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Abstract Introduction: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Methods: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. Results: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. Conclusion: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.
RESUMO Introdução: O glifosato é o herbicida mais utilizado no mundo e no Brasil. Atualmente, há uma preocupação crescente com os efeitos do glifosato na saúde humana. O Instituto Brasileiro de Defesa do Consumidor apresentou dados sobre a presença de glifosato em alguns dos produtos ultraprocessados mais consumidos no Brasil. Atualmente, as regulamentações sobre o limite máximo desses resíduos em alimentos ultraprocessados ainda não foram estabelecidas pela Vigilância Sanitária Nacional, e o consumo de alimentos ultraprocessados está independentemente associado a um risco maior de doença renal crônica incidente. Métodos: Como uma dieta desbalanceada pode interferir na função renal, este estudo tem como objetivo investigar o efeito da ingestão diária de 5 mg/kg pc de glifosato em conjunto com uma dieta equilibrada e o possível impacto na função renal em ratos. Foram avaliados função renal, peso dos rins, marcadores de lesão renal e estresse oxidativo. Resultados: Houve redução no peso dos rins. As principais alterações histopatológicas nos tecidos renais foram vacuolização no estágio inicial e regulação positiva do marcador de lesão renal KIM-1. A lesão renal está associada à produção aumentada de espécies reativas de oxigênio nas mitocôndrias. Conclusão: Esse estudo mostrou alterações nos rins de ratos expostos a uma dieta balanceada com glifosato, sugerindo um risco potencial ao rim humano. Presumivelmente, alimentos ultraprocessados que contenham glifosato podem potencializar esse risco. A relevância desses resultados está no fato de chamar a atenção para a necessidade de regulamentar a concentração de glifosato em alimentos ultraprocessados no futuro.
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SUMMARY: Traumatic ankle osteoarthritis is a degenerative condition resulting from traumatic injuries. The objective of this study was to evaluate the impact of minimally invasive ankle joint fusion surgery on ankle function, oxidative damage, and inflammatory factor levels in traumatic ankle osteoarthritis patients. A total of 112 traumatic ankle osteoarthritis patients treated in our hospital from January 2022 to January 2023 were enrolled. They were randomly rolled into a control group (Group C) and an experimental group (Group E), with the former undergoing conventional open ankle joint fusion surgery and the latter receiving minimally invasive ankle joint fusion surgery. A comparison was made between the two groups based on American Orthopedic Foot and Ankle Society (AOFAS), bony fusion rates, and visual analog scale (VAS) scores at pre-operation, and at 1, 2, and 3 months post-operation. Additionally, serum oxidative damage indicators and inflammatory factor levels were measured to evaluate the recovery effects in both groups. Relative to Group C, Group E showed drastically increased AOFAS scores and bony fusion rates (P<0.05), as well as greatly decreased VAS scores (P<0.05). Moreover, Group E exhibited more pronounced improvements in oxidative damage indicators and inflammatory factors versus Group C (P<0.05). Minimally invasive ankle joint fusion surgery drastically improves ankle function in traumatic ankle osteoarthritis patients and reduces levels of oxidative damage and inflammatory response. This provides an important clinical treatment option.
