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Current Pharmaceutical Biotechnology Jun 2024Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are...
INTRODUCTION
Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases.
METHOD
The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart.
RESULTS
It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status.
CONCLUSION
Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.
PubMed: 38918977
DOI: 10.2174/0113892010303097240605105013 -
BMC Veterinary Research Jun 2024In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of...
BACKGROUND
In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed.
RESULTS
IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20-40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs.
CONCLUSIONS
The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA).
Topics: Animals; Horses; Oocytes; Follicular Fluid; In Vitro Oocyte Maturation Techniques; Cumulus Cells; Female; Culture Media; Secretome
PubMed: 38918770
DOI: 10.1186/s12917-024-04129-1 -
Clinica Chimica Acta; International... Jun 2024Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to...
BACKGROUND-AIM
Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to non-pregnant counterparts. Such variations may lead to inaccurate diagnosis of hemolysis.
METHODS
We report a case of a patient in second trimester of pregnancy receiving induction chemotherapy due to B-cell acute lymphocytic leukemia with undetectable haptoglobin levels in a routine laboratory sample collected less than 12 h posttransfusion of red cell unit. Despite undetectable haptoglobin, lactate dehydrogenase (LD) was within reference intervals (RI). The patient was evaluated for acute hemolytic transfusion reaction (AHTR) and followed up. Haptoglobin levels showed an upward trend during follow-up visits, reaching 15 mg/dL, and within RI in the third trimester.
RESULTS
The patient did not meet the Center for Disease Control (CDC) criteria for AHTR. Alternative explanations for the observed laboratory findings were explored. Undetectable haptoglobin levels were attributed to various factors, including recent RBC transfusion, pregnancy-related physiological changes, and potential hyperhydration treatment plan due to chemotherapy.
CONCLUSION
This case underscores the importance of cautious interpretation of laboratory results in pregnant patients, necessitating trimester-specific reference intervals for haptoglobin. A multidisciplinary approach to patient care is crucial for accurate diagnosis and management.
PubMed: 38917868
DOI: 10.1016/j.cca.2024.119829 -
Journal of Artificial Organs : the... Jun 2024Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a rescue therapy for severe respiratory failure in which conventional mechanical ventilation therapy is...
Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a rescue therapy for severe respiratory failure in which conventional mechanical ventilation therapy is unsuccessful. Hemolysis during VV-ECMO support arises from multiple factors associated with organ damage and poor outcomes. Therefore, close and prompt monitoring is needed. Hemolytic uremic syndrome (HUS) is characterized by hemolysis, acute renal failure, and thrombocytopenia. Hemolytic features of the disease may complicate VV-ECMO management. A 26-year-old man with a history of cerebral palsy underwent VV-ECMO for acute respiratory distress syndrome (ARDS) due to septic shock caused by bacterial translocation during treatment for HUS. He showed features of hemolysis, with elevated lactate dehydrogenase (LDH), fragmented red blood cells, and low haptoglobin levels. Plasma free hemoglobin was measured daily throughout the whole course of ECMO with levels higher than 10 mg/dL but not exceeding 50 mg/dL. The extracorporeal membrane oxygenation (ECMO) circuit pressures were carefully monitored to ensure the pump generated no excessive negative pressure. The patient was weaned off ECMO on the eleventh day. There have been several cases of VA-ECMO in patients with HUS; however, there is limited literature on VV-ECMO. As the days on VV-ECMO tend to be longer than those on VA-ECMO, features of hemolysis may complicate management. Although HUS did not directly influence the clinical course in the present case, features of hemolysis were continuously observed. This case highlighted the importance of standard ECMO monitoring, especially daily measurement of plasma free hemoglobin.
PubMed: 38916825
DOI: 10.1007/s10047-024-01457-9 -
Ocular Immunology and Inflammation Jun 2024The aim of this study was to evaluate the prevalence, type and treatment outcomes of ocular involvement in patients with brucellosis.
PURPOSE
The aim of this study was to evaluate the prevalence, type and treatment outcomes of ocular involvement in patients with brucellosis.
METHODS
This prospective, single-center study enrolled patients admitted to the infectious disease outpatient clinic with diagnosed brucellosis between July 15, 2022 and July 15, 2023. Diagnosis was based on clinical symptoms and a standard Brucella tube agglutination test (≥1/160) or a positive blood culture. Ophthalmologic examinations were performed at baseline and in the first month of treatment. Third and sixth month follow-up examinations were also performed for patients with ocular findings.
RESULTS
Ocular involvement occurred in 60 (24.8%) of 242 patients. Conjunctivitis was the most common ocular involvement and was observed in 39 patients (16.1%). Uveitis was the second most common ocular involvement in 14 patients (5.8%). Scleritis was the least common ocular involvement and was observed in only one patient. Patients with ocular involvement were older ( = 0.027) and had higher rates of weight loss and spondylodiscitis ( = 0.044 and 0.001, respectively). Among laboratory parameters, erythrocyte sedimentation rate and lactate dehydrogenase levels were significantly higher in patients with ocular involvement ( = 0.001 and 0.036, respectively). There were no significant differences in other demographic, clinical, and laboratory characteristics between patients with and without ocular involvement. In 56 (93.3%) patients, the ocular findings improved during the follow-up examination.
