LDH Concentrations Research Articles

Role of molybdenum in ameliorating busulfan-induced infertility in female mice

BackgroundMolybdenum (Mo) plays a crucial role in regulating normal physiological function. However, its potential effect on female infertility has received little attention. MethodsIn this study, we explored the potential molecular mechanisms of Mo’s action on mouse ovaries and oocytes by establishing a busulfan-induced infertility model. Adult female Kunming mice were randomly divided into three groups: control, +busulfan, and +busulfan+Mo. After 30 days of busulfan treatment [Myleran, 20 mg/kg body weight ip], mice in the busulfan+Mo group were provided with 7.5 mg/L Mo per day in drinking water for an additional 42 days. On day 72, we examined the morphology of the oocytes and ovarian tissue after H&E staining, measured the concentrations of serum hormones by ELISA, and detected Bax, Bcl-2, caspase-3 and caspase-9 by immunohistochemical staining and western immunoblotting. We also assessed the oxidative stress in cells by measuring the activity of the antioxidant enzyme, SOD, the concentrations of MDA and LDH, and the percentage of apoptotic cells using kits. The number of litters born was counted after mating with male mice, and the organ coefficients were calculated after weighing on an analytic balance. ResultsResults showed that Mo treatment restored female reproductive hormone levels to near normal. Mo also significantly inhibited the mitochondrial stress-induced expression of apoptotic proteins. ConclusionOur findings demonstrate that Mo treatment at a dose of 7.5 mg/L can ameliorate busulfan-induced infertility in female mice. These data may provide a reference for the development of treatments for female infertility.

To investigate the relation between LDH and CRP levels and mortality of COVID-19 (SARS-CoV-2) patients admitted in SURGERY ICU at Shariati Hospital from 19 February 2020 till 19 February 2021

Background: The aim of this study is to investigate the relationship between LDH and CRP levels and the mortality of COVID-19 (SARS-CoV-2) patients admitted to the SURGERY ICU at Shariati Hospital from 19 February 2020 to 19 February 2021. Methods: Our study is a cross-sectional descriptive study. A total of 81 patients were enrolled in this study. We examined lab reports, including CBC parameters (WBC, neutrophil count, neutrophil percentage), other inflammatory markers ESR and CRP, and also studied the medical records of cases to collect details about age, gender, length of stay in SURGERY ICU, BMI, fever, survival status, comorbidity, intubation, and NIV. These patients were referred to Shariati Hospital, Tehran, from 19 February 2020 to 19 February 2021, regarding the relationship between LDH and CRP levels and the mortality of COVID-19 (SARS-CoV-2) patients admitted to the SURGERY ICU. The data obtained was analyzed using SPSS software, and a significance value of < 0.05 was considered. Results: In this study, the data of 81 patients were considered. The data were obtained from the medical records of Shariati Hospital, Tehran. We used 11 variables to compare data from different patients that were recorded in the registry and system of medical records in Shariati Hospital, Tehran. The study population included 81 patients, of which 41 were female and 40 were male, ranging in age from 25 to 89. In total, 80.2% had mild disease versus 18.5% who had severe disease. Sixty-five patients survived, and 16 were admitted to the SURGERY ICU with endotracheal intubation and later died. The length of stay in the SURGERY ICU ranged from 1 to 25 days. Out of 81 patients, 52 (62.4%) had comorbidity, and 29 (35.8%) did not have comorbidity. Twelve patients (14.8%) received NIV, and 69 patients (85.2%) did not receive NIV. Most of the patients did not have a fever. The minimum and maximum levels of CRP were 4 and 416, respectively, and for LDH were 9 and 2401, respectively. The prognostic factors for the severity of COVID-19 infection identified in this study (CRP and LDH) help predict the course of the disease at an early stage. Elevated concentrations of CRP and LDH at admission were found to be associated with a higher risk for COVID-19 severity as they were significant (p-value =0.049 and 0.048, respectively). Conclusions: This study’s laboratory investigation showed that the SURGERY ICU patients had significantly higher values of inflammatory markers CRP and LDH than the non-SURGERY ICU patients. LDH and CRP were superior and effective biomarkers in predicting the severity of COVID-19.

Changes in Physical Fitness, Muscle Damage and Cognitive Function in Elite Rugby Players over a Season.

This study proposes to monitor the physical, immune and cognitive responses and adaptations of elite rugby players throughout the season based on the loads performed. Anthropometric measurements, physical fitness tests (e.g., muscle strength and power, linear and change-of-direction speed, cardiorespiratory fitness) and analyses of serum concentrations of markers of muscle damage (creatine kinase [CK] and lactate dehydrogenase [LDH]) and brain-derived neurotrophic factor (BDNF) were carried out over a sporting season (24 weeks) for 17 elite rugby players (10 forwards and 7 backs) aged 18.91 ± 0.76 years. The physical fitness test results show improvements in the performance of both forwards and backs over the season (p < 0.05), with an advantage for backs compared with forwards in most tests (p < 0.05). Muscle damage markers decreased at the end of the season compared with the baseline levels for forwards (p < 0.05). CK levels were unchanged for the backs, but there were increased LDH concentrations at the end of the season compared with baseline (p < 0.05). Serum BDNF levels decreased for the total group between the second and third sampling (p < 0.05). The muscular and physical capacities of rugby players differ according to their playing position. Immune responses and adaptations, as well as BDNF levels, vary throughout the season and depend on the physical load performed.

Intramammary administration of lipopolysaccharides at parturition does not affect the transfer of passive immunity in goat kids

This study evaluated the effect of feeding colostrum obtained from an intramammary administration (IA) of LPS from Escherichia coli (O55:B5) to dairy goats at parturition, on goat kid performance, biochemical parameters (i.e., calcium, lactate dehydrogenase, glucose, total proteins, albumin, and urea) and immune status (i.e., IgG and IgM) during the first month of life. At birth, goat kids were weighted (d 0) and immediately allocated into either the LPS group (n = 15) or the control (CON) group (n = 21) based on the experimental group of the dam. At parturition, 20 multiparous dairy goats were allocated in 1 of the 2 experimental groups (LPS vs. CON). The LPS group received an IA of saline solution (2 mL) containing 50 µg of LPS in each half udder whereas goats in the CON group received an IA of saline solution (2 mL) without LPS. Goat kids were bottle-fed dam colostrum equivalent to 10% of the birth BW divided in 2 meals (i.e., at 3 and 12 h relative to birth), and then fed twice daily with milk replacer ad libitum. Individual milk intake (MI) and BW were recorded on d 7, 15, 21 and 30 of life. Blood samples were collected on d 0, 1, 2, 4, 7, 15, 21 and 30 after birth. Data were analyzed using the MIXED procedure of SAS (9.4; SAS Institute Inc.). The model included IA, time (T), and their interaction (IA × T) as fixed effects, and sex and litter size as random effects. Both groups showed similar MI, except on d 7 relative to birth as the LPS group showed higher MI than the CON group (910.5 ± 69.77 and 683.9 ± 59.64 mL, respectively; mean ± SEM). No differences in BW or rectal temperature were observed between groups, neither in plasma IgG nor IgM concentrations. Despite the IA did not affect calcium, glucose, LDH, total protein, and albumin concentrations an interaction between the IA and T was observed for urea concentration, showing the LPS group higher urea concentrations than the CON group on d 0 (20.1 ± 1.34 and 20.0 ± 1.25 mg/dL, respectively). In conclusion, feeding colostrum from goats that received an IA of LPS at parturition does not affect goat kid performance, plasma immunoglobulin concentrations and serum metabolites during the first month of life.

Outcomes of oxytocin treatment on intestinal ischemia-reperfusion injury in rats

Ischemia-reperfusion injury is a clinical condition that poses life-threatening risks and can be caused by diseases or operations such as trauma, shock, and gastric dilatation volvulus. The objective of this study was to examine the effect of oxytocin on intestinal damage in rats induced by experimental ischemia-reperfusion injury. Three groups of Wistar albino rats were established: a control group (CTR, n=6), an intestinal ischemia-reperfusion group (I-IR, n=6), and an intestinal ischemia-reperfusion with oxytocin group (I-IR+Oxt, n=6). The I-IR+Oxt group received an intraperitoneal injection of 1 mg/kg oxytocin 30 minutes before anesthesia. In the I-IR and I-IR+Oxt groups, the superior mesenteric artery was ligated for 1 hour to induce ischemia-reperfusion injury, followed by one hour of reperfusion by opening the ligatures. At the end of the reperfusion period, the rats were euthanized, and blood and intestinal tissue samples were collected. From the blood samples, ALT, ALP, AST, LDH, BUN, creatinine, IL-1β, and TNF-α concentrations were evaluated. Tissue samples were analyzed for IL-1β, TNF-α, and MDA activity. Serum and tissue IL-1β and TNF-α concentrations were higher in both the I-IR and I-IR+Oxt groups compared to the CTR group. However, these levels were found to be lower in the I-IR+Oxt group compared to the I-IR group. The histopathological analysis showed that the I-IR+Oxt group had better epithelial regeneration and less inflammatory cell infiltration compared to the I-I/R group. In conclusion, oxytocin inhibited the release of IL-1β and TNF-α and the harmful effect of I/R on intestinal cells.

A Comparative Analysis of Acute Physiological and Perceptual Responses in Whole-Body and Ergometer-Based High-Intensity Interval Training Protocols.

The primary aim of the present investigation was to compare the acute physiological and perceptual responses between two modes of interval training using a randomized crossover design. More specifically, eleven young adult participants (23 ± 4 years, 77 ± 13 kg, 178 ± 7 cm) performed two protocols: one composed of whole-body calisthenics exercises and another on a cycle ergometer. Both protocols encompassed eight 20 s bouts at intensities equivalent to all-out (HIIT-WB) and 170% of the maximal power output (HIIT-C), respectively, interspersed with 10 s of passive rest. The peak and average heart rate, the rating of perceived effort, and blood lactate, creatine kinase, and lactate dehydrogenase concentrations were measured. Aside from blood lactate (HIIT-WB = 9.4 ± 1.8 mmo/L; HIIT-C = 12.5 ± 2.5 mmol/L, p < 0.05) and the rating of perceived exertion (HIIT-WB = 8.8 ± 0.9; HIIT-C = 9.6 ± 0.5, p < 0.05), physiological responses did not significantly differ between protocols (all p > 0.05), with high average heart rate values (HIIT-WB = 86 ± 6% HRmax; HIIT-C = 87 ± 4% HRmax) and a low magnitude of muscle damage, as inferred by CK and LDH concentrations (HIIT-WB = 205.9 ± 56.3 and 203.5 ± 72.4 U/L; HIIT-C = 234.5 ± 77.1 and 155.1 ± 65.3 U/L), respectively. It can be concluded that both protocols elicit vigorous heart rate responses and a low magnitude of muscle damage and, therefore, appear as viable alternatives to improve aerobic fitness. The inclusion of a whole-body HIIT protocol may be an interesting alternative for training prescription in relation to more common interval training protocols.

Effect of a biomimetic pathogen adsorbing device on inflammatory biomarkers in COVID-19 patients.

The Seraph 100 Microbind Affinity blood filter eliminate bacteria, viruses, fungi and toxins from blood stream. This is a prospective multicenter observational biomarker trial in PCR-positive SARS-CoV-2 patients with acute respiratory failure. Biomarkers were sequentially tested at three time points. Forty-two patients with SARS-CoV-2 detected by PCR with acute respiratory failure were included. When receiving hemoperfusion treatment, 27 (64%) patients were on mechanical ventilation, 41 (98%) patients were treated in the ICU. The 3-month survival was 52%. After one hemoperfusion treatment cycle, D-dimer (p = 0.014), hemoglobin (p = 0.003) and LDH (p = 0.001) concentrations were significantly reduced 4 days after treatment. From the multiplex assay IL-1b, CXCL8/ IL-8, IL-10, IL-13, IL-15, CCL11/Eotaxin, G-CSF, and CXCL10/IP-10 were significantly reduced 1 h after treatment, however not 4 days later. Hemoperfusion with Seraph 100 Microbind Affinity Filter in patients with severe COVID-19 can transiently reduce several inflammatory biomarkers in the blood.

Association between CTX-1 and Fibulin-1 Serum Levels with Pathogenesis of Multiple Myeloma Cancer.

Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis. This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer. This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM. Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.

Hemoglobin, Ferritin, and Lactate Dehydrogenase as Predictive Markers for Neonatal Sepsis.

