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Chinese Medicine Jun 2024Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of...
BACKGROUND
Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig's protective role against DOX-induced cardiotoxicity.
METHODS
C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice.
RESULTS
The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1β (IL-1β), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis.
CONCLUSION
The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.
PubMed: 38877519
DOI: 10.1186/s13020-024-00955-5 -
Fish & Shellfish Immunology Jun 2024The impact of environmental factors on the health of the endangered Chinese sturgeon (Acipenser sinensis) and the potential hazards associated with sample collection for...
The impact of environmental factors on the health of the endangered Chinese sturgeon (Acipenser sinensis) and the potential hazards associated with sample collection for health monitoring pose urgent need to its conservation. In this study, Chinese sturgeons were selected from indoor and outdoor environments to evaluate metabolic and tissue damage indicators, along with a non-specific immune enzyme in fish mucus. Additionally, the microbiota of both water bodies and fish mucus were determined using 16S rRNA high-throughput sequencing. The correlation between the indicators and the microbiota was investigated, along with the measurement of multiple environmental factors. The results revealed significantly higher levels of two metabolic indicators, total protein (TP) and cortisol (COR) in indoor fish mucus compared to outdoor fish mucus (p < 0.05). The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were significantly higher in indoor fish, serving as indicators of tissue damage (p < 0.05). The activity of lysozyme (LZM) was significantly lower in indoor fish (p < 0.01). Biomarker analysis at the phylum and genus levels in outdoor samples revealed that microorganisms were primarily related to the catabolism of organic nutrients. In indoor environments, microorganisms displayed a broader spectrum of functions, including ecological niche establishment, host colonization, potential pathogenicity, and antagonism of pathogens. KEGG functional enrichment corroborated these findings. Dissolved oxygen (DO), electrical conductivity (EC), ammonia nitrogen (NH-N), turbidity (TU), and chemical oxygen demand (COD) exerted effects on outdoor microbiota. Temperature (TEMP), nitrate (NO), total phosphorus (TP), and total nitrogen (TN) influenced indoor microbiota. Changes in mucus indicators, microbial structure, and function in both environments were highly correlated with these factors. Our study provides novel insights into the health impacts of different environments on Chinese sturgeon using a non-invasive method.
PubMed: 38876409
DOI: 10.1016/j.fsi.2024.109700 -
Eastern Mediterranean Health Journal =... May 2024Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200...
BACKGROUND
Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region.
AIMS
To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention.
METHODOLOGY
Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples.
RESULTS
The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully.
CONCLUSION
The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.
Topics: Humans; Iraq; Child; Child, Preschool; Male; Disease Outbreaks; Female; Meningitis, Viral; Adolescent; Infant; Meningitis, Bacterial
PubMed: 38874294
DOI: 10.26719/2024.30.5.350 -
Oncology Reports Jul 20242',3',4'‑trihydroxyflavone (2‑D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma...
2',3',4'‑trihydroxyflavone (2‑D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (Ut‑LMS) are unknown. The anticancer activity of 2‑D08 was explored in an model using SK‑LMS‑1 and SK‑UT‑1B cells (human Ut‑LMS cells). Treatment with 2‑D08 inhibited cell viability in a dose‑ and time‑dependent manner and significantly inhibited the colony‑forming ability of Ut‑LMS cells. In SK‑UT‑1B cells treated with 2‑D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2‑D08 in SK‑UT‑1B cells. 2‑D08‑induced production of reactive oxygen species and apoptosis progression were observed in SK‑LMS‑1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2‑D08 suppressed proliferation in SK‑LMS‑1 cells, while treatment for 48 h led to cell‑cycle arrest. 2‑D08 upregulated p21 protein expression in SK‑LMS‑1 cells and promoted apoptosis through caspase‑3. Evaluation of α‑SM‑actin, calponin 1 and TAGLN expression indicated that 2‑D08 did not directly initiate smooth muscle phenotypic switching in SK‑LMS‑1 cells. Transcriptome analysis on 2‑D08‑treated SK‑LMS‑1 cells identified significant differences in gene expression and suggested that 2‑D08 modulates cell‑cycle‑ and apoptosis‑related pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2‑D08 exerts antitumor effects in Ut‑LMS cells by modulating multiple signaling pathways and that 2‑D08 may be a promising candidate for the treatment of human Ut‑LMS. The present study expanded and developed knowledge regarding Ut‑LMS management and indicated that 2‑D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.
