplasm, followed by interaction with intracellular ferritin (ferritin heavy chain 1), releasing iron ions and generating ROS. Subsequently, it induced ferroptosis and disrupted bacterial basal metabolism, thereby inhibiting TCP biodegradation. Oppositely, As(V) bound to a critical component sphingosine and triggered sphingosine polymerization, increasing membrane permeability, which was evidenced by measuring lactate dehydrogenase release. This process facilitated TCP transmembrane permeation by reducing membrane or extracellular secretion resistance. As(V) concurrently upregulated energy metabolism and accelerated TCP degradation. Our study elucidates the influence of prevalent arsenic on biodegradation efficacy, particularly amidst changing redox conditions associated with varying arsenic valences.

Clinical characteristics of SARS-CoV-2 Omicron pneumonia in immunocompromised and immunocompetent patients: A retrospective cohort study

ObjectivePrevious studies evaluating the differences in COVID-19 mortality rates between immunocompromised patients and other patient groups have shown conflicting findings. This research aimed to compare the mortality rates of immunocompromised and immunocompetent patients during the Omicron-dominant period of the SARS-CoV-2 pandemic, and to identify factors associated with prognosis. MethodsWe conducted a retrospective analysis of 1085 adult patients (aged ≥18 years) admitted with COVID-19 pneumonia to the China-Japan Friendship Hospital between December 1, 2022, and January 31, 2023. We assessed the prevalence of comorbidities, incidence of co-infections and nosocomial infections, and 30-day mortality. ResultsAmong the 1085 patients, 254 were immunocompromised, and 831 were immunocompetent. Immunocompromised patients had higher rates of non-invasive ventilation use (30.3 % vs. 21.1 %), invasive ventilation (12.2 % vs. 5.3 %), and 30-day mortality (19.7 % vs. 13.7 %) compared to immunocompetent patients. However, overall mortality rates did not significantly differ based on immunocompromised status. Cox regression analysis identified that elevated troponin T (≥0.15 ng/mL), respiratory failure, high lactate dehydrogenase (≥272.5 U/L), elevated D-dimer (≥1.295 mg/L), increased C-reactive protein (≥90 mg/L), elevated interleukin-6 (>11.67 ng/L), high peripheral blood neutrophil count (>9.84 × 10⁹/L), and immunocompromised status were independent predictors of poor COVID-19 prognosis. In the immunocompetent group, current smoking and a history of interstitial lung disease were related to a worse prognosis. ConclusionsCOVID-19 pneumonia due to the Omicron variant may lead to worse outcomes in immunocompromised patients. In immunocompetent patients, careful monitoring is essential for those with respiratory failure, smoking history, or interstitial lung disease to prevent adverse outcomes.

HELLP syndrome and associated factors among pregnant women with preeclampsia/eclampsia at a referral hospital in southwestern Uganda: a cross-sectional study

BackgroundHemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, a complication of preeclampsia/eclampsia, is associated with severe maternal morbidity and mortality. In resource-limited settings, such as Uganda, gaps in routine laboratory assessments may lead to underdetection of HELLP syndrome. This study determined the prevalence and factors associated with HELLP syndrome among pregnant women with preeclampsia/eclampsia at Mbarara Regional Referral Hospital (MRRH), southwestern Uganda.MethodsA cross-sectional study was conducted at the high-risk ward of the MRRH from December 2022 to June 2023. Pregnant women diagnosed with preeclampsia or eclampsia were enrolled consecutively. Participants’ sociodemographic and clinical data were collected using an interviewer-administered questionnaire. The diagnosis of complete HELLP syndrome was made based on the Tennessee classification: aspartate aminotransferase enzyme ≥ 70 IU/L, platelet counts < 100,000 cells/µL, and serum lactate dehydrogenase enzyme ≥ 600 IU/L. We used multivariable modified Poisson regression analysis to determine factors associated with HELLP syndrome.ResultsA total of 129 participants with a mean age of 28 ± 6.6 years were enrolled in the study. The prevalence of HELLP syndrome was 18.6% (n = 24; 95% CI: 12.7–26.3%). Independent factors associated with HELLP syndrome were maternal age (adjusted prevalence ratio [aPR]: 4.96; 95% CI: 1.57–15.65; for mothers aged < 20 years compared to those aged 20–34 years), the presence of epigastric pain (aPR: 5.89; 95% CI: 1.41–14.63), and referral from other health facilities (aPR: 3.14; 95% CI: 1.27–7.72).ConclusionApproximately 2 of the 10 women who presented with preeclampsia or eclampsia had HELLP syndrome. It is more common among teenage mothers, those with a history of epigastric pain and those referred from lower health facilities. Incorporating routine laboratory testing for HELLP syndrome in the diagnostic protocol for preeclampsia or eclampsia, especially among adolescent mothers, those experiencing epigastric pain, and those referred from lower health facilities, could enhance timely detection and management of mothers with preeclampsia whose pregnancies are complicated by HELLP syndrome.

