Human & experimental toxicology最新文献

{"title":"Subchronic oral toxicity assessment of <i>Bacillus velezensis</i> strain BV379 in sprague-dawley rats.","authors":"Mark R Bauter, Laura M Brutscher, Laurie C Dolan, Jessica L Spears","doi":"10.1177/09603271241278977","DOIUrl":"https://doi.org/10.1177/09603271241278977","url":null,"abstract":"<p><strong>Introduction: </strong>The spore-forming bacterial species <i>Bacillus velezensis</i> is commonly utilized in feed for livestock and aquaculture. In recent years, there has been increased interest in introducing <i>B</i>. <i>velezensis</i> into human supplements and food. Before it can be safely administered in humans, the safety of each <i>B</i>. <i>velezensis</i> strain needs to be established. The objective of this study was to evaluate the in vivo safety of <i>Bacillus velezensis</i> strain BV379 by high-dose oral administration to rats in a 28-day subchronic toxicity study.</p><p><strong>Methods: </strong>In this study, 80 animals were assigned to four groups: vehicle control, 1 × 10¹⁰, 4 × 10¹⁰, or 10 × 10¹⁰ CFU/kg bw/day by gavage. The following toxicological assessments were performed: ophthalmological examinations; observations for viability, signs of gross toxicity, and behavioral changes; in-life parameters, including body weight and food consumption; urinalysis, hematology, clinical chemistry, and coagulation assessments; macroscopic and microscopic tissue assessments; and bacterial enumeration in selected tissues.</p><p><strong>Results: </strong>Under the conditions of this study, no adverse clinical endpoints were attributed to the administration of <i>Bacillus velezensis</i> strain BV379, which was well-tolerated up to the highest dose of 10 × 10¹⁰ CFU/kg bw/day.</p><p><strong>Conclusion: </strong>These results support the in vivo pre-clinical safety of <i>Bacillus velezensis</i> strain BV379 for use in food and supplements.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241278977"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MG132 inhibits proliferation and induces apoptosis of acute lymphoblastic leukemia via Akt/FOXO3a/Bim pathway.","authors":"Zhong Fan, Wen-Hao Lin, Cong Liang, Yu Li, Chun-Jin Peng, Jie-Si Luo, Wen-Yan Tang, Li-Min Zheng, Dan-Ping Huang, Zhi-Yong Ke, Li-Na Wang, Xiao-Li Zhang, Li-Bin Huang","doi":"10.1177/09603271241303030","DOIUrl":"https://doi.org/10.1177/09603271241303030","url":null,"abstract":"<p><strong>Background: </strong>Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers, characterized by the malignant proliferation of leukemic cells. Despite advancements in treatment, the prognosis for refractory and relapsed ALL remains poor, underscoring the need for novel therapeutic targets and approaches.</p><p><strong>Methods: </strong>To investigate the anti-leukemic properties of MG132, MTS assays were employed to assess cell viability, and flow cytometry was used to evaluate apoptosis. Mechanistic studies, including qRT-PCR, Western blotting, and lentivirus-mediated FOXO3a knockdown, were conducted to explore MG132's effects on the Akt/FOXO3a/Bim signaling pathway. A xenograft mouse model was utilized to validate the in vivo efficacy of MG132 in suppressing tumor growth.</p><p><strong>Results: </strong>MG132 inhibited cell proliferation and induced apoptosis in both ALL cell lines and primary cells in a concentration-dependent manner. Mechanistic studies revealed that MG132 promoted FOXO3a nuclear localization by suppressing Akt phosphorylation and preventing FOXO3a degradation, leading to increased Bim expression. Furthermore, FOXO3a knockdown significantly reduced MG132's anti-proliferative effects. In vivo, MG132 markedly inhibited tumor growth in the xenograft model.</p><p><strong>Conclusion: </strong>These findings suggest that MG132 exerts potent anti-leukemic effects through modulation of the Akt/FOXO3a/Bim axis, offering a promising therapeutic avenue for treating ALL.