Serum LDH Levels Research Articles

The role of haptoglobin in the diagnosis of preeclampsia and HELLP syndrome and in predicting neonatal outcomes.

The study aimed to determine whether maternal serum haptoglobin values could have an effect on predicting diagnosis and neonatal outcomes in preeclampsia and HELLP syndrome. Hundred sixteen pregnant women who met the inclusion criteria were included in the study. To evaluate whether serum haptoglobin level in maternal blood could be used in early diagnosis of preeclampsia and HELLP syndrome, 49 pregnant women diagnosed with preeclampsia and 13 pregnant women diagnosed with HELLP syndrome were included in the study group, and 54 healthy pregnant women in the control group. The groups were compared regarding maternal serum haptoglobin level, platelet count, ALT, AST, LDH, and uric acid levels. Moreover, the age, obstetric histories, and newborn outcomes of all pregnant women were recorded and compared between groups. The mean haptoglobin values were 0.29 ± 0.23 g/L in the HELLP syndrome group, 1.01 ± 0.52 g/L in the preeclampsia group, and 1.16 ± 0.37 g/L in the control group. The mean haptoglobin result was lower in the HELLP syndrome group compared to the preeclampsia and control groups (p < 0.001). While the differences between HELLP syndrome and the control and preeclampsia groups were statistically significant, no significant difference was determined between the preeclampsia and control groups. There was a significant positive correlation between haptoglobin value with the week of delivery, umbilical cord pH value, and the first and fifth-minute Apgar scores (p < 0.05). It was concluded that haptoglobin values could be used together with other biochemical parameters to diagnose HELLP syndrome and predict newborn outcomes.

Examining hepatoprotective effects of astaxanthin against methotrexate-induced hepatotoxicity in rats through modulation of Nrf2/HO-1 pathway genes.

Methotrexate (MTX), as a folic acid antagonist, is an effective drug in treating a wide range of malignancies and autoimmune diseases. However, the clinical use of MTX has been limited due to its side effects, the most common of which is hepatotoxicity. In this study, rats were randomly divided into six groups: three treatment groups received methotrexate and different doses of astaxanthin (AX) for 14days. At the end of the study, blood samples were collected to determine serum levels of ALT, AST, ALP, and LDH. Also, liver tissues were isolated to evaluate antioxidant enzymes and markers of oxidative stress, histopathological damage, and expression of NF-E2-related transcription factor (Nrf2) and Heme oxygenase-1 (HO-1) genes. The results showed that administration of MTX significantly increased the levels of ALT, AST, ALP, and LDH in the blood, markers of oxidative stress, and histopathological damage in liver tissue and significantly reduced the levels of antioxidant enzymes and the expression of Nrf2 and HO-1 genes. On the other hand, treatment with AX decreased blood levels of ALT, AST, ALP, and LDH and oxidative stress markers and remarkably raises the activity of antioxidant enzymes and expression of Nrf2 and HO-1 genes in liver tissue. In addition, histopathological lesions were improved with AX administration. The findings of this study indicated that AX may be useful for the prevention of MTX-induced hepatotoxicity by improving oxidative and inflammatory changes.

Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes

BackgroundThe development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels of cytokines and clinical features and investigate their impact on the prognosis of patients with DLBCL. MethodsWe conducted a retrospective study of 77 patients with newly diagnosed DLBCL to explore the relationships between different cytokines, adverse clinical features, and poor outcomes. The Mann–Whitney U test was used to compare the cytokine profiles between patients with DLBCL and healthy controls. The Kaplan–Meier method was used to analyze the probability of survival, and the log-rank tests were used to evaluate the differences between survival curves. The Cox proportional hazards regression model was used to performed univariate and multivariate analyses to evaluate prognostic variables for survival analyze. ResultsSerum levels of interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, and IFN-γ were significantly elevated in patients with untreated DLBCL. Serum levels of IL-6 and IL-10 were significantly higher in patients with an International Prognostic Index (IPI) of 3–5, bone marrow involvement, serum levels of LDH ≥ 250 U/L, and β2-microglobulin (β2-MG) levels ≥ 2.3 mg/L. Patients with B symptoms only had higher serum IL-10 levels, whereas patients with a partial response or no response to treatment had significantly elevated serum levels of IL-6 as well as IL-10. Significant positive correlations were observed between the levels of IL-6 and IL-10 with those of β2-MG and LDH. Patients with levels of IL-6 ≥ 4.5 or IL-10 ≥ 5.0 pg/mL, as well as combined elevated IL-6 and IL-10 levels, exhibited shorter progression-free survival and overall survival. Additionally, univariate and multivariate analyses revealed that serum levels of IL-6 ≥ 4.5 pg/mL and IL-10 ≥ 5.0 pg/mL and IPI 3–5 were independent prognostic factors for relapse and survival in patients with DLBCL. ConclusionsPre-treatment serum IL-6 and IL-10 levels in patients with newly diagnosed DLBCL might be powerful markers for determining treatment response and predicting the prognosis of DLBCL.