La osteoartritis traumática del tobillo es una afección degenerativa resultante de lesiones traumáticas. El objetivo de este estudio fue evaluar el impacto de la cirugía mínimamente invasiva de fusión de la articulación talocrural sobre la función del tobillo, el daño oxidativo y los niveles de factor inflamatorio en pacientes con osteoartritis traumática del tobillo. Se inscribieron un total de 112 pacientes con artrosis traumática de tobillo tratados en nuestro hospital desde enero de 2022 hasta enero de 2023. Fueron divididos aleatoriamente en un grupo de control (Grupo C) y un grupo experimental (Grupo E), donde el primero se sometió a una cirugía de fusión de la articulación talocrural abierta convencional y el segundo recibió una cirugía de fusión de la articulación talocrural mínimamente invasiva. Se realizó una comparación entre los dos grupos según la Sociedad Estadounidense de Ortopedia de Pie y Tobillo (AOFAS), las tasas de fusión ósea y las puntuaciones de la escala visual analógica (EVA) antes de la operación y 1, 2 y 3 meses después de la operación. Además, se midieron los indicadores de daño oxidativo sérico y los niveles de factor inflamatorio para evaluar los efectos de la recuperación en ambos grupos. En relación con el grupo C, el grupo E mostró puntuaciones AOFAS y tasas de fusión ósea drásticamente aumentadas (P <0,05), así como puntuaciones VAS muy disminuidas (P <0,05). Además, el grupo E exhibió mejoras más pronunciadas en los indicadores de daño oxidativo y factores inflamatorios en comparación con el grupo C (P <0,05). La cirugía de fusión de la articulación talocrural mínimamente invasiva mejora drásticamente la función del tobillo en pacientes con osteoartritis traumática del tobillo y reduce los niveles de daño oxidativo y la respuesta inflamatoria. Esto proporciona una importante opción de tratamiento clínico.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Osteoarthritis/surgery , Arthrodesis/methods , Ankle Injuries/surgery , Osteoarthritis/etiology , Ankle Injuries/complications , Oxidative Stress , Minimally Invasive Surgical Procedures , Inflammation , Ankle/physiopathology , Ankle Joint/surgeryABSTRACT
Abstract Introduction: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. Methods: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. Results: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. Conclusions: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.
Resumo Introdução: Síndrome nefrótica (SN) é uma das causas de doença renal em estágio terminal. É importante elucidar a patogênese e oferecer novas opções de tratamento. Estresse oxidativo pode desencadear a patogênese sistemicamente ou isoladamente nos rins. O octreotide (OCT) tem efeitos antioxidantes benéficos. Nosso objetivo foi investigar a fonte de estresse oxidativo e efeito do OCT no modelo experimental de SN. Métodos: Dividimos 24 ratos albinos Wistar não urêmicos em 3 grupos. Grupo controle, 2 mL de solução salina intramuscular (im); grupo SN, adriamicina 5 mg/kg intravenosa (iv); grupo tratamento SN, adriamicina 5 mg/kg (iv) e OCT 200 mcg/kg (im) foram administrados no início do estudo (Dia 0). Aos 21 dias, mediram-se os níveis de creatinina e proteína em amostras de urina de 24 horas. Mediu-se a catalase (CAT) eritrocitária e renal e a substância reativa ao ácido tiobarbitúrico (TBARS). Avaliou-se também histologia renal. Resultados: Não houve diferença significativa entre os três grupos em termos de CAT e TBARS em eritrócitos. O nível de CAT renal foi menor no grupo SN e significativamente menor que no grupo controle. No grupo tratamento, o nível de CAT aumentou significativamente em comparação com o grupo SN. Quanto à histologia renal, as avaliações tubular e intersticial foram semelhantes em todos os grupos. O escore glomerular foi significativamente maior no grupo SN em comparação com o grupo controle e diminuiu significativamente no grupo de tratamento em comparação com o grupo SN. Conclusões: Estresse oxidativo na SN pode ser devido à diminuição do mecanismo de proteção antioxidante nos rins. O octreotide melhora níveis de antioxidantes e histologia do tecido renal e pode ser uma opção de tratamento.
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SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.
Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.
Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Sodium-Potassium-Exchanging ATPase/drug effects , Diabetic Nephropathies/drug therapy , Acacia/chemistry , Superoxide Dismutase , Glycated Hemoglobin/analysis , Plant Extracts/pharmacology , Gene Expression , Rats, Sprague-Dawley , Sodium-Potassium-Exchanging ATPase/genetics , Oxidative Stress , Microscopy, Electron, Transmission , Disease Models, Animal , Drug Therapy, Combination , Glycemic Control , Insulin/administration & dosage , Kidney/drug effects , MalondialdehydeABSTRACT
Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.
