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Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world's poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family. The search for biomarkers associated with konzo disease has been a long-standing question within the research community. Here, the authors have uncovered a potential biomarker for konzo that is associated with the ability to manage oxidative damage. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction. [ABSTRACT FROM AUTHOR]

Organic selenium is a major antioxidant that can protect against oxidative stresses by stimulating the antioxidant cascades. We have evaluated the capacity of dietary selenium-enriched yeast (Se-Y) to alleviate thermal stress in juvenile Penaeus vannamei shrimp. The Se-Y level in the control group (Cont) was 0 mg Se kg−1 ration and 0.4 mg Se kg−1 in the AlkoSel and SelPlex groups (commercial Se-Y products). The shrimp were initially provided the three experimental diets while being maintained in their thermal comfort zone (28 °C) for 30 days, following which time the temperature was increased up to 33 °C for 1 and 6 h of induced heat stress challenge (IHSC). Variations in the levels of malondialdehyde (MDA), glutathione, and several transcriptional factors encoding antioxidant variables and stress-responsive proteins were analyzed in the gill, muscle, and hepatopancreas. The results revealed that the MDA and glutathione content of the shrimp were significantly impacted by Se-Y supplementation both before and after the IHSC. Prior to the IHSC, in all evaluated tissues, Se-Y supplementation enhanced the antioxidant variables (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) and heat shock protein (HSP) biosensors HSP70 and HSP90 while depressing the immune stress-related indices (gamma-interferon inducible lysosomal thiol reductase-like and aspartate aminotransferase cytoplasmic-like (AST). After IHSC, in all evaluated tissues, the AST gene was significantly downregulated in all Se-Y-fed groups while the other genes were upregulated. These results imply an important role of organic selenium in preventing organ dysfunctions after exposure to IHSC. Taken together, these findings on gene regulation after Se-Y pretreatment will be useful for monitoring organ dysfunction and preparing therapeutic agents for thermal endurance in P. vannamei. [ABSTRACT FROM AUTHOR]

λ-cyhalothrin, a synthetic type II pyrethroid, has become increasingly popular for control of aphids, butterfly larvae, and beetles, replacing other agricultural chemicals. As a result of which, residues of this synthetic pesticide are being reported across the globe in natural water, which poses a serious threat to aquatic life. Therefore, the present study was designed to understand the toxicity effects of λ-cyhalothrin on behaviour, oxidative stress and neurotoxicity in a vertebrate aquatic model, zebrafish (Danio rerio). The fish were exposed to 0.129, 0.194 and 0.388 µg/L corresponding to 5%, 10% and 20% of 96hLC50 (1.94 µg/L) for 28 days. Upon exposure to the highest concentration (0.388 µg/L), the test animal exhibited significant alterations in behavioural patterns like number of entries to the top zone (n), decrease in average speed (m/s) and decrease in time spent in top zone (s). Moreover, the shoaling test demonstrated a significant decrease (p < 0.05) in the relative time spent by the tested fish (%) near the stimulus fish. The change in behavioural alterations might be linked to a significant decrease (p < 0.05) in the brain acetylcholine esterase activity. Furthermore, the present study also illustrates oxidative stress exerted by λ-cyhalothrin through an increase in the production of reactive oxygen species, which is again clearly depicted by a significant increase (p < 0.05) in Superoxide dismutase, Catalase and Glutathione peroxidase activities. Overall, the present study systematically demonstrates the chronic effects of λ-cyhalothrin on adult fish behaviour and physiology, which will contribute to assessing the risks of λ-cyhalothrin to organismal health. [ABSTRACT FROM AUTHOR]

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

A 60 days study was conducted to evaluate the physiological response of indigenous species Labeo rohita (LR) and indigenous predator Chitala chitala (CC) in presence of an invasive species Piaractus brachypomus (PB). Two treatment groups as LR + PB (T1) and LR + PB + CC (T2) with individual control groups as T0LR, T0PB and T0CC were designed in triplicates. Fingerlings of LR, PB and CC were randomly distributed into 15 circular tanks with a stocking ratio of 1:1 and 1:1:0.3 in T1 and T2 group, respectively and 10 nos. each of LR, PB and CC in respective control groups. At first 15 min of the experiment, cortisol level was found significantly (P < 0.05) higher in all three experimental fishes in T1 and T2 groups. With the experimental duration, the level of stress hormone (cortisol), oxidative stress enzymes (superoxide dismutase, catalase, and glutathione peroxidase), tissue metabolic enzymes (lactate dehydrogenase and malate dehydrogenase), serum metabolic enzymes (transaminase enzymes) and blood glucose level were significantly (P < 0.05) increased in T1 and T2 groups for LR and CC whereas, no variation (P > 0.05) were observed for PB in both T1 and T2 groups. The total antioxidant capacity (TAC), liver glycogen, total protein, albumin and globulin were found to be significantly (P < 0.05) decreased in LR in the presence of PB and CC. The present study provides a preliminary insight into the biological interaction between native and invasive species and their physiological responses in the presence of native predator with higher trophic index. Thus, the results of the study suggest the superior traits of invasive P. brachypomus try to dominate the other two native species by negatively influencing the native fauna even with a higher trophic index (C. chitala). [ABSTRACT FROM AUTHOR]

Testicular torsion is a common disorder in males and results in blockage of testicular circulation with subsequent damage of testicular germ cells. The current work aimed to compare the therapeutic effect of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) on torsion/detorsion (T/D) injury in rats. Forty mature male Wister rats were arranged into 4 groups; (1) Control, (2) T/D, (3) T/D + PRP, and (4) T/D+ i-PRF. The right testis was twisting 1080° clockwise for 3 h in groups 2, 3 and 4, then 10 μl of PRP or i-PRF was injected intra-testicular 3 h after detorsion in groups 3 and 4, respectively. After 30 days postoperatively, the semen quality and hormonal assay were improved in PRP and i-PRF-treated groups with superiority of i-PRF (P < 0.001). High significance of Catalase, Glutathione Peroxidase (GPx), Superoxide Dismutase, Interleukin-1β (IL-1β), Caspase-3 and Tumor necrosis factor-α (TNF-α) was reported in treated rats with PRP and i-PRF (P < 0.001) with superiority to i-PRF-treated rats (P < 0.001). Testicular histoarchitectures were improved in PRP and i-PRF-treated rats with superiority of i-PRF-treated rats. It was concluded that PRP and i-PRF have regenerative efficacy on testicular damage after induced T/D injury with a superior efficacy of i-PRF. [ABSTRACT FROM AUTHOR]

The autolysis during live sea cucumber transportation is the main concern for the industry. This study aims to determine the effectiveness of ascorbic acid (AA) in reducing autolysis during the storage of live sea cucumbers. The live sea cucumbers were exposed for 5 days to seawater containing different concentrations of AA: 0, 5, 10, 15, 20, 25, 30, and 35 mg/L. Stored sea cucumber evaluation factors, including individual appearance, sensory score, histologic section, seawater ammonia nitrogen content, and free protein content, were tested. The reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation, activity change of catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), and genes expression level change of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), SOD, and GSH-PX were compared after storage. The results showed that the AA addition of 25 mg/mL led to a good live sea cucumber condition. The sensory score for AA treatment reached 79.8% of the fresh group, and its stored seawater contained the lowest levels of ammonia nitrogen and soluble protein among all treatment groups. Although the villi in the 25 mg/L treatment group showed slight breakage, they maintained a relatively intact structure with clear cytoplasm and nuclei. The lowest ROS and MDA levels were observed in the intestine and respiratory tree of the 25 mg/L treatment group. The addition of 25 mg/L of AA maximized the activities of CAT, GSH-PX, and SOD. Moreover, the expression of SDH, LDH, SOD, and GSH-PX genes was upregulated 8.8-fold, 5.8-fold, 5.1-fold, and 16-fold compared with the fresh group, respectively. Live sea cucumbers can be transported with 25 mg/L AA treatment, which prevents autolysis-induced deterioration. [ABSTRACT FROM AUTHOR]

