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1.
Article in English | MEDLINE | ID: mdl-38743886

ABSTRACT

Context: At present, medical practitioners commonly use surgery and perioperative chemotherapy, radiotherapy, and biological targeted therapy in clinical treatment of gastric cancer. Western medicine treatment can quickly treat patients' lesions but may cause adverse reactions. TCM can prevent the occurrence of toxic side effects and alleviate the side effects of Western medicine. Objectives: The study intended to explore the clinical efficacy of traditional Chinese medicine (TCM) combined with Western medicine in the treatment of advanced gastric cancer. Design: The research team performed a randomized, double-blind, controlled clinical trial. Setting: The study took place at the Cangzhou Central Hospital in Hebei, China. Participants: Participants were 102 patients with advanced gastric cancer who had been admitted to the hospital between February 2021 and March 2023. Interventions: The research team randomly divided participants into two groups, with 51 participants in each group: (1) the TCM group, who received TCM only, and (2) the combination group, who received chemotherapy combined with TCM. Outcome Measures: The research team measured: (1) clinical efficacy; (2) TCM syndrome efficacy; (3) levels of the blood tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen Sialyl-Lewis a (CA199), and carbohydrate antigen 72-4 (CA72-4); (4) psychological status using the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS); and (5) incidence of adverse reactions. Results: At baseline, no significant differences existed between the two groups in the clinical indicators. Postintervention compared to the TCM group, the combination group had significantly: (1) higher clinical efficacy (P = .003), (2) higher TCM syndrome efficacy (P = .003), (3) higher level of CEA and lower levels of CA199, and CA72-4 (all P = .000); (4) lower SAS scores and SDS scores (both P = .000); and (5) lower incidence of adverse reactions (P = .007). Conclusions: TCM, in the treatment of patients with advanced gastric cancer, can achieve good therapeutic effects. Combined with chemotherapy, patients' clinical efficacy can improve, level of blood tumor markers can decrease, psychological state can improve, and incidence of adverse reactions can decrease. Its clinical use had significant effects, and physicians can promote and use them.

2.
Article in English | MEDLINE | ID: mdl-38743885

ABSTRACT

Objective: Our aim was to investigate the effect of the clinical application of Traditional Chinese Medicine (TCM) combined with chemotherapy in the treatment of advanced pancreatic cancer. Methods: The study participants were divided into 2 groups: the combined treatment group, comprised of 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received TCM combined with chemotherapy; and the control group: 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received chemotherapy alone. The TCM symptom score, TCM clinical efficacy, Western medicine clinical efficacy, patient quality of life (QoL) and incidence of adverse events (AEs) were compared in the 2 groups. Results: Prior to treatment, there was no significant difference in the patients' general clinical condition in the 2 groups (P > .05); after treatment, the TCM symptom score in the combined treatment group (16.62±2.77) was better than in the control group (21.44±2.53), with a P < .05. The TCM and Western medicine clinical efficacy was better than in the control group, with a P < .05; QoL score was higher than in the control group, P < .05; the incidence of AEs (3.12%) was lower than in the control group (28.12%); P < .05. Conclusion: In the treatment of patients with advanced pancreatic cancer, the application of TCM combined with chemotherapy can achieve good therapeutic results, improve the patients' prognosis, effectively reduce the occurrence of AEs and continuously restore patients' QoL.

3.
Pak J Med Sci ; 40(4): 723-729, 2024.
Article in English | MEDLINE | ID: mdl-38544991

ABSTRACT

Objective: To investigate the clinical value of the expression levels of tumor protein D52 (TPD52) and miR-133a on the prognosis assessment of pancreatic cancer surgery. Methods: This was a retrospective study. Ninety-seven patients who underwent radical surgery for pancreatic cancer in Cangzhou Central Hospital from January 2018 to January 2022 were selected and divided into four groups: TPD52 high expression group, TPD52 low expression group, miR-133a high expression group and miR-133a low expression group. The relationship between the expression levels of TPD52 and miR-133a and the clinicopathological features of patients with pancreatic cancer was analyzed. The COX regression model was used to analyze the risk factors affecting the prognosis of patients with pancreatic cancer. Results: The high expression rate of TPD52 and the low expression rate of miR-133a in pancreatic cancer tissues were higher than those in normal paracancerous tissues(P<0.05). Based on the comparison of prognosis and survival, the median survival time of patients with high expression of TPD52 and low expression of miR-133a was lower than that of patients with low expression of TPD52 and high expression of miR-133a, with a statistically significant difference(P<0.05). Moreover, multivariate Cox regression analysis showed that low differentiation of pancreatic cancer, III-IV stage of TNM, high expression of TPD52, as well as low expression of miR-133a were independent risk factors for postoperative survival of patients with pancreatic cancer(P<0.05). Conclusion: TPD52 is expressed at a high level whereas miR-133a at a low level in pancreatic cancer tissues, both of which together with low differentiation of pancreatic cancer and III-IV stage of TNM constitute independent risk factors affecting the surgical prognosis of patients with pancreatic cancer.