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RESUMEN Objetivo: Identificar la influencia del consumo de hidratos de carbono (HCO) sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional (DMG). Materiales y métodos: Se realizó un estudio transversal, observacional y comparativo a dos grupos de 21 mujeres con y sin DMG, respectivamente, en la ciudad de Toluca, México, de enero a diciembre del 2022. Para evaluar parámetros sociodemográficos, se les aplicó un cuestionario de historia clínica; en cuanto a los parámetros antropométricos, se les midió peso corporal y estatura; y respecto a los parámetros bioquímicos, colesterol total (CT) y triglicéridos (TG). Para evaluar el estado oxidante/antioxidante se cuantificaron, como marcador oxidante, el malondihaldeído (MDA), y como antioxidantes, catalasa (cat), superóxido dismutasa (SOD) y capacidad antioxidante total (CAT). Los hábitos dietéticos se evaluaron a través de un recordatorio de 24 horas, en ambos grupos de mujeres, para obtener los macronutrientes: proteínas, lípidos e HCO. A partir de los hidratos de carbono totales (HCOT), se calcularon los hidratos de carbono complejos (HCOC) e hidratos de carbono simples (HCOS) como la sacarosa. Para el cálculo de HCOS por día, se usó la lista de alimentos con contenido de sacarosa por cada 100 gramos de consumo que emplea el Sistema Mexicano de Equivalentes; para el análisis de dieta, se utilizó el programa Nutrikcal VO. Se usaron las pruebas estadísticas t de Student para muestras independientes, U de Mann-Whitney para las variables no homogéneas y se realizó la correlación de Spearman (p < 0,05) en el programa SPSS, versión 19. Resultados: Los resultados mostraron que la diferencia entre los valores de CT (p < 0,029), TG (p < 0,029), las enzimas: cat (p < 0,011), SOD (p < 0,013), así como el MDA (p < 0,039), fueron significativamente mayores en las pacientes del grupo con DMG en comparación con el grupo sin DMG. Además, el grupo con DMG consumió mayor proporción de sacarosa. Conclusiones: Las mujeres con DMG tienen un desequilibrio en el estado oxidante/antioxidante influenciado por el tipo de HCO que consumen, en particular los HCOS como la sacarosa.
ABSTRACT Objective: To identify the influence of carbohydrate (CHO) intake on oxidative status among women with and without gestational diabetes mellitus (GDM). Materials and methods: A cross-sectional, observational and comparative study was carried out with two groups of 21 women each with and without GDM in the city of Toluca, Mexico, from January to December 2022. The sociodemographic parameters were determined by administering the patients a medical history questionnaire; anthropometric parameters such as body weight and height were measured; and biochemical parameters including total cholesterol (TC) and triglycerides (TG) were calculated. The oxidant/antioxidant status was assessed as follows: malondialdehyde (MDA) as oxidative stress marker; and catalase (CAT), superoxide dismutase (SOD) and total antioxidant capacity (TAC) as antioxidants. Dietary habits were evaluated through a 24-hour reminder in both groups of women to obtain the macronutrient classes, i.e., proteins, fats and CHOs. Based on the total carbohydrates (TCHOs), complex (CCHOs) and simple carbohydrates (SCHOs) such as sucrose were calculated. SCHOs per day were measured using the list of foods with sucrose content per 100 grams according to the Mexican Food Equivalence System (SMAE). The NutriKcal VO program was used for the dietary analysis. Statistical tests such as Student's t test and Mann-Whitney U test were performed for the independent samples and nonhomogeneous variables, respectively, and Spearman's rank correlation coefficient (p < 0.05) was determined using the IBM SPSS Statistics V19. Results: The results showed that the difference between the levels of TC (p < 0.029), TG (p < 0.029), enzymes CAT (p < 0.011) and SOD (p < 0.013), as well as MDA (p < 0.039) was significantly higher among patients in the group with GDM compared to that in the group without GDM. In addition, the group with GDM consumed a higher proportion of sucrose. Conclusions: Women with GDM have an imbalance in the oxidant/antioxidant status, influenced by the type of CHO they consume, particularly SCHOs such as sucrose.
