Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Antioxidantes naturales y su efecto contra el estrés oxidante provocado por la contaminación por material particulado / Natural Antioxidants and their Effect Against Oxidative Stress Caused by Particulate Matter Pollution

Resumen La contaminación ambiental es uno de los factores que favorece el estrés oxidante, ya que expone al organismo a materiales diversos que generan radicales libres y afectan al sistema respiratorio, cardiovascular, inmunológico y nervioso de las personas más vulnerables como los niños, adultos mayores y personas con enfermedades crónicas. Para prevenir o reducir el estrés oxidante, el cual es un desequilibrio entre la producción de radicales libres y la capacidad del organismo de neutralizarlo, se recomienda consumir una dieta equilibrada y rica en antioxidantes naturales los cuales se encuentran diversos alimentos, especialmente en frutas y verduras con colores intensos, en las semillas y las especias. En las últimas décadas se ha demostrado la eficacia del consumo de antioxidantes naturales como: el resveratrol vino, el café, la curcumina, el ajo, la vitamina C, la vitamina E y el té verde que presentan efectos benéficos como: proteger membranas celulares, regular la expresión de genes relacionados con la inflamación, prevenir o reducir el daño endotelial, disminuir la frecuencia o severidad de enfermedades neurodegenerativas, hepáticas y pulmonares, así como estimular al sistema inmunológico.

Abstract Environmental pollution can promote oxidative stress by exposing the body to various elements and substances that generate free radicals, such as lead and vanadium. These free radicals can negatively impact the respiratory, cardiovascular, immune, and neurological systems of vulnerable populations, including children, the elderly, and those with chronic diseases. To prevent or reduce oxidative stress, it is recommended to consume a balanced diet rich in natural antioxidants. These antioxidants can be found in various foods, especially in fruits and vegetables with intense colors, seeds, and spices. In recent decades, the effectiveness of consuming natural antioxidants such as resveratrol found in wine, coffee, curcumin, garlic, vitamin C, vitamin E, and green tea has been demonstrated. These antioxidants have beneficial effects on the body, including the protection of cell membranes, regulation of gene expression associated with inflammation, prevention or reduction of endothelial damage, and the decrease or diminished severity of neurodegeneration, liver, and pulmonary disorders. Additionally, they stimulate the immune response.

Diferencia en las distintas funciones de las lipoproteínas de alta densidad en respuesta a la infección por SARS-CoV-2 / Differential Functions of High-density Lipoproteins in Response to SARS-CoV-2 Infection

RESUMEN Introducción. El síndrome post COVID (SPC), que se caracteriza por síntomas que se extienden superando las 4 semanas post-infección, podría desencadenar aumento en el riesgo cardiovascular. Las lipoproteínas de alta densidad (HDL) presentan funciones antiaterogénicas, como su capacidad para promover el transporte inverso del colesterol (TIC) y su actividad antioxidante, en la que es clave la enzima paraoxonasa 1 (PON 1). Objetivo. Evaluar funcionalidad de HDL en pacientes con SPC comparados con pacientes asintomáticos (PA) y controles. Material y métodos. Se incluyeron 9 individuos con SPC, 18 PA y 10 controles. Se midieron el hemograma, el perfil lipoproteico básico, las apolipoproteínas A-I y B, y marcadores inflamatorios por métodos automatizados. La actividad de PON 1 se evaluó empleando un método espectrofotométrico y los 3 pasos del TIC, eflujo de colesterol (ECC), y actividades de lecitina:colesterol aciltransferasa (LCAT) y proteína transportadora de colesterol esterificado (CETP), por métodos radiométricos. Resultados. No se observaron diferencias en sexo, edad, ni parámetros generales. El grupo PA presentó mayor actividad PON que los controles (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, en controles, PA y SPC, respectivamente; p=0,049). No se observaron diferencias en el TIC. El ECC (r=-0,45; p=0,049) y CETP (r=-0,38; p=0,028) correlacionaron negativamente con el índice neutrófilos/linfocitos. LCAT correlacionó inversamente con la ferritina (r=-0,34; p=0,046). Conclusiones. El incremento de PON 1 en el grupo PA representaría un mecanismo de defensa frente al estrés oxidativo post-infección. Todos los pasos del TIC mostraron una correlación negativa con marcadores inflamatorios. Nuestros resultados podrían explicar, en parte, el vínculo entre COVID y ateroesclerosis.