Bradykinin receptor participates in doxorubicin-induced cardiotoxicity by modulating iNOS signal pathway.

Doxorubicin (DOX), an effective and broad-spectrum anthracycline antibiotic, is widely used in the treatment of numerous malignancies. However, dose-dependent cardiotoxicity limits the clinical application of DOX, and the molecular mechanisms are still unknown. In this study, we used the BK receptor B1/B2 double-knockout (B1B2 -/- ) mice to observe the role of BK receptor in cardiotoxicity induced by DOX and the underlying mechanisms. DOX induced myocardial injury with increased serum levels of AST, CK, and LDH, upregulated tissue expression of bradykinin B1/B2 receptor, FABP4 and iNOS, and downregulated expression of eNOS. However, these altered releases of myocardial enzyme and the expression level of iNOS were significantly prevented in the B1B2-/- mice. We concluded that the activation of both B1 and B2 receptors of BK were involved in the DOX-induced acute myocardial injury, possibly mediated through iNOS signaling pathways.

Potential combined effect of Spirulina platensis and Momordica charantia fruits on attenuation of isoproterenol-induced myocardial infarction in rats: identification and prediction its mechanism

We established in vivo models of isoproterenol-induced myocardial infarction (MI) to determine the cardioprotective effect of Spirulina platensis (Spi), Momordica charantia fruit (MC) and their combination. MI was induced in six groups of Male Wistar albino with isoproterenol, and cardioprotection was evaluated by measuring SGOT, SGPT, LDH, CK, CK-MB with commercially available test kits and analyzing histopathology. Online PASS was used to predict the mechanism of action of a marker compound in Spi and MC. Rat serum levels of LDH, SGOT, CK-MB, and CK were significantly reduced by the Spi and MC combination extract (P &amp;lt; 0.05). The combination extract at a dose of 50:50 mg/kg body weight preserve the integrity of the myocardial cell membrane. Identified compounds by LC-MS/MS in the ethanol extract of Momordica charantia are (3β,16α-Dihydroxy-lanosta-8,24-dien-21-oic acid), Eclalbasaponin II, Epianhydrobelachinal, Epianhydrobelachinal, Paeonenolide F, Ziyu glycoside II. Identified compounds by LC-MS/MS in Spirulina platensis extract are d-Lirioferine, Lycopodine, Yuanhunine, Candidate Mass C18H26N2O5 and Candidate Mass C36H38N4O5. In PASS analysis, Phycocyanobilin’s cardioprotective mechanism of action is predicted to be kinase inhibitor, cytoprotectant, and platelet aggregation inhibitor, with Probable activities (Pa) of 0.06, 0.53, and 0.443, respectively. The Pa values for cholesterol antagonist, proliferative disease treatment, nitric oxide scavenger, and anti-inflammatory agents in Momordicoside A are respectively 0.841, 0.666, 0.59, and 0.55. These findings suggest that the cardioprotective activity of the combination of Spi and MC extracts at a dose of 50 mg/kg was synergistic.