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241303030"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problems with the effectiveness of L-carnitine and paraffin oil in acute aluminum phosphide poisoning.","authors":"Maryam Zaare Nahandi,&nbsp;Ali Banagozar Mohammadi","doi":"10.1177/09603271231210974","DOIUrl":"10.1177/09603271231210974","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231210974"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50164248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ozone in the adjunct medical treatment. The round personality of a molecule with hormetic properties.","authors":"Salvatore Chirumbolo, Umberto Tirelli, Marianno Franzini, Sergio Pandolfi, Giovanni Ricevuti, Francesco Vaiano, Luigi Valdenassi","doi":"10.1177/09603271231218926","DOIUrl":"https://doi.org/10.1177/09603271231218926","url":null,"abstract":"<p><p>Ozone, an allotrope of oxygen, is enjoying an increasing interest in the setting and management of the medical adjunct treatment, which is called, maybe too simplistically, \"ozone therapy\". Ozone is not a medicine, so the word therapy does not properly fit this gaseous molecule. Like many natural compounds, for example plant flavonoids, even ozone interacts with aryl hydrocarbon receptors (AhRs) and, at low doses, it works according to the paradoxical mechanism of hormesis, involving mitochondria (mitohormesis). Ozone, in the hormetic range, exerts cell protective functions via the Nrf2-mediated activation of the anti-oxidant system, then leading to anti-inflammatory effects, also via the triggering of low doses of 4-HNE. Moreover, its interaction with plasma and lipids forms reactive oxygen species (ROS) and lipoperoxides (LPOs), generally called ozonides, which are enabled to rule the major molecular actions of ozone in the cell. Ozone behaves as a bioregulator, by activating a wide population of reactive intermediates, which usually target mitochondria and their turnover/biogenesis, often leading to a pleiotropic spectrum of actions and behaving as a tuner of the fundamental mechanisms of survival in the cell. In this sense, ozone can be considered a novelty in the medical sciences and in the clinical approach to pharmacology and medical therapy, due to its ability to target complex regulatory systems and not simple receptors.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231218926"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice: \"Long noncoding RNA SNHG14 regulates ox-LDL-induced atherosclerosis cell proliferation and apoptosis by targeting miR-186-5p/WIPF2 axis\".","authors":"","doi":"10.1177/09603271231215964","DOIUrl":"https://doi.org/10.1177/09603271231215964","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231215964"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.","authors":"Xiaocheng Liu, Guojuan Li, Jing Zhong, Ouyan Rang, Guifang Ou, Xinru Qin, Yonghong Tang, Mu Wang","doi":"10.1177/09603271231217992","DOIUrl":"10.1177/09603271231217992","url":null,"abstract":"<p><p><b>Background</b>: Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited.<b>Purpose</b>: To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.<b>Method</b>: 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months.<b>Results</b>: combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose.<b>Conclusions</b>: these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231217992"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antioxidant properties of resveratrol on sperm parameters, testicular tissue, antioxidant capacity, and lipid peroxidation in isoflurane-induced toxicity in mice.","authors":"Zahra Mohammadi, Sanaz Alaee, Mohammad Reza Namavar, Zahra Khodabandeh, Nahid Ahmadi, Niloofar Rashidipour, Somayyeh Karami-Mohajeri","doi":"10.1177/09603271231215036","DOIUrl":"10.1177/09603271231215036","url":null,"abstract":"<p><p>This study explores whether resveratrol effectively protects the reproductive system against isoflurane-induced toxicity in testicular tissue. In this experiment, we randomly divided 60 adult male C57BL/6 mice into six groups (<i>n</i> = 10). Five consecutive days per week, mice were exposed to 1.5% isoflurane for 1 h/day and were given 50 and 100 mg/kg resveratrol. After 35 days (the completion of the mouse spermatogenesis period), the left testis was removed for histomorphometric evaluations, while the right testis was used to determine the Capacity of total antioxidants and lipid peroxidation. To analyze the Parameters of sperm, chromatin maturation, and DNA fragmentation, the left caudal epididymis was used. Based on a one-way analysis of variance (ANOVA), we considered a difference in means of 0.05 to be significant (P0.05). Compared to the control group, the isoflurane group showed a significant decrease in testicular weight, volume, sperm parameters, and tissue histomorphometry. Comparatively, to the control group, malondialdehyde levels increased, and the total antioxidant capacity decreased significantly. Resveratrol improved all of the above parameters in the simultaneous treatment groups compared to the isoflurane group. It did not, however, reach the level of the control group in all cases. It has been demonstrated that resveratrol, with its powerful antioxidant properties, reduces the reproductive toxicity of isoflurane by inhibiting free radicals and increasing the testicular tissue's antioxidant capacity.