CONCLUSION
Brucellosis, a systemic infection, can manifest with ocular involvement. Early detection and treatment through ophthalmological examination are crucial in managing brucellosis.
PubMed: 38916594
DOI: 10.1080/09273948.2024.2369655 -
Testicular Mixed Germ Cell Tumor (TMGCT) Management: Addressing Infection and Tumor Marker Dynamics.Cureus May 2024We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular...
We report the case of a 23-year-old male presenting with right testicular swelling, post-coital pain, and fever. Initial MRI and local examination suggested testicular carcinoma. Elevated serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) levels were observed. Biopsy confirmed a mixed germ cell tumor (MGCT). Concurrently, the patient was diagnosed with an infection and treated with antibiotics. Remarkably, following antibiotic therapy, fever resolved, and tumor marker levels significantly decreased. Subsequent orchidectomy confirmed the diagnosis of MGCT. This case underscores the importance of recognizing and treating concurrent infections, which may influence both clinical presentation and tumor marker levels in testicular germ cell tumors.
PubMed: 38915994
DOI: 10.7759/cureus.61062 -
Drug Design, Development and Therapy 2024This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5...
PURPOSE
This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis.
METHODS
Rats were injected with Freund's complete adjuvant to establish a rat model of AA. Then, some modeled rats were given normal saline or drugs only, and some modeled rats were injected with adeno-associated viruses or necrosulfonamide (NSA; a pyroptosis inhibitor) before drug administration. Toe swelling and arthritis index (AI) were calculated. Pathological and morphological changes in synovial and myocardial tissues were analyzed with hematoxylin-eosin staining, and pyroptotic vesicles and the ultrastructural changes of myocardial tissues were observed with transmission electron microscopy. The serum levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were detected, and lactate dehydrogenase (LDH) release was measured in myocardial tissues, accompanied by the examination of GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD) expression in myocardial tissues.
RESULTS
After AA modeling, rats presented with significantly increased toe swelling and AI scores, synovial and myocardial tissue damage, elevated pyroptotic vesicles, and markedly enhanced serum levels of IL-1β, IL-18, IL-6, and TNF-α, accompanied by significantly diminished GAS5 expression, substantially augmented miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression, greatly increased LDH release in myocardial tissues. XFC treatment significantly declined toe swelling, AI scores, synovial and myocardial tissue damage, and the serum levels of IL-1β, IL-18, IL-6, and TNF-α in AA rats. Additionally, XFC treatment markedly elevated GAS5 expression and substantially lowered LDH release and miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression in myocardial tissues of AA rats. Moreover, the above effects of XFC in AA rats were further promoted by GAS5 overexpression or NSA treatment.
CONCLUSION
XFC alleviated myocardial injury in AA rats by regulating the GAS5/miR-21/TLR4 axis and inhibiting pyroptosis and pro-inflammatory cytokine secretion.
Topics: Animals; Toll-Like Receptor 4; Pyroptosis; Rats; Arthritis, Experimental; MicroRNAs; Drugs, Chinese Herbal; Rats, Sprague-Dawley; Male; Phosphate-Binding Proteins; Freund's Adjuvant; Gasdermins
PubMed: 38915862
DOI: 10.2147/DDDT.S456783 -
Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes.Clinical Kidney Journal Jun 2024Acute kidney injury (AKI) has been reported after CAR-T cells, but available data are limited. We sought to describe the incidence of AKI in a cohort of patients...
BACKGROUND
Acute kidney injury (AKI) has been reported after CAR-T cells, but available data are limited. We sought to describe the incidence of AKI in a cohort of patients hospitalized in the intensive care unit (ICU) following CAR-T cell reinjection, identify the primary factors linked to the onset of AKI, and ascertain the key determinants associated with kidney outcomes and mortality.
METHODS
We retrospectively analyzed 119 patients hospitalized in ICU after CAR-T cell therapy between 2017 and 2023. Factors associated with AKI, mortality, and kidney sequelae were identified using multivariate analyses.
RESULTS
Of the 119 patients, 41 patients fulfilled diagnostic criteria of AKI (34%). By multivariate analysis, grade ≥3 cytokine release syndrome (CRS) [OR = 1.20 CI95% (1.01-1.43)] and elevated lactate dehydrogenase (LDH) levels at admission [OR = 1.44 CI95% (1.04-1.99)] were significantly associated with the occurrence of AKI during ICU stay. AKI KDIGO ≥2 was an independent risk factor for hospital mortality [OR = 1.50 (1.22-1.85), < 0.001]. Nine out of 12 (75%) and 6/9 (67%) patients who had experienced AKI and survived had chronic kidney disease (CKD) at 6 months and 1 year, respectively. We did not identify any specific factor associated with kidney recovery.
