Search Results (152)

Background/Objectives: Tacrolimus is an immunosuppressant drug widely used to prevent organ transplant rejection. Preclinical and clinical studies report that tacrolimus has destructive impacts on the male reproductive system owing to the induction of oxidative stress and inflammation. This study aimed at examining defensive impacts of agmatine against tacrolimus-induced testicular toxicity in rats. Methods: Male Wistar rats were randomly divided into six groups and treated based on the experimental design for 14 days. By the end of this study, blood samples were obtained to measure testosterone and luteinizing hormone. Also, both testes were removed for molecular analysis and histopathological examinations. Results: Agmatine administration increased serum levels of testosterone and luteinizing hormone and ameliorated all histopathological and toxicological changes induced by tacrolimus. Agmatine administration attenuated tacrolimus-induced oxidative stress as evidenced by the reduction of malondialdehyde content and inducible nitric oxide synthase expression and the elevation of reduced glutathione. This was parallel to the restoration of nuclear factor erythroid 2-related factor2 and hemeoxygenase-1 expression. Moreover, agmatine decreased the expressions of nuclear factor kappa B and interleukin-17. Agmatine also decreased the cell death revealed by decreased caspase-3 expression and increased expression of the antiapoptotic marker Bcl-2 in a dose-dependent manner. The antioxidant, anti-inflammatory, and antiapoptotic effects of agmatine were explained by increased expression of sirtuin-1. Conclusions: agmatine effectively attenuated testicular injuries induced by tacrolimus and enhanced spermatogenesis. This protective effect of agmatine might be mediated via the upregulation of sirtuin-1 expression that in turn restores oxidative status and regulates nuclear factor erythroid 2-related factor2/nuclear factor kappa B/Bcl-2 signaling. Full article

Previous research has documented broad benefits of spiritual intervention programs, including improved spirituality and ameliorated mental health symptoms. However, long-term follow-up examinations of such interventions have yet to be conducted. This study reports on changes in psychological and spiritual variables from posttest to 3-month follow-up in a sample of U.S. undergraduate students. N = 84 undergraduate students ages 18–25 (M = 19.75, SD = 1.6; 69 female, 11 male, and 4 nonbinary) received Awakened Awareness for Adolescents (AA-As), a spirit–mind–body (SMB) intervention composed of 8 weekly 90-min sessions, and completed measures of spirituality (spirituality, spiritual growth, spiritual decline, and Awakened Awareness) and mental health (depression, anxiety, and posttraumatic stress) at posttest and again at 3-month follow-up. Paired-sample t-tests revealed maintenance of spiritual improvements (Awakened Awareness, spiritual growth, and relational spirituality with the Higher Power) with the exception of reversal of spiritual decline and significant ongoing improvements in clinical measures in the months following posttest. Additionally, we observed a moderating effect such that changes in spiritual decline after posttest were associated with follow-up posttraumatic stress. An ongoing lived transcendent relationship with the Higher Power, Awakened Awareness, and spiritual growth appears to offer sustained protection at three-month follow-up against depression and symptoms of trauma. Our findings support the efficacy of AA-A as well as the need for ongoing SMB wellness resources. Full article

Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV), against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms. Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV. Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2, SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl, BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway, and downregulated P53 expression. Additionally, immunohistochemical staining revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and ameliorated histopathological alterations by enhancing autophagy-inducing pathways. Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical staining of Nrf2, which promoted the synthesis and activity of antioxidant enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy. Full article

