Lamiophlomis rotata attenuates rheumatoid arthritis by regulating sphingolipid and steroid hormone metabolism.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. Lamiophlomis rotata (L. rotata) (Benth.) Kudo, an essential medicinal plant in traditional Tibetan medicine, is useful in treating RA. The purpose of this study was to evaluate L. rotata's anti-RA effect and to analyze its serum metabolites and lipids to predict the possible action pathways. Female and male rats were immunized with CFA to induce arthritis. Paw volumes were measured, and arthritis index analysis and histological analysis were performed to check the effects of L. rotata. ELISA was used to measure the levels of inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-10) and oxidative stress (MDA, SOD, GSH, and CAT). UPLC/Q-Orbitrap-MS was used to identify untargeted metabolites and lipids in serum. Metabolite validation was performed using UPLC/QQQ-MS. L. rotata application significantly reduced arthritis indices and paw swelling in AIA rats, and diminished inflammation and bone fractures in joint tissues. Sphingolipid (SP) and steroid hormone biosynthesis was found to be closely related to L. rotata's intervention in RA. In addition, our experiments also confirmed that females were more likely than males to develop RA. These findings provide clues and a scientific basis for the mechanism of L. rotata in treating RA.

Dose-response relationship between urinary PAH metabolites and blood viscosity among coke oven workers: a cross-sectional study.

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) have been proven to be a risk factor for cardiovascular disease in coke oven workers, and increased plasma viscosity is a signal for higher risk of catching up cardiovascular disease. We want to explore whether the plasma viscosity is affected by the concentration of PAHs. DESIGN: Our study is a cross-sectional dose-response study. SETTING: Participants in this study came from a coke plant in Taiyuan, Shanxi. PARTICIPANTS: We used data of 693 coke oven workers in Taiyuan. PRIMARY AND SECONDARY OUTCOME MEASURES: We assumed that plasma viscosity would increase as the concentration of PAHs metabolites in urine increases. We found that 2-hydroxyfluorene (OHFLU2) and plasma viscosity have a stable linear relationship in different statistical methods. RESULTS: We found that plasma viscosity increased by 1.14 (mPa.s,30/s) for each ng/mL of 2-OHFLU urinary (correlation coefficient range: 0.54-1.74, p<0.05). CONCLUSIONS: The results of this study could provide evidence for coke oven workers to prevent cardiovascular disease by checking whether plasma viscosity is elevated.

The Role of PKC in Regulating NMDARs in Aluminum-Induced Learning and Memory Impairment in Rats.

Aluminum is a widespread environmental neurotoxicant that can induce Alzheimer's disease (AD)-like damage, such as neuronal injury and impairment of learning and memory. Several studies have shown that aluminum could reduce the synaptic plasticity, but its molecular mechanism remains unclear. In this study, rats were treated with aluminum maltol (Al(mal)3) to establish a toxic animal model and PMA was used to interfere with the expression of PKC. The Morris water maze and open field test were used to investigate the behavioral changes of the rats. Western blotting and RT-PCR were used to detect the expression levels of NMDAR subunits, PKC and CaMKII. The results showed that Al(mal)3 damaged learning and memory function and reduced anxiety in rats. During this process, the expression of PKC was downregulated and it inhibited the expression of NMDARs through the phosphorylation of CaMKII.

Integrating chemical profiling and network pharmacology analysis based on anti-inflammatory effects for quality control of Scutellaria barbata.

INTRODUCTION: With the wide application of Scutellaria barbata D. Don for hepatitis and mastitis, its quality control issues have also received increasing attention. Based on the multi-component and multi-target characteristics of traditional Chinese medicine, there is an urgent need to establish a quality evaluation system. OBJECTIVES: This study intends to integrate the "quality-activity-quantification" strategy and establish an activity-related quality control method to ensure the safety and effectiveness of S. barbata. MATERIAL AND METHODS: Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was used to characterize the chemical components of S. barbata, and network pharmacological analysis was carried out on the identified components. The index components were determined on the basis of comprehensive activity prediction results and content information. At the same time, the contents of 16 batches of S. barbata from different origins were determined. RESULTS: A total of 94 compounds were identified according to mass spectrometric data, 12 of which were isolated and structure-confirmed by nuclear magnetic resonance technology. Network pharmacological analysis was applied to predict their key targets and the major pathways mediating their anti-inflammatory effects. On the basis of comprehensive activity prediction and content information, five components were chosen as crucial quality indicators of S. barbata, including scutellarin, scutellarein, luteolin, apigenin, and hispidulin. CONCLUSION: In this study, 16 different S. barbata batches were compared, and five quality indicators were determined on the basis of qualitative and activity results. The present study provides useful information for evaluating the quality of S. barbata in different areas, and also provides a new basis for the development of quality evaluation methods.