Lead (Pb) is a common heavy metal, which negatively influences the health and performance of aquatic organisms. The aquatic pollution with Pb is increasing day after day due to the increase in human activities, agricultural, and mining activities among others. Lead was regarded as oxidative stressor causing mutagenic and physiological disorders in aquatic animals. Hence, the current perspective assessed the promoting effects of dietary mixture of rosemary plus cinnamon (R + C) intervention on growth, hemato-biochemical, and hepatic oxidative biomarkers in Nile tilapia (Oreochromis niloticus) exposed to a sub-lethal dose of lead nitrate (7.94 mg Pb/L) for 60 days. Fish were distributed into four equal groups; T1 was kept as a control group, T2 was fed on 10 g R + C/kg feed, and T3 and T4 were fed on the control diet and 10 g R + C/kg feed, respectively, along with lead nitrate exposure. Findings of the present study indicated that, upon exposure to Pb (T3), growth, hemato-biochemical, and immune indices in Nile tilapia were notably reduced compared with that of the control group (T1). Meanwhile, stress (blood glucose, cortisol, total cholesterol, lactate dehydrogenase, alanine and aspartate aminotransferase, and alkaline phosphatase), hepatic oxidative stress (superoxide dismutase, catalase, and glutathione peroxidase) biomarkers, and DNA fragmentation percentage were significantly augmented in T3 vs T1. Additionally, exposing fish to lead nitrate caused immune suppression compared with the control group (T3 vs T1). On the other hand, the dietary supplementation of R + C mix to Nile tilapia (T2) enhanced its growth performance, antioxidant, and immune status. Feeding Pb-intoxicated Nile tilapia on R + C mix (T4) mitigated the oxidative damage and immune suppression induced by lead nitrate exposure compared with T3. Based on the present study outcomes, we opine that feeding Nile tilapia with rosemary plus cinnamon mixture (10 g/kg feed) has protective effects against lead nitrate-induced stress, physiological alterations, and oxidative damage. [ABSTRACT FROM AUTHOR]

Ischemic stroke involves various pathological processes, among which ferroptosis is crucial. Previous studies by our group have indicated that electroacupuncture (EA) mitigates ferroptosis after ischemic stroke; however, the precise mechanism underlying this effect remains unclear. In the present study, we developed a rat model of middle cerebral artery occlusion/reperfusion. We chose the main acupoint of the treatment methods of the "Awakening and Opening of the Brain". Rats' neurological function and motor coordination were evaluated by neurological function score and the rotarod test, respectively, and the volume of cerebral infarction was analyzed by 2,3,5-triphenyltetrazolium chloride Staining. The cerebrovascular conditions were visualized by time-of-flight magentic resonance angiography. In addition, we detected changes in lipid peroxidation and endogenous antioxidant activity by measuring the malondialdehyde, glutathione, superoxide dismutase activities, glutathione/oxidized glutathione and reduced nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide adenine dinucleotide phosphate ratios. Inductively coupled plasma-mass spectrometry, western blot, reverse transcription-polymerase chain reaction, fluoro-jade B staining, immunofluorescence analysis, and transmission electron microscopy were utilized to examine the influence of EA. The results indicate that EA treatment was effective in reversing neurological impairment, neuronal damage, and protecting mitochondrial morphology and decreasing the cerebral infarct volume in the middle cerebral artery occlusion/reperfusion rat model. EA reduced iron levels, inhibited lipid peroxidation, increased endogenous antioxidant activity, modulated the expression of several ferroptosis-related proteins, and promoted nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation. However, the protective effect of EA was hindered by the Nrf2 inhibitor ML385. These findings suggest that EA can suppress ferroptosis and decrease damage caused by cerebral ischemia/reperfusion by activating Nrf2 and increasing the protein expression of solute carrier family 7 member 11 and glutathione peroxidase 4. [ABSTRACT FROM AUTHOR]

Lilium brownii (L. brownii) is a plant that can be used for both medicine and food. Its bulbs are commonly used to treat neurological disorders like depression, insomnia, and Parkinson's disease (PD). However, the mechanism by which it treats PD is not yet fully understood. This study aims to investigate the possible mechanism of L. brownii extract in treating PD and to compare the efficacy of ethanol and aqueous extracts of L. brownii. In this study, mice with PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) were given L. brownii extracts for 30 days, and the effects of both extracts were then evaluated. Our study demonstrated that both extracts of L. brownii effectively improved motor dysfunction in PD mice induced by MPTP. Additionally, they increased the number of neurons in the substantia nigra region of the mice. Moreover, both extracts reduced levels of malondialdehyde (MDA) and ferrous ion (Fe2+), while increasing levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum. They also influenced the expression of proteins associated with the p62-Keap1-Nrf2 pathway. Interestingly, while both extracts had similar behavioral effects, the ethanol extract appeared to have a more significant impact on individual proteins in the p62-Keap1-Nrf2 pathway compared to the aqueous extract, possibly due to its higher phenolic acid glyceride content. In conclusion, L. brownii shows promise as an effective and safe treatment for PD. [ABSTRACT FROM AUTHOR]

Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders. [ABSTRACT FROM AUTHOR]

Vesicle-associated membrane protein 8 (VAMP8), a soluble n-ethylmaleimide-sensitive factor receptor protein, acts as an oncogenic gene in the progression of several malignancies. Nevertheless, the roles and mechanisms of VAMP8 in colorectal cancer (CRC) progression remain unknown. The expression and prognostic significance of VAMP8 in CRC samples were analyzed through bioinformatics analyses. Cell proliferation was detected using CCK-8 and EdU incorporation assays and apoptosis was evaluated via flow cytometry. Western blot analysis was conducted to examine the protein expression. Ferroptosis was evaluated by measurement of iron metabolism, lipid peroxidation, and glutathione (GSH) content. VAMP8 was increased in CRC samples relative to normal samples on the basis of GEPIA and HPA databases. CRC patients with high level of VAMP8 had a worse overall survival. VAMP8 depletion led to a suppression of proliferation and promotion of apoptosis in CRC cells. Additionally, VAMP8 knockdown suppressed beclin1 expression and LC3-II/LC3-I ratio, elevated p62 expression, increased Fe2+, labile iron pool, lipid reactive oxygen species, and malondialdehyde levels, and repressed GSH content and glutathione peroxidase activity. Moreover, VAMP8 knockdown inhibited the activation of janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in CRC cells. Mechanistically, activation of the JAK/STAT3 pathway by JAK1 or JAK2 overexpression attenuated VAMP8 silencing-mediated anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on CRC cells. In conclusion, VAMP8 knockdown affects the proliferation, apoptosis, autophagy, and ferroptosis by the JAK/STAT3 pathway in CRC cells. [ABSTRACT FROM AUTHOR]