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ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 (PI3K/Akt/Nrf2) pathway in the aorta of spontaneously hypertensive rats (SHR) and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction (VED). MethodTen 10-week-old Wistar Kyoto (WKY) rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group, and fifty SHR rats were randomized according to body weight into model, valsartan (8×10-3 g·kg-1·d-1), and high-, medium-, and low-dose (0.2, 0.1, 0.05 g·kg-1·d-1, respectively) earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period, the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention, enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ (Ang-Ⅱ) and endothelin-1 (ET-1) in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide (NO), malondialdehyde (MDA), glutathione peroxidase (GPX), superoxide dismutase (SOD), and ferrous ion (Fe2+). Hematoxylin-eosin (HE) staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to measure the mRNA levels of PI3K, Akt, Nrf2, heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K (Tyr467/199), PI3K, p-Akt (Ser473), Akt, Nrf2, HO-1, and GPX4 in the thoracic aorta. ResultCompared with the normal group, the model group had decreased body mass, increased irritability, severe endothelial damage, elevated blood pressure and serum levels of Ang-Ⅱ, ET1, MDA, and Fe2+ (P<0.01), lowered NO level (P<0.01), and down-regulated mRNA and protein levels of p-PI3K (Tyr467/199), PI3K, p-Akt (Ser473), Akt, Nrf2, HO-1, and GPX4 in the aortic tissue (P<0.01). Compared with the model group, drug intervention caused no significant change in the body mass, calmed the rats, alleviated the endothelial damage, lowered blood pressure and serum levels of Ang-Ⅱ, ET1, MDA, and Fe2+ (P<0.01), elevated the NO level (P<0.05), and up-regulated the mRNA and protein levels of p-PI3K (Tyr467/199), PI3K, p-Akt (Ser473), Akt, Nrf2, HO-1, and GPX4 (P<0.05). ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically, it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.
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ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway in chronic heart failure (CHF) rats after myocardial infarction (MI). MethodSD rats randomly divide into sham operation group (normal saline ,thread only without ligature), model group (normal saline, ligation of the left anterior descending coronary artery proximal to the heart), Linggui Zhugantang group (4.8 g·kg-1) and Captopril group (0.002 57 g·kg-1), with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin (HE) staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species (ROS). JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate (ATP), superoxide dismutase (SOD), malondialdehyde (MDA), mitochondrial respiratory chain complex activity (Ⅰ-Ⅳ). TdT-mediated dUTP nick end labeling (TUNEL) staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3, phosphorylated AMPK (p-AMPK), phosphorylated dynamic-related protein 1(p-Drp1), mitochondrial fission protein 1(Fis1), mitochondrial fission factor (MFF), optic atrophy protein 1(OPA1). ResultCompared to the sham group, the left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) were significantly increased in model group (P<0.01), while the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (P<0.01). There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS, MDA levels and myocardial cell apoptosis rate were significantly increased (P<0.01), SOD level, ATP content, and membrane potential were significantly decreased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) was significantly decreased (P<0.01). Levels of p-Drp1, Fis1, MFF proteins were significantly up-regulated (P<0.01), while Sirt3, p-AMPK, OPA1 proteins level were significantly down-regulated (P<0.01). Compared with model group, LVIDd and LVIDs were significantly decreased (P<0.01), LVEF and LVFS were significantly increased (P<0.01). Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS, MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group (P<0.01), SOD level, ATP content, and membrane potential significantly increased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) increased significantly (P<0.01),and p-Drp1, Fis1, MFF protein levels were significantly down-regulated (P<0.01), Sirt3, p-AMPK, OPA1 protein were significantly up-regulated (P<0.01). ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells, maintain mitochondrial function stability, and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
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Ginseng Radix et Rhizoma(GRR) has the function of replenishing vital energy and can lighten the body and prolong the life when taken for a long time, which is suitable for the development of anti-aging products, so this paper intends to sort out the progress of anti-aging research on GRR. After combing, the results of modern studies have shown that a variety of components in GRR have anti-aging effect, which can prolong the lifespan of aging animal models, as well as delay the aging of various systems. The anti-aging mechanisms mainly include anti-cellular senescence, anti-oxidative stress, inhibiting telomere shortening, maintaining mitochondrial homeostasis and so on. The anti-aging ingredients of GRR involved in the researches mainly include ginsenoside Rg1 and ginsenoside Rb1, in addition, ginsenoside Rg3, ginsenoside Rd, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb2, oligosaccharides of GRR, polysaccharides of GRR, water extract of GRR, total saponins of Panax ginseng stems and leaves are also included. Therefore, under current background of population aging, the in-depth development of GRR and its transformation into anti-aging products are of great significance for delaying senility and improving the health conditions of aging population.