ABSTRACT Background. Post-COVID syndrome (PCS), characterized by symptoms that persist for more than 4 weeks after initial infection, could increase cardiovascular risk. High-density lipoproteins (HDL) have antiatherogenic functions, such as the ability to promote reverse cholesterol transport (RCT) and antioxidant activity. In this regard, paraoxonase 1 (PON 1) plays a key role. Objective. The aim of this study was to evaluate HDL functions in patients with PCS and compare them with asymptomatic patients (AP) and controls. Methods. The study included 9 patients with PCS, 18 AP and 10 controls. Complete blood count, basic lipoprotein profile, apolipoproteins A-I and B, and inflammatory markers were measured using automated methods. PON 1 activity was evaluated by a spectrophotometric assay, and the 3 steps of RCT, cellular cholesterol (efflux CCE), lecithin-cholesterol acyltransferase (LCAT) activity and cholesteryl ester transfer protein (CETP) activity were evaluated by radiometric assays. Results. There were no differences in sex, age, or general parameters. The AP group had higher PON activity than the control group (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, in controls, AP and PCS, respectively; p=0.049). There were no differences in RCT. Cellular cholesterol efflux (r=-0.45; p=0.049) and CETP (r=- 0.38; p=0.028) had a negative correlation with neutrophil-to-lymphocyte ratio. LCAT had an inverse correlation with ferritin (r=-0.34; p=0.046). Conclusions . Increased antioxidant activity of PON 1 would represent a defensive mechanism against oxidative stress after infection. All the RCT steps had a negative correlation with inflammatory markers. Our findings may explain, at least in part, the link between COVID-19 and atherosclerosis.

Morphological and Morphometric Analysis, Apoptosis and Oxidative Stress Study in Hep 2 Cells Treated by Resveratrol or Quercetine / Análisis Morfológico y Morfométrico, Estudio de Apoptosis y Estrés Oxidativo en Células Hep 2 Tratadas con Resveratrol o Quercetina

SUMMARY: Resveratrol (RES) and quercetine (QRC), is a promising agent relevant for both cancer chemoprevention and treatment via several signaling pathways, involved in their anticancer activity related to its chemotherapeutic potential, associated with the induction of ROS generation in cancer cells, leading to apoptosis. In our study, we have summarized the mechanisms of action of RES and QRC, and their pharmacological implications and potential therapeutic applications in cancer therapy. After treatment of Hep 2 cells with QRC or RES, the death pathways such as the cytochrome c release, ERK1/2 and IRS-1 pathways were upregulated, while cell survival pathway, including PI3K/AKT were downregulated. The RES and QRC caused oncosis, cells hypertrophy, hypercondensatin of chromatin, rupture of the plasma membrane and nuclear membrane, and formation of apoptotic bodies. Morphometric measurements of some cellular and nuclear parameters showed that RES and QRC induced an increase in cells and nuclear size, the nucleocytoplasmic ratio remained below 1 (N-Cyt R < 1), sign of low nuclear activity. The RES and QRC induced apoptosis of Hep2 cells by increasing of oxidative stress markers, MDA, and by modulating detoxifying enzymes, CAT and SOD. Our study results prove antiproliferative and proapoptotic properties of quercetin and resveratrol with regard to larynx cancer.