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231215036"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138178330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of polycyclic aromatic hydrocarbon exposure on mitochondrial DNA copy number.","authors":"Sun-Haeng Choi, Bolormaa Ochirpurev, Hwa Yeong Jo, Jong-Uk Won, Akira Toriba, Heon Kim","doi":"10.1177/09603271231216968","DOIUrl":"10.1177/09603271231216968","url":null,"abstract":"<p><p>Airborne polycyclic aromatic hydrocarbon (PAH) exposure can adversely affect human health by generating reactive oxygen species (ROS) and increasing oxidative stress, which causes changes in mitochondrial DNA copy number (mtDNAcn), a key indicator of mitochondrial damage and dysfunction. This study aimed to determine the effects of atmospheric benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP) exposure on mtDNAcn in humans. One hundred and eight adults living in Cheongju, South Korea, were included in this study. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene concentrations were measured. Blood samples were also collected to assess mtDNAcn. The mean mtDNAcn was 9.74 (SD 4.46). mtDNAcn decreased significantly with age but was not significantly associated with sex, sampling season, or smoking habit. While there was a borderline significant increase in mtDNAcn with increasing ambient total PAH levels, ambient PAH or urinary 1-hydroxypyrene concentrations showed no significant association with mtDNAcn. However, urinary 6-OHNP or 1-NAAP concentrations, 1-NP metabolites, were significantly associated with mtDNAcn. These results suggest that the metabolism of absorbed NPs generates excess ROS, which damages mitochondrial DNA, resulting in increased mtDNAcn.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231216968"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice: \"Sulforaphane triggers iron overload-mediated ferroptosis in gastric carcinoma cells by activating the PI3K/IRP2/DMT1 pathway\".","authors":"","doi":"10.1177/09603271231212067","DOIUrl":"https://doi.org/10.1177/09603271231212067","url":null,"abstract":"","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231212067"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis.","authors":"Ying Zhang, Qian Fang, Yinan Liu, Dan Zhang, Ying He, Fei Liu, Kun Sun, Jinghong Chen","doi":"10.1177/09603271231219480","DOIUrl":"10.1177/09603271231219480","url":null,"abstract":"<p><p>This study evaluated the effect of fibroblast growth factor receptor 3 (FGFR3) on damaged hypertrophic chondrocytes of Kashin-Beck disease (KBD). Immunohistochemical staining was used to evaluate FGFR3 expression in growth plates from KBD rat models and engineered cartilage. In vitro study, hypertrophic chondrocytes were pretreated by FGFR3 binding inhibitor (BGJ398) for 24 h before incubation at different T-2 toxin concentrations. Differentiation -related genes (Runx2, Sox9, and Col Ⅹ) and ECM degradation -related genes (MMP-13, Col Ⅱ) in the hypertrophic chondrocytes were analyzed using RT-PCR, and the corresponding proteins were analyzed using western blotting. Hypertrophic chondrocytes death was detected by the Annexin V/PI double staining assay. The integrated optical density of FGFR3 staining was increased in knee cartilage of rats and engineered cartilage treated with T-2 toxin. Both protein and mRNA levels of Runx2, Sox9, Col Ⅱ, and Col Ⅹ were decreased in a dose-dependent manner when exposed to the T-2 toxin and significantly upregulated by 1 μM BGJ398. The expression of MMP-1, MMP-9, and MMP-13 increased in a dose-dependent manner when exposed to T-2 toxin and significantly reduced by 1 μM BGJ398. 1 μM BGJ398 could prevent early apoptosis and necrosis induced by the T-2 toxin. Inhibiting the FGFR3 signal could alleviate extracellular matrix degradation, abnormal chondrocytes differentiation, and excessive cell death in T-2 toxin-induced hypertrophic chondrocytes.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"42 ","pages":"9603271231219480"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}