The clinical use of gentamicin (GM) is restricted by its nephrotoxic effects. This study aimed for the first time to elucidate the ameliorative effects of the monoterpene linalool (Lin) against GM-mediated acute kidney injury in rats. A total of thirty-two rats were subdivided into four equal groups: control (saline), Lin (100 mg/kg/day), GM (100 mg/kg/day), and GM + Lin (100 and 100 mg/kg/day). Lin and GM were intraperitoneally administered for 12 days. Our results illustrated that Lin ameliorated GM-mediated renal histopathological abnormalities and reduced serum urea and creatinine levels in rats exposed to GM. Lin treatment mitigated oxidative stress in nephrotoxic animals as manifested by reducing serum and renal levels of malondialdehyde and increasing the activities of serum and renal glutathione peroxidase and renal catalase. Moreover, Lin markedly inhibited GM-triggered inflammation by downregulating NF-κB, iNOS, TNF-α, and IL-1β and reducing renal myeloperoxidase activity and nitric oxide levels. Interestingly, Lin repressed GM-induced apoptosis, as reflected by a marked downregulation of Bax and caspase-3 expression, concurrent with the upregulation of Bcl2 expression. Finally, Lin administration led to a significant downregulation of TGF-β expression in nephrotoxic animals. In summary, Lin ameliorated GM-mediated nephrotoxicity in rats, at least through its antioxidant, anti-inflammatory, and anti-apoptotic activities and by modulating TGF-β. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a severe inflammatory disorder that has a high morbidity and mortality rate. Urolithin A (UA) is reported to have anti-inflammatory and anti-oxidative effects in ALI. However, its molecular mechanisms in ALI remain to be explored. Mice and BEAS-2B cells were administrated with lipopolysaccharide (LPS) to mimic the ALI model in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to detect the pathological injury of lung tissues. The levels of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and culture supernatant and the levels of oxidative stress markers in lung tissues were measured using ELISA. DCFH-DA probe was used to assess the reactive oxygen species (ROS) level. TUNEL staining and flow cytometry were performed to determine cell apoptosis. The key targets and pathways were confirmed by immunohistochemistry (IHC) and western blot. UA suppressed the pathologic damage, wet/dry weight ratio, and total protein and inflammatory cells in BALF. UA decreased neutrophil infiltration and proinflammatory cytokines production. UA reduced the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in pulmonary tissues. UA also inhibited cell apoptosis in lung tissues by decreasing Bax expression and increasing Bcl-2 expression. In addition, UA suppressed LPS-induced inflammatory factor production, ROS level, and cell apoptosis in BEAS-2B. Importantly, UA decreased the expression of HMGB1 in LPS-treated mice and BEAS-2B cells. HMGB1 overexpression greatly abrogated the inhibition of UA on inflammation, ROS, and cell apoptosis in LPS-administrated BEAS-2B. Furthermore, UA treatment suppressed the phosphorylated levels of p38, JNK, ERK, and p65 in LPS-administrated mice and BEAS-2B cells. UA alleviated lung inflammation, oxidative stress, and apoptosis in ALI by targeting HMGB1 to inactivate the MAPK/NF-κB signaling, suggesting the potential of UA to treat ALI. [ABSTRACT FROM AUTHOR]

The ecotoxicological consequences of azoxystrobin on land snails have not yet been addressed. Therefore, the present study aims to provide novel data on the threat of a commercial grade azoxystrobin (AMISTAR) at two environmentally relevant concentrations (0.3 µg/ml) and tenfold (3 µg/ml) on the model species, Theba pisana by physiological, biochemical, and histopathological markers for 28 days. Our results showed a reduction in animal food consumption and growth due to exposure to both azoxystrobin concentrations. It also induced oxidative stress and led to a significant decrease in lipid peroxidation (LPO) levels after 7 days of exposure, while the opposite effect occurred after 28 days. Except for the 7-day exposure, all treated snails had significantly reduced glutathione (GSH) content and increased catalase (CAT) activity at all-time intervals. Glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and protein content (PC) were elevated in treated snails at all-time intervals. Moreover, alterations in acetylcholinesterase (AChE) activity between a decrease and an increase were noticed. Additionally, azoxystrobin exerted changes in T. pisana hepatopancreas architecture. Our study suggests that azoxystrobin may have negative ecological consequences for T. pisana and highlights its potential risks to the natural environment. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression. [ABSTRACT FROM AUTHOR]

The present study aimed to find whether low doses of mixed mycotoxins would affect egg quality in laying hens, and to explore the oxidative stress induced liver damage through endoplasmic reticulum during summer stress. A total of 96 Jinghong laying hens, 36 wks of age, were divided into four treatments, with eight repetitions per treatment and three hens per repetition. All the hens were raised in summer (average temperature: 31.3 ± 0.5℃; average humidity: 85.5 ± 0.2%) for 28d. One treatment was fed a basal diet as control (CON), and the other three treatments were fed the same diets containing 3.0 mg/kg deoxynivalenol (DON), 0.5 mg/kg T-2 toxin (T-2), and 1.5 mg/kg DON + 0.25 mg/kg T-2 toxin (Mix). Albumen height and Haugh unit were decreased (P < 0.05) in the Mix group on day 14 and 28. The activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase were decreased (P < 0.05) in the DON, T-2, and Mix groups. The alkaline phosphatase level in DON, T-2, and Mix groups was significantly increased (P < 0.05). The level of interleukin-1β, interferon-γ, and tumor necrosis factor-α in the Mix group were higher (P < 0.05) than CON, DON, and T-2 groups. Mix group upregulated the mRNA expressions of protein kinase RNA-like ER kinase, activating transcription factor4, IL-1β, nuclear factor-κ-gene binding, and nuclear respiratory factor 2 in the liver (P < 0.05). The results showed that low doses of DON and T-2 toxin could cause oxidative stress in the liver, but DON and T-2 toxin have a cumulative effect on virulence, which can reduce egg quality and cause endoplasmic reticulum stress in the liver. [ABSTRACT FROM AUTHOR]

Sorafenib, as a first-line drug for advanced hepatocellular carcinoma (HCC), could trigger ferroptosis by inhibiting cystine/glutamate transporter. However, low-level intracellular iron and insufficient activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) confer impaired response to sorafenib. In this study, a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier (sora@Fe-MIL) was synthesized to escalate intracellular iron level and activate AMPK, further potentiating the ferroptotic effect of sorafenib. Remarkably, this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells, while manifesting negligible deleterious impact on normal cells. Two prominent ferroptosis biomarkers, glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), underwent pronounced downregulation, underscoring the efficacy of this strategy in inducing ferroptosis. Furthermore, the bioactivity of AMPK was considerably elevated, and its downstream targets were conspicuously inhibited by the treatment with sora@Fe-MIL. Using orthotopic HCC animal models, we observed a substantial suppression of primary in situ tumor growth, and ribonucleic acid (RNA) sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@Fe-MIL. In conclusion, we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib, thus resuscitating its therapeutic response in HCC patients. [ABSTRACT FROM AUTHOR]

Human disturbance and seawater intrusion have unpredictable effects on coastal species. Dune systems are crucial coastal habitats because they provide natural front protection against seawater influence. Adult plant stands in dunes are important since they maintain dune structure. This study evaluated salinity stress responses in adult plants of two key dune-building grasses differing in salt tolerance: Thinopyrum junceum (tolerant) and Calamagrostis arenaria (less tolerant). Cultivated plants were exposed to various seawater (SW) dilutions (Tap-Water, 6.25%, 12.5%, 25%, 50%, and 100%) and gas exchange measurements and oxidative stress biomarkers were determined after two months of treatment. Stress conditions were maintained until flowering to assess effects on the reproductive effort. The reproductive response showed high plasticity at various inflorescence stages in T. junceum, minimizing abortion processes. C. arenaria showed lower plasticity and higher abortion rates. Physiological traits responded similarly to salinity in both species, with greater effect on Fv/Fm decrease and non-photochemical quenching increase for T. junceum. Biochemical patterns of response were also similar, with increasing enzymatic activities at 25% SW treatment, mainly for glutathione reductase and peroxidase (GSH and GPx), and stress damage occurring at 50% and 100% SW treatments for increased malonaldehyde (MDA) levels. These findings provide insight into the salinity tolerance mechanisms of dune-building grasses. Higher salinity tolerance is suggested for T. junceum based on better reproductive effort. Higher juvenile tolerance, faster growth, and plant cycle adjustments are indicated as key traits for higher salinity tolerance of T. junceum in contrast to C. arenaria. [ABSTRACT FROM AUTHOR]