Resveratrol (RES) y quercetina (QRC), es un agente prometedor y relevante tanto para la quimioprevención como para el tratamiento del cáncer a través de varias vías de señalización, involucrado en su actividad anticancerígena relacionada con su potencial quimioterapéutico, asociado con la inducción de la generación de especies reactivas del oxígeno (ROS) en células cancerosas, lo que lleva a apoptosis. En nuestro estudio, hemos resumido los mecanismos de acción de RES y QRC, y sus implicaciones farmacológicas y posibles aplicaciones terapéuticas en la terapia del cáncer. Después del tratamiento de las células Hep 2 con QRC o RES, las vías de muerte, tal como la liberación de citocromo c, las vías ERK1/2 e IRS-1, se regulaban positivamente, mientras que la vía de supervivencia celular, incluida PI3K/AKT, se regulaba negativamente. El RES y el QRC provocaron oncosis, hipertrofia celular, hipercondensación de la cromatina, rotura de la membrana plasmática y nuclear y formación de cuerpos apoptóticos. Las mediciones morfométricas de algunos parámetros celulares y nucleares mostraron que RES y QRC indujeron un aumento en las células y el tamaño nuclear, la proporción nucleocitoplasmática se mantuvo por debajo de 1 (N- Cyt R <1), signo de baja actividad nuclear. RES y QRC indujeron la apoptosis de las células Hep2 aumentando los marcadores de estrés oxidativo, MDA, y modulando las enzimas desintoxicantes, CAT y SOD. Los resultados de nuestro estudio demuestran las propiedades antiproliferativas y proapoptóticas de la quercetina y el resveratrol con respecto al cáncer de laringe.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet / Efeitos da ingestão do herbicida glifosato na função renal de ratos em uma dieta balanceada

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.

An Assessment of Ankle Function, Oxidative Damage, and Inflammatory Factor Levels in Minimally Invasive Ankle Joint Fusion Surgery for the Treatment of Traumatic Ankle Osteoarthritis

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.

El estrés oxidativo en el perioperatorio: implicaciones clínicas / Oxidative stress in the perioperative period: clinical implications

Resumen: El trauma de la cirugía altera la homeostasis y desarrolla complicaciones en el postoperatorio, particularmente en los pacientes de alto riesgo. Las respuestas al estrés quirúrgico se producen por un proceso inflamatorio agudo y por un estado de desbalance entre los niveles de moléculas prooxidantes y la actividad de los sistemas antioxidantes conocido como estrés oxidativo (EOx). Estos dos mecanismos subyacen a las complicaciones en el perioperatorio. Por otro lado, las complicaciones pueden disminuirse con el manejo anestésico adecuado, ya que algunos anestésicos presentan capacidad antioxidante. El EOx puede tener un impacto negativo en todas las formas de cirugía mayor, particularmente en los pacientes de edad avanzada y con comorbilidades, por lo que es importante disminuir o evitar este fenómeno. El objetivo de esta revisión es presentar brevemente el concepto y las bases celulares del EOx y su relación con las complicaciones más comunes en el perioperatorio de cirugía cardíaca y no cardíaca, así como la determinación cuantitativa del nivel de EOx mediante biomarcadores séricos. Además, se revisa el efecto de los anestésicos sobre el EOx y el uso de terapias antioxidantes en la prevención de las complicaciones postoperatorias inducidas por el EOx.

Abstract: The trauma of surgery induces systemic stress that alters homeostasis and develops postoperative complications, particularly in high-risk patients. Surgical stress is produced by an acute inflammatory process and by the imbalance between the levels of pro-oxidant molecules and the activity of antioxidant systems. This imbalance is known as oxidative stress (OS). These two mechanisms underlie perioperative complications are reduced with anaesthetic management since some anaesthetics have antioxidant capacity. OS could negatively impact all forms of major surgery, particularly in elderly patients and patients with comorbidities. This review aims to present the concept and cellular bases of OS and its relationship with the most common complications in the perioperative period of cardiac and non-cardiac surgery, as well as the quantitative determination of the level of OS through serum biomarkers. Furthermore, the effect of anaesthetics on OS and the use of antioxidant therapies in preventing postoperative complications induced by OS are reviewed.

Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model / Efeito do octreotide no estresse oxidativo em eritrócitos e no tecido renal no modelo de síndrome nefrótica experimental induzida por adriamicina

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.

Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

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.

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

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.

Influencia del consumo de hidratos de carbono sobre el estado oxidante en mujeres con y sin diabetes mellitus gestacional / Influence of carbohydrate intake on oxidative status among women with and without gestational diabetes mellitus

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.