Topics: Humans; Leiomyosarcoma; Female; Uterine Neoplasms; Cell Line, Tumor; Apoptosis; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Reactive Oxygen Species; Signal Transduction; Flavones; Antineoplastic Agents; Cell Cycle; Autophagy
PubMed: 38874019
DOI: 10.3892/or.2024.8756 -
Molecular Medicine Reports Aug 2024Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS....
Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS. However, its molecular mechanisms of regulating the pyroptosis signaling pathway and inhibiting macrophage pyroptosis remain unexplored. The present study aimed to determine whether H2S mitigates macrophage pyroptosis by downregulating the pyroptosis signaling pathway and S‑sulfhydrating caspase‑1 under the stimulation of oxidized low‑density lipoprotein (ox‑LDL), a pro‑atherosclerotic factor. Macrophages derived from THP‑1 monocytes were pre‑treated using exogenous HS donors sodium hydrosulfide (NaHS) and D,L‑propargylglycine (PAG), a pharmacological inhibitor of endogenous HS‑producing enzymes, alone or in combination. Subsequently, cells were stimulated with ox‑LDL or the desulfhydration reagent dithiothreitol (DTT) in the presence or absence of NaHS and/or PAG. Following treatment, the levels of HS in THP‑1 derived macrophages were measured by a methylene blue colorimetric assay. The pyroptotic phenotype of THP‑1 cells was observed and evaluated by light microscopy, Hoechst 33342/propidium iodide fluorescent staining and lactate dehydrogenase (LDH) release assay. Caspase‑1 activity in THP‑1 cells was assayed by caspase‑1 activity assay kit. Immunofluorescence staining was used to assess the accumulation of active caspase‑1. Western blotting and ELISA were performed to determine the expression of pyroptosis‑specific markers (NLRP3, pro‑caspase‑1, caspase‑1, GSDMD and GSDMD‑N) in cells and the secretion of pyroptosis‑related cytokines [interleukin (IL)‑1β and IL‑18] in the cell‑free media, respectively. The S‑sulfhydration of pro‑caspase‑1 in cells was assessed using a biotin switch assay. ox‑LDL significantly induced macrophage pyroptosis by activating the pyroptosis signaling pathway. Inhibition of endogenous HS synthesis by PAG augmented the pro‑pyroptotic effects of ox‑LDL. Conversely, exogenous HS (NaHS) ameliorated ox‑LDL‑and ox‑LDL + PAG‑induced macrophage pyroptosis by suppressing the activation of the pyroptosis signaling pathway. Mechanistically, ox‑LDL and the DTT increased caspase‑1 activity and downstream events (IL‑1β and IL‑18 secretion) of the caspase‑1‑dependent pyroptosis pathway by reducing S‑sulfhydration of pro‑caspase‑1. Conversely, NaHS increased S‑sulfhydration of pro‑caspase‑1, reducing caspase‑1 activity and caspase‑1‑dependent macrophage pyroptosis. The present study demonstrated the molecular mechanism by which H2S ameliorates macrophage pyroptosis by suppressing the pyroptosis signaling pathway and S‑sulfhydration of pro‑caspase‑1, thereby suppressing the generation of active caspase-1 and activity of caspase-1.
Topics: Hydrogen Sulfide; Pyroptosis; Humans; Caspase 1; Macrophages; NLR Family, Pyrin Domain-Containing 3 Protein; Lipoproteins, LDL; Phosphate-Binding Proteins; THP-1 Cells; Intracellular Signaling Peptides and Proteins; Signal Transduction; Gasdermins; Alkynes; Glycine; Sulfides
PubMed: 38873985
DOI: 10.3892/mmr.2024.13259 -
Frontiers in Medicine 2024Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine...
