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Alternative Therapies in Health and... Jun 2024Cadmium poisoning is mainly caused by inhalation of cadmium dust or cadmium compound dust, which greatly harms people's lives. Tea polyphenols extracted from green tea...
Effect of Tea Polyphenols on Nuclear Factor Erythroid 2-related Factor 2 (NRF2) and Kelch-like ECH-associated Protein 1 (KEAP1) Gene Expression in Mice with Acute Cadmium Poisoning.
BACKGROUND
Cadmium poisoning is mainly caused by inhalation of cadmium dust or cadmium compound dust, which greatly harms people's lives. Tea polyphenols extracted from green tea have wide biological properties, including anti-cardiovascular disease, anti-tumor, anti-inflammatory, and immune regulation. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and Kelch-like ECH-associated protein 1 (KEAP1) are involved in the regulation of cadmium-induced oxidative damage. However, whether tea polyphenols relieve acute cadmium poisoning via regulating NRF2 and KEAP1 gene expression remains unclear.
OBJECTIVE
To explore the influences of tea polyphenols on NRF2 and KEAP1 gene expression in mice with acute cadmium poisoning.
DESIGN
This is an animal experiment that adopts hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) staining.
SETTING
This study was carried out in Zunyi Medical and Pharmaceutical College.
PARTICIPANTS
Fifty specific pathogen-free (SPF) male Kunming mice aged 9 weeks, weighing 18-22 g were divided into five groups: normal group, model group, low-dose tea polyphenols group, middle-dose tea polyphenols group, and high-dose tea polyphenols group.
INTERVENTIONS
Tea polyphenols were administered intraastrically into mice with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg for 10 consecutive days, respectively.
OBSERVATION INDICATORS
(1) liver coefficient, (2) pathological liver injury, (3) liver function, (4) oxidative damage, and (5) NRF2 and KEAP1 gene expression.
RESULTS
The liver coefficient, pathological liver injury, serum aspartate transaminase and alanine transaminase levels of the model group were higher relative to the normal group (P < .05). Relative to the model group, different doses of tea polyphenols treatment significantly relieved liver coefficient, pathological liver injury, serum aspartate transaminase, and alanine transaminase levels (P < .05). Malondialdehyde content in liver tissues of the model group was significantly higher compared to the normal group, while glutathione together with glutathione peroxidase contents of the model group was lower (P < .05). Compared to the model group, malondialdehyde content in liver tissues declined while glutathione together with glutathione peroxidase contents were elevated after different doses of tea polyphenols treatment (P < .05). Relative to the normal group, NRF2 expression in the liver tissues of the model group was significantly lower, while KEAP1 expression was higher (P < .05). Relative to the model group, NRF2 expression in the liver tissues was elevated after treatment of different doses of tea polyphenols, while KEAP1 expression was declined (P < .05).
CONCLUSION
Tea polyphenols can relieve liver injury in mice with acute cadmium poisoning by regulating NRF2 and KEAP1 expression. Our study might provide a promising treatment strategy for acute cadmium poisoning.
PubMed: 38940783
DOI: No ID Found -
ACS Applied Materials & Interfaces Jun 2024Biothiol assays offer vital insights into health assessment and facilitate the early detection of potential health issues, thereby enabling timely and effective...
Biothiol assays offer vital insights into health assessment and facilitate the early detection of potential health issues, thereby enabling timely and effective interventions. In this study, we developed ultrasmall CuMn-Histidine (His) nanozymes with multiple enzymatic activities. CuMn-His enhanced peroxidase (POD)-like activity at neutral pH was achieved through hydrogen bonding and electrostatic effects. In addition, CuMn-His possesses laccase (LAC)-like and superoxide dismutase (SOD)-like activities at neutral pH. Based on three different enzyme mimetic activities of CuMn-His at neutral pH, the colorimetric sensing array without changing the buffer solution was successfully constructed. The array was successfully used for the identification of three biothiols, glutathione (GSH), cysteine (Cys), and homocysteine (Hcy). Subsequently, excellent application results were shown in complex serum and cellular level analyses. This study provides an innovative strategy for the development of ultrasmall bimetallic nanozymes with multiple enzymatic activities and the construction of colorimetric sensing arrays.
PubMed: 38940445
DOI: 10.1021/acsami.4c04844 -
Oncology Reports Aug 2024Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis... (Review)
Review
Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase‑4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells.