(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case-control study conducted on neonates hospitalized at the Clinical Hospital "Louis Turcanu", Timisoara, Romania, from October 2018 to July 2023. Using a vacutainer collection device, venous blood was collected at admission for complete blood tests, including ferritin, hemoglobin, LDH, and blood culture analysis. Neonates were divided into two groups: sepsis-positive and sepsis-negative. The outcome of interest was a diagnosis of sepsis. (3) Results: Data from 86 neonates, 51 of whom had been confirmed to have sepsis, were analyzed. This study found no significant difference in gestational age, infant weight, fetal growth restriction, or APGAR score between neonates with and without sepsis. However, there was a higher incidence of sepsis among neonates delivered via cesarean section. Neonatal patients with sepsis showed significantly higher levels of neonatal serum ferritin and LDH compared to those without sepsis. Ferritin and LDH biomarkers demonstrated excellent discriminatory capabilities in diagnosing neonatal sepsis. Logistic regression analysis revealed a significant association between elevated ferritin and LDH levels and the likelihood of neonatal sepsis, while anemia did not show a significant association. (4) Conclusions: LDH and ferritin concentrations are found to be predictive biomarkers for neonatal sepsis, indicating a potential role in detecting susceptible neonates and implementing prompt interventions to improve patient outcomes.

Associations of \(\textit{OTUBAIN-1, STAT, SHP}\) and \(\textit{NF-KB2}\) expression with clinical features in Non-Hodgkin’s lymphoma patients

Non-Hodgkin's lymphoma (NHL) is a group of lymphoproliferative disorders characterized by the abnormal proliferation and accumulation of lymphocytes in the lymphatic system. An ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (Otubain-1) is a deubiquitinating enzyme that cleaves ubiquitin or ubiquitin-like molecules and is expressed in various human tissues. The pathogenesis of NHL is associated with activations of the nuclear transcription factor (NF-κB) and signal transducer and activator of transcription proteins (JAK/STAT) signaling pathways. In this study, all the expressions of Otubain-1, NF-κB2, SHPs and STATs genes, the concentrations of cytokines IL-1β, IL-6 and TNF-α and clinical features in NHL patients were examined. To the end, gene expression levels of 82 NHL patients and 56 healthy individuals were determined by quantitative real time RT-PCR and secretion of cytokines by ELISA. As a result, concentrations of IL-6 and TNF-α in the patient group were found higher than in the healthy individuals and patients with higher LDH concentrations in the clinical cutoff, 280 U/L showed increased concentrations of AST, ALT and GGT than those with normal LDH concentrations. Interestingly, NHL patients with high Otubain-1 expression had significant elevations of GGT and ferritin concentrations as well as STAT-5 expression compared to those with low Otubain-1 expression. In conclusion, the present study indicates that up-regulation of Otubain-1 led to activation of STAT5 in lymphoma cells and liver dysfunction and metabolic syndrome in NHL patients.

In Vivo Study on Doxycycline Protective Mechanisms during Myocardial Ischemia Injury in Rats.

The fact that during myocardial ischemia/reperfusion (I/R) injury, myosin light chain 1 (MLC1) and troponin I (TnI) are degraded by matrix metalloproteases activity has already been well established in both in vitro and ex vivo studies. However, I/R injury is a complex issue based on several overlapping mechanisms. Increased activity of myosin light chain kinase and nitric oxide synthase due to oxidative stress leads to post-translational modifications of MLC1, thus leading to the increased degradation of these proteins. Wistar rats were subjected to left anterior descending coronary artery occlusion. To measure the pharmacological effect of doxycycline, transthoracic echocardiography as well as biochemical tests, concentrations of TnI, LDH, MLC1, MMP-2 and MMP-9 were performed. Gelatinize activity and cytotoxicity level were also assessed; Results: I.p., administration of doxycycline before LAD occlusion surgery increased TnI and LDH content in the heart and decreased cytotoxicity. A reduction of MMP-2 and MMP-9 concentration and MMP-2 activity after administration of Doxy was also observed, as well as improvement in echocardiographic parameters just 7 days after surgery. Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

Melitoxin Inhibits Proliferation, Metastasis, and Invasion of Glioma U251 Cells by Down-regulating F2RL1.