4.
Sci Rep ; 13(1): 17689, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37848602

ABSTRACT

The vibration generated during the construction of subway tunnels with double-shield tunnel boring machine (TBM) has a significant impact on the environment, which has caused multiple complaints from residents. Taking a double-shield TBM tunnel project as the background, vibration measurements were conducted by installing vibration sensors on-site. By combining theoretical methods-such as normalization, polynomial fitting prediction, and gray correlation analysis-the vibration characteristics, impact range on the environment, and factors affecting the vibration of TBM construction were studied. The key research results included: (1) The amplified zone of X and Y vibration acceleration occurred on the left-hand side of the tunnel from 3.15 to 13.85 m, but rapidly decayed away from the amplification zone. (2) The impact range of TBM vibrations on residential areas at night and during the day was studied according to the official "Urban Regional Environmental Vibration Standard" and it was found to be larger at night than during the day. (3)The main factors affecting the TBM vibration level was studied-including the cutter-head torque, TBM thrust, cutter-head speed, penetration, field penetration index (FPI) and so on. In summary, when the double-shield TBM construction tunnel is adjacent to residential areas, the vibration generated exceeds the national standard limit. In order to reduce the impact of TBM vibration on residential areas, excavation parameters such as cutter head torque, TBM thrust, cutter head speed, and penetration should be appropriately reduced.

6.
Int Wound J ; 20(9): 3682-3689, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37277912

ABSTRACT

A meta-analysis was conducted to assess the impact of robotic and laparoscopic pancreaticoduodenectomies on postoperative surgical site wound infections. A comprehensive computerised search of databases, such as PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data, was performed to identify studies comparing robotic pancreaticoduodenectomy (PD) with laparoscopicPD. Relevant studies were searched from the inception of the database construction until April 2023. The meta-analysis outcomes were analysed using odds ratios (OR) with corresponding 95% confidence intervals (CI). The RevMan 5.4 software was used for the meta-analysis. The findings of the meta-analysis showed that patients who underwent laparoscopic PD had a significantly lower incidence of surgical-site wound (16.52% vs. 18.92%, OR: 0.78, 95% CI: 0.68-0.90, P = .0005), superficial wound (3.65% vs. 7.57%, OR: 0.51, 95% CI: 0.39-0.68, P < .001), and deep wound infections (1.09% vs. 2.23%, OR: 0.53, 95% CI: 0.34-0.85, P = .008) than those who received robotic PD. However, because of variations in sample size between studies, some studies suffered from methodological quality deficiencies. Therefore, further validation of this result is needed in future studies with higher quality and larger sample sizes.


Subject(s)
Laparoscopy , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Incidence , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Laparoscopy/adverse effects , China
7.
Sci Rep ; 13(1): 9440, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37296194