The progression of type 2 diabetes is associated with multiple complications, one of which is diabetic nephropathy (DN). This study aimed at investigating the nephroprotective potential of two doses 150 mg/kg and 300 mg/kg of Tanacetum balsamita leaf extract (ETB) on metabolic-induced renal injury (MIRI) in rats. Markers of renal oxidative stress and antioxidant defense, histopathology, serum biochemistry, and urinalysis were measured. Blood glucose level and arterial blood pressure were assessed weekly for the experimental period of eight weeks. ETB at a high dose significantly decreased the blood glucose levels and mildly lowered systolic pressure in diabetic rats. In the kidney, ETB restored the antioxidant marker malondialdehyde, reduced glutathione, and markedly increased enzymatic activity related to GSH turnover by 46% (GPx), 22% (GR), 32% (GST), and 96% (SOD). ETB reduced elevated urea and creatinine levels and alleviated the proteinuria along with other urinalysis parameters. Histopathological examination of the kidney supported the observed protective effects. Both doses of the ETB ameliorated most of the investigated parameters similarly to positive controls enalapril and acarbose. ETB benefits on MIRI-induced damages could be associated with high levels of mono- and dicaffeoylquinic acids together with a series of methoxylated flavones and flavonols, which may hold significance for its antidiabetic and nephroprotective activity. Full article

High-fat diets (HFDs) usually trigger disruptions in lipid metabolic processes and immune suppression in fish. As an eco-friendly and potent additive, the inclusion of probiotics in fish diets ameliorates dysregulations in lipid metabolism, mitigates oxidative stress, and reduces inflammatory reactions triggered by HFDs. However, little current research has focused on the improvement of the hazards of HFDs in fish by probiotics. Therefore, we employed 4-dimensional data-independent (4D-DIA) proteomic analysis to investigate the mechanism of the protective impact of probiotics against HFD-induced hepatic injury in Coilia nasus between the HFD group and the probiotic supplementation in HFD (PHFD) group. Additionally, lipid accumulation and antioxidant indicators in the liver were also measured via Oil Red O staining and activity detection. Administration of probiotics markedly attenuated the hepatic concentrations of triglycerides (TG), cholesterol (CHO), and low-density lipoprotein cholesterol (LDL-C) in C. nasus subjected to HFDs. Furthermore, it significantly upregulated the expression of the differentially expressed proteins (DEPs) implicated in cholesterol metabolism and fatty acid oxidation, while concurrently downregulating the DEPs associated with fatty acid synthesis. Additionally, probiotic supplementation significantly reduced the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels induced by HFDs. It also upregulated the activities of catalase (CAT) and superoxide dismutase (SOD). Probiotic supplementation significantly upregulated the DEPs related to antioxidants, while significantly downregulating the DEPs associated with inflammatory responses and autophagy. These findings suggested that probiotics ameliorated HFD-induced hepatic lipid accumulation in C. nasus by enhancing cholesterol metabolism and fatty acid oxidation, concomitantly with the suppression of fatty acid synthesis pathways. Additionally, probiotics protected against HFD-induced hepatic injury by enhancing antioxidant defenses and suppressing inflammation in C. nasus. Full article

Background/Objectives: Brain insulin resistance is a potential causal factor for dementia in Alzheimer’s disease (AD). Insulin-like growth factor-1 (IGF-1), a neurotrophin, plays a key role in central insulin signaling and neuroprotection. Intracerebrovenitricular (ICV) administration of streptozotocin (STZ) disrupts insulin signal transduction, leading to brain insulin resistance, which may mimic the early pathophysiological changes in sporadic AD (sAD). In this study, we investigated whether restoring insulin signaling through ICV injection of IGF-1 could ameliorate spatial memory deficits during sAD progression in a rat model induced by ICV STZ injection. Methods: Male Wistar rats (n = 40) were subjected to double ICV injections of STZ (0.75 mg/kg/ventricle, days 2 and 4) and IGF-1 (1 μg/single injection, days 1 and 3), and placed at the Morris water maze (MWM) at baseline, 7, 45 and 90 days after injections. Reference (days 1–3 and day 4 MWM)) and working (days 5–8 MWM) memory, microglia activation (CD68⁺ cells), and amyloid β (Aβ) deposition (immunohistochemistry) were measured. Results: We found that ICVIGF-1 administration protected working memory demonstrated as (1) reduced latency to reach the platform, and reduced swimming distance in trials 3 (p < 0.05) and 4 (p < 0.01) on days 45 and 90 post-injection and (2) a short-term (up to 45 days post-injection) enhancement of reference memory, manifested by a reduction in swimming distance and latency (p < 0.05). Furthermore, IGF-1 treatment reduced neuroinflammation in CA2 (p < 0.05) and Aβ deposition in CA1(p < 0.01) of the hippocampus. Conclusions: Central IGF-1 attenuates spatial memory deficits in the ICVSTZ-induced sAD model by reducing neuroinflammation and Aβ accumulation in the hippocampus. Full article