As the principal active component of bee venom, melittin has an anti-cancer effect in different cancers. This study was aimed to investigate the effect of melittin in glioma and explore whether F2RL1 is closely involved in glioblastoma cells proliferation. TCGA and GES databases were used to evaluate the role of F2RL1 in gliomas. The U251 cells were divided into a control lentivirus + PBS group (NC-PBS), F2RL1 intervention lentivirus + PBS group (KD-PBS), control lentivirus + melittin group (NC-melittin), and F2RL1 intervention lentivirus + melittin group (KD-melittin). Cell proliferation was detected by MTT and EDU staining assays. The apoptosis rate was assessed by flow cytometry. Expressions of genes related to apoptosis, cycle arrest, migration, and invasion were detected by qRT-PCR. Cellular LDH concentrations were detected by ELISA. The subcutaneous tumor volume of nude mice was analyzed by xenograft method. F2RL1 was significantly overexpressed in glioma tissues and were reduced in the melittin-treated group compared to the blank group. F2RL1 knockdown and melittin alone or in combination increased the proportion of cells in the G1-phase, and the combination was more pronounced. The KD-melittin group showed a decrease in the number of viable cells at 24, 48, 72, and 96 h compared to the NC-PBS group. The number of cell migration and invasion was decreased in the KD-melittin group compared to the other groups. Moreover, the genes related to cell cycle arrest and apoptosis were significantly changed in the KD-melittin group. At weeks 4, 5, and 6, the tumor volume in the KD-melittin group was smaller than that in the KD-PBS group and NC-melittin group. Interference with the target gene F2RL1 inhibited the proliferation of glioma U251 cells, and melittin treatment inhibited the proliferation of glioma U251 cells. Melittin inhibited the proliferation of glioma U251 cells by suppressing the expression of target gene F2RL1.

Hypouricemia as a novel predictor of mortality in anti-MDA5 positive dermatomyositis patients with ILD: A retrospective cohort study

ObjectiveAnti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+ DM) is a unique subtype of idiopathic inflammatory myopathy (IIM) that is associated with rapidly progressive interstitial lung disease (RPILD) and high mortality. This retrospective study aimed to identify predictors of mortality and discover novel easily detectable indicators. MethodsWe retrospectively reviewed 183 MDA5+ DM-ILD patients who were from West China Hospital of Sichuan University myositis cohort, the largest single-center cohort of southwest China, from January 2016 to October 2021. Clinical characteristics were reviewed, and risk factors for mortality were determined by univariate and multivariable Cox regression analyses. ResultsOf the 183 MDA5+ DM-ILD patients, 59 were presented with RP-ILD, and 53 died during the follow-up period. Compared with the survived patients, deceased patients had higher rates of dyspnea, higher concentrations of CRP, and LDH, but lower rates of heliotrope sign, lower quantity of lymphocyte and lower levels of serum uric acid (SUA). Notably, patients with hypouricemia (SUA <154 μmol/L) had higher concentrations of CRP and LDH, higher neutrophil counts, lower lymphocyte counts and higher mortality rate when compared with the non-hypouricemia group. Multivariate Cox regression analyses confirmed that hypouricemia, smoking, RPILD, high HRCT score, elevated LDH, and lymphopenia were independent risk factors for mortality in MDA5+ DM-ILD patients. Moreover, patients with hypouricemia had significantly lower survival rates than non-hypouricemia patients. ConclusionOur study identified hypouricemia as a non-redundant promising prognostic factor for the mortality of MDA5+ DM-ILD patients, which may hopefully provide insight into the prevention and pathogenesis study.

The Hepatorenal Protective Potential of Caffeic Acid Consumption on the Arsenic-Exposed Syrian Mice.

Arsenic can induce lethal hepatorenal insufficiency by inducing progressive cytotoxicity in the two main body's hemostatic regulators, the kidney and liver. In the current study, the hepatorenal protective impact of caffeic acid was investigated in arsenic-exposed Syrian mice. Twenty-four male Syrian mice (30 8g) were provided and randomly divided into 4 groups of 6 receiving nothing, arsenic, arsenic and caffeic, and caffeic acid. The mice passed the 21-day treatment program. The mice's blood was collected and analyzed by measuring the serum ALT/AST enzymes and creatinine/urea levels, respectively. Finally, the histopathological properties in both the kidney and liver organs of the mice were studied. Arsenic administration significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, urea, and creatinine concentrations (p < 0.05). Simultaneous administration of caffeic acid with arsenic decreased the serum AST and creatinine (p < 0.05). Moreover, the renal glomerulus and liver regeneration in the mice receiving caffeic acid supplements exhibited the caffeic acid hepatorenal protective potential. The histopathological changes caused by arsenic in the mice's liver and kidney tissue including degeneration, necrosis, hyperemia, and tissue hypotrophy were shifted to normal conditions following the caffeic acid administration dose, which was verified by the mice blood biochemical analysis results.