Topics: Humans; Neoplasms; Ferroptosis; S100 Calcium-Binding Protein A4; Ubiquinone; Lipid Peroxidation; Drug Resistance, Neoplasm; Animals; Glutathione; Antineoplastic Agents; Molecular Targeted Therapy
PubMed: 38940330
DOI: 10.3892/or.2024.8764 -
Journal of Integrative Neuroscience Jun 2024Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly... (Review)
Review
Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly by an imbalance in the activity of inhibitory and excitatory neural networks. Recurrent or prolonged seizures lead to neuronal death, which in turn promotes epileptogenesis and epileptic seizures. Ferrous ion-mediated cell death is known as ferroptosis, which is due to the accumulation of lipid peroxidation products resulting from compromise of the glutathione (GSH)-dependent antioxidant system. The pathophysiology of epilepsy has been linked to anomalies in the glutathione peroxidase 4 (GPX4)/GSH redox pathway, lipid peroxidation, and iron metabolism. Studies have shown that inhibiting ferroptosis may alleviate cognitive impairment and decrease seizures, indicating that it is neuroprotective. With the hope of aiding the development of more novel approaches for the management of epilepsy, this research aimed to examine the role of ferroptosis in this disease.
Topics: Ferroptosis; Humans; Epilepsy; Animals; Lipid Peroxidation; Iron
PubMed: 38940095
DOI: 10.31083/j.jin2306113 -
Frontiers in Bioscience (Landmark... Jun 2024The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by... (Review)
Review
The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by the accumulation of misfolded proteins, elevated reactive oxygen species (ROS) levels, and abnormal Ca2+ signaling, which was referred to ER stress (ERS). Ferroptosis was a unique programmed cell death model mediated by iron-dependent phospholipid peroxidation and multiple signaling pathways. The changes of mitochondrial structure, the damage of glutathione peroxidase 4 (GPX4) and excess accumulation of iron were the main characteristics of ferroptosis. ROS produced by ferroptosis can interfere with the activity of protein-folding enzymes, leading to the accumulation of large amounts of unfolded proteins, thus causing ERS. On the contrary, the increase of ERS level could promote ferroptosis by the accumulation of iron ion and lipid peroxide, the up-regulation of ferroptosis related genes. At present, the studies on the relationship between ferroptosis and ERS were one-sided and lack of in-depth studies on the interaction mechanism. This review aimed to explore the molecular mechanism of cross-talk between ferroptosis and ERS, and provide new strategies and targets for the treatment of liver diseases.
Topics: Ferroptosis; Humans; Endoplasmic Reticulum Stress; Liver Diseases; Reactive Oxygen Species; Animals; Signal Transduction; Iron; Lipid Peroxidation; Endoplasmic Reticulum
PubMed: 38940044
DOI: 10.31083/j.fbl2906221 -
Frontiers in Bioscience (Landmark... Jun 2024Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments...
BACKGROUND
Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments including cancer. Nevertheless, little is known regarding the toxic and therapeutic doses of AMG, particularly in terms of male reproduction. Hence, this study evaluates selected qualitative characteristics of rabbit testicular tissue following administration of AMG or apricot kernels for 28 days.
METHODS
The rabbits were randomly divided into five groups (Control, P1, P2, P3, P4). The Control received no AMG/apricot kernels while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose of 0.6 and 3.0 mg/kg of body weight (b.w.) for 28 days, respectively. P3 and P4 received a daily dose of 60 and 300 mg/kg b.w. of crushed apricot kernels mixed with feed for 28 days, respectively. Changes to the testicular structure were quantified morphometrically, while tissue lysates were subjected to the evaluation of reactive oxygen species (ROS) production, total antioxidant capacity, activities of antioxidant enzymes, and glutathione concentration. The extent of damage to the proteins and lipids was quantified as well. Levels of selected cytokines were determined by the enzyme-linked immunosorbent assay while a luminometric approach was used to assess the activity of caspases.
RESULTS
Rabbits treated with 3.0 mg/kg b.w. AMG presented a significantly increased protein oxidation ( = 0.0118) accompanied by a depletion of superoxide dismutase ( = 0.0464), catalase ( = 0.0317), and glutathione peroxidase ( = 0.0002). Significantly increased levels of interleukin-1 beta ( = 0.0012), tumor necrosis factors alpha ( = 0.0159), caspase-3/7 ( = 0.0014), and caspase-9 ( = 0.0243) were also recorded in the experimental group P2 when compared to the Control. No effects were observed in the rabbits treated with apricot kernels at the oxidative, inflammatory, and histopathological levels.
CONCLUSIONS
Apricot kernels did not induce toxicity in the testicular tissues of male rabbits, unlike pure AMG, which had a negative effect on male reproductive structures carried out through oxidative, inflammatory, and pro-apoptotic mechanisms.
Topics: Animals; Male; Rabbits; Testis; Amygdalin; Prunus armeniaca; Oxidative Stress; Reactive Oxygen Species; Antioxidants; Inflammation
PubMed: 38940029
DOI: 10.31083/j.fbl2906235 -
Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant...