Dexmedetomidine alleviates TNF-α-induced injury of human neuroblastoma cell line SH-SY5Y through activating AMPK / 基础医学与临床

Objective To study the effect of dexmedetomidine(DEX)on TNF-α-induced injury of human neuro-blastoma cell line SH-SY5Y and its mechanism.Methods CCK8 assay was used to detect cell activity and deter-mine the optimal dose of DEX and TNF-α.The cells were divided into control group,model group,DEX interven-tion model group,and the intervention group of DEX plus compound C.Western blot was used to detect the expres-sion of p-AMPK,SNHP,KIF5B,Drp1 and OPA1,and ELISA was used to detect the level of IL-1β and IL-6.Mitochondrial membrane potential(Δψm),respiratory chain complex enzyme activity(complex Ⅰ-Ⅳ),ATP,MDA,SOD,GSH,ROS were determined with commercially available kits.Results Compared with control group,level of p-AMPK,OPA1 and SNPH l in model group significantly decreased,while the level of Drp1 and KIF5B significantly increased(P＜0.01).The level of complexⅠ～Ⅳ,Δψm,ATP,GSH and SOD in DEX group signifi-cantly increased as compared with model group.The level of MDA,IL-1β and IL-6 significantly decreased(P＜0.01).Compared with DEX group,the level of Complex Ⅰ-Ⅳ,Δψm,ATP,GSH and SOD in DEX+CC group significantly decreased,while the level of MDA,IL-1β and IL-6 significantly increased(P＜0.01).Conclusions DEX improves mitochondrial function,alleviates oxidative stress and inflammatory response as well as TNF-α-induced cell damage with an AMPK dependent mechanism.

Guanxinning tablet alleviates carotid atherosclerotic plaque injury in rats / 基础医学与临床

Objective To investigate the effect and its mechanism of Guanxinning tablet on carotid atherosclerotic plaque in a rat model.Methods The rats were randomly divided into control group,model group(to construct carot-id atherosclerosis plaque model),Guanxinning groups with low,medium and high dose of Guanxinning tablet(150,300 and 600 mg/kg),atorvastatin group(2 mg/kg),lithiumchloridemonohydrate(LiCl)(Wnt/β-catenin pathway activator)group(15 mg/kg),and Guanxinning plus LiCl group(600 mg/kg Guanxinning tablets+15 mg/kg LiCl),with 12 rats in each group.The intervention began at the third week and was administered once a day for 8 weeks.Olympus Au2700 automatic biochemical analyzer was used to detect the level of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL)and high-density lipoprotein(HDL)in rat serum;ELISA was applied to detect the level of monocyte chemotactic protein(MCP-1)and hyper-sensitive C-reactive protein(hs-CRP)in rat se-rum;the level of oxidized low density lipoprotein(ox-LDL)and malondialdehyde(MDA)in rat serum were detected by spectrophotometry;HE staining was applied to find pathological changes in the common carotid artery of rats;Western blot was applied to detect the expression of Wnt3a,matrix metalloproteinase-9(MMP-9)and β-catenin in rat common carotid artery.Results Compared with the control group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,protein expression of MDA,MMP-9,Wnt3a,β-catenin and total plaque area/total arterial area ratio in-creased,the HDL level decreased in model group(P＜0.05);compared with the model group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,MDA,expression of MMP-9,Wnt3a,β-catenin protein and total plaque area/total arterial area ratio in the low,medium,and high dose groups of Guanxinning tablets decreased,the HDL level in-creased.The effect of Guanxinning tablets was dose-dependent,and the change trend of corresponding indicators in the LiCl group was opposite to the above(P＜0.05);compared with the high dose group of Guanxinning tablets,the TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,MDA levels,MMP-9,Wnt3a,β-catenin protein expression,and total plaque area/total arterial area ratio in the high dose+LiCl group of Guanxinning tablets increased,the HDL level de-creased(P＜0.05).Conclusions Guanxinning tablet can inhibit the formation of atherosclerotic plaque in rats and the mechanismis potentially related to the regulation of Wnt/β-catenin pathway.