Dietary Theobroma cocao Prevents Hepatotoxicity Secondary to Myocardial Injury

Dietary products like cocoa with high flavonoids may play a role to boost the integrity of the liver against insults resulting from myocardial injury. Twenty-four male Wistar rats, divided into four groups of 6 rats were used for the study. Group 1 was control and received 0.9% normal saline via oral gavage. Group 2 was the acute myocardial injury group, and received two doses of subcutaneous injection of isoproterenol (100 mg/kg body weight) at an interval of 24 hours between doses. Group 3 was administered Theobroma cacao (100 mg/kg body weight orally) only for 2 weeks. Group 4 was pretreated with Theobroma cacao for 2 weeks and then followed by injection of isoproterenol (100 mg/kg body weight) on day 15 and 16. At the end of the experimental period, the rats were euthanized and serum collected for laboratory investigations of lactate dehydrogenase, troponin, alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Administration of isoproterenol resulted in a significant (p&lt;0.001) elevation in the serum concentrations of the cardiac biomarkers, troponins and LDH when compared with the control group. Pretreatment with Theobroma cacao before myocardial infarction caused a significant (p&lt;0.01) reduction in the concentrations of LDH and troponins with values similar to the control group. The serum liver enzymes AST, ALT, and ALP levels were also significantly (p&lt;0.01) but were reversed in the Theobroma cacao cocoa treatment groups. It is concluded that Theobroma cacao prevents hepatic and heart damage thus providing a support for the prophylactic use of dietary Theobroma cacao against hepatotoxicity.

Early Prediction of Treatment Response By Circulating Tumor DNA Profiling in Patients with Diffuse Large B-Cell Lymphoma Receiving CAR T-Cell Therapy

Introduction Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) are characterized by a particularly poor prognosis. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of patients with r/r DLBCL, yet a substantial proportion of patients still experiences relapse or progression after CAR T-cell treatment. Identifying patients at high risk of CAR T-cell therapy resistance or future lymphoma progression remains challenging. Here, we explored the value of circulating tumor DNA (ctDNA) as a prognostic biomarker at baseline and early into treatment in DLBCL patients undergoing standard-of-care CAR T-cell therapy, without the need for matched tumor genotypes. We further investigated associations between ctDNA and other known clinical risk factors. Methods We applied targeted next-generation sequencing (NGS) to a total of 53 samples from r/r DLBCL patients receiving CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel, n=16) at the University Medical Center Freiburg (Germany), using a modified version of the AVENIO ctDNA analysis workflow (Roche; Research Use Only) that covered ~314kb and targeted 466 distinct genes recurrently mutated in DLBCL (based on the CAPP-Seq workflow, Kurtz DM et al. J Clin Oncol 2018). Tumor genotypes were assessed noninvasively from plasma samples obtained at baseline before lymphodepletion with matched germline controls. Concentrations of ctDNA were quantified at baseline and early after CAR T-cell therapy at day 7-10. Initial treatment response was assessed by conventional PET-CT obtained 4-6 weeks after treatment based on the Lugano criteria. Results At baseline prior to lymphodepletion, we detected somatic mutations in 100% of plasma samples by noninvasive genotyping, with a median of 19.5 mutations per patient (range: 3-97). The most frequently mutated genes were IGHV, IGLL5, BCL2, MYC, BTG1, CREBBP, and TP53. Patients with high baseline ctDNA concentrations (mean allele frequency [AF] &amp;gt;= 1%) showed shorter progression-free survivial (PFS) and overall survival (OS) than patients with ctDNA levels below this threshold (median PFS: 86.5 days vs. not reached, p=0.04, HR: 6.3, 95% CI: 1.7-23.6; median OS: 219 days vs. not reached, p=0.048, HR: 4.1, 95% CI 1.0-16.6, Figure 1). Pretreatment ctDNA levels were significantly correlated with LDH concentrations ( p=0.049, r=0.5). We further found significantly higher ctDNA concentrations in patients with transformed DLBCL (vs. non-transformed, p=0.008) and in those with 3 or more prior treatment lines (vs. 1-2, p=0.04). At day 7-10 after CAR T-cell therapy, ctDNA levels dropped a median of 10-fold compared to the pretreatment time point ( p=0.008). Patients achieving a complete (CMR) or partial metabolic response (PMR) by PET-CT after 4-6 weeks showed a significant decrease of ctDNA ( p=0.001), while those with a stable (SD) or progressive disease (PD) had no significant ctDNA reduction at day 7-10 after CAR T-cell infusion. Vice versa, while 100% of patients with a &amp;gt;1.5-log-fold drop of ctDNA level between the pretreatment and interim time point revealed a CMR or PMR in early PET-CT scans, only 62% of patients with a smaller ctDNA decline responded to treatment according to PET-CT. Conclusions Our data suggests, together with previously published studies (Sworder BJ et al., Cancer Cell, 2023; Frank MJ et al. J Clin Oncol, 2021), that ctDNA profiling may allow robust noninvasive genotyping, accurate risk-stratification, and early prediction of clinical outcomes in r/r DLBCL patients undergoing CAR T-cell therapy. Although limited by small sample size, this pilot study highlights a potential future role of ctDNA measurements for personalized treatment selection and guidance in clinical trials.

Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes

Abstract Because of the potential bioactivities, nanoparticles have engendered hope in scientific communities for developing novel therapeutic strategies. In the present study, it was tested whether selenium nanoparticles (Se-NPs) can protect the liver in mothers with gestational diabetes (DM). The gestational rats were divided into three groups (n = 8). Group 1 (CN) received the vehicle, Group 2 (DM) received a single intraperitoneal injection of 165 mg/kg of alloxan, and Group 3 (DM + Se-NPs) received a single intraperitoneal injection of 165 mg/kg alloxan and then treated with Se-NPs at a dose of 2.5 mg/kg twice a week for 6 weeks; 1 week before gestation and continued for 5 weeks. The structure of the fabricated Se-NPs modified with ascorbic acid indicated that nano-Se was associated with a carbon matrix. The body weight of diabetic mothers was lower compared to control animals. The use of Se-NPs as a treatment has led to significant restoration of the body weight in diabetic rat mothers compared to those diabetic animals without treatment. Concentrations of alanine transaminase, aspartate aminotransferase, LDH, malondialdehyde, cholesterol, triglycerides, and glucose were significantly increased in diabetic rats, while glutathione significantly declined in comparison to control gestational rats. Interestingly, Se-NPs in DM + Se-NPs rats were found to restore all these parameters to values close to the control levels. Se-NPs could improve the histological structure of the liver in gestational rats with diabetes (DM + Se-NPs). Our data demonstrate that Se-NPs shield the liver structure and function in gestational rats against alloxan-induced diabetes.

Extracorporeal light-chain elimination in myeloma with simple medium cutoff membrane hemodialysis: a retrospective cohort study.

We determined the efficacy of free light chain (FLC) removal by regular dialysis equipment (high-flux filtration) with medium cutoff (MCO) membrane hemodialysis (HD) as an adjuvant treatment to standard chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM) and its impact on further dialysis dependency. Sixty patients with acute dialysis-dependent renal failure secondary to MM were treated with MCO-HD (55 patients) or HCO (high cutoff)-HD (5 patients) as a control. FLC serum concentration, total protein, immunoglobulins, and LDH were measured throughout the dialysis therapy. The kidney function of the patients was followed up for 1 year. The median age was 69 years; 25 female and 35 male patients were enrolled. HD significantly reduced FLC kappa levels in the MCO/HCO group by 58%/84% (MCO/HCO group; p < 0.05) and FLC lambda by 39%/33% (MCO/HCO group; p < 0.05). Single HD data (MCO) showed a relative reduction of 70% in kappa and 37% in lambda FLC concentration, as expected by the different sizes of the light chains. Renal function improved significantly and continuously from starting creatinine 5.7/3.8 mg/dl (MCO/HCO group) before HD to 1.4/2.0 mg/dl (MCO/HCO group; p < 0.001) after 1 year. No significant alteration of total protein, immunoglobulins, and LDH concentrations by HD (HCO and MCO group) was observed. After 1 year, 37 of 60 patients were alive and 34 of them were off dialysis. FLC elimination with MCO-HD is effective, technically easy, and less cost-intensive as compared with HCO-HD. Kidney function recovery in MM patients is achievable.