In the present study, plasma activated water (PAW) immersion with different discharge times were applied to investigate their effects on broccoli seed germination, sprouts growth, antioxidant enzyme activities, polyphenol and anthocyanin content as well as sulforaphane formation. The seed germination rate, germination index, vigor index, water absorption, wettability and sprouts growth were promoted by PAW treatments, and plasma discharge for 30 min (PAW30) treatment showed the best germination rate and sprouts growth. No significant difference was found in color, polyphenol and anthocyanin content as well as myrosinase activity among different PAW treatments. The superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione peroxidase (GPX) enzyme activities of broccoli sprouts were enhanced significantly by all PAW treatments. Besides, PAW15, PAW30 and PAW60 treatments also increased significantly the sulforaphane formation of 5 d sprouts, which increased by 7.09%, 10.34% and 5.43% compared to the control, respectively. Therefore, these data indicated that seeds immersed with PAW30 could be used as a promising strategy to enhance the seed germination and quality of broccoli sprouts. [ABSTRACT FROM AUTHOR]

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities. This illustrates that gamma radiation–induced intestinal injury in mice is indicated by an increase in mitochondrial oxidative stress, reactive oxygen species, and intestinal inflammation. The apoptosis marker was increased after irradiation that leads to intestinal damage through the TLR-4 and Hmgb-1 pathways. MitoQ and its hyaluronic acid–based nanopreparation improve all previously mentioned parameters. [ABSTRACT FROM AUTHOR]

In this study, 7500 Anabas testudineus (climbing perch) larvae were fed different diets, including vitamin E-enriched Moina micrura and egg custard-based inert diet, to study their growth, survival and physio-metabolic responses over a 30-day rearing period. The study comprised two control groups: C1, which received 100% vitamin E-enriched Moina for 30 days, and C2, which received a 100% egg custard-based inert diet for 30 days. Additionally, three treatment groups were included, which were fed with varying levels of enriched Moina and egg custard in different ratios and for different durations through co-feeding regimens. The egg custard-based inert diet had 40.98% crude protein and 6.69% ether extract. The results of the present study indicated that final body weight, weight gain, and specific growth rate were significantly (p ˂ 0.05) higher in T3 group, in which larvae fed with 75% enriched Moina + 25% egg custard for first 15 days, 50% enriched Moina + 50% egg custard for next 5 days, 25% enriched Moina + 75% egg custard for next 5 days; 0% enriched Moina + 100% egg custard for next 5 days. In addition, significantly (p ˂ 0.05) higher survival was obtained in C1 followed by T3 group. The appropriate co-feeding strategy based on digestive enzyme activity was observed in T3 and T2 groups. In terms of glucose, cortisol, superoxide dismutase (SOD), and catalase (CAT) levels, no significant difference (p ˃ 0.05) was observed between C1 and T3 groups. Moreover, significantly (p ˂ 0.05) higher levels of glutathione peroxidase (GPx) activity were observed in C1 and T3 groups. The activity of metabolic enzymes was also significantly affected by the co-feeding strategy. Overall, the T3 group showed improved growth and enzyme activity compared to other treatments. Thus, the present study establishes a co-feeding strategy by using vitamin E-enriched M. micrura and egg custard-based inert diet at levels as followed for the T3 group to boost the growth performance and physio-metabolic activity in A. testudineus larvae. [ABSTRACT FROM AUTHOR]

Background: Echis ocellatus venom toxins have the ability to impact multiple organ systems subsequent to envenomation. Kaempferol have been reported to have several therapeutic benefits. In this study, the therapeutic value of kaempferol was investigated in relation to the cardio-nephrotoxicity in rats resulting from E. ocellatus envenoming. Methods: Fifty male wistar rats were allotted unbiased into five groups (n = 10) for this study. Group 1 was the control, while rats in groups 2 to 5 were envenomed with LD50 of E. ocellatus venom (0.22 mg/kg bw; i.p.). Group 2 was not treated after envenomation while groups 3, 4 and 5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respectively. Results: E. ocellatus envenomation caused considerable reduction in organ weight and relative organ weight in the envenomed untreated rats. The venom induced intense oxidative stress, inflammation, apoptotic damage to the cardiac and renal tissues accompanied with severe histomorphology in the organ tissues of untreated envenomed rats. In contrast, kaempferol treatment post-envenomation attenuated the venom-induced cardio-nephrotoxic responses in a dose dependent effect. Kaempferol substantially (p < 0.05) decreased malondialdehyde levels while enhancing reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities in the heart and kidney of envenomed treated rats. Treatment of envenomed rats with kaempferol successfully decreased nitric oxide levels and myeloperoxidase activity. Overexpression of apoptotic caspase 3 and caspase 9 in cardiac and renal tissues were suppressed by kaempferol (p < 0.05). The histopathological result supports kaempferol's ameliorative ability by convalescing the severe morphological alterations of cardiac and renal tissues induced by the venom. Conclusion: Findings elucidate the significance of kaempferol as promising agent in the management of cardio-nephrotoxicity resulting from snakebite envenoming. [ABSTRACT FROM AUTHOR]

Triclosan (TCS), an antimicrobial additive in various personal and health care products, has been widely detected in aquatic environment around the world. The present study investigated the impacts of TCS in the gills of the fish, Cyprinus carpio employing histopathological, biochemical, molecular docking and simulation analysis. The 96 h LC50 value of TCS in C. carpio was found to be 0.968 mg/L. Fish were exposed to 1/1000th (1 µg/L), 1/100th (10 µg/L), and 1/10th (100 µg/L) of 96 h LC50 value for a period of 28 days. The histopathological alterations observed in the gills were hypertrophy, hyperplasia, edematous swellings, and fusion of secondary lamellae in TCS exposed groups. The severity of these alterations increased with both the concentration as well as the duration of exposure. The present study revealed that the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and reduced glutathione content decreased significantly (p < 0.05) in both concentration and duration dependent manner. However, a significant (p < 0.05) increase in the activity of the metabolic enzymes such as acid phosphatase and alkaline phosphatase was observed in all three exposure concentrations of TCS from 7 to 28 days. The activity of acetylcholinesterase declined significantly (p < 0.05) from 7 to 28 days whereas the content of acetylcholine increased significantly at the end of 28 day. The experimental results were further confirmed by molecular docking and simulation analysis that showed strong binding of TCS with acetylcholinesterase enzyme. The study revealed that long-term exposure to sublethal concentrations of TCS can lead to severe physiological and histopathological alterations in the fish. [ABSTRACT FROM AUTHOR]

In this study, effect of different stocking densities on growth, oxidative stress, antioxidant enzymes, and hematological and immunological values in European catfish (Silurus glanis) was examined. The control (0.06 kg fish/L) and trial (T) 1 (0.08 kg fish/L), T2 (0.10 kg fish/L), and T3 (0.12 kg fish/L) stocking groups were used. Each stocking group with three replicates was carried out in a tank at 22 ± 2 °C water temperature. The fish were fed three times daily for 60 days. The highest final weight (123.3–171.6 g), weight gain (84.13–159.6%), specific growth rate (1.40–2.66%), feed intake (138.5–178.2 g/fish), and feed conversion rate (1.12–1.65%) were provided from the control and T1 stockfish (p > 0.05), followed by the T2 and T3 stockfish (p < 0.05), respectively. The lowest oxidant level and the highest reduced glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities were obtained from the control fish, followed by the T1, T2, and T3 stockfish, respectively (p < 0.05). In addition, parallel to the increase in stocking density, the erythrocyte count, hematocrit, hemoglobin, erythrocyte volume, corpuscular hemoglobin, and corpuscular hemoglobin concentration values of fish increased (p < 0.05), but the leukocyte count, nitroblue tetrazolium activity, total protein, and immunoglobulin-M values decreased (p < 0.05). The high stocking densities caused oxidative stress in fish, negatively affecting their health and growth and feed evaluation values. However, the stocking density could increase to 0.08 kg/L from 0.06 kg/L in the European catfish fingerling reared in the recirculating aquaculture system by maintaining the water quality and applying good care and feeding. [ABSTRACT FROM AUTHOR]