CONCLUSION
AKI may occur in ICU patients receiving CAR-T cell therapy, especially those who experience CRS and exhibit elevated LDH levels. Early recognition of AKI is of utmost importance as it substantially compromises survival in these patients. Future studies should aim to elucidate the underlying pathophysiological mechanisms of AKI in this context and pinpoint predictive factors for long-term risks of CKD.
PubMed: 38915438
DOI: 10.1093/ckj/sfae123 -
Journal of Ethnopharmacology Jun 2024Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle....
ETHNOPHARMACOLOGICAL RELEVANCE
Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle. Iridoid glycosides are the predominant components of this plant, including monotropein, asperuloside, deacetylasperuloside and deacetylasperulosidic acid with their contents reaching more than 2%. Methotrexate (MTX) is the drug of choice for the treatment of rheumatoid arthritis (RA), but liver injury induced by MTX limits its wider use for RA. Morindaofficinalis iridoid glycoside (MOIG) is reported as having anti-RA and hepatoprotective effects, but the exact efficacy on MTX-induced liver injury and the underlying molecular mechanism remain unclear.
AIM
To elucidate the mitigating effect of MOIG against liver injury in RA rats treated with MTX, and explore the possible mechanism.
MATERIALS AND METHODS
The effect and mechanism of MOIG were investigated in Wistar rats with collagen-induced arthritis (CIA) which were then treated with MTX, and MTX-induced hepatocyte injury in vitro. Network pharmacological and transcriptomic analyses were conducted to predict the possible mechanisms of MOIG in mitigating MTX-induced liver injury, and lipidomic analysis was performed to further verify the regulatory effects of MOIG on lipid metabolism. BRL-3A hepatocytes were used to evaluate the regulatory effects of MOIG against MTX-associated liver injury.
RESULTS
MOIG treatment enhanced the anti-RA effect of MTX, and mitigated oxidative damage, inflammation and apoptosis of liver tissues in CIA rats treated with MTX. Network pharmacological and transcriptomic analyses demonstrated that MOIG attenuated liver injury by regulating autophagy and lipid metabolism. The result of lipidomic analysis showed that MOIG reversed the disturbance of lipid metabolism of the liver tissue in CIA rats after MTX treatment. In addition, MOIG also inhibited the apoptosis, reduced the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (ALT) and alanine aminotransferase (AST), regulated oxidative stress, and increased the formation of autophagosome and translocation of LC3 in the nucleus and expression of autophagy regulatory genes Beclin-1, ATG5, LC3Ⅱ, ATG7 and ATG12 in hepatocytes subjected to MTX damage.
CONCLUSION
Our findings demonstrated that MOIG could ameliorate MTX-induced liver injury in the treatment of RA through increasing hepatocyte autophagy and improving lipid metabolism homeostasis.
PubMed: 38914148
DOI: 10.1016/j.jep.2024.118486 -
Heliyon Jun 2024To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By...
Exploring the correlation and difference between cerebrospinal fluid in the lateral ventricle and lumbar subarachnoid based on infants with intraventricular hemorrhage treated by the ommaya reservoir.
OBJECTIVE
To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By assessing the viability of substituting lumbar puncture, we aim to minimize the associated medical risks and trauma faced by infants with intraventricular hemorrhage(IVH) from anesthesia and lumbar puncture.
METHODS
We retrospectively analyzed CSF data from 27 infants diagnosed with IVH treated by Ommaya reservoir and lumbar puncture at our center, comprising 35 paired samples. Paired-sample and regression analyses were employed to determine test correlations, differences, and to derive transformation equations for the measurements.
RESULTS
Comparative analyses between the CSF from the lateral ventricle and the lumbar vertebrae revealed significant differences in the levels of chloride, glucose, protein, erythrocytes, total cells, and Pandy's test. Specifically:1. Levels of chloride, glucose, protein, and Pandy's test were higher in the lumbar vertebrae.2. Conversely, erythrocyte and total cell counts were higher in the lateral ventricle.There were no significant differences observed for lumbar lactate dehydrogenase(LDH), leukocytes, occult blood, clot, clarity, and color. Nevertheless, significant correlations were identified between various measures, including LDH, glucose, chloride, protein, erythrocyte, leukocyte, total cell count, Pandy's test, occult blood, clot, transparency, and color. Interestingly, the correlation strength and equation fit for each component are inversely proportional to its molecular weight.Notably, well-fitting regression equations were found for LDH, glucose, chloride, protein, leukocytes, erythrocytes, and total cells.
CONCLUSION
In infants with IVH and unobstructed CSF channels, a robust correlation was noted between ventricular CSF sourced via the Ommaya reservoir and lumbar CSF. This correlation tended to be inversely related to molecular weight, with smaller molecular weights showing lesser disparities. Ventricular CSF data could anticipate lumbar CSF trends, and using regression equations with Ommaya-obtained CSF, one can derive approximate values for lumbar CSF.
PubMed: 38912498
DOI: 10.1016/j.heliyon.2024.e32252