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Chronic obstructive pulmonary disease (COPD) is a common disease in clinical practice. It is associated with obvious exposure to toxic particles or gases and has become the leading cause of death and disability worldwide. The pathogenesis of COPD is complex, and the oxidative stress involved in COPD plays a crucial role in the pathological process of the disease. Patients with COPD usually have high levels of oxidative stress in the lungs, which will affect the whole body for a long time, causing a variety of complications and accelerating the development of the disease. On the one hand, oxidative stress can directly damage the airway and lung tissue. On the other hand, it also drives other pathological mechanisms to jointly promote the development of disease, such as participating in inflammatory reactions and protease/anti-protease imbalance, promoting mucus secretion, accelerating cellular senescence, causing autoimmunity, and involving in genetic regulatory pathways. At present, western medicine treatment is mostly based on conventional drug treatment, and antioxidant-targeted oxidative stress is adopted, but there are still some challenges in efficacy and safety. Traditional Chinese medicine has a long history of preventing and treating COPD. In particular, Chinese herbal medicine formulas have great potential to interfere with the oxidative stress of COPD. Whether it is the modified classical traditional Chinese medicine or the new formulation developed by modern doctors, the research results reflect the multi-target and multi-channel advantages of traditional Chinese medicine treatment, and their efficacy and safety are gradually verified. This paper reviewed the literature in recent years, starting with the basic and clinical research on the intervention of traditional Chinese herbal medicine formulas on oxidative stress of COPD, so as to provide further ideas for related research on the prevention and treatment of oxidative stress of COPD by traditional Chinese medicine.
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Objective To investigate the role and mechanism of spliced X-box binding protein 1 (XBP1s) in the senescence of primary renal tubular epithelial cells induced by hypoxia/reoxygenation (H/R). Methods Primary renal tubular epithelial cells were divided into the normal control group (NC group), H/R group, empty adenovirus negative control group (Ad-shNC group), targeted silencing XBP1s adenovirus group (Ad-shXBP1s group), empty adenovirus+H/R treatment group (Ad-shNC+H/R group) and targeted silencing XBP1s adenovirus+H/R treatment group (Ad-shXBP1s +H/R group), respectively. The expression levels of XBP1s in the NC, H/R, Ad-shNC and Ad-shXBP1s groups were measured. The number of cells stained with β-galactosidase, the expression levels of cell aging markers including p53, p21 and γH2AX, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in the Ad-shNC, Ad-shNC+H/R and Ad-shXBP1s+H/R groups. Chromatin immunoprecipitation was employed to verify Sirtuin 3 (Sirt3) of XBP1s transcription regulation, and the expression levels of Sirt3 and downstream SOD2 after down-regulation of XBP1s were detected. Mitochondrial reactive oxygen species (mtROS) were detected by flow cytometry. Results Compared with the NC group, the expression level of XBP1s was up-regulated in the H/R group. Compared with the Ad-shNC group, the expression level of XBP1s was down-regulated in the Ad-shXBP1s group (both P<0.001). Compared with the Ad-shNC group, the number of cells stained with β-galactosidase was increased, the expression levels of p53, p21 and γH2AX were up-regulated, the levels of ROS, MDA and mtROS were increased, the SOD activity was decreased, the expression level of Sirt3 was down-regulated, and the ratio of Ac-SOD2/SOD2 was increased in the Ad-shNC+H/R group. Compared with the Ad-shNC+H/R group, the number of cells stained with β-galactosidase was decreased, the expression levels of p53, p21 and γH2AX were down-regulated, the levels of ROS, MDA and mtROS were decreased, the SOD activity was increased, the expression level of Sirt3 was up-regulated and the ratio of Ac-SOD2/SOD2 was decreased in the Ad-shXBP1s+H/R group (all P<0.05). Conclusions Down-regulation of XBP1s may ameliorate the senescence of primary renal tubular epithelial cells induced by H/R, which probably plays a role through the Sirt3/SOD2/mtROS signaling pathway.
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Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.