Dose-response relationships between polycyclic aromatic hydrocarbon exposure and blood cell counts among coke oven workers: a sex-stratified analysis.

OBJECTIVES: To explore sex differences and dose-response relationships between nine urinary polycyclic aromatic hydrocarbon (PAH) metabolites and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and complete blood counts among coke oven workers. DESIGN AND SETTING: A cross-sectional study with stratified sex was conducted in Shanxi, China. PARTICIPANTS: A total of 458 male workers and 226 female workers were selected. PRIMARY AND SECONDARY OUTCOME MEASURES: General linear models, p values for trend tests and natural cubic spline models were used to explore the dose-response relationships between nine urinary PAH metabolites and NLR, PLR and complete blood counts. RESULT: Compared with male workers, female workers had lower exposure level of PAH (0.95 ng/mL vs 1.38 ng/mL). Only among female workers did we observe that a 1-unit increase in lg(1-OHPyr) was related to a 0.149 (95% CI: 0.055 to 0.242; p for trend=0.041) and 0.103 (95% CI: 0.025 to 0.181; p for trend=0.007) increase in lg(NLR) and lg(PLR), and a 0.116 (95% CI: -0.179 to -0.054; p for trend=0.007) decrease in lg(lymphocyte counts (LYMs)). A 1-unit increase in lg(2-OHNap) was related to a 0.045 (95% CI: 0.003 to 0.086; p for trend=0.037) increase in lg(PLR) and a 0.029 (95% CI: -0.056 to -0.002; p for trend=0.030) and 0.016 (95% CI: -0.029 to -0.003; p for trend=0.010) decrease in lg(white blood cell counts (WBCs)) and lg(haemoglobin (HGB)). CONCLUSION: Female workers' NLR, PLR, WBCs, HGB and LYMs may be more susceptible than those of male workers when affected by PAH.

Efficacy and association analysis of high-dose methotrexate in the treatment of children with acute lymphoblastic leukemia.

Effect of high-dose methotrexate (MTX) on children with acute lymphoblastic leukemia (ALL) with different subtypes and disease courses was investigated. A retrospective analysis of 207 children with ALL who were admitted to the People's Hospital of Pingyi County from March 2014 to June 2017 was carried out. According to the subtype of the disease, the children were divided into two groups. B-lineage group: ALL occurred in B-lineage lymphocytes (n=128); T-lineage group: ALL occurred in T-lineage lymphocytes (n=79). According to the disease course, the children were divided into three groups. High-risk group: disease course >15 days (n=67); moderate-risk group: disease course >8 and <15 days (n=58); low-risk group: disease course <8 days (n=82). The plasma concentration, calcium formyltetrahydrofolate (CF) rescue times and adverse reactions were compared at 12 h (T1), 48 h (T2), and 72 h (T3) after MTX infusion. The plasma concentration in B-lineage group was significantly higher than that in the T-lineage group at T2 and T3 (P<0.05). The incidence of adverse reactions in children with ALL in the B-lineage group was significantly higher than that in the T-lineage group (P<0.05). The CF rescue times in high-risk group were more than that in moderate- and low-risk groups (P<0.05). The incidence of adverse reactions in the high-risk group was significantly higher than that in the moderate- and low-risk groups (P<0.05), and in the moderate-risk group was significantly higher than that in the low-risk group (P<0.05). Compared with T-lineage ALL children, high-dose MTX causes more toxic injury to B-lineage ALL children. During clinical application of MTX in the treatment of ALL, close attention should be paid to the changes of the vital signs of patients, and timely CF rescue should be performed.

Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers.

PURPOSE: To investigate the pharmacokinetics of L-carnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy volunteers after single L-carnitine administration. METHODS: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC. RESULTS: The maximum plasma concentration (Cmax) and area under the curve (AUC 0-infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3 micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08 micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01). The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively. CONCLUSION: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC.