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1.
Arch Biochem Biophys ; 756: 109990, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636690

RESUMO

Nucleus pulposus (NP) cell apoptosis is a significant indication of accelerated intervertebral disc degeneration; however, the precise mechanism is unelucidated as of yet. Ephrin B2 (EFNB2), the only gene down-regulated in the three degraded intervertebral disc tissue microarray groups (GSE70362, GSE147383 and GSE56081), was screened for examination in this study. Subsequently, EFNB2 was verified to be down-regulated in degraded NP tissue samples. Interleukin-1 (IL-1ß) treatment of NP cells to simulate the IDD environment indicated that IL-1ß treatment decreased EFNB2 expression. In degenerative NP cells stimulated by IL-1ß, EFNB2 knockdown significantly increased the rate of apoptosis as well as the apoptosis-related molecules cleaved-caspase-3 and the Bax to Bcl-2 ratio. EFNB2 was found to promote AKT, PI3K, and mTOR phosphorylation; the PI3K/AKT signaling role was investigated using the PI3K inhibitor LY294002. EFNB2 overexpression significantly increased PI3K/AKT pathway activity in IL-1ß-stimulated NP cells than the normal control. Moreover, EFNB2 partially alleviated NP cell apoptosis induced by IL-1ß, reduced the cleaved-cas3 level, and decreased the Bax/Bcl-2 ratio after the addition of the inhibitor LY294002. Additionally, EFNB2 overexpression inhibited the ERK1/2 phosphorylation; the effects of EFNB2 overexpression on ERK1/2 phosphorylation, degenerative NP cell viability, and cell apoptosis were partially reversed by ERK signaling activator Ceramide C6. EFNB2 comprehensively inhibited the apoptosis of NP cells by activating the PI3K/AKT signaling and inhibiting the ERK signaling, obviating the exacerbation of IDD. EFNB2 could be a potential target to protect against degenerative disc changes.


Assuntos
Apoptose , Efrina-B2 , Degeneração do Disco Intervertebral , Núcleo Pulposo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Núcleo Pulposo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Efrina-B2/metabolismo , Efrina-B2/genética , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interleucina-1beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Adulto , Feminino , Serina-Treonina Quinases TOR/metabolismo , Células Cultivadas , Pessoa de Meia-Idade
2.
J Clin Biochem Nutr ; 71(3): 238-244, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36447492

RESUMO

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (ß = 0.47, 95% CI: -0.86-1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (ß = 1.93, 95% CI: 0.22-3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (ß = 0.30, 95% CI: -2.74-3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: ß = 2.98, 95% CI: 0.34-5.62, p = 0.027; TT: ß = 3.00, 95% CI: -0.51-6.51, p = 0.095; CT combined with TT: ß = 2.99, 95% CI: 0.90-5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.

3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(12): 1252-4, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21138693

RESUMO

AIM: To investigate the effects of different anesthesia and analgesia on erythrocyte immune function of patients with ovarian benign tumor treated by laparoscopic therapeutic. METHODS: 120 patients with ovarian benign tumor treated by laparoscopic therapeutic were randomly divided into two groups with 60 cases each.In group A, patients received general anesthesia eombined with thoracic epidural anesthesia during surgery, patients in group B received general anesthesia. The cervical venous blood samples were obtained at the following time points: before induction of anesthesia(T0), 30 min after anesthesia (T1), 1 h during operation (T2), 24 h after operation (T3), 48 h after operation (T4) and 72 h after operation (T5).RRCR, RRICR and RTRR were measured at different time points. RESULTS: RRCR, RRICR and RTRR in two groups decreased significantly from T1(P<0.05). RRCR in two groups was on the low-water mark at T4 and RRICR, RTRR was on the low-water mark at T3.There were no significantly different of RRCR, RRICR and RTRR in two groups at T0. There were significantly different of RRCR, RRICR and RTRR in two groups from T1 to T4(P<0.05), the increase in group A was less than that in group B(P<0.05). CONCLUSION: Anesthesia may harm on erythroeyte immune function of patients with ovarian benign tumor treated by laparoscopic therapeutic. The effect of general anesthesia combined with thoraeic epidural anesthesia on erythrocyte immune function was less.


Assuntos
Analgesia/efeitos adversos , Anestesia/efeitos adversos , Eritrócitos/imunologia , Laparoscopia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
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