Spinal cord injury (SCI) affects millions globally, leading to severe motor and sensory deficits with no effective clinical treatment. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a critical role in bioenergetics and apoptosis. Emerging evidence suggests that CL alterations contribute to secondary SCI pathology, but their precise role and underlying mechanisms remain fully understudied. In this study, we investigated the protective effects of SS-31 on CL alteration, neuronal death, tissue damage, and behavioral recovery after SCI using both in vitro and in vivo models, lipidomics analysis, histological evaluation, and behavioral assessments. In vitro investigations used primary spinal cord neuron cultures, challenged with either rotenone or glutamatergic excitotoxicity, with protective capabilities measured via cell death assays and neurite morphological analysis. In vivo investigations used female adult C57Bl/6 mice, challenged with a contusive SCI. The results showed that SS-31 reduced rotenone- and glutamate-induced mitochondrial dysfunction and neuronal death in a dose-dependent manner in vitro. Additionally, SS-31 attenuated rotenone- and glutamate-induced neurite degeneration in vitro. Lipidomics analysis revealed a reduction in CL at 24 h post-SCI in adult mice, which was attenuated by SS-31 in a dose-dependent manner. Consistent with this effect, SS-31 improved behavioral recovery after SCI in adult mice, although it had no significant effect on tissue damage. These findings suggest that CL alteration may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary SCI. Full article

Polysaccharides possessing hypoglycemic effects have shown promising results in treating diabetes. Polygonatum sibiricum polysaccharide (PSP) is one of the most active ingredients in the Chinese medicine P. sibiricum Redoute with many biological activities. However, its efficacy in alleviating type 2 diabetes mellitus (T2DM) remains unexplored. Our aim is to evaluate the protective effect of PSP against T2DM by measuring body weight and serum biochemical indicators, examining the histopathological images of pancreatic and liver tissues, detecting fecal short-chain fatty acid (SCFA) content, and analyzing the intestinal flora diversity and the microbiota structure in T2DM mice. The findings indicated that PSP treatment in T2DM mice could obviously decrease the fasting blood glucose and fasting insulin levels, ameliorate glucose tolerance, insulin resistance, lipid, and inflammatory factor levels, attenuate pancreatic and liver damage, and increase the fecal SCFA content. In addition, PSP could modulate the composition of gut microbiota in T2DM mice, resulting in the relative abundance of Firmicutes decreasing and that of Bacteroidetes increasing, along with the abundance of beneficial flora significantly increasing, especially SCFA-producing bacteria. The findings indicate that PSP administration protected against diabetes by controlling disordered glucolipid metabolism and modulating the gut microbiota, which provides a valuable strategy for the utilization of PSP to treat T2DM. Full article