ABSTRACT

Severe acute pancreatitis (SAP) presents with an aggressive clinical presentation and high lethality rate. Early prediction of the severity of acute pancreatitis will help physicians to further precise treatment and improve intervention. This study aims to construct a composite model that can predict SAP using inflammatory markers. 212 patients with acute pancreatitis enrolled from January 2018 to June 2020 were included in this study, basic parameters at admission and 24 h after hospitalization, and laboratory results such as inflammatory markers were collected. Pearson's test was used to analyze the correlation between heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP). Risk factors affecting SAP were analyzed using multivariate logistic regression, inflammatory marker models were constructed, and subject operating curves were used to verify the discrimination of individual as well as inflammatory marker models and to find the optimal cut-off value based on the maximum Youden index. In the SAP group, the plasma levels of HBP, CRP, and PCT were 139.1 ± 74.8 ng/mL, 190.7 ± 106.3 mg/L and 46.3 ± 22.3 ng/mL, and 25.3 ± 16.0 ng/mL, 145.4 ± 67.9 mg/L and 27.9 ± 22.4 ng/mL in non-SAP patients, with a statistically significant difference between the two groups (P < 0.001), The Pearson correlation analysis showed a positive correlation between the three values of HBP, CRP, and PCT. The results of the multivariate logistic regression analysis showed that HBP (OR = 1.070 [1.044-1.098], P < 0.001), CRP (OR = 1.010 [1.004-1.016], P = 0.001), and PCT (OR = 1.030[1.007-1.053], P < 0.001) were risk factors for SAP, and the area under the curve of the HBP-CRP-PCT model was 0.963 (0.936-0.990). The HCP model, consisting of HBP, CRP, and PCT; is well differentiated and easy to use and can predict the risk of SAP in advance.


Subject(s)
Pancreatitis , Procalcitonin , Humans , C-Reactive Protein/analysis , Pancreatitis/diagnosis , Acute Disease , Biomarkers , Prognosis
8.
J Adv Res ; 46: 87-100, 2023 04.
Article in English | MEDLINE | ID: mdl-37003700

ABSTRACT

INTRODUCTION: Lead (Pb) is an environmental toxicant that poses severe health risks to humans and animals, especially renal disorders. Pb-induced nephrotoxicity has been attributed to oxidative stress, in which apoptosis and autophagy are core events. OBJECTIVES: Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a major contributor to counteract oxidative damage, while hyperactivation or depletion of Nrf2 pathway can cause the redox imbalance to induce tissue injury. This study was performed to clarify the function and mechanism of Nrf2 in Pb-triggered kidney injury. METHODS AND RESULTS: First, data showed that Pb exposure activates Nrf2 pathway in primary rat proximal tubular cells. Next, Pb-induced Nrf2 activation was effectively regulated by pharmacological modulation or siRNA-mediated knockdown in vitro and in vivo assays. Notably, Pb-triggered cytotoxicity, renal injury and concomitant apoptosis were improved by Nrf2 downregulation, confirming that Pb-induced persistent Nrf2 activation contributes to nephrotoxicity. Additionally, Pb-triggered autophagy blockage was relieved by Nrf2 downregulation. Mechanistically, we found that Pb-induced persistent Nrf2 activation is attributed to reduced Nrf2 ubiquitination and nuclear-cytoplasmic loss of Keap1 in a p62-dependent manner. CONCLUSIONS: In conclusion, these findings highlight the dark side of persistent Nrf2 activation and potential crosstalk among Pb-induced persistent Nrf2 activation, apoptosis and autophagy blockage in Pb-triggered nephrotoxicity.


Subject(s)
Lead , NF-E2-Related Factor 2 , Humans , Rats , Animals , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Lead/toxicity , Lead/metabolism , Apoptosis , Kidney , Autophagy
9.
Environ Pollut ; 324: 121394, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36906059

ABSTRACT

Glyphosate (Gly) is the most widely used herbicide with well-defined hepatotoxic effects, but the underlying mechanisms of Gly-induced hepatic steatosis remain largely unknown. In this study, a rooster model combined with primary chicken embryo hepatocytes was established to dissect the progresses and mechanisms of Gly-induced hepatic steatosis. Data showed that Gly exposure caused liver injury with disrupted lipid metabolism in roosters, manifested by significant serum lipid profile disorder and hepatic lipid accumulation. Transcriptomic analysis revealed that PPARα and autophagy-related pathways played important roles in Gly-induced hepatic lipid metabolism disorders. Further experimental results suggested that autophagy inhibition was involved in Gly-induced hepatic lipid accumulation, which was confirmed by the effect of classic autophagy inducer rapamycin (Rapa). Moreover, data substantiated that Gly-mediated autophagy inhibition caused nuclear increase of HDAC3, which altered epigenetic modification of PPARα, leading to fatty acid oxidation (FAO) inhibition and subsequently lipid accumulation in the hepatocytes. In summary, this study provides novel evidence that Gly-induced autophagy inhibition evokes the inactivation of PPARα-mediated FAO and concomitant hepatic steatosis in roosters by mediating epigenetic reprogramming of PPARα.