Paricalcitol inhibition of oxidative stress alleviates the damage of hepatocyte tight junction in mice / 基础医学与临床

Objective To explore the impact of paricalcitol(Pal)on the oxidative stress-induced tight junction dam-age of mouse hepatocytes and its mechanism.Methods A model of cholestatic liver injury was created by routine bile duct ligation.The mice were randomly divided into control group(control),model group(BDL)and treatment group(BDL+Pal).HE staining microscopy was used to observe the morphological changes of liver tissues.The human hepa-toma cell line HepG2 was cultured and divided into blank group,model group(400 μmol/L H2O2)and treatment group(400 μmol/L H2O2+20 nmol/L Pal).Western blot was used to examine the level of tight junction protein 1(ZO-1),occludin,phosphorylated p65(p-p65),phosphorylated ERK(p-ERK)and phosphorylated myosin II regulated light chain(p-MLC)protein were checked in each group.Results Compared with the control group,the level of p-p65,p-ERK and p-MLC in the model group was significantly increased(P＜0.000 1 or P＜0.01 or P＜0.001).The protein expression of ZO-1 and occludin was significantly decreased(P＜0.01).HE staining mi-croscopy showed an increased hepatocyte necrosis and inflammatory cell infiltration.In contrast,the above levels in the treatment group showed an opposite trend relative to the model group.Conclusions Pal is able to alleviate the damage of hepatocyte tight junctions by inhibiting oxidative stress in cholestatic mice and HepG2 cells.Its mecha-nism is potentially related to the inhibition of reactive oxygen species and NF-κB/p65 and ERK signaling pathways.

Research progress of strontium and pregnancy and pregnancy diseases / 基础医学与临床

Strontium(Sr)is a trace element naturally found in the human skeletal system.In recent years,the po-tential impact of strontium on bone and cardiovascular health has called significant attention,particularly during pregnancy,when alterations in mineral metabolism may affect the health of both the mother and the fetus.This com-prehensive review assesses the current understanding of the role of strontium as a nutritional substance during preg-nancy,its effects on maternal health and fetal development,and its potential associations with pregnancy complica-tions such as preeclampsia,gestational hypertension,and lactation-induced osteoporosis.The review also summarizes the possible effects of strontium deficiency,excess,and supplementation,and provides information for developing prenatal nutrition supplementation guideline.

Effect of NF-κB-regulated Drp-1 and PGC-1α in lung tissue of neonatal rats with meconium aspiration syndrome and its mechanism / 解放军医学杂志

Objective To investigate the role of dynamin-related protein 1(Drp-1)and peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)in the lung tissues of neonatal rats with meconium aspiration syndrome(MAS)and its mechanism.Methods Fifty 2-3-week-old SD neonatal rats were randomly divided into five groups(n=10):control group,model group and SN50 low,medium and high concentration groups.In control group,2 ml/kg of saline was injected into the trachea after tracheal exposure,and 2 ml/kg of meconium suspension was injected into the trachea of the rest of groups;after 24 h,control and model groups were left untreated,and 100 μl of each of SN50 concentrations of 10,30,and 60 μg/ml was injected into SN50 low,medium,and high concentration groups intraperitoneally;the rats of each group were killed after 6 h,and the chest X-rays,the gross views of the lungs,the lung wet/dry weight ratios(W/D),and the lungs of the rats in control group and model group were examined.After 6 h,the rats in each group were executed,and the pathological changes of lung tissue were observed by chest radiographs,lung gross view,lung wet/dry weight ratio(W/D)and HE staining;Western blotting was used to detect the changes of nuclear factor κB(NF-κB)(p65),p-NF-κB p65(p-p65),Drp-1,and PGC-1α proteins expression in neonatal rat lung tissues,and immuno-histochemistry was used to observe the expression of p65,Drp-1,and PGC-1α related proteins expression in neonatal rat lung tissues.Results Compared with control group,model group showed inflammatory infiltration in the chest radiograph and gross view,and the W/D and lung injury pathology scores were significantly higher(P＜0.05);compared with model group,the chest radiograph and gross view of inflammation were slightly reduced in SN50 low,medium and high concentration groups,and the W/D and lung injury pathology scores were significantly lower(P＜0.05).Western blotting showed that,compared with control group,the protein expression levels of p-p65 and Drp-1 in the lung tissues of neonatal rats were significantly higher in model group(P＜0.05),and the protein expression level of PGC-1α was significantly lower(P＜0.05);compared with model group,the protein expression levels of p-p65 and Drp-1 were significantly lower in SN50 low,medium,and high concentration groups(P＜0.05),and the difference in the protein expression level of PGC-1α in SN50 low concentration group was not statistically significant(P＞0.05),whereas the PGC-1α expression levels in SN50 medium and high concentration groups were significantly higher(P＜0.05);the difference in the total p65 protein expression levels in each group was not statistically significant(P＞0.05).Immunohistochemical assay results showed that,compared with control group,p65 and Drp-1 protein expression levels were significantly higher in model group(P＜0.05),and PGC-1α protein expression level was significantly lower(P＜0.05);compared with model group,p65 protein expression level was significantly lower in SN50 low concentration group(P＜0.05),and the difference in Drp-1 and PGC-1α protein expression levels were not statistically significant(P＞0.05),Drp-1 protein expression level was significantly lower(P＜0.05),and PGC-1α protein expression level was significantly higher(P＜0.05)in SN50 middle and high concentration groups.Conclusion Fecal inhalation can induce lung tissue inflammation in neonatal rats,and the mechanism may be related to enhanced oxidative stress,promotion of mitochondrial dysfunction,activation of the Drp-1/NF-κB signaling pathway,and inhibition of PGC-1α protein expression.