Loss of LEAP-2 alleviates obesity-induced myocardial injury by regulating macrophage polarization

BackgroundObesity is a serious public health issue worldwide, which is a risk factor of cardiovascular disorders. Obesity has been shown to be associated with subclinical myocardial injury, increasing the risk of heart failure. Our study aims to explore novel mechanisms underlying obesity-induced myocardial injury. MethodsMice were fed a high-fat diet (HFD) to establish a mouse model of obesity, and serum levels of TG, TCH, LDL, CK-MB, LDH, cTnI and BNP were examined. Inflammatory response was evaluated by determining the expression and secretion of proinflammatory cytokines IL-1β and TNF-α. Macrophage infiltration in the heart was examined by IHC staining, and H&E staining was applied to evaluate myocardial injury. Primary peritoneal macrophages were isolated from mice and treated with palmitic acid (PA). Macrophage polarization was evaluated by determine the expression of CCL2, iNOS, CD206 and arginase I via Western blot, RT-qPCR, and flow cytometry. Co-IP assays were performed to examine the interaction between LEAP-2, GHSR and ghrelin. ResultsHyperlipidemia, increased proinflammatory cytokines and myocardial injury were observed in mice with obesity, and silencing of LEAP-2 ameliorated HFD-induced hyperlipidemia, inflammation, and myocardial injury. Moreover, HFD-induced macrophage infiltration and M1 polarization were reversed by LEAP-2 knockdown in mice. Furthermore, silencing of LEAP-2 suppressed PA-induced M1 polarization but enhanced M2 polarization in vitro. LEAP-2 interacted with GHSR in macrophages, and knockdown of LEAP-2 promoted the interaction of GHSR and ghrelin. Overexpression of ghrelin enhanced LEAP-1 silencing-mediated suppression of inflammatory response and upregulation of M2 polarization in PA-induced macrophages. ConclusionKnockdown of LEAP-2 ameliorates obesity-induced myocardial injury via promoting M2 polarization.

Irbesartan has a curative effect on lipopolysaccharide-induced cardiotoxicity by antioxidant and antiapoptotic pathways

Introduction and ObjectiveLipopolysaccharide (LPS) has been associated with myocardial inflammation, oxidative stress, apoptosis, and cardiac dysfunction, as well as death by causing sepsis. In this study, we investigated the effect of irbesartan (IRB), an angiotensin receptor antagonist, on cardiotoxicity caused by LPS. MethodsThe experiment involved 24 Wistar albino rats divided into three groups of eight: control, LPS (5 mg/kg), and LPS (5 mg/kg)+IRB (3 mg/kg). Parameters including total oxidative status, total antioxidant status, oxidative stress index, and ischemia-modified albumin were measured to assess oxidative stress in heart tissues and serum. Serum CK, CK-MB, and LDH levels were measured spectrophotometrically. RT-qPCR was used to detect the mRNA expression levels of Bcl-2, BAX, p53, caspase-3, and sirtuin 1. Tissues taken from the heart and aorta were examined by immunohistochemistry and histopathology. ResultsWhile there was an increase in the parameters indicating heart damage, oxidative stress, and apoptosis in the group given LPS, there was an improvement in all parameters and heart damage in the group treated with IRB. ConclusionAs a result of our study, we determined that IRB has an ameliorating effect on myocardial damage caused by oxidative stress and apoptosis developed by the LPS-induced sepsis model.

Fructose supplementation shifts rat brain metabolism in experimental migraine

AimsWe have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. Main methodsMale Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). Key findingsThere were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SignificanceWe provide novel evidence linking nutrition and metabolism with migraine.

Vitamin D3 supplementation could ameliorate the inflammatory and redox status in the muscular phase of trichinellosis.

Nutritional supplements, particularly vitamin D, have been widely used worldwide in the treatment of various infections, including parasites. This study aimed to evaluate the potential effects of vitamin D3 supplementation on the muscular phase of trichinellosis in experimental animals. Mice were divided as follows: (group I): infected untreated, (group IIa) infected and treated with vitamin D3 for 12 doses beginning 2weeks before infection and continuing after infection, (group IIb) infected and treated with vitamin D3 for 8 doses beginning on the same day of infection, (group III) normal control, (group IVa) which received vitamin D3 for 12 doses and (group IVb) which received vitamin D3 for 8 doses. Mice were sacrificed 35days after infection and total muscle larval count, and histopathological examination of muscle samples with immunohistochemical staining of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) were performed. Muscle relative cathelicidin mRNA expression was assessed, as well as serum levels of muscle enzymes CK and LDH, interleukin-4 (IL-4), IL-10, IL-17 and interferon-gamma (INF-γ). Vitamin D3 supplementation significantly reduced muscle larval count, inflammatory cellular infiltration, COX2 and iNOS expression. Furthermore, it increased cathelicidin gene expression, decreased serum levels of CK and LDH and affected serum cytokine levels, increasing serum IL-4 and IL10 levels while decreasing serum INF γ and IL-17. In conclusion, vitamin D3 supplementation has favorable outcomes on the muscle phase of trichinellosis, including anti-inflammatory, antioxidant, and immunomodulatory effects.

