Risk factors associated with high-dose methotrexate induced toxicities.

INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

Active substances and molecular mechanisms of the anti-myocardial ischemia effects of Carthami flos by network pharmacology and in vitro experiments.

Myocardial ischemia is a predominant cardiovascular disorder that can result in a series of life-threatening cardiovascular diseases. Carthami flos (CF), the flower of Carthamus tinctorius L., is a commonly used herbal medicine in Chinese medicine for treating coronary atherosclerotic heart diseases based on its anti-myocardial ischemia (MI) effects. This paper aimed to investigate the active substances and mechanisms of the anti-MI effects of CF by network pharmacology and in vitro experiments. The results indicated that 9 constituents showed high degree of association with multiple targets of MI, including quercetin, kaempferol, ß-sitosterol, luteolin, baicalein, safflomin A, safflomin C, safflower-yellow-B and hydroxysafflor yellow A. In addition, AKT1, EGFR, CASP3, MYC, JUN, ALB, CTNNB1, VEGFA, ESR1, and IL1B were screened as the leading targets with a degree number ≥50. Bioinformatic annotation of GO-MF and KEGG showed that the anti-MI effects of CF are related to apoptosis and response to antioxidative stress pathways. The in vitro results showed that CF reduced LDH and CK levels, alleviated cell cycle arrest, and decreased ROS levels in H2O2-treated H9c2 cells. In addition, CF also promoted the nuclear shift of Nrf2 and the mRNA expressions of Akt, Nrf2 and Bcl-2 but decreased the expression of caspase-3 in H2O2-treated H9c2 cells. Collectively, the anti-MI effects of CF involve inhibiting apoptosis and antioxidative stress in cardiomyoblasts by regulating Akt/Nrf2/Caspase-3/Bcl-2, and the possible active substances of CF are quercetin, kaempferol, ß-sitosterol, luteolin, baicalein, safflomin C, safflower-yellow-B, and hydroxysafflor yellow A. The results of this study will be helpful for further drug development of CF and its active monomers.

Insight on efficiently oriented oxidation of petroleum hydrocarbons by redistribution of oxidant through inactivation of soil organic matter coupled with passivation of manganese minerals.

While extensive works focused on the enhancement of the activity of heterogeneous Fenton catalysts, little was paid attention to the inhibition of soil organic matter (SOM) and Mn minerals in soil remediation. Here, the oxidation of petroleum hydrocarbons in soils (S1: 4.28 % SOM, S2: 6.04 % SOM, S3: 10.33 % SOM) with inactivated SOM and passivated Mn oxides regulating by calcium superphosphate (Ca(H2PO4)2) was carried out. Oily sludge pyrolysis residue was used as precursors to prepare an oleophilic iron-supported solid catalyst (Fe-N @ PR). For regulated systems, under the optimal conditions of 1.8 mmol/g H2O2 and 0.05 g/g Fe-N @ PR, 72 ∼ 91 % of total petroleum hydrocarbons (TPHs: 15,616.58 mg/kg) were oxidized, which was 38 ∼ 45 % higher than that of control systems. The mechanism of efficient oxidation was proposed that the passivated Mn minerals stabilized H2O2 redistributing more H2O2 to sustainably produce •OH, and the inactivated SOM improved the relative reactivity of •OH to TPHs. Additionally, the passivation of Mn oxides was mainly related to the binding of H2PO4-, and the inactivation of SOM was realized by Ca2+ combing with -OH and C-O-C to form stable complexes. This study brought us a new perspective on soil remediation through passivating Mn minerals and inactivating SOM.

Mechanistic insight into cost-effective dedicated oxidation of alkanes by inactivating soil organic matter with FeOOH formed in situ.

Modified Fenton technique has been widely used to remediate soils contaminated with crude oil but significantly limited to soil organic matter (SOM) consuming oxidants. In this study, soils with developed SOM inactivation by FeOOH formed in situ were created and spiked with crude oil (total petroleum hydrocarbons (TPH): 19453 mg/kg), then treated by modified Fenton reagents. The reaction activity of hydroxyl radicals (•OH) relative to TPH (K) notably increased to 0.65 when the degree of developed inactivation of the SOM (ß) was 100% (DIS-100), which was 1.45, 2.03 and 2.83-fold than that of DIS-50, DIS-15 and control (CK), respectively. Meanwhile, the higher the K, the more •OH transferred, which realized the efficient oriented oxidation of TPH. Moreover, improving the transfer of •OH from SOM to TPH was more important than increasing •OH production in soil remediation. With the ß increasing to 100%, the ratio of invalid H2O2 decomposition to produce O2 decreased to 22%, equal to 25% reduction compared to CK. Therefore, when ß was 100%, the utilization efficiency of H2O2 was improved to 1.48 mg/mmol, which was approximately 1.39, 3.35 and 5.43-fold higher than the efficiency got by DIS-50, DIS-15 and CK, respectively, achieving the cost-effective dedicated oxidation of TPH. In addition, the FeOOH cross-linked with SOM via Fe-O-C and Fe-N bonds to develop inactivation of SOM. In general, this study highlighted a new insight into the effect of developed inactivation of SOM on soil remediation.