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ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata(ALRP) in attenuating toxicity by processing from the aspects of amino acid metabolism, oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group, raw group and processed group, 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day, the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days, the urine, serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin(HE) staining, and the activities of lactate dehydrogenase(LDH) and creatine kinase-MB(CK-MB) in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to perform urine metabolomics analysis, and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing, and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group, while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group, indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group, indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group, the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group, and those were significantly decreased in serum and heart tissue of the processed group, suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes, of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism, arginine and proline metabolism, phenylalanine metabolism, aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products, the mechanism mainly involves amino acid metabolism, oxidative stress and energy metabolism, which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.
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ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage (固本防哮饮) for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group, model group, low-, medium-, and high-dose of Guben Fangxiao Beverage group and montelukast sodium group, with 6 mice in each group. Except for the normal group, ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding, the low-, medium-, and high-dose groups of Guben Fangxiao Beverage were respectively given 12, 24, and 36 g/(kg·d), the montelukast sodium group was given montelukast sodium granule 2.6 mg/(kg·d), and the mice in the normal group and model group were given 20 ml of double-distilled water, all by gavage, once a day for 28 days. The levels of interleukin 4 (IL-4) and interleukin 5 (IL-5) in the lung tissue of mice were detected; HE staining was used to observe the pathology of the lung tissue and to score the inflammation; DHE staining was used to observe the level of reactive oxygen species (ROS) in the lung tissue, and the activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ in the lung tissue were detected; the levels of serum superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and adenosine triphosphate (ATP) were detected; the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cAMP responsive element binding protein (CREB) in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group, the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score; DHE staining showed an increase in the level of ROS, and an increase in the levels of IL-4 and IL-5 in the lung tissues; the levels of serum SOD, CAT, and ATP were reduced, and the level of MDA was elevated; the activities of the mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ of the lung tissues were reduced, and the activities of p-AMPK, Nrf2, CREB protein expression decreased (P<0.05). Compared with the model group, the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced; the levels of ROS, IL-4 and IL-5 in the lung tissue were reduced; the levels of CAT and ATP in the serum increased, and the content of MDA was reduced; and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ, as well as the expression of CREB protein, were elevated in the lung tissue (P<0.05). Compared with the high-dose group, the MDA level of the medium-dose Guben Fangxiao Beverage group decreased (P<0.05). The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group, and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group (P<0.05). ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission, and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.
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The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.
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Objective To explore the role and potential mechanisms of all-trans retinoic acid (ATRA) on activation and oxidative stress of hepatic stellate cell (HSC). Methods Platelet-derived growth factor (PDGF-bb, 10 ng/ml) was applied to induce the activation of HSCs, which was then treated with ATRA at a dosage of 5 μmol/L for 48 h. The effects of ATRA on HSC activation were evaluated by detecting changes in cell growth viability and phenotypic marker expression. The effects of ATRA on HSC oxidative stress were evaluated by detecting changes in intracellular reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA), and the expression of antioxidant genes. The effects of ATRA on HSC autophagic activity were evaluated by detecting changes in autophagy marker expression and autophagic flow. Results Compared with the PDGF-bb group, the cell viability was significantly reduced in ATRA-treated HSCs (P<0.01), as well as the expression of α-SMA and Collagen I. The intracellular levels of ROS and MDA were significantly reduced in ATRA-treated HSCs (P<0.01), whereas the GSH level was significantly increased (P<0.01). The expression levels of antioxidant genes (NRF2, HO-1, and ATF4), were significantly higher in ATRA-treated HSCs than those in the normal ones under PDGF-bb condition (P<0.01). Meanwhile, the expression of autophagy markers Beclin 1 and LC3 Ⅱ/I, and signal of autophagy flow in ATRA-treated HSCs were found to be significantly reduced (P<0.01). Conclusion ATRA significantly inhibited PDGF-bb-induced HSC activation and reduced the level of oxidative stress and autophagic activity of HSCs, which had potential applications in the prevention and treatment of liver fibrosis.
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Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.