Association of blood donor characteristics with in vitro platelet storage properties

Background and objectiveThe study was planned to determine the association of blood donor characteristics with in vitro quality of platelets. Material and methodsIn the prospective observational study, a total of 85 male whole blood donors in the age group of 18–30 and 45–65 years were enrolled using purposive sampling method. Serum total cholesterol, glycosylated hemoglobin (HbA1c), and LDH levels were performed on donor pre-donation sample. Buffy coat platelet concentrates were prepared from 450 mL quadruple blood bags. Samples from platelets were taken on day one and five of storage and biochemical properties were observed. ResultsMedian MPV was higher in platelets from older blood donors on day five (9.8 vs 9.4, p = 0.037). Median LDH levels were also higher in platelets on day one and five from older donors (Day one: 204.5 vs 147, p = <0.000; day five: 278 vs 224, p = 0.001 respectively). Platelets from donors with high HbA1c levels had lower median pH (Day one: 7.31 vs 7.37, p = 0.024) and higher median glucose levels on day one of storage (Day one: 358 vs 311, p = 0.001). Higher median lactate levels throughout the storage period were also seen in platelets from donors with higher HbA1c levels (Day one: 7 vs 5.7, p = 0.037; Day five: 16 vs 12.2, p = 0.032). Glucose consumption (108 vs 66, p = 0.025) and lactate production (9 vs 6.4, p = 0.019) was higher in platelets from donors with higher HbA1c levels. ConclusionIn vitro platelet storage properties are affected by blood donor characteristics.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1), endemic in some areas of the world, such as Brazil. Between 3% and 5% of HTLV-1-infected individuals develop ATL after a long latency. The clinical features are heterogeneous and classified into acute, lymphoma, chronic and smoldering types. Acute and lymphoma types are defined as aggressive whereas the others as indolent ATL. On April 2017, the T-cell Brazil project was launched. Methods: Ambispective observational study design collected 90 ATL patients from 606 registered cases in the T-Cell Brazil Project. Its main goal is to describe demographic and clinical features, analyze the overall and progression-free survival (OS and PFS), and try to identify factors that could influence them. REDcap Platform has been used to collect and store data, and the IBM-SPSS version 24 for statistical analysis. Results: The median age was 50 years (23–88), 59% female; 50% was lymphoma subtype, followed by 33% acute (both aggressive), 12% chronic and 5% smoldering (indolent); 87% had advanced stage disease (III-IV, Ann Arbor), 57% had B symptoms and 11% had Central Nervous System involved. Both indolent and aggressive had elevated serum LDH levels. 25% received chemotherapy plus immunotherapy, whilst 46% took chemotherapy alone with anthracycline-based regimens (46% CHOEP; 33% CHOP; 21% others). The best response (complete plus partial) after 1st line of treatment reached 50%; 31% had no response or progression; 13% was undetermined due early death; 5% were on treatment, and 1% had stable disease (without treatment). Median follow-up was ten months (0–78) and 18 months for 35% of alive cases. OS for 24 months was 34% (95% CI: 24%–44%), whereas 24-month PFS was 20% (95% CI: 12%–28%). Indolent presented better OS and PFS when compared with Aggressive; 86% versus 33%, P = 0.001 for OS and 45% versus 12%, P = 0.002 for PFS. Public medical care had worst OS and PFS than private (P = 0.14 and P = 0.05). The multivariate Cox Regression for OS resulted hypoalbuminemia - albumin <3.5 g/dL (HR 2.13 CI95% 1.10–4.12, P = 0.024) plus LDH twice the normal value (HR 2.49 CI95% 1.17–5.32, P = 0.018) as predictors. And for PFS were male (HR 1.83 CI95% 1.03–3.24, P = 0.037), ECOG > 1 (HR 2.01 CI95% 1.10–3.70, P = 0.023) and hypoalbuminemia (HR 3.35 CI95% 1.82–6.17, P < 0.0001). The research was funded by: Educational Support by Takeda Keyword: aggressive T-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

The plant-derived alkaloid aloperine prevents ischemia/reperfusion injury-induced sudden cardiac death.

Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti-inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury-associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion-provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage-gated potassium (Kv) channels were performed using two-electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK-MB, α-HBDH, and cTnI post-I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT-3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT-3 (with Ag490) abolished aloperine-induced anti-arrhythmic effects and ERK1/2 and STAT-3 phosphorylation. Interestingly, while aloperine (100 μM) had no effect on cloned Kv4.3 activity, aloperine (1 μM and up) negative-shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti-arrhythmic effects against myocardial ischemia and reperfusion injury-induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT-3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.

Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

The Obesity Controversy: Does It Impact Treatment Response in Diffuse Large B-Cell Lymphoma?

Background: We aimed to investigate the association of body mass index (BMI) with treatment response in patients with DLBCL. Material and Methods: Seventy-nine DLBCL subjects were included in this study. Data about patient age, sex, serum LDH level, presence of B symptoms, IPI score, ECOG performance score, disease stage, extranodal involvement, and BMI values at diagnosis were retrieved by retrospective patient record review. Patients were staged according to Ann Arbor classification using CT and/or PET/CT findings, and the presence of B symptoms. Body mass index was calculated by dividing weight in kilograms by height in meters squared (kg/m2). Patients were divided into groups according to their BMI as underweight (BMI≤ 18.5 kg/m2), normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI≥ 30 kg/m2), as defined by the World Health Organization. Results: Patients were divided into four groups according to their BMIs, but because there was only one patient in the underweight group, comparisons were performed between normal-weight, overweight, and obese patients. There was no statistically significant difference between these groups in terms of age, sex, serum LDH level, disease stage, presence of B symptoms, extranodal involvement, ECOG performance score, IPI score and treatment response (p= 0.070, 0.704, 0.325, 0.464, 0.254, 0.152, 0.658, 0.620, and 0.947, respectively). Conclusion: In our study, we showed that BMI has no significant impact on treatment response in patients with DLBCL.

Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes.

Hydroxysafflor yellow A (HSYA) is the principal bioactive compound isolated from the plant Carthamus tinctorius L. and has been reported to exert neuroprotective effects against various neurological diseases, including traumatic brain injury (TBI). However, the specific molecular and cellular mechanisms underlying HSYA-mediated neuroprotection against TBI are unclear. This study explored the effects of HSYA on autophagy and the NLRP3 inflammasome in mice with TBI and the related mechanisms. Mice were subjected to TBI and treated with or without HSYA. Neurological severity scoring, LDH assays and apoptosis detection were first performed to assess the effects of HSYA in mice with TBI. RNA-seq was then conducted to explore the mechanisms that contributed to HSYA-mediated neuroprotection. ELISA, western blotting, and immunofluorescence were performed to further investigate the mechanisms of neuroinflammation and autophagy. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was applied to determine the connection between autophagy and the NLRP3 inflammasome. HSYA significantly decreased the neurological severity score, serum LDH levels and apoptosis in mice with TBI. A total of 921 differentially expressed genes were identified in the cortices of HSYA-treated mice with TBI and were significantly enriched in the inflammatory response and autophagy. Furthermore, HSYA treatment markedly reduced inflammatory cytokine levels and astrocyte activation. Importantly, HSYA suppressed neuronal NLRP3 inflammasome activation, as indicated by decreased levels of NLRP3, ASC and cleaved caspase-1 and a reduced NLRP3+ neuron number. It increased autophagy and ameliorated autophagic flux dysfunction, as evidenced by increased LC3 II/LC3 I levels and decreased P62 levels. The effects of HSYA on the NLRP3 inflammasome were abolished by 3-MA. Mechanistically, HSYA may enhance autophagy through AMPK/mTOR signalling. HSYA enhanced neuronal autophagy by triggering the AMPK/mTOR signalling pathway, leading to inhibition of the NLRP3 inflammasome to improve neurological recovery after TBI.