This study was designed to evaluate the protective effects of eleutheroside B (EB) in high-altitude-induced myocardial injury (HAMI) and to unravel the underlying molecular mechanisms. SD rats were used for in vivo experiments. Following pretreatment with EB, the SD rats were exposed to a hypobaric environment within a hypobaric chamber for 48 h. Electrocardiograms, H&E staining, and serum biochemical indices were measured to evaluate the protective effects of EB on HAMI. Immunofluorescence and Western blotting were utilized to detect the expression of associated proteins. In parallel, a hypobaric hypoxic cell incubator was used to establish an in vitro model of hypobaric hypoxia-induced cell injury. The anti-necroptotic effect and its potential underlying mechanisms were investigated and verified in vitro. Exposure to hypobaric hypoxia led to electrocardiogram disorders, pathological changes in myocardial tissue, increased concentrations of BNP and CK-MB, and elevated levels of oxidative stress indicators and inflammatory factors. Additionally, the expression of necroptosis-related proteins was upregulated. Pretreatment with EB effectively ameliorated myocardial injury caused by hypobaric hypoxia, mitigated oxidative stress and inflammation, and suppressed necroptosis. Furthermore, EB facilitated the translocation of Nrf2 into the nucleus. In conclusion, this study provides evidence suggesting that EB may exert a protective effect against HAMI by inhibiting cardiomyocyte necroptosis via the Nrf2/HO-1 signaling pathway. Full article

Background/Objectives: Rhamnetin 3-O-α-rhamnoside (ARR) is a major flavonoid of the herb Loranthus tanakae Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. Methods: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. Results: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. Conclusions: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway. Full article

Noise pollution is a known health risk factor and evidence for cardiovascular diseases associated with traffic noise is growing. At least 20% of the European Union’s population lives in noise-polluted areas with exposure levels exceeding the recommended limits of the World Health Organization, which is considered unhealthy by the European Environment Agency. This results in the annual loss of 1.6 million healthy life years. Here, we investigated the protective effects of cardiovascular drug interventions against aircraft noise-mediated cardiovascular complications such as elevated oxidative stress or endothelial dysfunction. Using our established mouse exposure model, we applied mean sound pressure levels of 72 dB(A) for 4 d. C57BL/6 mice were treated with the beta-blocker propranolol (15 mg/kg/d s.c. for 5 d) or the alpha-blocker phenoxybenzamine (1.5 mg/kg/d s.c. for 5 d) and noise-exposed for the last 4 d of the drug administration. Short-term noise exposure caused hypertension (measured by tail-cuff blood pressure monitoring) and impaired endothelial function (measured by isometric tension recording in the aorta and video microscopy in cerebral arterioles in response to acetylcholine). Noise also increased markers of oxidative stress and inflammation. Treatment of mice with propranolol and phenoxybenzamine prevented endothelial and microvascular dysfunction, which was supported by a decrease in markers of inflammation and oxidative stress in heart tissue and the brain. Amelioration of noise-induced hypertension (systolic blood pressure) was not observed, whereas pulse pressure was lowered by trend. This study provides a novel perspective mitigating the adverse effects of noise pollution, especially in vulnerable groups with medication, a rationale for further pharmacological human studies. Full article