This study investigated the dietary thiamine (vitamin B1) requirement of Pacific white shrimp (Penaeus vannamei) for optimal growth performance, feed utilization, and innate immunity. Six test diets were formulated to contain thiamine at 3.32, 20.8, 38.7, 60.2, 80.7, and 108 mg/kg of diet (designated as T0, T20, T40, T60, T80, and T100, respectively). A total of 360 shrimp (6.03 ± 0.03 g) were randomly assigned into 24 acryl tanks (240 L) to be quadruplicated per treatment, and feeding was done in six equal portions daily for 58 days. The T20 diet fed group exhibited significantly higher growth performance compared to shrimp fed T0 and T100 diets. Feed conversion ratio and protein efficiency ratio were not significantly different among experimental groups. A significantly higher phenoloxidase activity was exhibited in T20 dietary group than T0 and T100 groups. Lysozyme activity was significantly enhanced in T20, T40, T60, and T80 groups than in T0 group and antiprotease activity was not significantly affected. Antioxidant parameters: superoxide dismutase and glutathione peroxidase activities were significantly elevated in T20 dietary treatment group. Significantly upregulated proPO gene expression was observed in T20 and T40 dietary treatment groups, although penaidine 3a and insulin-like growth factor-1 relative gene expressions were not significantly different. Glucose, total cholesterol, triglyceride, and total protein levels in hemolymph were not significantly different. Intestinal histology observations did not show significant differences in villi heights. A piecewise regression of weight gain percentage (WG%) estimates the optimal dietary thiamine requirement of P. vannamei at 19.7 mg/kg of diet. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by oxidative stress and neuroinflammation as key pathological features. Emerging evidence suggests that nuclear factor erythroid 2 related factor 2-antioxidant response element (Nrf2-ARE), phosphatidylinositol 3‑kinase-protein kinase B (PI3K-Akt), c-Jun N-terminal kinase-extracellular signal-regulated kinase 1/2 (JNK-ERK1/2), and toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kB) pathways play pivotal roles in PD pathogenesis. Orientin, a phenolic phytoconstituent, has demonstrated modulatory potential on these pathways in various experimental conditions other than PD. In this study, we aimed to evaluate the neuroprotective effects of Orientin against rotenone-induced neurodegeneration in SH-SY5Y cell lines and the Swiss albino mice model of PD. Orientin was administered at doses 10 and 20 µM in cell lines and 10 and 20 mg/kg in mice, and its effects on rotenone-induced neurodegeneration were investigated. Oxidative stress markers including mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as inflammatory markers including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured. The expression levels of genes related to Nrf2-ARE (Nrf2), PI3K/Akt (Akt), JNK-ERK1/2 (TNF-α), and TLR4/NF-kB (TNF-α) pathways were measured to understand the modulatory effect of Orientin on these pathways. Additionally, behavioral studies assessing locomotor activity, muscle coordination, and muscle rigidity were conducted with mice. Our results indicate that Orientin dose-dependently attenuated rotenone-induced changes in oxidative stress markers, inflammatory markers, gene expression levels, and behavioral parameters. Therefore, our study concludes that Orientin exhibits significant neuroprotective benefits against rotenone-induced PD by modulating Nrf2-ARE, PI3K-Akt, JNK-ERK1/2, and TLR4/NF-kB pathways. [ABSTRACT FROM AUTHOR]

Ferroptosis of the retinal pigment epithelial (RPE) cells leads to retinal neuron injury and even visual loss. Our study aims to investigate the role of the SET domain with lysine methyltransferase 7/9 (SET7/9) in regulating high glucose (HG)-induced ferroptosis in RPE cells. The cell model was established by HG treatment. The levels of SET7/9 and Sirtuin 6 (SIRT6) were inhibited and Runt-related transcription factor 1 (RUNX1) was overexpressed through cell transfection, and then their levels in ARPE-19 cells were detected. Cell viability and apoptosis was detected. The levels of reactive oxygen species, malondialdehyde, glutathione, ferrous ion, glutathione peroxidase 4, and acyl-CoA synthetase long-chain family member 4 were detected. SET7/9 and trimethylation of histone H3 at lysine 4 (H3K4me3) levels in the RUNX1 promoter region and RUNX1 level in the SIRT6 promoter region were measured. The relationship between RUNX1 and SIRT6 was verified. SET7/9 and RUNX1 were highly expressed while SIRT6 was poorly expressed in HG-induced ARPE-19 cells. SET7/9 inhibition increased cell viability and inhibited cell apoptosis and ferroptosis. Mechanistically, SET7/9 increased H3K4me3 on the RUNX1 promoter to promote RUNX1, and RUNX1 repressed SIRT6 expression. Overexpression of RUNX1 or silencing SIRT6 partially reversed the inhibitory effect of SET7/9 silencing on HG-induced ferroptosis. In conclusion, SET7/9 promoted ferroptosis of RPE cells through the SIRT6/RUNX1 pathway. [ABSTRACT FROM AUTHOR]

The antioxidant (AO) defense complex in tissues of the scallop Flexopecten glaber ponticus (Bucquoy, Dautzenberg et Dollfus, 1889) from a natural habitat in the Black Sea is studied for the first time. The results indicate a pronounced tissue specificity of the scallop AO complex along with close levels of TBA-reactive substances in all the studied organs. In the gills of the scallop, the activity of glutathione reductase (GR), superoxide dismutase (SOD), and catalase is higher than in the hepatopancreas. The activity of glutathione peroxidase (GP), GR, and catalase in the gills is higher than in the muscle. The reduced glutathione (GSH) reserve in the gills is lower than in the hepatopancreas. This indicates that both the glutathione system and the key antioxidant enzymes, SOD and catalase, significantly contribute to the antioxidant defense of the scallop gills. In the hepatopancreas, the level of glutathione is the highest and the activity of GP is high and similar to that in the gills. This reflects their significant role in the AO defense of this organ. However, the activity of GR, SOD, and catalase in the hepatopancreas is significantly lower than in the gills. The scallop muscle is characterized by the lowest GP activity and a low GSH level, close to that in the gills. The SOD activity in the muscle is comparable to its value in the gills, and the activity of catalase and GR is comparable to the values in the scallop's hepatopancreas. [ABSTRACT FROM AUTHOR]

Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3′-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents. [ABSTRACT FROM AUTHOR]

The histogenesis of reaction wood in woody plants is a promising area of exploration for emerging wood technology products and for a generalized understanding of stress physiology. The activity of total protein and antioxidant enzymes were measured during the development of normal and reaction wood (opposite wood and tension wood) in the bole of poplar trees (Populous alba L.) induced by two levels of sustained bending stress to produce moderate and severe reaction wood. Four-year-old poplars were induced to produce reaction wood by sustained bending to 0, 35 and 80° from the vertical position. The activity of antioxidant enzymes was studied with repeated sampling during one growing season. Severe reaction wood showed higher levels of H2O2 and enzymes than moderate reaction wood. Tension wood showed a higher accumulation of total protein than opposite wood at the beginning and end of the bending treatment and opposite wood showed higher enzymatic activity. H2O2 and antioxidant enzymes were also sensitive to mechanical bending stress; compared to normal wood, tension wood and opposite wood which showed higher enzymatic activity coupled with higher amounts of total H2O2. Ascorbate peroxidase was more active than glutathione peroxidase in both tension and opposite wood at some periods of sampling. [ABSTRACT FROM AUTHOR]