Phenotypic Evaluation of TREX1 Null Mice as a Model for Lupus-Like Autoimmune Disease

Abstract TREX1 (DNase III) is the major mammalian 3’-5’ DNA exonuclease and thought to play a major role in cell death and genomic DNA degradation. Dysfunction of Trex1 has been suggested to activate immune response by self DNA, as TREX1 null mice develop inflammatory myocarditis similar to autoimmune cardiomyopathy and produce type 1 IFN. TREX1 D18N causes a monogenic cutaneous form of lupus called familial chilblain lupus and exhibits dysfunctioned dsDNA-degrading activity, providing a link between dsDNA degradation and nucleic acid-mediated autoimmune diseases. Using CRISPR-Cas9, we generated a Trex1 −/−mouse by knocking out exon 2 and performed comprehensive phenotypic analyses to evaluate the loss of function of TREX1 and its potential application in SLE research. Both female and male TREX1 null mice showed dramatically increased post-wean morbidity and significantly increased serum ALT, AST and LDH levels, compared to wildtype and heterozygotes from 6 to 24 weeks of age, indicating liver and heart injuries. Pathohistological analysis showed inflammatory immune cell infiltration in liver, heart, spleen, kidney, lung and skin among TREX1 null mice. Serum anti-dsDNA antibody levels were significantly increased and remained high from 7 to 25 weeks of age, consistent with Trex1’s being the major DNA exonuclease. Urine protein to creatinine ratio was dramatically increased at 28 weeks of age among TREX1 null mice. In conclusion, the Trex1 −/−mice we generated in this work showed lupus-like inflammatory autoimmune responses in multiple organs, providing an urgently needed tool to study Trex1-mediated autoimmunity and to evaluate potential therapeutic treatments for lupus.

Clinical significance of microscopic polyangiitis with interstitial lung disease and bronchiectasis: probability of preexisting comorbidities

Background The association between pulmonary involvement and microscopic polyangiitis (MPA) has been increasingly recognized in recent years. Whether interstitial lung disease (ILD) and bronchiectasis (BE) are disease manifestations of MPA, preexisting comorbidities or important complications remains unclear. The purpose of this study was to determine the clinical characteristics and prognosis of MPA with pulmonary involvement to further guide clinical management. Methods The data for 97 patients with a definitive diagnosis of MPA were retrospectively reviewed. The MPA diagnosis was based on the 2012 revised Chapel Hill Consensus Conference (CHCC) criteria. The baseline clinical information and laboratory parameters were collected and analysed at each patient’s initial diagnosis. Results Forty-seven out of the 97 (48.5%) patients who were diagnosed with MPA presented with pulmonary involvement, including 37 patients with ILD, 12 patients with BE and two patients with diffuse alveolar haemorrhage (DAH). ILD and BE antedated MPA in 56.76% and 75.00% of the patients, respectively. Compared with that in the MPA-BE group, the serum LDH level (222.86 ± 68.19 vs. 171.58 ± 31.43, p = .016) in the MPA-ILD group was significantly higher. In the multivariate Cox analysis, elevated serum creatinine (HR 4.08, confidence interval (CI) 1.38–12.05, p = .011) was an independent risk factor for shorter survival in MPA patients with pulmonary involvement, and treatment with glucocorticoid pulse cyclophosphamide therapy (HR 0.095, 95% CI 0.019–0.47, p = .004) was independently associated with prolonged survival. Among the patients in the MPA-ILD group, acute exacerbations of ILD (HR 4.55 CI 1.16–17.86, p = .029) and elevated serum creatinine (HR 4.95, CI 1.39–17.54, p = .014) were independently associated with a poor prognosis, and treatment with glucocorticoids (HR 0.057, 95% CI 0.012–0.28, p < .001) was independently associated with significant prolongation of survival. Conclusions Patients with MPA have a high prevalence of pulmonary involvement, and ILD is the most common subtype of MPA. ILD and BE can be considered preexisting comorbidities of MPA. Elevated serum creatinine was associated with shorter survival. However, remission induction regimens with glucocorticoids and/or immunosuppressants may improve this outcome.