Efficient catalytic degradation of alkanes in soil by a novel heterogeneous Fenton catalyst of functionalized magnetic biochar.

In this study, sodium dodecyl sulfate (SDS) functionalized magnetic biochar (SDS-Fe@BC) was successfully prepared. Compared to other traditional heterogeneous Fenton catalysts, more total petroleum hydrocarbons (TPH) (3499.40 mg kg-1) was adsorbed from soil to the surface of SDS-Fe@BC through hydrophobic interaction between alkyls in alkanes and SDS-Fe@BC, which formed an efficient interface oxidation system. In SDS-Fe@BC-mediated heterogeneous Fenton system, 10,191.41 mg kg-1 (88.10%) TPH was degraded in the presence of 400 mM H2O2, which was 1.38-5.67 folds than that of H2O2 alone, Fe2+, zero valent iron (ZVI), Fe3O4, pristine biochar (BC), and Fe@BC. Moreover, all individual alkanes were efficiently degraded (>75%), and the higher the initial amount of individual alkane, the more the degradative amount in the SDS-Fe@BC/H2O2 system. Additionally, TPH degradation was highly related to the mass ratio of SDS/Fe@BC, H2O2 concentration, SDS-Fe@BC dosage, and initial pH in the SDS-Fe@BC/H2O2 system, and the optimal values were 1:5, 400 mM, 50 mg g-1, and pH 7, respectively. Radical quenching experiments revealed that hydroxyl radicals (•OH) generated on the surface of SDS-Fe@BC was the dominated reactive oxidative species (ROS) responsible for alkanes degradation. After five cycles, SDS-Fe@BC still remained a high catalytic activity for alkanes degradation (73.21%), showing its excellent reusability. This study proved that the SDS-Fe@BC can be used as a potential heterogeneous Fenton catalyst for petroleum-contaminated soil remediation.

[Observation on therapeutic effect of electroacupuncture therapy for promoting consciousness of patients with coma].

OBJECTIVE: To observe the promoting consciousness effect of electroacupuncture therapy on the patients with long-term coma caused by severe craniocerebral trauma. METHODS: Twenty-nine cases with coma more than 3 weeks and Glasgow Coma Scales (GCS) of 8 or less were divided into an observation group (n=15) and a control group (n=14). They were treated with the same western medicine. In addition to ordinary treatment, the observation group was treated with electroacupuncture at Baihui (GV 20), Shuigou (GV 26), Yongquan (KI 1) etc. for 30 min and the needles were retained for 30 min, once each day. RESULTS: The average awake time and awake rate were 40.1 days and 73.3% (11/15) respectively in the observation group, which were higher than 51.8 days and 28.6% (4/14) in the control group. CONCLUSION: Electroacupuncture therapy combine with western medicine is more effective in improving consciousness of patients in coma caused by severe craniocerebral trauma.

Effects of nimodipine on the cerebrovascular hemodynamics in patients with severe head injuries.

OBJECTIVE: To observe the effects of calcium-antagonist nimodipine on the cerebrovascular hemodynamic indices (CVHI) in patients with severe head injuries, thereby to facilitate the clinical application of this drug. METHODS: Eighty patients with severe head injuries were randomly divided into two groups: one group received conventional therapy, including craniotomy, hemostasis, dehydration, anti-infection and corticosteroid administration and the other group received nimodipine on the basis of conventional therapy lasting till 30 d after injuries. CVHI, including mean blood flow velocity (Vmean), mean blood flow (Qmean) in the carotid artery on the injured side, resistance (R) and dynamic resistance (DR) of cerebral vessels, were measured by CVA LH-450 cerebrovascular hemodynamics analyzer (Fudan University, Shanghai, China). RESULTS: Obvious reduction in Vmean and Qmean with marked increase in R and DR occurred after severe head injury. The indices of nimodipine group were significantly improved and the patients had better prognosis in comparison with conventional therapy group. CONCLUSION: Nimodipine is effective in promoting cerebral circulation and improving the prognosis of patients with severe head injuries.