Outcomes for high-risk defining events in follicular lymphoma following frontline immunochemotherapy

Progression of follicular lymphoma (FL) or transformation (tFL) within 24 months of immunochemotherapy (ICT) represent high-risk defining events (HRDE) with poor overall survival (OS). We examined baseline clinical characteristics, imaging and outcomes for patients experiencing HRDE in an international retrospective cohort of newly diagnosed FL patients requiring ICT. We defined HRDE groups as: relapse or progression of FL within 24 months (FL24); Early TFL (transformation <24 months of ICT); Late TFL (transformation >24 months of ICT). 433 patients were categorised: reference FL n=352 (no HRDE), FL24 n=43, Early TFL n=29, or Late TFL n=9. Chemotherapy regimens included bendamustine (63%), CHOP (27%) or CVP (10%); 85% received rituximab/15% obinutuzumab and 48% received maintenance therapy. Compared to the reference FL group, OS from HRDE was inferior for FL24 (HR 3.93, 95% CI 2.14-7.23), Early TFL (HR 8.16, 95% CI 4.38-15.2) and Late TFL (HR 8.23, 95% CI 3.18-21.25). OS from HRDE was inferior for Early TFL compared to FL24 (HR 2.08, 95% CI 1.02-4.21). In multivariable analysis, baseline performance status, elevated lactate dehydrogenase, elevated beta-2-microglobulin and grade 3A were associated with Early TFL. Clinical characteristics were not able to differentiate Early TFL from FL24. Standardised uptake value max was higher in Early TFL but not FL24 compared to reference FL. Early TFL and FL24 represent different HRDEs in FL after ICT and are associated with inferior OS. Distinguishing between early TFL and FL24 is important for biomarker development, management and to develop and interpret clinical trials in this area of unmet need.

Impact of Etonogestrel-releasing contraceptive implant use in cisgender women with Sickle cell disease

BackgroundSickle cell disease is a hereditary hemolytic anemia that exposes women to increased health risks especially in pregnancy, with serious implications for the woman and fetus. Acute pain episodes can occur multiple times per month and result in reduction of quality of life and disruption of her life. ObjectiveTo assess the clinical, including pain and metabolic parameters of women with sickle cell disease using etonogestrel-releasing contraceptive implants. MethodsWomen with sickle cell disease, aged 18–40 years, with reports of pain crises in the preceding 3 months were included and followed up for 12 months. Blood samples were collected to evaluate the blood count, reticulocytes, liver profile (alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin and its fractions), lipid profile, and lactate dehydrogenase levels before and 6 and 12 months after implant insertion. The following clinical variables were analyzed every 3 months: bleeding pattern, blood pressure, weight, body mass index, pain intensity (assessed using a visual analogic scale (VAS) from 0 to 10), and frequency of pain crises. ResultsTwenty-three women completed the study. There were no differences in laboratory variables between baseline and 6 and 12 months after implant insertion. Similarly, clinical variables did not differ, except for pain intensity (VAS pre-insertion = 8 vs. VAS 12 months post insertion = 4; p = 0.005) and frequency of pain crises (pre-insertion = 6 vs. 12 days/month post insertion = 0; p = 0.000). ConclusionsEtonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in women with sickle cell disease. Moreover, it was safety among these population due to no changes in laboratory parameters during the first 12 months of use.

Aqueous Extract of Rhubarb Promotes Hepatotoxicity via Facilitating PKM2-Mediated Aerobic Glycolysis in a Rat Model of Diethylnitrosamine-Induced Liver Cancer.

To identify the polar parts in Rhubarb that cause hepatotoxicity and explore the underlying mechanisms. The rat model of liver cancer was established by gavage of diethylnitrosamine (DEN; 0.002 g/rat) for 14weeks. Starting from the 11th week, Rhubarb granule (4 g/kg), aqueous, ethyl acetate and n-butanol extract of Rhubarb or Rhein equivalent to a dose of 4 g/kg Rhubarb granule were administered intragastrically for 4 consecutive weeks. Liver tissues from rats treated with DEN and Rhubarb granules were used for non-targeted metabolomics analysis. The correlation between pyruvate kinase isozyme type M2 (PKM2) expression level and the progress and prognosis of hepatocellular carcinoma (HCC) was evaluated through bioinformatics analysis based on TCGA database. Liver tissues and blood samples from rats treated with DEN and aqueous, ethyl acetate and n-butanol extract of Rhubarb were used for the screening of hepatotoxic polar parts of Rhubarb. The liver injuries were evaluated by the changes in pathology, liver function, and the expression levels of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta1 (TGF-β1). The mechanism studies focus on PKM2 expression, and the metabolic reprogramming via detecting the activities of lactate dehydrogenase A (LDHA) and isocitrate dehydrogenase (ICDH). Furthermore, molecular docking analysis was performed to validate the target interaction between Rhein and PKM2, and the hepatotoxicity of Rhein was evaluated by testing liver function in the DEN-induced liver cancer model. The non-targeted metabolomics analysis revealed that Rhubarb promoted aerobic glycolysis in the rat model of DEN-induced liver cancer. And bioinformatics analysis revealed that high PKM2 expression was closely related to the progression and poor prognosis of HCC. In vivo studies indicated that the aqueous extract of Rhubarb, but not ethyl acetate and n-butanol extract, promoted the liver injuries induced by DEN. The mechanism study showed that the aqueous extract of Rhubarb increased the expression of PKM2 and promoted aerobic glycolysis. Moreover, Rhein had a strong binding affinity for PKM2 and aggravated liver injury in the DEN-induced liver cancer model. Aqueous extract of Rhubarb promoted hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in the rat model of DEN-induced liver cancer.