Vitamin C injection improves antioxidant stress capacity through regulating blood metabolism in post-transit yak

Transportation stress is one of the most serious issues in the management of yak. Previous studies have demonstrated that transport stress is caused by a pro-oxidant state in the animal resulting from an imbalance between pro-oxidant and antioxidant status. In this context, vitamin C has the ability to regulate reactive oxygen species (ROS) synthesis and alleviate oxidative stress. Although this effect of vitamin C is useful in pigs, goats and cattle, the effect of vitamin C on the mitigation of transport stress in yaks is still unclear. The purpose of this study was to better assess the metabolic changes induced by the action of vitamin C in yaks under transportation stress, and whether these changes can influence antioxidant status. After the yaks arrived at the farm, control or baseline blood samples were collected immediately through the jugular vein (VC_CON). Then, 100 mg/kg VC was injected intramuscularly, and blood samples were collected on the 10th day before feeding in the morning (VC). Relative to the control group, the VC injection group had higher levels of VC. Compared with VC_CON, VC injection significantly (P < 0.05) decreased the blood concentrations of ALT, AST, T-Bil, D-Bil, IDBIL, UREA, CRP and LDH. However, VC injection led to greater (P < 0.05) AST/ALT and CREA-S relative to VC_CON. There was no difference (P > 0.05) in GGT, ALP, TBA, TP, ALBII, GLO, A/G, TC, TG, HDL-C, LDL-C, GLU and l-lactate between VC_CON and VC. The injection of VC led to greater (P < 0.05) concentration of MDA, but did not alter (P > 0.05) the serum concentrations of LPO and ROS. The injection of VC led to greater (P < 0.05) serum concentrations of POD, CAT and GSH-PX. In contrast, lower (P < 0.05) serum concentrations of SOD, POD and TPX were observed in VC relative to VC_CON. No difference (P > 0.05) in GSH, GSH-ST and GR was observed between VC_CON and VC. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 156 differential metabolites with P < 0.05 and a variable importance in projection (VIP) score > 1.5 in the VC injection group. The injection of VC resulted in significant changes to the intracellular amino acid metabolism of glutathione, glutamate, cysteine, methionine, glycine, phenylalanine, tyrosine, tryptophan, alanine and aspartate. Overall, our study indicated that VC injections were able to modulate antioxidant levels by affecting metabolism to resist oxidative stress generated during transport.

Combination of glycyrrhizic acid and compound probiotics alleviates deoxynivalenol-induced damage to weaned piglets

Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to investigate the effect of glycyrrhizic acid combined with compound probiotics, i.e. Enterococcus faecalis plus Saccharomyces cerevisiae (GAP) on improving growth performance, intestinal health and its fecal microbiota composition change of piglets challenged with DON. A total of 160 42-day-old weaned piglets (Landrace × Large White) were used and the experimental period was 28 d. The results showed that supplementing GAP in the diet significantly improved the growth performance of piglets challenged with DON and alleviate DON-induced intestinal damage by reducing ALT, AST and LDH concentrations in serum, increasing the morphological parameters of jejunum, and decreasing DON residues in serum, liver and feces. Moreover, GAP could significantly decrease the expressions of inflammation and apoptosis genes and proteins (IL-8, IL-10, TNF-α, COX-2, Bax, Bcl-2 and Caspase 3), and increase the expressions of tight-junction proteins and nutrient transport factor genes and proteins (ZO-1, Occludin, Claudin-1, ASCT2 and PePT1). In addition, it was also found that GAP supplementation could significantly increase the diversity of gut microbiota, maintain microbial flora balance and promote piglet growth by significantly increasing the abundance of beneficial bacterium such as Lactobacillus and reducing the abundance of harmful bacterium such as Clostridium_sensu_stricto_1. In conclusion, GAP addition to piglet diets contaminated with DON could significantly promote the health and growth performance of piglets though alleviating DON-induced hazards. This study provided a theoretical basis for the application of GAP to alleviate DON toxicity for animals.