Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is easily found in the environment. Excessive daily exposure of it may lead to an increased risk of cardiovascular disease (CVD). Lycopene ...(LYC), as a natural carotenoid, has been shown to have the potential to prevent CVD. However, the mechanism of LYC on cardiotoxicity caused by DEHP exposure is unknown. The research was aimed to investigate the chemoprotection of LYC on the cardiotoxicity caused by DEHP exposure. Mice were treated with DEHP (500 mg/kg or 1,000 mg/kg) and/or LYC (5 mg/kg) for 28 d by intragastric administration, and the heart was subjected to histopathology and biochemistry analysis. The results indicated that DEHP caused cardiac histological alterations and enhanced the activity of cardiac injury indicators, and interfered with mitochondrial function and activating mitophagy. Notably, LYC supplementation could inhibit DEHP-induced oxidative stress. The mitochondrial dysfunction and emotional disorder caused by DEHP exposure were significantly improved through the protective effect of LYC. We concluded that LYC enhances mitochondrial function by regulating mitochondrial biogenesis and dynamics to antagonize DEHP-induced cardiac mitophagy and oxidative stress.
DEHP exposure can cause heart damage and destroy the pathophysiological integrity of the mouse heart. LYC can alleviate this phenomenon. LYC can alleviate the heart oxidative stress damage induced by the imbalance of mitochondrial biogenesis and mitochondrial dynamics disorder DEHP. This study provides new insights and shows that LYC can prevent DEHP-induced heart damage by activating mitophagy, which may be the target molecule of DEHP toxicity and LYC effect mechanism in the future.
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Di(2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant, which is mainly used as a plasticizer to improve the flexibility of products; however, its extensive use causes male ...reproductive damage. Lycopene (LYC) has a protective effect on male reproductive toxicity. Nevertheless, the underlying role of LYC in DEHP-induced spermatogenic cell damage remains unclear. Our study aimed to investigate the role of LYC in DEHP-induced spermatogenic cell damage and its underlying mechanism. Male ICR mice were treated with LYC (5 mg kg
−1
) and/or DEHP (500 mg kg
−1
or 1000 mg kg
−1
) for 28 days. The results showed that LYC alleviated the DEHP-induced decrease in mitochondria volume density and mitochondrial membrane potential (Δ
Ψ
m
). Subsequently, LYC prevented the DEHP-induced PGC-1α-mediated reduction in mitochondrial biogenesis in spermatogenic cells. LYC exhibited a potential preventive effect against DEHP-induced mitophagy caused by mitochondrial dynamics disorder in the spermatogenic cells. Meanwhile, LYC relieved DEHP-induced mitochondrial stress in the spermatogenic cells by activating UPR
mt
. These results proved that mitochondrial quality control may be related to the beneficial role of LYC in preventing DEHP-induced mitophagy in spermatogenic cells. This study provides new evidence of mitochondrial quality control as a target for LYC treatment, which can prevent DEHP-induced toxicity.
This study provides new insights and indicates that LYC prevents DEHP-induced mitophagy of spermatogenic cells
via
the mitochondrial quality regulation, which may be the target molecule for future DEHP toxicity and the LYC effector mechanism.
Background
To explore whether robotic lobectomy (RL) is superior to video‐assisted lobectomy (VAL) in terms of short‐term outcomes in patients with pulmonary neoplasms.
Methods
From January 30, 2019 ...to February 28, 2022, a series of consecutive minimally invasive lobectomies were performed for patients with pulmonary neoplasms. Perioperative outcomes such as operation time, blood loss, dissected lymph nodes (LNs), surgical complications, postoperative pain control, length of postoperative stay in hospital, and total cost of hospitalization were compared.
Results
A total of 336 cases including 173 RLs and 163 VALs were enrolled. Baseline characteristics were comparable between groups. RLs were associated with shorter operation time (median interquadrant range, IQR, 107 min 90–130 vs. 120 min 100–149, p < 0.001), less blood loss (median IQR, 50 mL 30–60 vs. 50 mL 50–80, p = 0.02), and lower blood transfusion rate (3.5% vs. 9.8%, p = 0.02) compared with VALs. More LNs were harvested by the robotic approach (median IQR, 29 20–41 vs. 22 15–45, p = 0.04). The incidences of conversion, major postoperative complications, extra analgesic usage, and postoperative length of stay were all comparable between the RL and VAL groups. As predicted, the total cost of hospitalization was greater in the RL group (median IQR, $16728.35 15682.16–17872.15 vs. $10713.47 9662.13–11742.15, p < 0.001).