INTRODUCTION
Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine the prevalence of hyperuricemia and parameters associated with serum uric acid (SUA) and urine uric acid (UUA) in patients with lymphoma and myeloproliferative neoplasms (MPN).
METHODS
This cross-sectional study included adult patients with newly diagnosed lymphoma and MPN at the university-based hospital. Clinical characteristics were collected, and independent risk factors for hyperuricemia and hyperuricosuria were determined using multiple logistic regression.
RESULTS
One hundred and sixty-five patients were included with a median age of 55 years (45.5-64) and 51.5% were males. There were 91 patients (55.2%) with lymphoma and 74 cases (44.8%) of MPN. Overall, hyperuricemia was prevalent in 43.6% with a median SUA of 6.3 mg/dl (4.6-8) and hyperuricosuria was detected in 39.4% with a median 24-h UUA of 545 mg (365.4-991). Hyperuricemia was observed in patients with lymphoma and MPN in 20.9% and 71.6%, respectively, and hyperuricosuria in 15.4% and 68.9%, respectively. In lymphoma patients, estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m and serum lactate dehydrogenase (LDH) ≥ 250 U/L were associated with hyperuricemia with odds ratio (OR) 3.24, 95% confidence interval (CI) 1.95-11.07, = 0.006 and OR 2.07, 95%CI 1.62-6.97, = 0.039), and only elevated serum LDH was related to hyperuricosuria (OR 2.37, 95%CI 1.56-14.29, = 0.036). In MPN patients, hemoglobin levels <10 g/dl and serum LDH ≥ 640 mg/dl were independent risk factors of hyperuricosuria (OR 1.88, 95%CI 1.42-8.39, = 0.045 and OR 6.21, 95%CI 1.49-25.74, = 0.012).
CONCLUSION
Hyperuricemia in patients with hematologic malignancies was common, notably MPN, and parameters associated with hyperuricosuria were provided. In addition to the utilization of allopurinol in patients at high risk of tumor lysis syndrome, patients without hyperuricosuria may also be of significant interest.
PubMed: 38873194
DOI: 10.3389/fmed.2024.1343000 -
Veterinary Clinical Pathology Jun 2024A 3-year-old male neutered domestic shorthair cat presented with lethargy, hyporexia, and pyrexia of unknown origin. Biochemical analysis using a Beckman Coulter AU480...
A 3-year-old male neutered domestic shorthair cat presented with lethargy, hyporexia, and pyrexia of unknown origin. Biochemical analysis using a Beckman Coulter AU480 demonstrated marked increases in creatine kinase and aspartate aminotransferase, indicative of severe muscle injury, with concurrent presumptive myoglobinuria on urinalysis. A marked, non-physiologic increase in measured bicarbonate and resultant negative anion gap was documented; however, calculated bicarbonate obtained via a point-of-care blood gas analyzer was within normal limits. Laboratory error due to interference by lactate dehydrogenase was suspected and supported by the results of subsequent biochemical testing. Artifactual increases in bicarbonate have been documented in cases of rhabdomyolysis in horses, cows, and a bird. However, to the best of the authors' knowledge, this is the first report to demonstrate this spurious change in a cat.
PubMed: 38872478
DOI: 10.1111/vcp.13371 -
Zhonghua Yi Xue Za Zhi Jun 2024To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. A...
To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [=356, (,) for age were 43 (31, 61) years] and internal validation group [=153, age 42 (31, 60) years] by 7∶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Five variables including age (=1.040,:1.000-1.050,=0.002), carbohydrate antigen 125 (CA125) (=1.001, 95%: 1.000-1.010, =0.017), human epididymis protein 4 (HE4) (=1.020, 95%: 1.000-1.030, =0.002), carbohydrate antigen 199 (CA199) (=1.001, 95%:1.000-1.020, =0.023) and lactate dehydrogenase (LDH) (=1.020, 95%: 1.010-1.022, =0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%:0.910-0.932)for modeling group, 0.891(95%:0.874-0.905) for internal validation group, and 0.924(95%:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.