Indoxacarb is one of the most extensively used oxadiazine insecticides worldwide, but it may exert detrimental effects on ecosystems, population dynamics, and health. Due to the lack of knowledge on the ecotoxicity of indoxacarb, it is still challenging to assess whether this insecticide poses an ecotoxicological impact on terrestrial environments. Therefore, our study aims to provide novel data on the toxic effects of 28-day dietary exposure to commercial grade indoxacarb at two environmentally relevant concentrations, 0.02 µg/mL and tenfold (0.2 µg/mL) on the model species, Theba pisana. Their effects were studied using a multiple biomarker approach by evaluating physiological, biochemical, and histopathological responses. After 28 days of treatment, indoxacarb at both concentrations significantly reduced the food intake and growth of the treated snails. Also, it caused decreases in lipid peroxidation (LPO) levels after 7 and 14 days of exposure, whereas an opposite effect occurred after 21 and 28 days. All treated snails were found to exhibit a lower content of glutathione (GSH) after all times of exposure. Moreover, catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) activities, as well as protein content (PC), were elevated in the treated snails after all time intervals. Post exposure to both realistic indoxacarb concentrations, changes in acetylcholinesterase (AChE) activity between a decrease and an increase were observed. Furthermore, indoxacarb caused histo-architectural changes in the hepatopancreas of T. pisana. Our results demonstrate that, at environmentally relevant concentrations, indoxacarb poses negative consequences for T. pisana, indicating its ecotoxicological impacts. [ABSTRACT FROM AUTHOR]

Bakuchiol (Bak) possesses a protective effect in acute lung injury (ALI). Nonetheless, the molecular processes that regulate the protective activity of Bak in ALI remain elusive. Lipopolysaccharide (LPS)–treated rats and RLE-6TN cells were used as the ALI models in vivo and in vitro to investigate the function and mechanism of Bak. Rats were divided into four groups: control, LPS, LPS + Bak (30 mg/kg), and LPS + Bak (60 mg/kg). RLE-6TN cells were assigned into four groups: control, LPS, LPS + Bak (10 µM), and LPS + Bak (20 µM). Myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) levels were detected by immunohistochemistry (IHC). The levels of TNF-α, IL-6, and IL-1β were quantified by ELISA. Apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were assayed to evaluate oxidative stress. In LPS-induced rats, Bak attenuated pathological injury, lung wet/dry weight ratio, MPO expression, and protein concentration and cell number in bronchial alveolar lavage fluid (BALF). Bak decreased the secretion of TNF-α, IL-6, and IL-1β in BALF. Bak reduced MDA content and 4-HNE expression, and increased SOD and GSH-Px activities in lung tissues. Bak also repressed pulmonary apoptosis by decreasing Bax expression and enhancing Bcl-2 expression. In LPS-treated RLE-6TN cells, Bak downregulated the mRNA levels of TNF-α, IL-6, and IL-1β and inhibited the protein expression of iNOS and COX2. Bak decreased MDA level and ROS production and increased SOD and GSH-Px activities. Bak also suppressed cell apoptosis, reduced Bax expression, and increased Bcl-2 expression. Moreover, Bak decreased the expression of TLR4, MyD88, p-IκBα, and p-p65. Additionally, Bak inhibited Keap1 expression and increased Nrf2 and HO-1 levels. Bak protects against LPS-induced inflammation, oxidative stress, and apoptosis in ALI by regulating TLR4/MyD88/NF-κB and Keap1/Nrf2/HO-1 pathways. [ABSTRACT FROM AUTHOR]

The control of biological cell death is essential for the body's appropriate growth. The resistance of cells to the apoptotic process presents a new difficulty in the treatment of cancer. To combat cancer cells, researchers are working to find new apoptotic pathways and components to activate. One of the processes of regulated cell death (RCD) is referred to as ferroptosis marked by a decline in the activity of lipid glutathione peroxidase 4 (GPX4) after the buildup of reactive oxygen species (ROS). Since lipid peroxidation is a crucial component of ferroptosis and is required for its start, numerous medicines have been studied, particularly for the treatment of cancer. In this context, autophagy is an additional form of RCD that can govern ferroptosis through shared signaling pathways/factors involved in both mechanisms. In this review, we will explore the molecular mechanisms underlying ferroptosis and its association with autophagy, to gain fresh insights into their interplay in cancer advancement, and the potential of natural products for its treatment. [ABSTRACT FROM AUTHOR]

In Egypt, the temperature of the water fluctuates drastically, reaching a daytime high of 25 °C and a nighttime low of 15 °C, respectively, in the spring and the fall. To understand the mechanism behind fish kill in fish farms, an indoor experiment was conducted wherein 240 Nile tilapia weighing 24 ± 2.5 g were stocked in 12 glass aquaria (20 fish/aquarium). Water temperature was regulated throughout the day at 27 ± 1.5 °C for 12 h from 8:00 a.m. to 8:00 p.m. and at 18 ± 1.5 °C for the remaining 12 h. Fish samples (mucus and tissues) were collected four times with a week interval. Proinflammatory tumor necrosis factor-α and interleukin (IL)-1β were decreased during the 4 weeks, while anti-inflammatory IL-10 was highly upregulated during the first week and then decreased compared to the control. Heat shock protein-70 was significantly raised, but IL-8 was unaffected. The gene expressions of antioxidant enzymes catalase and glutathione peroxidase were markedly elevated in the first week and then decreased linearly until they no longer differed from the control group. Mucus lysozyme significantly decreased in weeks 1 and 2 and then began to increase in weeks 3 and 4. Every week, Aeromonas hydrophila infection resulted in clinical signs that were delayed by over 2 days compared to the control group. The mortality rate increased from 35 to 40%, and bacteria were isolated at a rate of 61.54 to 75% from the surviving fish, compared to a rate of 41.67% in the control group. Fluctuations in water temperature suppress the immunity of Nile tilapia, making them vulnerable to bacterial infection. [ABSTRACT FROM AUTHOR]

The Pacific white shrimp (Litopenaeus vannamei) is an economically important aquaculture species worldwide. Antioxidant immune performance is an important indicator of healthy growth and physiology of aquatic organisms. In this study, we compared the antioxidant capacity and immune response between a low salt tolerant hybrid and a normal variety of shrimp (control) cultured at different salinities (1‰, 5‰, and 15‰). At 1‰ salinity, the apoptotic cell numbers, apoptosis rate, and reactive oxygen content of the hybrid group were significantly lower than those of the control group. The hybrid group also had stronger antioxidant enzyme activities (glutathione peroxidase, glutathione transferase, superoxide dismutase, catalase) and higher gene expression levels. In addition, the hybrid group cultured at low salinity (1‰ and 5‰) had significantly higher total hemocyte count, phagocytic rate, and respiratory burst than the control group. Similarly, the hybrid group had higher immune-related enzyme (acid phosphatase, alkaline phosphatase, lysozyme, phenol oxidase) activities and gene expression levels than the control group at low salinity. These results show that the hybrid population had better antioxidant and immune capacity than the normal variety when cultured under low salinity conditions, and they lay the foundation for selection and breeding of low-salt tolerant, high-quality Pacific white shrimp. [ABSTRACT FROM AUTHOR]

Medicinal plants have been proposed as potential therapeutic agents for the treatment and prevention of various oxidative stress-related disorders. The purpose of this study was to investigate the effect of Echinops persicus (Ec.P) extract on catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in different rat tissues after carbon tetrachloride (CCl4) intoxication. A total of 38 rats weighing 180–210 g were randomly divided into eight groups of five. Rats in group 1 received only a standard diet and served as the control group, those in group 2 were given olive oil, and the rats in group 3 received olive oil + CCl4. Groups 4 to 8 were experimental groups. Rats of the experimental groups received olive oil + CCl4 in a ratio of 1 : 1 v/v daily for 7 days. After this period, vitamins C and E were given in 10 mg/kg doses to groups 4 and 5, respectively. Rats of groups 6, 7, and 8 were also treated with 0.5, 1, and 2 g/kg body weight of Ec.P extract, respectively, for the next seven days. The kidney, liver, and heart supernatants of all rats were used to measure enzyme activities. Results: Decreased activity of SOD, CAT, and GPx were found in the liver, kidney, and heart after CCl4 intoxication. The aqueous extract of Ec.P showed a significant protective effect by elevating antioxidant enzyme activities, compared to vitamins C and E in a dose and tissue-dependent manner. The obtained results of the current study highlighted the protective effect of Ec.P extract on antioxidant enzyme activities. The Ec.P could probably be significant in treating oxidative stress-related disorders. [ABSTRACT FROM AUTHOR]