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
METHODS
The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
RESULTS
PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
CONCLUSION
PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Ferroptosis; STAT3 Transcription Factor; Cell Line, Tumor; Bone Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Reactive Oxygen Species; Signal Transduction; Cell Movement; Disease Progression; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38940027
DOI: 10.31083/j.fbl2906207 -
Lab on a Chip Jun 2024Zeolitic imidazolate framework-8 (ZIF-8) encapsulating enzymatically active biomolecules has emerged as a novel biocompatible nanozyme and offers significant...
Zeolitic imidazolate framework-8 (ZIF-8) encapsulating enzymatically active biomolecules has emerged as a novel biocompatible nanozyme and offers significant implications for bioanalysis of various biomarkers towards early diagnosis of severe diseases such as cancers. However, the rapid, continuous and scalable synthesis of these nanozymes still remains challenging. In this work, we proposed a novel microfluidic approach for rapid and continuous synthesis of hemin@ZIF-8 nanozyme. By employing a distinctive combination of zigzag-shaped channel and spiral channel with sudden expansion structures, we have enhanced the mixing efficiency within the chip and achieved effective encapsulation of hemin in ZIF-8. The resulting hemin@ZIF-8 nanoparticles exhibit peroxidase-like activity and are capable of detecting free HO with a limit of detection (LOD) as low as 45 nM, as well as HO secreted by viable cells with a detection threshold of approximately 10 cells per mL. By leveraging this method, we achieved successful detection of cancer cells and effective screening of anticancer drugs that induce oxidative stress injury in cancer cells. This innovative microfluidic strategy offers a new avenue for synthesizing functional nanocomposites to facilitate the development of next-generation diagnostic tools for early disease detection and personalized medicine.
PubMed: 38939907
DOI: 10.1039/d4lc00290c -
Przeglad Gastroenterologiczny 2024Regulated cell death is a fundamental biological process that plays a crucial role in maintaining tissue homeostasis and eliminating damaged or unnecessary cells.... (Review)
Review
Regulated cell death is a fundamental biological process that plays a crucial role in maintaining tissue homeostasis and eliminating damaged or unnecessary cells. Ferroptosis is an iron-dependent process, characterized by the accumulation of oxidized and damaged lipids, which leads to programmed cell death. Among the ferroptotic pathway genes regulating this process, GPX4, TFRC, ACSL4, FSP1, SLC7A11, and PROM2 could be considered. There are many well-known ferroptotic pathway regulators, which are discussed in this compact review. Cells with tissues of different origin display sensitive or resistant phenotypes to such regulators. In some cases, unexpected changes during cell treatment occurred, suggesting the possibility of regulating the death pathway. We assumed that possible changing of ferro-sensitivity to ferro-resistance in cells, especially in colorectal cancer cell lines, is responded for induced chemoresistance. Using novel techniques, such as CRISPR/Cas-9 genome editing, an induced phenotype "switching" is possible.
PubMed: 38939059
DOI: 10.5114/pg.2024.134872 -
PeerJ 2024Tungsten (W) is an emerging heavy metal pollutant, yet research remains scarce on the biomonitor and sensitive biomarkers for W contamination.
BACKGROUND
Tungsten (W) is an emerging heavy metal pollutant, yet research remains scarce on the biomonitor and sensitive biomarkers for W contamination.
METHODS
In this study, celery and pepper were chosen as study subjects and subjected to exposure cultivation in solutions with five different levels of W. The physiological and biochemical toxicities of W on these two plants were systematically analyzed. The feasibility of utilizing celery and pepper as biomonitor organisms for W contamination was explored and indicative biomarkers were screened.
RESULTS
The results indicated that W could inhibit plants' root length, shoot height, and fresh weight while concurrently promoting membrane lipid peroxidation. Additionally, W enhanced the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and total antioxidant capacity (TAOC) to counteract oxidative damage. From a physiological perspective, pepper exhibited potential as a biomonitor for W contamination. Biochemical indicators suggested that SOD could serve as a sensitive biomarker for W in celery, while TAOC and POD were more suitable for the roots and leaves of pepper. In conclusion, our study investigated the toxic effects of W on celery and pepper, contributing to the understanding of W's environmental toxicity. Furthermore, it provided insights for selecting biomonitor organisms and sensitive biomarkers for W contamination.
Topics: Apium; Capsicum; Tungsten; Lipid Peroxidation; Superoxide Dismutase; Antioxidants; Catalase; Biomarkers; Ecotoxicology; Plant Roots; Plant Leaves; Oxidative Stress
PubMed: 38938608
DOI: 10.7717/peerj.17601