Topics: Humans; Female; Middle Aged; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Adult; Retrospective Studies; Nomograms; CA-125 Antigen; ROC Curve; Neoplasm Staging; Logistic Models; Risk Factors; WAP Four-Disulfide Core Domain Protein 2
PubMed: 38871475
DOI: 10.3760/cma.j.cn112137-20231019-00823 -
Biomedicine & Pharmacotherapy =... Jun 2024Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and...
Cardioprotective effects of the aqueous extract of Echinops cephalotes on myocardial ischemia-reperfusion in rats by modulation of MMP-2, MMP-9, TIMP, and oxidative stress.
Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and anti-inflammatory characteristics. The major purpose of the present study was to investigate the cardioprotective benefits of Echinops cephalotes (Ech) against myocardial ischemia-reperfusion (MI/R) injury. Male Wistar rats were randomly allocated to three groups: sham, MI, and MI + Ech. The left coronary artery (LAD) was blocked for 30 minutes to induce MI. In the treatment group, rats were given 150 mg/kg/day of Ech extract for 28 days. Aqueous extracts were made from Echinops plants. To study heart function, fibrosis, cardiac damage indicators, and oxidative stress factors, echocardiography, Masson's trichrome staining, and biochemical tests were used. The expression of matrix metalloproteinase 2 and 9 (MMP2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) was determined using Western blotting. Tissue damage was assessed using hematoxylin and eosin staining. MI group exhibited significantly reduced ejection fraction (EF) and fractional shortening (FS), enhanced levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), cardiac Troponin I (cTnI), and malondialdehyde (MDA), as well as a decrease in the Glutathione (GSH) tissue content, reduced activity of superoxide dismutase (SOD), increasing fibrosis, upregulations of MMP-2 and MMP-9, and reduction of TIMP compared to the sham group. The findings suggest that Ech in particular, could be a promising therapeutic agent to reduce the damage in MI by targeting oxidative stress and modulating the activities of matrix metalloproteinases and their tissue inhibitors.
PubMed: 38870633
DOI: 10.1016/j.biopha.2024.116927 -
Folia Microbiologica Jun 2024Herein, we investigated the anti-amoebic activity of phosphonium-chloride-based deep eutectic solvents against pathogenic Acanthamoeba castellanii of the T4 genotype....
Herein, we investigated the anti-amoebic activity of phosphonium-chloride-based deep eutectic solvents against pathogenic Acanthamoeba castellanii of the T4 genotype. Deep eutectic solvents are ionic fluids composed of two or three substances, capable of self-association to form a eutectic mixture with a melting point lower than each substance. In this study, three distinct hydrophobic deep eutectic solvents were formulated, employing trihexyltetradecylphosphonium chloride as the hydrogen bond acceptor and aspirin, dodecanoic acid, and 4-tert-butylbenzoic acid as the hydrogen bond donors. Subsequently, all three deep eutectic solvents, denoted as DES1, DES2, DES3 formulations, underwent investigations comprising amoebicidal, adhesion, excystation, cytotoxicity, and cytopathogenicity assays. The findings revealed that DES2 was the most potent anti-amoebic agent, with a 94% elimination rate against the amoebae within 24 h at 30 °C. Adhesion assays revealed that deep eutectic solvents hindered amoebae adhesion to human brain endothelial cells, with DES2 exhibiting 88% reduction of adhesion. Notably, DES3 exhibited remarkable anti-excystation properties, preventing 94% of cysts from reverting to trophozoites. In cytopathogenicity experiments, deep eutectic solvent formulations and dodecanoic acid alone reduced amoebae-induced human brain endothelial cell death, with DES2 showing the highest effects. Lactate dehydrogenase assays revealed the minimal cytotoxicity of the tested deep eutectic solvents, with the exception of trihexyltetradecylphosphonium chloride, which exhibited 35% endothelial cell damage. These findings underscore the potential of specific deep eutectic solvents in combating pathogenic Acanthamoeba, presenting promising avenues for further research and development against free-living amoebae.
PubMed: 38869777
DOI: 10.1007/s12223-024-01180-1