Nuclear Factor Erythroid 2-Related Factor 2 as a Potential Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.

Diagnosing sentinel lymph node metastasis of T1/T2 breast cancer with conventional ultrasound combined with double contrast-enhanced ultrasound: a preliminary study.

Background: In patients with T1/T2 breast cancer (BC), sentinel lymph node (SLN) status is essential for prognosis and treatment. This study investigated the value of conventional ultrasound combined with double contrast-enhanced ultrasound in diagnosing the metastasis of SLNs in patients with T1/T2 BC. Methods: This study employed a prospective design (this diagnostic study was not registered on a clinical trial platform), and the participants formed a convenience series. Based on the inclusion and exclusion criteria, 163 patients with BC who received treatment in the First Affiliated Hospital of Soochow University from July 2017 to December 2021 were included in this study. A total of 165 SLNs from 163 patients with T1/T2 BC were analyzed. All patients underwent percutaneous contrast-enhanced ultrasound (PCEUS) to trace SLNs before the operation. Subsequently, all patients underwent conventional ultrasound and intravenous contrast-enhanced ultrasound (ICEUS) examinations to observe the SLNs. The results of the conventional ultrasound, ICEUS, and PCEUS of the SLNs were analyzed. The associations between the risk of SLN metastasis and imaging features were evaluated via a nomogram based on the pathological results. Results: Overall, 54 metastatic SLNs and 111 nonmetastatic SLNs were evaluated. Metastatic SLNs displayed a greater cortical thickness, area ratio, eccentric fatty hilum, and hybrid blood flow on conventional ultrasound compared with nonmetastatic SLNs (P<0.001). According to PCEUS, 75.93% of metastatic SLNs showed heterogeneous enhancement (type II and III), and 73.88% of nonmetastatic SLNs showed homogeneous enhancement (type I; P<0.001). According to ICEUS, heterogeneous enhancement (type B/C, 20.37% vs. 11.71%) and overall enhancement (55.56% vs. 23.42%) were more common in metastatic SLNs than in nonmetastatic SLNs (P<0.001). Logistic regression analysis showed that the cortical thickness and enhancement type of PCEUS were independent predictors of SLN metastasis. Moreover, a nomogram combining these factors showed a high diagnostic ability for SLN metastasis (unadjusted concordance index 0.860, 95% CI: 0.730-0.990; bootstrap-corrected concordance index 0.853). Conclusions: The nomogram of cortical thickness and enhancement type of PCEUS could effectively diagnose SLN metastasis in patients with T1/T2 BC.

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway.

Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

Dynamic changes and correlation between symptoms and quality of life in patients with breast cancer during chemotherapy.

BACKGROUND: Standardized chemotherapy for breast cancer can improve the survival of patients, but during the process, it is accompanied by a variety of symptoms. OBJECTIVE: To explore the dynamic changes of symptoms and quality of life in breast cancer patients at different time points during chemotherapy, and to explore the correlation with quality of life. METHOD: A prospective study method was used to collect 120 breast cancer patients undergoing chemotherapy as the research objects. The general information questionnaire, the Chinese version of the M.D. Anderson Symptom inventory (MDASI-C), and the European Organization for Cancer Research and Treatment (EORTC) Quality of Life questionnaire were used in the first week (T1), first month (T2), three month (T3) and 6 months after chemotherapy (T4) to conduct dynamic investigation. RESULTS: The symptoms of breast cancer patients at four time points during chemotherapy period were: psychological symptoms, pain-related symptoms, perimenopausal symptoms, impaired self-image, and neurological related symptoms etc. At T1, it exhibited 2 symptoms, however as moving along the chemotherapy process, the symptoms are increasing. The severity is (F= 76.32, P< 0.001), life of quality (F= 117.64, P< 0.001) vary. At T3, there were 5 symptoms, and at T4 symptom number increased to 6 with worsening quality of life. It exhibited positive correlation with scores in multiple domains of quality of life (P< 0.05), and the above symptoms showed positive correlation with multiple domains of QLQ-C30 (P< 0.05). CONCLUSION: After T1-T3 of chemotherapy in breast cancer patients, the symptoms become more serious and the quality of life reduced. Therefore, medical staff should pay attention to the occurrence and development of patient's symptoms, create a reasonable plan from the perspective of symptom management and carry out personalized interventions to improve patient's quality of life.

Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells.

AIM: To determine the influence of Adriamycin (ADM) on the changes in Nanog, Oct4, Sox2, as well as, in ARID1 and Wnt5b expression in liver cancer stem cells. METHODS: The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study, and were routinely cultured. The 50% lethal dose (LD50) in the cell lines was detected by the MTT assay. Expression changes in liver cancer stem cell related genes (Nanog, Oct-4, Sox2, ARID1, and Wnt5b) were detected by western blot following treatment with ADM (LD50). RESULTS: The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells (0.4123 ± 0.0236 µmol/L vs 0.5259 ± 0.0125 µmol/L, P < 0.05). Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells, while only Sox2 was expressed in HCCLM3 cells. However, neither ARID1A nor Oct4 was detected in these two cell lines. Genes, related to the stem cells, showed different expression in liver cancer cells with different metastatic potential following treatment with ADM (LD50). Wnt5b protein increased gradually within 4 h of ADM (LD50) treatment, while Nanog decreased (P < 0.05). After 12 h, Wnt5b decreased gradually, while Nanog increased steadily (P < 0.05). In addition, only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM (LD50) treatment. The expression of Sox2 increased gradually with ADM (LD50) in HCCLM3 cells (P < 0.05). CONCLUSION: ADM increased the death rate of MHCC97-L and HCCLM3 cells, while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.

[Effect of ridge & terraced ecological rice farming on rice photosynthetic characteristics and yield].

Taking super hybrid rice Y-liangyou 1, and hybrid rice Xianyou 63 and conventional rice Huanghuazhan as test materials, a field experiment was conducted in Changsha City of Hunan Province in 2011 and 2012 to investigate the effects of ridge & terraced ecological rice farming (RT) and bed ecological rice farming (B) on rice grain yield and photosynthetic characteristics. Compared with conventional rice farming (CK) , yield of Y-liangyou 1 in the RT was increased significantly by 28.7%, the effective panicles per unit area and spikelets per panicle were increased by 16.1% and 6.8%, respectively. Yields of Xianyou 63 and Huanghuazhan in the RT and B were 24.3% and 19.7%, 12.0% and 16.2% higher than those of CK, respectively. Leaf area index, dry matter accumulation before and after full-heading, total dry matter accumulation of Y-liangyou 1 in the RT was higher than that of CK. Number of spikelets/leaf area, number of filled grains/leaf area, grain mass/leaf area of Y-liangyou 1 in the RT were 8.1%, 14.8% and 15.8% higher than those of CK, respectively, the photosynthetic potential was increased by 32.2% while the net assimilation rate was declined by 9.3%.

Prourokinase mutant that induces highly effective clot lysis without interfering with hemostasis.

Prourokinase (proUK) is a zymogenic plasminogen activator that at pharmacological doses is prone to nonspecific activation to urokinase. This has handicapped therapeutic exploitation of its fibrin-specific physiological properties. To attenuate this susceptibility without compromising specific activation of proUK on a fibrin clot, a Lys300-->His mutation (M5) was developed. M5 had a lower intrinsic activity and, therefore, remained stable in plasma at a 4-fold higher concentration than did proUK. M5 had a higher 2-chain activity and induced more rapid plasminogen activation and fibrin-specific clot lysis in vitro. Sixteen dogs embolized with radiolabeled clots were infused with saline, proUK, tissue plasminogen activator, or M5. The lower intrinsic activity allowed a higher infusion rate with M5, which induced the most rapid and efficient clot lysis (50% clot lysis by approximately 600 microg/kg M5 versus approximately 1200 microg/kg proUK). In association with this, M5 caused neither a significant increase in the primary bleeding time nor secondary bleeding (total blood loss). By contrast, these measurements increased 4-fold and 5-fold, respectively, with proUK and >5-fold and 8-fold, respectively, with tissue plasminogen activator. Clot lysis by M5 and hemostasis were further evaluated in 6 rhesus monkeys. M5 again induced rapid clot lysis without a significant increase in the primary bleeding time, and secondary bleeding did not occur. In conclusion, a site-directed mutation designed to improve the stability of proUK in blood at therapeutic concentrations induced superior clot lysis in vitro and in vivo without causing significant interference with hemostasis.