Subject(s)
Fatty Liver , PPAR alpha , Chick Embryo , Male , Animals , PPAR alpha/genetics , PPAR alpha/metabolism , Chickens/metabolism , Fatty Liver/chemically induced , Liver/metabolism , Lipid Metabolism , Fatty Acids/metabolism , Autophagy , Epigenesis, Genetic , Glyphosate
10.
Vet Res Commun ; 47(2): 651-661, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36261742

ABSTRACT

Glyphosate (Gly) is a globally spread herbicide that can cause toxic injuries to hepatocytes. Dietary trehalose (Tre) exerts cytoprotective effect in numerous liver diseases through anti-oxidant and anti-inflammatory properties. However, it is yet to be investigated whether Tre affords protection against Gly-induced hepatotoxicity. To evaluate the negative effect of Gly in liver and assess the possible protective role of Tre, sixty Hy-line Brown roosters were allocated into three groups: the first group presented the control with a normal diet, the second group fed normal feed containing 200mg/kg Gly, and the third group fed normal feed containing 200 mg/kg Gly and 5 g/kg Tre. Plasma and liver tissues were collected and analyzed after 120 days. Firstly, Gly-elevated serum levels of hepatic injury markers and liver histopathological damages were evidently alleviated by Tre administration. Also, Tre normalized Gly-altered serum and hepatic lipid profiles and Oil Red O-stained lipid levels, suggesting the improvement of hepatic steatosis. The severely accumulated malondialdehyde levels and impaired antioxidant status in Gly-exposed roosters were markedly improved by administration with Tre. Simultaneously, Gly-inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) level and consequent reduced levels of Nrf2-downstream targets in liver were markedly normalized by Tre treatment. Additionally, Tre treatment evidently mitigated Gly-induced inflammasome response via inhibiting NLRP3 inflammasome activation. Overall, these observations provide novel insights that the protective action of Tre against Gly-induced hepatic steatosis is attributed to activation of Nrf2 pathway and inhibition of NLRP3 inflammasome activation.


Subject(s)
Inflammasomes , Liver Diseases , Male , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Trehalose/pharmacology , Trehalose/metabolism , Chickens/metabolism , Liver/metabolism , Antioxidants/pharmacology , Liver Diseases/veterinary , Lipids/pharmacology , Glyphosate
11.
Chem Biol Interact ; 368: 110249, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36347317

ABSTRACT

Pyroptosis is a pro-inflammatory type of cell death involved in the pathogenesis of multiple kidney diseases, while transcription factor EB (TFEB) is shown to be important for rescuing renal function. Cadmium (Cd) is an omnipresent toxic heavy metal with definite nephrotoxicity, but there is lacking of evidence regarding an interplay between TFEB activity and pyroptosis during Cd exposure. In this study, Cd-exposed NRK-52E cells were used to clarify this issue as an in vitro model of acute kidney injury. First, our results showed that Cd exposure evidently elevated the protein levels involved in pyroptosis, increased lactate dehydrogenase (LDH) release, and disrupted the cell membrane integrity, suggesting the occurrence of pyroptosis in NRK-52E cells. It is also shown that Cd induced a burst of reactive oxygen species (ROS) to mediate pyroptosis. Simultaneously, downregulated TFEB expression with its inhibited nuclear translocation was revealed in Cd-exposed NRK-52E cells. Further investigations have demonstrated that TFEB knockdown promoted Cd-induced ROS production to exacerbate the pyroptosis, while TFEB overexpression inhibited Cd-induced ROS production to alleviate the pyroptosis in NRK-52E cells. In summary, these findings demonstrate that Cd-inhibited TFEB function results in ROS overproduction to promote pyroptosis in NRK-52E cells, which provide new insight into the therapeutic targets for Cd-induced kidney diseases.