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Growth/differentiation factor-5 (GDF-5) belongs to transforming growth factor-β (TGF-β) family, which is expressed in bone, cartilage, heart, brain, kidney, skeletal muscle and tendon, liver, fat and other organs and tissues as well. GDF-5 binds to receptor BMPR-I/BMPR-II and activates different signaling pathways such as smad1/5/8, PI3K/Akt, p38-MAPK. For a long time, numerous studies have shown that GDF-5 plays an important role in protecting joints. However, researchers have found GDF-5 also plays significant biological functions in other organs. For example, GDF-5 improves cardiac function by reducing oxidative stress and fibrosis in infarcted hearts. GDF-5 can also reduce oxidative stress in the brain and increase the number of neurons in effort to delay the progression of Alzheimer’s disease and Parkinson’s disease. It is a situation, research on GDF-5, at present, mainly focuses on the growth and repair of bone, cartilage and tendons, while there are few reports on its biological effects in other organs. Therefore, this article reviews and summarizes the research progress on GDF-5 and metabolic diseases in recent years in order to provide new insights and theoretical basis for the role of GDF-5 in improving metabolic diseases.
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ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in intervening in oxidative stress in the rat model of Alzheimer's disease (AD) via modulating the rat sarcoma (RAS)/rapidly accelerating fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. MethodOne hundred 4-month-old SPF-grade Wistar male rats were randomly grouped as follows: 10 in the blank group, 10 in the sham group (bilateral hippocampus injected with 1 μL normal saline), and 80 in the modeling group [bilateral hippocampus injected with 1 μL amyloid beta protein 1-42 (Aβ1-42) solution for the modeling of AD]. Fifty rats qualified for modeling were selected and randomized into the model, donepezil hydrochloride (0.5 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs by gavage once a day for 42 consecutive days. At the end of gavage, Morris water maze test was performed to examine the learning and memory abilities of the rats, and Nissl staining was used to observe the pathological changes of neurons in CA3 region of the hippocampus. The immunofluorescence assay was used to observe Aβ deposition and tau phosphorylation. Western blot was employed to determine the protein levels of RAS, RAF, phosphorylated (p)-RAF, MEK, p-MEK, ERK, and p-ERK in the hippocampal tissue. Biochemical methods were used to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the hippocampal tissue. ResultCompared with the sham group, the model group showed prolonged escape latency (P<0.01), shortened swimming distance in the target quadrant (P<0.01), reduced and uneven stained Nissl bodies, enhanced fluorescence intensity of Aβ and p-tau (P<0.01), up-regulated protein levels of RAS, p-RAF, p-MEK, and p-ERK in the hippocampal tissue (P<0.01), increased ROS and MDA content (P<0.01), and decreased SOD activity (P<0.01) on day 5. Compared with the model group, donepezil hydrochloride and high-, medium-, and low-dose Hei Xiaoyaosan shortened the escape latency (P<0.01), increased the swimming distance in the target quadrant (P<0.01), improved the arrangement, morphology, and structures of neurons and the number and distribution of Nissl bodies, decreased the fluorescence intensity of Aβ and p-tau (P<0.01), up-regulated the protein levels of RAS, p-RAF, p-MEK, and p-ERK (P<0.05, P<0.01), decreased the ROS and MDA content (P<0.01), and increased the SOD activity (P<0.01) on day 5. ConclusionHei Xiaoyaosan may ameliorate oxidative stress, reduce Aβ and p-tau levels, and inhibit hippocampal neuronal damage by regulating the RAS/RAF/MEK/ERK signaling pathway, thus improving learning and memory abilities.
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Diabetic gastroparesis (DGP) is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically, it often manifests as abdominal distension, nausea and vomiting, early satiety, dyspepsia, etc. The pathogenesis of DGP is multifactorial, closely related to many factors, such as chronic hyperglycemia, neuropathy, autonomic nervous system disorders, inflammation, and oxidative stress. These factors can interact with each other, leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine (TCM) has significant advantages in the prevention and treatment of DGP, including a long history, remarkable efficacy, individualized treatment, diverse therapeutic formulations, and improvement in the quality of life. Additionally, TCM is known for its low adverse reactions, good tolerance, and multi-targeted effects, making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones, inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and modulation of related signaling pathways such as stem cell factor (SCF)/cellular growth factor receptor (c-Kit), adenosine monophosphate-activated protein kinase (AMPK), Ras homologous genome member A (RhoA)/Rho-associated coiled-coil forming kinase (ROCK). This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses, reduction of oxidative stress, enhancement of interstitial cells of Cajal activity, inhibition of pyroptosis, and regulation of related signaling pathways, aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.