Environmental stress, notably the exposure to low temperatures during the early developmental stages of seedlings, has been identified as a critical determinant impacting the yield and quality of tomato crops cultivated in greenhouses. Silicon (Si), recognized as a beneficial element, is posited to mitigate the adverse effects of such stress on plant physiology. This study explores whether exogenous Si fertilizer can effectively alleviate the stress of low temperature and cold damage on tomato plant growth, fruit yield, and quality. Tomato plants were placed under low temperature conditions (6 °C at night, daily average temperature 15 °C), with normal temperature conditions as the control (below 16 °C at night, daily average temperature 28 °C), and two different concentrations of nano Si and ionic Si (50 mg·L⁻¹ and 200 mg·L⁻¹) were sprayed on the leaves, with an equivalent amount of deionized water as the control, for a total of 10 treatments. Relevant indexes were measured to investigate the effects of exogenous Si on tomato resistance, yield, and quality under low-temperature stress. The results show that compared with the control treatment, the plant height, stem diameter, and fresh weight of above-ground and underground parts of tomato seedlings decreased significantly by 46.52%, 42.53%, 28.81%, and 28.97%, respectively, after 15 days of low-temperature stress (p < 0.05), and in order to resist low temperature, the activity of antioxidant enzymes and the content of osmotic adjustment substances were up-regulated in seedlings. Ultimately, low-temperature stress inhibited the morphological growth, nutritional quality, and yield of fruits. Both concentrations of Si application can promote the growth and biomass accumulation of tomato plants under low temperature conditions. Moreover, it significantly ameliorated the osmotic adjustment and antioxidant capacity of the plants, thereby alleviating the low-temperature stress. Under low-temperature stress, 50 mg L⁻¹ ionic Si was the most effective for increasing tomato yield per plant, which was significantly increased by 22.44% compared with the control treatment (p < 0.05). Consequently, the study advocates for the application of 50 mg·L⁻¹ ionic Si fertilizer as a strategy to mitigate the impact of low-temperature stress on tomato plants. Furthermore, the use of nano Si fertilizer has been demonstrated to exert a significant influence on enhancing both the yield and quality of tomatoes, with a 50 mg·L⁻¹ concentration of nano Si fertilizer leading to a notable increase in yield by 20.15% under normal temperature conditions (p < 0.05). These findings are intended to furnish a theoretical foundation and practical direction for advancing research aimed at combating the detrimental effects of low-temperature stress in the context of protected vegetable cultivation. Full article

Background: 5-Fluorouracil (5-FU) is a common chemotherapeutic medication used to treat cancer. However, the intestinal tract may sustain oxidative damage as a result. Objectives: The purpose of this study was to clarify the underlying molecular mechanisms and examine the preventive benefits of cereal-based fermented drinks (CFBs) against intestinal injury in mice caused by 5-FU. Methods: The mice were injected intraperitoneally with 5-FU to induce intestinal mucosal and treated with CFB. The factors for intestinal barrier integrity, oxidative stress and inflammation were measured. Results: The findings demonstrated that CFBs had high levels of polyphenol, flavonoids, and peptides and had in vitro high free radical scavenging capacity. Furthermore, CFBs effectively ameliorated 5-FU-induced intestinal epithelium damage, characterized by increasing intestinal tight junctions and reducing apoptosis in intestinal cells. These protective effects may attribute to the increased activity of antioxidant-related enzymes (SOD, CAT, and GSH) as well as decreased amounts of inflammatory and oxidative damage markers (IL-1β, TNF-α, and MDA) in the intestinal tract. Conclusions: Overall, these results show that CFBs can mitigate intestinal damage caused by 5-FU by reducing oxidative stress, suggesting the potential utility of CFBs for therapeutic treatment against intestinal mucositis. Full article

Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO₂) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO₂ administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO₂ was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO₂ administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO₂ exerts protective effects in the myocardial IR model. Full article

5-Fluorouracil (5-Fu) is a chemotherapeutic agent widely used to treat various cancers, which causes intestinal mucositis as a common side effect. Ginsenoside Rc, an active compound with anti-inflammatory, antioxidant, immunomodulatory, and antitumor properties, has protective effects against chemotherapy-induced mucositis caused by 5-Fu. This study aims to evaluate the protective effects of Rc on 5-Fu-induced chemotherapy-related mucositis and to elucidate its underlying mechanisms. In vivo experiments were conducted to measure intestinal permeability and assess the effects of Rc on body weight loss, diarrhea, and intestinal pathology induced by 5-Fu. Network pharmacology was also employed to explore potential mechanisms. In vitro, IEC-6 cell models were used to validate the cytoprotective effects of Rc, including assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and changes in inflammatory cytokine levels. The results indicate that Rc significantly ameliorated body weight reduction, diarrhea, and intestinal damage in mice treated by 5-Fu. Rc significantly mitigated 5-Fu-induced cellular damage by reducing levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and decreasing apoptosis and cell permeability. Western blot analysis revealed that Rc upregulated the expression of Bcl-2 and tight junction proteins and downregulated the expression of Bax. Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis. Full article