Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Estimation of salivary malondialdehyde Levels in smokeless tobacco chewers with chronic periodontitis-A cross sectional clinico biochemical study / Estimación de los niveles de malondialdehído salival en masticadores de tabaco sin humo con periodontitis crónica: un estudio bioquímico clínico transversal

ABSTRACT: Despite the reported effects of smokeless tobacco (ST) on the periodontium and high prevalence of ST use in rural populations and in males studies on this specific topic are limited. The purpose of this cross-sectional investigation was to measure lipid peroxidation (as an end product of oxidative stress) end product i.e. Malondialdehyde (MDA) in saliva of patients with gingivitis, chronic periodontitis and to assess the influence of smokeless tobacco on Salivary Malondialdehyde (S-MDA). Total 30 patients with gingivitis, 30 with chronic periodontitis and 30 Smokeless Tobacco Chewers with Chronic Periodontitis and 30 periodontally healthy subjects were included in the study. Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PD), and Clinical Attachment Loss (CAL) were recorded followed by stimulated Saliva sample collection. Salivary MDA Levels were assessed by UV Spectrophotometry. There was a statistically significant increase in the salivary MDA levels in gingivitis, chronic periodontitis and in smokeless tobacco chewers with chronic periodontitis when compared with healthy group. Higher salivary MDA levels in gingivitis group, chronic periodontitis, and smokeless tobacco chewers with chronic periodontitis reflects increasedoxygen radical activity during periodontal inflammation.

RESUMEN: A pesar de los efectos reportados del tabaco sin humo (TS) sobre el periodonto y la alta prevalencia del uso de TS en poblaciones rurales y en hombres, los estudios sobre este tema específico son limitados. El propósito de esta investigación transversal fue medir el producto final de la peroxidación lipídica (como producto final del estrés oxidativo), es decir, malondialdehído (MDA) en la saliva de pacientes con gingivitis, periodontitis crónica y evaluar la influencia del tabaco sin humo en el malondialdehído salival (S-MDA). Se incluyeron en el estudio un total de 30 pacientes con gingivitis, 30 con periodontitis crónica y 30 masticadores de tabaco sin humo con periodontitis crónica y 30 sujetos periodontalmente sanos. Se registraron el índice de placa (PI), el índice gingival (GI), la profundidad de la bolsa de sondeo (PD) y la pérdida de adherencia clínica (CAL), seguidos de la recogida de muestras de saliva estimuladas. Los niveles de MDA en saliva se evaluaron mediante espectrofotometría UV. Hubo un aumento estadísticamente significativo en los niveles de MDA en saliva en gingivitis, periodontitis crónica y en masticadores de tabaco sin humo con periodontitis crónica en comparación con el grupo sano. Los niveles más altos de MDA en saliva en el grupo de gingivitis, periodontitis crónica y masticadores de tabaco sin humo con periodontitis crónica reflejan un aumento de la actividad de los radicales de oxígeno durante la inflamación periodontal.

An investigation of oxidative stress based effect and mechanism of Shenfu Injection on atherosclerosis of ApoE-/-mice / 中成药

AIM To investigate the effect of Shenfu Injection on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE-/-) mice,and to explore its anti-atherosclerosis mechanism through the observation of oxidative stress (OS) variation.METHODS C57 mice were used as controls.ApoE-/-mice fed with 20-week high fat diet were randomly divided into model group,Shenfu group for subsequent 4-week continuous corresponding intervention,after which the mice had their blood lipid levels measured,their levels of MPO and NOX4 identified by ELISA,and their T-SOD activity determined by hydroxylamine method,their MDA level detected by TBA,their plaque formation observation achieved by HE staining of aortic gross and red O of all the aorta,and their Nrf2 mRNA expression detected by real time qPCR method.RESULTS Compared with the control group,the model group manifested with increased contents of TG,TC,LDL,decreased HLD;decreased activity of SOD,increased contents of MPO,NOX4 and MDA,and down-regulated expression of aortic Nrf2 and Keap1 mRNA.Compared with the model group,Shenfu Injection group was observed with no obvious blood lipid level change,but a reduction of plaque area,and an effective inhibition on OS as revealed by improved levels of Nrf2 and Keap1 mRNA.CONCLUSION Shenfu Injection can activate Nrf2 and interfer the relevant enzymes,thus prevents the atherosclerosis progression through OS reduction.

Expressions of TXNIP,STAMP2 and GATA3 and the changes of serum oxidative stress indexes in diabetic patients with breast cancer / 中国糖尿病杂志

Objective To measure the expressions of TXNIP,STAMP2 and GATA3 in diabetes patients with breast cancer and to determine the changes of oxidative stress indexes before and after surgery.Methods The expression levels of TXNIP,STAMP2 and GATA3 mRNA in cancer tissues and adjacent normal tissues were measured in 45 diabetes patients with breast cancer.The levels of serum oxidative stress indexes including MDA,MPO,SOD and TAC were detected and compared before and after surgery.Results The expressions of TXNIP,STAMP2 and GATA3 mRNA and their protein levels in cancer tissues were lower than those in adjacent normal tissues (P<0.05).The positive expression rate of the three indexes were 60%,66.7% and 73.3%,higher than that of TXNIP protein with 2.2% in the adjacent normal tissues(P<0.05).The TXNIP,STAMP2 and GATA3 protein positive rate of breast cancer tissue were related to differentiation,lymph node metastasis and clinical grades (P<0.05).Serum MDA and MPO levels increased first and then decreased.SOD and TAC showed a trend of decrease first and then increase.The turning point is 6 d after surgery.Conclusion TXNIP,STAMP2,GATA3 and serum oxidative stress indicators may be the indicators for diagnosis and treatment of breast cancer in diabetes patients.

Effect of rosiglitazone on oxidative stress and collagen metabolism in rat cardiac fibroblasts induced by advanced glycation end products / 中国糖尿病杂志

Objective To investigate induction effect of AGE on oxidative stress and type Ⅰ ,Ⅲcollagen synthesis in rat cardiac fibroblasts and interference effect of RGZ during the course. Methods Incubate rat cardiac fibroblasts with AGE of different concentration ,add RGZ to interfere for 48 h ,and then collect supernatant fluid .Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by SOD kit and MDA kit separately ,and type Ⅰ ,Ⅲ collagen contents were measured by ELISA. Results When incubating cardiac fibroblasts with RGZ and 200 mg/L AGE together for 48 h , with the rise of RGZ concentration(0.1 ,1 and 10 mol/L) ,SOD activity in the supernatant fluid of cultured cardiac fibroblasts gradually increased [(21.564 ± 1.614) ,(22.323 ± 1.260) ,(23.661 ± 1.562) vs (19.320 ± 0.896) nU/ml ,P<0.05 or P<0.01] ,MDA content gradually decreased [(1.325 ± 0.048) ,(1.279 ± 0.032) ,(1.229 ± 0.045 ) vs (1.629 ± 0.043 ) nmol/ml ,P< 0.01 ] and type Ⅰ ,Ⅲ collagen Contents gradually decreased [(79.17 ± 3.25) ,(60.42 ± 3.58) ,(42.71 ± 5.11) vs (85.54 ± 2.28) ng/ml ,P<0.01 ;(37.52 ± 3.43) ,(27.09 ± 4.75) ,(20.81 ± 3.26) vs (40.75 ± 2.70) ng/ml ,P<0.01] as compared with 200 mg/L AGE group. Conclusion AGE can induce oxidative stress in cardiac fibroblasts and increase type Ⅰ ,Ⅲ collagen contents .RGZ can inhibit oxidative stress in cardiac fibroblasts and synthesis and secretion of type Ⅰ ,Ⅲ collagen induced by AGE. This finding indicates that RGZ may play an important role in the prevention of diabetic myocardial fibrosis.

The progression on the research of haem oxygenase-1 and diabetic peripheral neuropathy / 中国糖尿病杂志

[Summary] The pathogenesis of diabetic peripheral neuropathy (DPN ) is the result of complex multiple concurrent pathogenic factors ,among which oxidative stress and inflammation play important roles. Multiple data have indicated that haem oxygenase‐1 (HO‐1) and its degradation products products possess the functions of anti‐oxidation ,anti‐inflammation ,anti‐apoptosis and pro‐angiogenesis ,which now becomes a new target for the treatment of DPN. We will briefly review the progression on the research of HO‐1 and DPN.

Lipid Peroxidation, Sperm DNA Fragmentation Total Antioxidant Capacity and Semen Quality in Male Infertility.

Infertility is a major clinical problem, affecting people medically and psychosocially. Male factor plays a significant role in about 50% of infertile couples. Recent reports indicate that increasing male infertility could be due to genomic abnormalities. The etiology of sperm DNA damage is multi-factorial but compromised due to nuclear defects, protamine deficiency and oxidative stress. The present study was aimed to evaluate sperm DNA integrity and oxidative stress in infertile men. The study is prospective, comprises 96 infertile patients and 30 fertile controls. Sperm DNA integrity was assessed by flowcytometry. MDA and TAC were evaluated spectrophotometrically. The percentage of DNA Fragmentation Index and MDA were found to be significantly increased while TAC was significantly decreased in infertile men as compared to control. DFI and MDA were negatively correlated with TAC levels. Present study indicates significant increases in seminal MDA and sperm DNA damage in infertile men. Seminal MDA was significantly correlated with sperm DNA damage, TAC and standard sperm parameters. The elevated levels of seminal OS observed in these infertile patients could be responsible for poor sperm quality and sperm DNA fragmentation. Hence evaluation of DFI, MDA and TAC can be used for diagnosis, prognosis of male infertility in addition to routine semen parameters to decide the treatment strategies.

Effect of methylene blue on oxidative stress and antioxidant defence parameters of rat hepatic and renal tissues.

The objective of the present study was to investigate the effect of administration of 1 mM methylene blue (MB) in drinking water for 30 days on hepatic and renal antioxidant status in female adult Wistar strain rats (n=5). MB failed to induce significant change in any of the measured antioxidant defence parameters namely, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). However, a marginally significant (P<0.05) increase in the level of lipid peroxidation (LPx) was recorded in liver, while a reduction (P<0.05) in its level in the kidney was noticed. Serum alanine amino transferase (AlaAT) and creatinine levels significantly (P<0.001) decreased in MB treated rats without any change in blood urea nitrogen (BUN) level. Our findings suggest that the effect of MB as administered in the present study was tissue specific with regard to the level of LPx, however, in general, it does not impair liver and kidney functions as evidenced by serum parameters.