Metabolite identification and excretion of pinocembrin-7-O-ß-D-glucoside in rats by UHPLC/MS.

Pinocembrin-7-O-ß-D-glucoside (PCBG) isolated from Penthorum chinense Pursh was proven to display a wide range of pharmacological effects including hepatoprotection, anti-hepatoma and antifungal activities, etc. The research aims to qualitatively analyze the metabolites of PCBG in rat plasma, urine, bile and feces, and further perform the excretion study of PCBG and its major metabolite pinocembrin (PCB). Fifteen rats were divided into three groups (n=5 for each group) for blood, bile, urine and feces collection, respectively. After PCBG suspension was intragastrically administered to rats at 50 mg/kg, biological samples were collected and processed. The metabolites in each matrix were detected by UHPLC-Q-Exactive-MS/MS. A total of 111 metabolites were observed in plasma, urine, bile and feces, which include hydroxylated, sulfated and glucuronized metabolites, etc. In addition, an UHPLC-MS/MS method was established and applied for the excretion quantification of PCBG and PCB in rat urine, bile, and feces samples. Studies on excretion have shown that PCBG is mainly excreted through feces. The cumulative excretion rates of PCBG and PCB in rat urine, bile and feces were (4.5±2.4)%, (0.2±0.1)% and (18.4±10.5)%, respectively. After hydrolysis by ß-glucuronidase/sulfatase, the excretion rates of PCB in urine and bile were (5.7±2.8)% and (8.9±4.2)%. This study contributes to preclinical research on PCBG and explains its pharmacological effects.

Sudden ventricular fibrillation due to absence of pericardium in left upper lobectomy -a case report.

BACKGROUND: Congenital absence of the pericardium (CAP) is a rare cardiac abnormality. As pericardial defects are usually asymptomatic, most cases are diagnosed during surgery or on autopsy. The patient in this case was found to have CAP during thoracoscope. CASE: We present the unusual case of a 69-year-old patient with CAP who experienced sudden ventricular arrhythmia and developed ventricular fibrillation during left upper lobectomy. Surgical operations, the lateral decubitus position, and other external stimuli may be important risk factors for ventricular fibrillation. The patient regained sinus rhythm soon after intrathoracic cardiac compression and pharmacological treatment, including lidocaine spray (2%, 10 ml) administered to the heart surface. The surgery was then completed without any additional instances of ventricular arrhythmia. CONCLUSIONS: Patients with CAP are more susceptible to cardiac-related adverse events during thoracotomy or thoracoscopy. Treatment of ventricular arrhythmias that occur during lung resection in patients with CAP should be emphasized.

[Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress].

OBJECTIVE: To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). METHODS: A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1ß (IL-1ß) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. RESULTS: Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (µg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/ß-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/ß-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/ß-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/ß-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1ß [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1ß mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). CONCLUSIONS: Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.

Development and validation of an LC-MS/MS method for pharmacokinetic study of lobetyolin in rats

Abstract A simple and selective liquid chromatography tandem with mass spectrometry (LC-MS/ MS) method for quantification of lobetyolin in rat plasma was developed and validated. Chromatographic separation was achieved on a Thermo ODS C18 reversed-phase column using 0.1% aqueous formic acid-methanol (50:50, v/v) in an isocratic elution mode at a flow rate of 0.4 mL.min-1. LC/MS performance was done in a positive ion ESI mode and the MS/MS transitions were monitored at m/z 419.3 [M+Na]+ → m/z 203.1 for lobetyolin and m/z 394.9 [M+Na]+ → m/z 231.9 for IS, respectively. The assay exhibited a linear dynamic range over 1.0-500 ng.mL-1 for lobetyolin in plasma. Both the precision (%RSD) and accuracy (RE%) were within acceptable criteria (<15%). Recoveries ranged from 87.0% to 95.6%, and the matrix effects were from 91.0% to 101.3%. After oral administration, the peak plasma concentration of lobetyolin was obtained as 60.1 ng.mL-1 at 1.0 h. The proposed LC-MS/MS method could be applied to a pharmacokinetic study employing 66 samples from 6 Wistar rats

The role of macrophage-derived TGF-ß1 on SiO2-induced pulmonary fibrosis: A review.

Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-ß1 (TGF-ß1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-ß1 precursors, and secrete them out of the cell where they are activated. Activated TGF-ß1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-ß1, as well as the mechanisms through which TGF-ß1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.

Effect of dexmedetomidine on brain function and hemodynamics in patients undergoing lung cancer resection.