Subject(s)
Kidney Diseases , Pyroptosis , Humans , Reactive Oxygen Species/metabolism , Cadmium/toxicity , Cell Line , Epithelial Cells/metabolism , Kidney Diseases/metabolism
12.
Environ Pollut ; 314: 120314, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36183875

ABSTRACT

Glyphosate (GLY), one of the most extensively used herbicides in the world, has been shown to inhibit testosterone synthesis in male animals. Mitochondria are crucial organelles for testosterone synthesis and its dysfunction has been demonstrated to induce the inhibition of testosterone biosynthesis. However, whether low-dose GLY exposure targets mitochondria to inhibit testosterone synthesis and its underlying mechanism remains unclear. Here, an in vitro model of 10 µM GLY-exposed mouse Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that mitochondrial malfunction, mainly manifested by ultrastructure damage, disturbance of mitochondrial dynamics and mitochondrial reactive oxygen species (mtROS) overproduction, was responsible for GLY-decreased protein levels of steroidogenic enzymes, which leads to the inhibition of testosterone synthesis. Enhancement of autophagic flux and activation of mitophagy were shown in GLY-treated TM3 cells, and further studies have revealed that GLY-activated mitophagy is parkin-dependent. Notably, GLY-inhibited testosterone production was significantly improved by parkin knockdown. Finally, data showed that treatment with mitochondria-targeted antioxidant Mito-TEMPO (M-T) markedly reversed GLY-induced mitochondrial network fragmentation, activation of parkin-dependent mitophagy and consultant testosterone reduction. Overall, these findings demonstrate that GLY induces mtROS overproduction to activate parkin-dependent mitophagy, which contributes to the inhibition of testosterone synthesis. This study provides a potential mechanistic explanation for how GLY inhibits testosterone synthesis in mouse Leydig cells.


Subject(s)
Herbicides , Mitophagy , Male , Mice , Animals , Mitophagy/physiology , Reactive Oxygen Species/metabolism , Leydig Cells/metabolism , Antioxidants/metabolism , Mitochondria/metabolism , Ubiquitin-Protein Ligases/metabolism , Herbicides/toxicity , Herbicides/metabolism , Testosterone/metabolism , Glyphosate
13.
Adv Exp Med Biol ; 1370: 153-160, 2022.
Article in English | MEDLINE | ID: mdl-35882791

ABSTRACT

The aim of this study was to investigate the effects of taurine on tissue injury, protein metabolism, and basal metabolism of broilers after chronic heat stress by detecting serum physiological and biochemical indices. In the test, 240 AA + broilers at 7 days of age were randomly divided into five groups: the normal temperature control group (24 ± 2 °C) in group C, the heat stress control group (34 ± 2 °C) in HS group, and the LTau, MTau, and HTau groups in heat under stress conditions, 0.5, 2, and 8 g/L taurine were added to the drinking water, and each group was repeated three times. After 2 weeks of feeding at normal temperature, heat stress began. The test period was 4 weeks. Blood was collected at 6 h, 12 h, 7 d, 14 d, 21 d, and 28 d after heat stress, and serum was separated. The results showed that compared with the HS group, the MTau group had significantly higher total serum protein content (P < 0.05), while the other groups were not significantly different (P > 0.05). The MTau and HTau groups had significantly lower serum uric acid levels than the HS group (P < 0.05). At 7d and 14d, the LTau, MTau, and HTau groups all showed significantly increased T3 and T4 concentrations (P < 0.05). There was no significant difference between the groups thereafter (P > 0.05). Compared with HS group, the MTau group contained significantly reduced serum CK activity, LDH activity, AST activity, and ALT activity (P < 0.05). In conclusion, the effects of taurine on tissue damage, protein metabolism, and basal metabolism of broilers after chronic heat stress were studied by measuring serum physiological and biochemical indices. To provide a theoretical basis for the application of taurine in acute heat-stressed broilers.


Subject(s)
Chickens , Taurine , Animals , Chickens/physiology , Diet , Dietary Supplements , Heat-Shock Response , Hot Temperature , Taurine/pharmacology , Uric Acid
14.
Adv Exp Med Biol ; 1370: 161-169, 2022.
Article in English | MEDLINE | ID: mdl-35882792