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats. [ABSTRACT FROM AUTHOR]

Oxidation in living cells can be very detrimental, leading to the production of chemicals that can cause ill-health in these cells. These chemicals simply referred to as reactive oxygen species (ROS) have been implicated in causing different health problems, notably diabetes. Parquetina nigrescens is a medicinal plant that has been traditionally used in management of different kinds of ailments including diabetes over the years, but it lacks scientific proof. This study carried out the structural elucidation of aqueous leaf extract of P. nigrescens using HPLC. The study also investigated the antioxidant potentials of this extract in serum, liver, and kidney of diabetic male albino rats. The HPLC analysis revealed the presence of beta sitosterol, veraquensin, kaempferol, among others. Furthermore, aqueous leaf extract of P. nigrescens significantly (P < 0.05) improved the activities of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase, and reduced glutathione). Aqueous leaf extract of P. nigrescens may serve as an antioxidant to ameliorate activities of ROS that might cause advert effects in living cells. The coherent bioactive compounds in the aqueous leaf extract of this plant may be responsible for these antioxidant potentials. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the role of circSlc8a1 in cardiac hypertrophy (CH), a pathological change in various cardiovascular diseases. Methods: An in vitro CH model was established using angiotensin II (AngII) treated H9c2 cells, followed by western blotting and RT-qPCR for detecting relative expressions. Cell viability and proliferation were analyzed using CCK-8 and EdU assays, while lactate dehydrogenase (LDH), reactive oxygen species (ROS), glutathione (GSH), and iron levels were determined using corresponding kits. Moreover, dual-luciferase reporter and RNA pull-down assays were performed to demonstrate whether miR-673-5p is bound to circSlc8a1 or transferrin receptor (TFRC). Results: The results indicated that the expressions of circSlc8a1 and TFRC were increased, while miR-673-5p was decreased in the AngII treated H9c2 cells. The ferroptosis inhibitor treatment decreased the atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-major histocompatibility complex (β-MHC) protein expressions, and circSlc8a1 expressions. Knocking down of circSlc8a1 inhibited promoted the cell viability and proliferation, increased the GSH content, glutathione peroxidase 4, and solute carrier family 7 member 11 protein expressions, and decreased the LDH, ROS, iron levels, and RAS protein expressions. The MiR-673-5p inhibitor antagonized the role of si-circSlc8a1, and the over-expressed TFRC reversed the miR-673-5p mimicking effects in AngII treated H9c2 cells. Conclusion: CircSlc8a1 promoted the ferroptosis in CH via regulating the miR-673-5p/TFRC axis. [ABSTRACT FROM AUTHOR]

Increasing leaf chlorophyll content in crops through genetic improvement is a feasible way to increase crop yield. However, the genetic mechanism that regulates the chlorophyll content of rapeseed leaves is not clear, which is not conducive to improving it through genetic pathways. In this study, a population of 189 recombinant inbred lines of Brassica napus was used to identify quantitative trait loci (QTLs) that regulate leaf chlorophyll content. A total of 12 QTLs were identified, of which two QTLs, qCHC.A6-2 and qCHC.C5-1, explained 10.19% and 13.70% of the phenotypic variations in chlorophyll content, respectively, and were considered to be major QTLs. Furthermore, five of the 12 QTLs were inherited from APL01, while seven were inherited from Holly. Comparative transcriptomic analysis revealed that the differential expression of genes associated with the response to light stimulation, chloroplast organization, and glutathione peroxidase activity is the molecular basis for the difference in leaf chlorophyll content between APL01 and Holly. Further combining the variation analysis of the genomic DNA sequence and the functional annotation of homologous genes, four promising candidate genes (BnaA06g37690D, BnaA06g37710D, BnaC05g00280D, and BnaC05g00300D) were obtained, all of which are potentially involved in the response to light stimulation and/or chloroplast organization. These results help to clarify the genetic mechanism of chlorophyll content in B. napus leaves. [ABSTRACT FROM AUTHOR]

Drought stress negatively influences agricultural land and production worldwide. Therefore, it is crucial to reduce the deleterious impacts of drought on cereal crops. However, the potential of melatonin in the mitigation of drought stress is not clearly understood especially in crop plants. The present study investigates the impact of different methods (seed priming and foliar) and concentrations (0, 40, 80, 120, and 160 µM) of melatonin on pearl millet (Pennisetum glaucum L. R. Br.) under drought stress. Impact of melatonin was determined by examining the growth, photosynthesis, osmolyte production, oxidative damage, antioxidant enzyme activities, and expression pattern of antioxidant-responsive genes under drought. The exogenous melatonin at different concentrations differentially improved the growth, physiological, and biochemical traits of pearl millet under drought stress. In both treated methods, melatonin positively regulated the expression pattern of antioxidant-responsive genes that are involved in drought tolerance. Moreover, melatonin improved the proline content and reduced oxidative damage by decreasing hydrogen peroxide (H2O2) and malondialdehyde (MDA) content. Moreover, a significant improvement in the activities of antioxidants such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione peroxidase (GPX), and glutathione reductase (GR) was noted in pearl millet under drought on exposure to melatonin. The seed priming at 120 µM and foliar at 160 µM was found very effective for pearl millet growth under drought. Overall, the present study suggested that seed treatment and foliar treatment of melatonin differentially mitigated the drought stress in pearl millet. [ABSTRACT FROM AUTHOR]

Current technologies have become a source of electromagnetic pollution resulting from artificially generated electromagnetic radiation (EMR). To understand the influence of the EMR on living organisms, we investigated the long-term effects of EMR of 50 Hz frequency on duckweed (Lemna minor) clones. Experimental groups of duckweed were treated directly and indirectly by changing EMR generating magnetic flux (MF) starting from 2 µT (0–11 weeks from the beginning of the experiment) and switching to 300 µT (12–48 weeks) MF density during the second part of the experiment. The growth parameters (plant growth, frond area, and frond number) and the point mutations appearing at the antioxidant genes DNA sequences [ascorbate peroxidase (APx), glutathione peroxidase (GPx), and catalase (Cat)] were analyzed. The significantly enhanced number of nucleotide substitutions in DNA sequences of L. minor clones directly affected by LF EMR in comparison to indirectly affected clones was revealed at the introns of APx, GPx, and Cat genes starting from the 10th week of the experiment. The results indicate that even low-dose chronic electromagnetic radiation may contribute to the changes in growth parameters and generation of point mutations in antioxidant gene sequences, especially in the intron regions. [ABSTRACT FROM AUTHOR]