Conclusion
RL improved surgical efficacy with shortened operative time, less blood loss, and more thorough LN dissection compared with VAL, compromised by higher cost.
Robotic lobectomy improved surgical efficacy with shortened operative time, less blood loss, and more thorough lymph node dissection compared with video‐assisted lobectomy, compromised by higher cost.
Heparin saline (HS) is theoretically superior to normal saline (NS) for maintaining the patency of central venous catheters (CVCs), but the comparative efficacy of them remains controversial. The aim ...of this systematic review and meta-analysis was to assess the efficacy of NS versus HS in the maintenance of the patency of CVCs in adult patients.
We searched PubMed, Embase and the Cochrane library databases. Randomized controlled trials (RCTs) evaluating the use of NS vs. HS to maintain the permeability of CVCs among adult patients were included in our meta-analysis. References of relevant papers were reviewed manually. No language restriction was applied. Non-human studies were excluded. Pooled relative risk (RR) was calculated using a Mantel-Haenszel random-effects model. We also performed subgroup analysis examining the effect of the duration of catheter placement on the outcome. All statistical tests were two-sided using a significance level of 0.05.
Ten RCTs involving 7875 subjects (with analysis at patient, catheter, lumen and line access level) were included in this meta-analysis. Whether in terms of pooled or local analysis (RR with 95% confidence interval spans 1), NS can be equally, if not more effective, in keeping the CVCs open. Of studies reporting secondary outcomes (maneuver needed, heparin-induced thrombocytopenia, haemorrhage, central venous thrombosis and catheter-related bloodstream infection), heparinised saline was shown not to be superior to non-heparinised solution. Subgroup analysis in patients with short vs long term CVC placement was consistent with the main outcome partly and in particular for maintenance of catheter patency in patients with a long-term placement i.e. >30 days, the RR was 0.97 (n = 6589; 95% CI = 0.76 to 1.23; P = 0.796). However, for patients in whom the catheter was in place for <30 days, the RR was 1.52 (n = 1286; 95% CI = 1.02 to 2.27; P = 0.041).
Based on the results of this meta-analysis, HS is not superior to NS in reducing CVCs occlusion. But in the short term, the use of HS is slightly superior to NS for flushing catheters from a statistical point of view.
Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of ...SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.
The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with ...well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.
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•MT inhibits cerebellar damage caused by ATZ exposure.•MT can significantly improve the disorder of antioxidant response caused by ATZ exposure.•MT inhibits the cerebellar cGAS-STING-related pathway response induced by ATZ exposure.•MT inhibits ATZ-induced Caspase-1/NLRP3-dependent pyroptosis and inflammation.
To determine the tip position of the central venous catheter (CVC) in patients with dialysis, the guidelines recommend that it be determined using chest radiography (CXR) after catheterization, ...without fluoroscopy. However, some researchers have proposed that transthoracic echocardiography (TTE) can replace CXR, but this has not been widely adopted. This study aimed to determine which of the two aforementioned methods is more suitable for locating the tip position of the CVC. This prospective study included 160 patients who underwent hemodialysis at our hospital from March 2021 to December 2022. After inserting the CVC through the internal jugular vein, we used transthoracic echocardiography and CXR to determine the tip of the CVC and compared the results with those of computed tomography (CT). In the comparison between TTE and CXR for locating the CVC tip, we obtained three main findings. (1) TTE was associated with fewer misdiagnosed cases than CXR. (2) TTE provided higher sensitivity (similar sensitivity in position 2), specificity, positive/negative predictive values, and accuracy than CXR. (3) When comparing the receiver operating characteristic curves of TTE and CXR, the area under the curve (95% confidence interval) for the former was larger. Additionally, we made anatomical discoveries: the "hyperechoic triangle" recognized by TTE was equivalent to the entrance of the superior vena cava into the right atrium shown by transesophageal transthoracic echocardiography. TTE is more suitable than CXR as the first examination for CVC tip localization, as it improves diagnostic accuracy and reduces X-ray radiation damage.
Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present ...study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.
Asymmetric conjugate addition of PhMe2SiBPin to a wide range of N-heteroaryl alkenes proceeded in the presence of a copper catalyst coordinated with an easily accessible chiral phosphoramidite ligand ...to afford useful β-silyl N-heteroarenes in high yields (up to 96%) and excellent enantioselectivities (up to 97% ee).
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