ABSTRACT

The purpose of this study was to investigate the effects of taurine on blood indices of broilers with chronic heat stress and to provide theoretical basis for the application of taurine in the anti-chronic heat stress of broilers. In the test, 240 AA + broilers at 7 days of age were randomly divided into five groups: the normal temperature control group (24 ± 2 °C) in group C, the heat stress control group (34 ± 2 °C) in HS group, and the LTau, MTau, and HTau groups in heat under stress conditions, 0.5 g/L, 2 g/L, and 8 g/L taurine, were added to the drinking water, and each group was repeated three times. After 2 weeks of feeding at normal temperature, heat stress began. The test period was 4 weeks. Blood was collected at 6 h, 12 h, 7 d, 14 d, 21 d, and 28 d after heat stress, and serum was separated. The results showed that compared with the HS group, MTau significantly increased the total serum protein content (P < 0.05), but the other groups were not significantly different (P > 0.05). The MTau and HTau groups contained significantly lowered serum uric acid levels than the HS group (P < 0.05). At 7d and 14d, the LTau, MTau, and HTau groups all exhibited significantly increased T3 and T4 concentrations (P < 0.05). There was no significant difference between the groups at other times (P > 0.05). Compared with the HS group, the MTau group contained significantly reduced serum CK activity, LDH activity, AST activity, and ALT activity (P < 0.05). Compared with the LTau, MTau, and HTau groups, serum MDA content was significantly increased in the heat-stressed broilers (P < 0.05). MTau group contained significantly increased T-AOC, SOD, CAT, and GSH-PX levels (P < 0.05). The other groups were not significantly different (P > 0.05). Compared with group C, serum HSP60 and HSP70 levels were significantly elevated in the HS group (P < 0.05). Compared with the HS group, the LTau and MTau groups contained significantly increased serum HSP60 and HSP70 concentrations (P < 0.05), but the other groups were not significantly different (P > 0.05). In conclusion, taurine can alleviate the symptoms of chronic heat stress of broilers, regulate the metabolism of the body, and improve the antioxidant activity of the body.


Subject(s)
Antioxidants , Taurine , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Chickens/physiology , Dietary Supplements , HSP70 Heat-Shock Proteins , Heat-Shock Response , Hot Temperature , Taurine/pharmacology , Uric Acid
15.
Vet Res Commun ; 46(4): 1023-1032, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35835972

ABSTRACT

Manganese (Mn) is an essential microelement for broiler breeding and its deficiency causes tibial dyschondroplasia (TD). Tibial growth plate (TGP) development and metaphyseal vascularization are crucial for tibia growth in fast-growing broiler chickens, but their roles in Mn deficiency-induced TD in chicks remain unclear. This study was designed to clarify this issue. A total of 36 one-day-old broilers were divided into the control group and Mn-deficiency (Mn-D) group, which were fed with a standard diet (60 mg Mn/kg) and Mn deficiency diet (22 mg Mn/kg) for 42 days, respectively. TGP and proximal tibial metaphysis were collected to perform the related assays. This study found that Mn deficiency decreased the tibia length and TGP thickness in the TD model. Also, Mn deficiency increased the irregular and white tibial dyschondroplasia lesions (TDL) region under the TGP, and reduced the expression levels of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF). Combined with histological assessment, it was suggested that Manganese deficiency inhibited angiogenesis in the proximal tibial metaphysis. Meanwhile, Mn deficiency enhanced the expression levels of hypoxia-inducible factor-1 α (HIF-1α), autophagy-related protein 5 (ATG5), and microtubule-associated protein 1 light chain 3 ß (LC3-II) in TGP, but decreased the expression level of SQSTM1 (P62), which suggested that autophagy was activated during this process. Collectively, these data indicate that HIF-1α up-regulation and concurrent autophagy activation exert a protective effect against Mn deficiency-induced angiogenesis inhibition, which may provide useful guidance to prevent TD in broilers.


Subject(s)
Osteochondrodysplasias , Poultry Diseases , Animals , Chickens/metabolism , Osteochondrodysplasias/veterinary , Osteochondrodysplasias/metabolism , Osteochondrodysplasias/pathology , Poultry Diseases/prevention & control , Thiram/adverse effects , Thiram/metabolism , Tibia/metabolism , Tibia/pathology , Manganese/adverse effects , Manganese/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Up-Regulation
16.
Free Radic Biol Med ; 188: 35-44, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35675856