Protective effects of cinnamaldehyde on benzene-induced immune and oxidative stress injury in mice / 军事医学

Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.

Propofol Regulates MPP+-induced Mitochondrial Oxidative Stress and Apoptosis in SH-SY5Y Cells / 昆明医科大学学报

Objective To investigate the effects of different concentrations of PPF on oxidative stress and apoptosis of PD model cells induced by MPP+.Methods The human neuroblastoma cell SH-SY5Y was induced by 1 mM MPP+ to establish PD cell model.In PPF treatment group,SH-SY5Y cells were stimulated with 10,20,40 and 80 μM PPF for 4 h before MPP+ induction.Cell counting kit-8(CCK-8)was performed to evaluate cell proliferation activity.H2DCF-DA fluorescent probe was used to detect ROS in cells.The levels of MDA and NADPH oxidase were analyzed by the kit.Western blot examined the protein expression of cytochrome c in mitochondria and cytoplasm,as well as the relative expression of Bcl-2,Bax and cleaved caspase-3 in SH-SY5Y cells.Apoptosis rate was analyzed by flow cytometry.Results MPP+ significantly inhibited the proliferation of SH-SY5Y cells(P<0.001),promoted the level of ROS(P<0.001),MDA(P<0.001),NADPH oxidase(P<0.01),cytochrome c in cytoplasm(P<0.01)and induced apoptosis(P<0.001)and the relative expression of pro-apoptosis protein Bax and cleaved caspase-3(P<0.01),reduced cytochrome c protein in mitochondria(P<0.01)and the relative expression of anti-apoptosis protein(P<0.01).PPF pretreatment alleviated the proliferation inhibition,oxidative stress and apoptosis promotion of SH-SY5Y cells induced by MPP+(P<0.001),and the effects of 40 μM and 80 μM on cells were more significant.Conclusion PPF pretreatment can alleviate the oxidative stress of SH-SY5Y cells induced by MMP+ and reduce apoptosis rate.

Research progress on role of peroxisome proliferator-activated receptor-γ in neuropathic pain / 临床麻醉学杂志

Neuropathic pain(NP)is caused by leision or disease of the somatic sensory nervous system,and its pathological mechanism is complex,mainly related to abnormal neural structure and function.It is hard for existing treatment methods to obtain satisfactory results.With the deepening of the study of peroxisome proliferate activation receptor-γ(PPAR-γ),its role in neuroinflammation,oxidative stress,ion channels,mitochondrial function,neuroprotection and other aspects have been discovered succes-sively,PPAR-γ may be one new target for pain prevention and treatment.This paper reviews the role of PPAR-γ in NP and related mechanisms,in order to provide new thinking for the clinical treatment of NP.