Blocking RIPK2 Function Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating the AKT and NF-κB Pathways

ABSTRACT Objective Inflammation and oxidation brought on by myocardial ischemia-reperfusion (MI/R) injury lead to cardiomyocyte apoptosis and necrosis. The receptor interacting serine/threonine kinase 2 (RIPK2) plays significant roles in oxidative stress and excessive inflammation. The purpose of this research is to examine the roles of RIPK2 in MI/R injury. Methods The in vivo animal model was constructed by acute coronary I/R, and the in vitro cell model was established by oxygen and glucose deprivation/reperfusion (OGD/R)-stimulated cardiomyocyte injury. RIPK2 expression was examined using qRT-PCR and Western blot. CCK-8 was proposed as a method for detecting cell proliferation. ELISA was utilized to measure inflammatory cytokines (TNF-α, IL-6, and IL-1β) and myocardial injury indicators (CK-MB, Mb, cTnI, and LDH). The levels of MDA and ROS were determined by the kit and fluorescent probe. H&E was conducted to assess MI/R injury after silencing of RIPK2. Results In MI/R rats and OGD/R-treated H9C2 cardiomyocytes, RIPK2 was overexpressed at both the mRNA and protein levels. RIPK2 inhibition promoted cell proliferation while inhibiting apoptosis, as evidenced by decreased TUNEL-positive cells and cleaved caspase-3. RIPK2 inhibition reduced MDA and ROS levels, as well as the contents of inflammatory factors. RIPK2 silencing reduced CK-MB, Mb, cTnI, and LDH levels in rat serum and alleviated MI/R injury. Furthermore, RIPK2 inhibition increased p-AKT while decreasing NF-B p-p65 expression. Conclusion Silencing of RIPK2 reduced apoptosis, proinflammatory factors, and oxidative stress in MI/R by activating AKT and suppressing NF-κB signals, suggesting a potential therapeutic strategy for MI/R injury.

CORRELATION OF SERUM FERRITIN AND LDH ON CRITICALLY ILL PATIENTS OF COVID-19 DISEASE DURING 1ST AND 2ND WAVE OF COVID 19 PANDEMIC IN TERTIARY CARE HOSPITAL, INDIA

In both the earlier waves of COVID-19 variants, severe and fatal respiratory disease like acute respiratory distress syndrome (ARDS) became more fatal in population with comorbid conditions. Therefore, early identication of severe COVID-19 is very important for individual's precise management, including antiviral, oxygen support and intensive care unit (ICU) management. First case of COVID-19 got reported in the medical record of India on 30th January 2020 in a student who had returned from Wuhan, China. In 2020 and 2021 it was found that individuals with increased serum ferritin and LDH level landed up with severe and very severe COVID-19 if not treated timely and correctly. So correlation between S. Ferritin and LDH in 1st and 2nd wave was required to evaluate the condition of patients who remained admitted in critical care unit with or without comorbid conditions. This is hospital based cross- sectional observational study on 50-50 (total-100) critically ill patients admitted during 2020 and 2021 respectively. We found that In 2020 during the 1st wave serum LDH and serum Ferritin levels were signicantly high with the mean value of 481.65 U/L and 532.56 ng/ml respectively and in 2021 during 2nd wave serum LDH and serum Ferritin levels were again signicantly high with the mean value of 488.43 U/L and 667.27 ng/ml respectively. In 2020 patients with comorbid conditions showed S. LDH and Ferritin mean value of 543.47 U/L and 582.63 ng/ml respectively and in 2021 during 2nd wave it showed S.LDH and Ferritin levels mean value of 672.72 U/L and 727.38 ng/ml respectively. Both inammatory markers were signicantly more increased in the critically ill patients who presented with co-morbidities. This study will provide improved condence to health workers working in remote areas and COVID-19 hospitals in predicting transfer of COVID-19 patients to tertiary care hospitals for critical care management at the earliest.

Development of an Algorithm to Differentiate Uterine Sarcoma from Fibroids Using MRI and LDH Levels

This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined by four evaluators with different imaging experience and abilities, using a test set of 61 cases, including 14 cases of uterine sarcoma. From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroids, we found that all sarcomas were included in the group with a high T2WI and either a high T1WI, an unclear margin, or high LDH values. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings for T2WI, T1WI, margins, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators and the sensitivity of sarcoma detection ranged from 71% to 93%. We established an algorithm to distinguish uterine sarcoma if tumors in the myometrium with low T2WI and DWI are present.