ABSTRACT

Mercuric chloride (HgCl2) is an environmental pollutant with serious nephrotoxic effects, but the underlying mechanism of HgCl2 nephrotoxicity is not well understood. Ferroptosis and necroptosis are two programmed cell death (PCD) modalities that have been reported singly in heavy metal-induced kidney injury. However, the interaction between ferroptosis and necroptosis in HgCl2-induced kidney injury is unclear. Here, we established a model of HgCl2-exposed chicken embryo kidney (CEK) cells to dissect the progresses and mechanisms of these two PCDs. We found that ferroptosis was initially activated in CEK cells after HgCl2 exposure for 12 h, and necroptosis was activated subsequently at 24 h. Importantly, further study indicated that the shift from ferroptosis to necroptosis was driven by ROS, which was produced by iron-dependent Fenton reaction, and the iron chelation by DFO prevented the sequential activation of both ferroptosis and necroptosis. To investigate the source of intracellular iron, the regulation of iron homeostasis was first explored and demonstrated a tendency for intracellular iron overload in CEK cells. Interestingly, the cellular ferritin, a free iron depository, decreased in a time-dependent manner. Further studies revealed that the degradation of ferritin was attributed to the activation of selective cargo receptor nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, and the inhibition of ferritinophagy by CQ prevented the HgCl2-induced cell death. In conclusion, our study demonstrated that HgCl2 released excess free iron via ferritinophagy, led to a sustained accumulation of ROS and ultimately activated ferroptosis and necroptosis sequentially. These findings provide a new understanding for the nephrotoxic mechanism of HgCl2.


Subject(s)
Ferroptosis , Iron Overload , Animals , Autophagy , Chick Embryo , Chickens/metabolism , Ferritins/metabolism , Iron/metabolism , Kidney/metabolism , Mercuric Chloride/metabolism , Mercuric Chloride/toxicity , Necroptosis , Reactive Oxygen Species/metabolism
17.
Theriogenology ; 187: 188-194, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35605398

ABSTRACT

Mercuric chloride (HgCl2) is a well-known toxic heavy metal contaminant, which causes male reproductive function defects. Selenium (Se) has been recognized as an effective antioxidant against heavy metals-induced male reproductive toxicity. The aim of present study was to explore the potentially protective mechanism of Se on HgCl2-induced testis injury in chicken. Firstly, the results showed that Se mitigated HgCl2-induced testicular injury through increasing the blood-testis barrier (BTB) cell-junction proteins expression of occludin, zonula occludens-1 (ZO-1), connexin 43 (Cx43), and N-cadherin. Secondly, Se alleviated HgCl2-induced oxidative stress through decreasing the malondialdehyde (MDA) content and increasing the superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) activities as well as the total antioxidant capacity (T-AOC) level. Thirdly, Se inhibited the activation of p38 MAPK signaling through decreasing the proteins expression of phosphorylated-p38 (p-p38) and phosphorylated-ATF2 (p-ATF2), and alleviated inflammation response through decreasing the proteins expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), tissue necrosis factor-alpha (TNF-α), and cyclooxygenase 2 (COX2). Collectively, these results demonstrated that Se effectively alleviated HgCl2-induced testes injury via improving antioxidant capacity to reduce inflammation mediated by p38 MAPK/ATF2/iNOS signaling pathway in chicken. Our data shed a new light on potential mechanisms of Se antagonized HgCl2-induced male reproductive toxicity.


Subject(s)
Mercuric Chloride , Selenium , Animals , Antioxidants/pharmacology , Chickens/physiology , Inflammation/metabolism , Inflammation/veterinary , Male , Mercuric Chloride/metabolism , Mercuric Chloride/toxicity , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress , Selenium/pharmacology , Signal Transduction , Testis , p38 Mitogen-Activated Protein Kinases/metabolism
18.
J Inorg Biochem ; 229: 111716, 2022 04.
Article in English | MEDLINE | ID: mdl-35065321