We investigated the dietary effects of the single application of Saccharomyces cerevisiae, Lactobacillus bulgaricus, and their combination on growth, proximate composition of whole fish body, antioxidant defense, and histoarchitecture of hapa-reared Mugil capito. Healthy fish (Fish weighed = 10.30 ± 0.10 g at first) were randomly allocated into 4 equal groups, each with three replicates. These groups were designed as follows: (1) a group fed a basal diet without probiotics (control), (2) a group fed a diet containing S. cerevisiae (4 g/kg diet), (3) a group fed a diet containing L. bulgaricus (2 g/kg diet), and (4) the last group fed a diet containing a combination of both, all for a duration of 60 days. Probiotic-treated groups showed significantly better growth and nutrition utilization than the control group. Significant differences were observed in the crude fat and crude protein contents among the groups, with the combination group exhibiting the highest levels. However, there were no significant variations in ash content across all groups. The highest hepatic antioxidant capacity (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activities) was observed in the combination group. Thiobarbituric acid reactive substance (TBARS) concentrations were decreased significantly in all probiotic groups, suggesting improved oxidative stress resilience in these groups. The histomorphological analysis of the hepatopancreatic tissues revealed well-arranged parenchyma, increased glycogen storage, and melanomacrophage centers in probiotic-treated groups, particularly the combined probiotics group. Furthermore, the probiotic supplementation improved the histoarchitecture of the intestinal villi compared to the control group. To put it briefly, combined dietary administration of these probiotics improved growth, body composition, antioxidant defenses, and hepatic and intestinal health in hapa-reared M. capito, highlighting their promising role in promoting welfare and productivity. [ABSTRACT FROM AUTHOR]

As one of the most significant contaminants and stressors in aquaculture systems, ammonia adversely jeopardizes the health of aquatic animals. Ammonia exposure affects the development, metabolism, and survival of shellfish. However, the responses of the innate immune and antioxidant systems and apoptosis in shellfish under ammonia stress have rarely been reported. In this study, razor clams (Sinonovacula constricta) were exposed to different concentrations of non-ion ammonia (0.25 mg/L, 2.5 mg/L) for 72 h and then placed in ammonia-free seawater for 72 h for recovery. The immune responses induced by ammonia stress on razor clams were investigated by antioxidant enzyme activities and degree of apoptosis in digestive gland and gill tissues at different time points. The results showed that exposure to a high concentration of ammonia greatly disrupted the antioxidant system of the razor clam by exacerbating the accumulation of reactive oxygen species ( O 2 - , H2O2) and disordering the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and the level of activity remained at a significantly high level after recovering for 72 h (P < 0.05). In addition, there were significant differences (P < 0.05) in the expression of key genes (Caspase 7, Cyt-c, Bcl-2, and Bax) in the mitochondrial apoptotic pathway in the digestive glands and gills of razor clams as a result of ammonia stress and were unable to return to normal levels after 72 h of recovery. TUNEL staining indicated that apoptosis was more pronounced in gills, showing a dose and time-dependent pattern. As to the results, ammonia exposure leads to the activation of innate immunity in razor clams, disrupts the antioxidant system, and activates the mitochondrial pathway of apoptosis. This is important for comprehending the mechanism underlying the aquatic toxicity resulting from ammonia in shellfish. [ABSTRACT FROM AUTHOR]

The inland saline waters were continuously observed to have low potassium concentrations compared to their seawater counterpart of the same salinity. We hypothesize that the toxic effect of sulfate may manifest in low potassium saline (LPSW) waters compared to brackish water of the same salinity. Thus, LC50 trials were performed in GIFT (genetically improved farmed tilapia) fry (0.5 ± 0.02 g) to determine the acute sulfate toxicity in freshwater (FW, 0.5 g L−1), artificial seawater (ASW, 10 g L−1), and LPSW (10 g L−1). The median lethal concentrations (96h LC50) of sulfate ion in FW, LPSW, and ASW for the GIFT were 5.30 g L−1, 2.56 g L−1, and 2.98 g L−1, respectively. A second experiment was conducted for 21 days, exposing fish to a sub-lethal level of sulfate ion (SO42−) concentration (1000 mg L−1, one-fifth of FW LC50) with different types of waters (FW, freshwater, 0.5 g L−1; ASW, artificial seawater, 10 g L−1; LPSW, low potassium saline water, 10 g L−1) with and without sulfate inclusion to constitute the treatments as follows, (FW, FW + SO4, ASW, ASW + SO4, LPSW, LPSW + SO4). The effect of sulfate on GIFT reared in sulfate-rich potassium-deficient medium saline water was evaluated by focusing on the hematological adjustments, stress-induced oxidative damage, and osmoregulatory imbalances. The survival was not altered due to the sulfate concentration and K+ deficiency; however, there were significant changes in branchial NKA (Na+/K+-ATPase) activity and osmolality. The increase in NKA was highest in LPSW treatment, suggesting that internal ionic imbalance was triggered due to an interactive effect of sulfate and K+ deficiency. The cortisol levels showed a pronounced increase due to sulfate inclusion irrespective of K+ deficiency. The antioxidant enzymes, i.e., SOD (superoxide dismutase), catalase, GST (glutathione-S-transferase), and GPX (glutathione peroxidase), reflected a similar pattern of increment in the gills and liver of the LPSW + SO4 groups, suggesting a poor antioxidant status of the exposed group. The hepatic peroxidation status, i.e. TBARS (thiobarbituric acid reactive substances), and the peroxide values were enhanced due to both K+ deficiency and sulfate inclusion, suggesting a possible lipid peroxidation in the liver due to handling the excess sulfate anion concentration. The hematological parameters, including haemoglobin, total erythrocyte count, and hematocrit level, reduced significantly in the LPSW + SO4 group, indicating a reduced blood oxygen capacity due to the sulfate exposure and water potassium deficiency. The hepatic acetylcholine esterase activity was suppressed in all the treatments with sulfate inclusion, while the highest suppression was observed in the LPSW + SO4 group. Thus, it is concluded that sulfate-induced physiological imbalances manifest more in potassium-deficient water, indicating that environmental sulfate is more detrimental to inland saline water than freshwater or brackish water of the same salinity. [ABSTRACT FROM AUTHOR]

Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200–250 g were used (6–7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity. [ABSTRACT FROM AUTHOR]

Polyethylene terephthalate microplastics (PET MPs) are widespread in natural environment, and can enter organisms and accumulate in the body, but its toxicity has not been well studied. Therefore, in order to investigate the toxic effects of PET microplastics on mammals, this study investigated the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01). Meanwhile, Western blotting showed increased expression of the apoptosis-related protein Bax and decreased expression of PARP, caspase-3, and Bcl-2 proteins in both myocardial tissues and H9C2 cells. In addition, flow cytometry confirmed that PET MPs decreased the mitochondrial membrane potential and apoptosis in H9C2 cells; however, this trend was reversed by N-acetylcysteamine application. Moreover, PET MP treatment induced the accumulation of reactive oxygen species (ROS) in H9C2 cells, while the MDA level in the myocardial tissue was elevated, and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were decreased (P < 0.01), indicating a change in the redox environment. In conclusion, PET MPs promoted cardiomyocyte apoptosis by inducing oxidative stress and activating mitochondria-mediated apoptotic processes, ultimately leading to myocardial fibrosis. This study provides ideas for the prevention of PET MP toxicity and promotes thinking about enhancing plastic pollution control. [ABSTRACT FROM AUTHOR]

Aim: To explore the function of circ_UTRN in acute pancreatitis (AP). Methods: After exposing AR42J cells to caerulein, the levels of circ_UTRN, miR-760-3p, and glutathione peroxidase 4 (GPX4) were determined by quantitative polymerase chain reaction. Additionally, GPX4 and forkhead box O1 (FOXO1) protein levels were assessed by western blot. The levels of oxidative stress and ferroptosis in the supernatant of the treated AR42J cells were also assessed using commercial kits. Results: circ_UTRN inhibited caerulein-induced oxidative stress and ferroptosis by binding with miR-760-3p. Additionally, miR-760-3p directly targeted FOXO1, thereby regulating GPX4 levels. Furthermore, GPX4 knockdown abolished the effect of miR-760-3p downregulation in AP. Conclusion: circ_UTRN inhibited oxidative stress and ferroptosis by regulating the miR-760-3p/FOXO1/GPX4 axis. This is a potential new treatment strategy for AP. [ABSTRACT FROM AUTHOR]