ABSTRACT

Mercuric chloride (HgCl2), a heavy metal compound, causes neurotoxicity of animals and humans. Selenium (Se) antagonizes heavy metal-induced organ damage with the properties of anti-oxidation and anti-inflammation. Nevertheless, the molecular mechanism underlying the protective effects of sodium selenite (Na2SeO3) against HgCl2-induced neurotoxicity remains obscure. Therefore, the present study aimed to explore the protective mechanism of Na2SeO3 on HgCl2-induced brain damage in chickens. Morphological observations showed that Na2SeO3 alleviated HgCl2-induced brain tissues damage. The results also showed that Na2SeO3 decreased the protein expression of S100 calcium binding protein B (S100B), and increased the levels of nerve growth factors (NGF), doublecortin domain containing 2 (DCDC2), as well as neurotransmitter to reverse HgCl2-induced brain dysfunction. Further, Na2SeO3 attenuated HgCl2-induced oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Mechanistically, Na2SeO3 activated the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor type B (TrKB)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and suppressed the nuclear factor kappa B (NF-κB) signaling pathway to inhibit apoptosis and inflammation caused by HgCl2 exposure. In summary, Na2SeO3 ameliorated HgCl2-induced brain injury via inhibiting apoptosis and inflammation through activating BDNF/TrKB/PI3K/AKT and suppressing NF-κB pathways.


Subject(s)
Brain Diseases/drug therapy , MAP Kinase Signaling System/drug effects , Mercuric Chloride/toxicity , Mercury Poisoning, Nervous System/drug therapy , Neuroprotective Agents/therapeutic use , Sodium Selenite/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Apoptosis/drug effects , Brain Diseases/chemically induced , Brain-Derived Neurotrophic Factor/metabolism , Chickens , Inflammation/drug therapy , Male , NF-kappa B/metabolism , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, trkB/metabolism
19.
Environ Toxicol ; 37(5): 1047-1057, 2022 May.
Article in English | MEDLINE | ID: mdl-34995020

ABSTRACT

Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl2 )-induced thymus and bursa of Fabricius (BF) damage in chickens. The results showed that HgCl2 caused immunosuppression by reducing the relative weight, cortical area of the thymus and BF, and the number of peripheral blood lymphocytes. Meanwhile, HgCl2 induced oxidative stress and imbalance in cytokines expression in the thymus and BF. Further, we found that thioredoxin-interacting protein (TXNIP) and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome mediated HgCl2 -induced oxidative stress and inflammation. Mechanically, the targeting and inhibitory effect of microRNA (miR)-135b/183 on forkhead box O1 (FOXO1) were an upstream event for HgCl2 -activated TXNIP/NLRP3 inflammasome pathway. Most importantly, Se effectively attenuated the aforementioned damage in the thymus and BF caused by HgCl2 and inhibited the TXNIP/NLRP3 inflammasome pathway by reversing the expression of FOXO1 through inhibiting miR-135b/183. In conclusion, the miR-135b/183-FOXO1/TXNIP/NLRP3 inflammasome axis might be a novel mechanism for Se to antagonize HgCl2 -induced oxidative stress and inflammation in the central immune organs of chickens.


Subject(s)
MicroRNAs , Selenium , Animals , Chickens/metabolism , Inflammasomes/metabolism , Mercuric Chloride/toxicity , MicroRNAs/genetics , MicroRNAs/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Selenium/pharmacology
20.
Biol Trace Elem Res ; 200(10): 4453-4464, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34851493

ABSTRACT

Manganese (Mn) is an essential trace element for broiler chickens; its deficiency causes tibial dyschondroplasia (TD) characterized by lameness and growth retardation. Inorganic and organic manganese sources are used in global poultry production, but there is a lack of systematic investigations to compare the bioavailability among them. In this study, 120 1-day-old Arbor Acres (AA) broilers were randomly divided into four groups (n = 30), i.e., control group (Mn sulfate, 60 mg/kg), Mn-D group (Mn deficiency, 22 mg/kg), Mn-Gly group (Mn glycinate, 60 mg/kg), and Mn-Pro group (Mn proteinate, 60 mg/kg). During the 42-day experiment, growth performance, tibial bone parameters, pathological index changes, serum biochemical changes, and oxidative stress indicators were evaluated. These results not only suggested that Mn plays a crucial role in the normal development of tibia and the maintenance of redox homeostasis in broilers, but also proved that organic Mn supplementation, especially Mn proteinate, improved the tibia development and the absorption efficiency, as well as overall oxidative stress status of broilers, suggesting that it had greater bioavailability than inorganic Mn. Thus, application of organic Mn source may be an effective way to reduce economic losses and resolve animal welfare concerns due to TD in commercial poultry farming.


Subject(s)
Chickens , Manganese , Animal Feed/analysis , Animals , Diet/veterinary , Dietary Supplements , Manganese/pharmacology , Oxidative Stress , Tibia
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