Effect of dexmedetomidine on the brain function and hemodynamics in patients undergoing lung cancer resection were explored. Eighty-seven patients with lung cancer undergoing lung cancer resection in Weifang People's Hospital from January 2014 to June 2018 were enrolled in this study. Patients conventionally anesthetized by propofol, midazolam, sufentanil, or cisatracurium besilate (41 cases) were assigned to the control group and those anesthetized by conventional anesthetic and dexmedetomidine (46 cases) were assigned to the research group. The hemodynamic parameters, neuron-specific enolase (NSE), and astrocyte S-100p protein (S-100ß) were compared between the two groups before induction (T0), 5 min after induction (T1), at the end of surgery (T2), time of extubation (T3), and 5 min after extubation (T4). The cognitive function of patients was graded by the mini-mental state examination (MMSE) after patients recovered from anesthesia. In both the control group and the research group, the levels of mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP). were statistically higher at T2 and T3 than those at T0 (all P<0.05). The levels of MAP, HR, and CVP were statistically lower in the research group than those in the control group at T2 and T3 (P<0.05). The levels of serum NSE and S100ß protein in the research group and the control group increased at T2, T3, and T4, the control group was higher than the research group at each time point, and the difference was statistically significant (P<0.05). Comparison of the MMSE score and the total case number of adverse reactions between the two groups showed no statistical difference (both P>0.05). The MMSE score was positively correlated with the serum levels of NSE and S100ß in the two groups (r-values were 0.661 and 0.585, P<0.05). Dexmedetomidine can effectively protect patients' perioperative brain function with small impacts on perioperative hemodynamics, so it is worthy of clinical application.

The effects of one-lung ventilation mode on lung function in elderly patients undergoing esophageal cancer surgery.

The objective of the present study was to explore the effects of different one-lung ventilation (OLV) modes on lung function in elderly patients undergoing esophageal cancer surgery. A total of 180 consecutive elderly patients (ASA Grades I-II, with OLV indications) undergoing elective surgery were recruited in the study. Patients were randomly divided into 4 groups (n = 45). In Group A, patients received low tidal volume (VT < 8 mL/kg) + pressure controlled ventilation (PCV), low tidal volume (VT < 8 mL/kg) + volume-controlled ventilation (VCV) in Group B, high tidal volume (VT ≥ 8 mL/kg) + PCV in Group C and high tidal volume (VT ≥ 8 mL/kg) + VCV in Group D. Two-lung ventilation involved routine tidal volume (8-10 mL/kg) at a frequency of 12 to 18 times/min, and VCV mode. Clinical efficacy among 4 groups was compared. The partial pressure of end-tidal carbon dioxide (PetCO2) did not significantly differ among 4 groups (all P > .05), and the oxygenation index and SO2 in Group A were significantly higher than in the other groups (P < .05). The PetCO2, peak airway pressure (Ppeak), platform airway pressure (Pplat), and mean airway pressure (Pmean) in Group A were significantly lower than those in the other groups (all P < .05). However, airway resistance (Raw) among 4 groups did not significantly differ (all P > .05). The incidence of pulmonary infection, anastomotic fistula, ventilator-induced lung injury, lung dysfunction, difficulty weaning from mechanical ventilation, and multiple organ dysfunction in Groups A and B were lower than that in Groups C and D (all P < .05). The expression levels of IL-6, tumor necrosis factor-α, and C-reactive protein in lavage fluid in Group A were significantly lower than those in the other groups (all P < .05). OLV with low tidal volume (VT < 8 mL/kg) + PCV (5 cmH2O PEEP) improved lung function and mitigated inflammatory responses in elderly patients undergoing esophageal cancer surgery.

[Autologous mononuclear bone marrow cell transplantation by intracoronary route for patients with ischemic heart disease: observation of 2-years follow-up].

OBJECTIVE: To investigate the long-term effect and safety of intracoronary autologous bone marrow mononuclear cell (BMMC) transplantation in patients with ischemic heart disease (IHD). METHODS: Seventy-six patients with IHD, 26 patients with acute myocardial infarction (AMI) and 26 patients with chronic ischemic heart failure (CIHF), underwent routine treatment plus intracoronary autologous BMMC transplantation, and 24 patients, including 10 patients with AMI and 14 patients with CIHF underwent routine treatment as controls. Autologous BMMC transplantation was performed via a balloon catheter placed into the infarct-related artery during balloon dilatation by high pressure infusion to occlude the artery, which was performed 6 - 8 times for 2 minutes each with 2-minute interval or via a balloon catheter without occluding the infarct-related artery. Follow-up was conducted for 2 years. RESULTS: The surgery was safety without major periprocedural complications. There were no other new arrhythmias found by Holter recorder during the 2-years follow-up. In the AMI patients receiving BNNC transplantation, the left ventricular ejection fraction (LVEF) 1 and 2 years later increased by 5.79% (P < 0.05), 3.79% (P > 0.05) respectively; but there was no change in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV). The LVEF 1 and 2 years later of the control group increased by 8.8% and 9.2% respectively (both P < 0.01) and the LVESV 1 and 2 years later decreased by 20.4% and 27.8% respectively (both P < 0.05), the myocardium defect area 2 years later was not significantly different from that 3 months later. The heart function of the control group became markedly worse. CONCLUSION: Autologous BMMC intracoronary transplantation is safe and effective, especially in patients with CIHF.

[The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction].

OBJECTIVE: To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. METHODS: Thirty patients with RIHF (LVEF < 40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0 +/- 0.7) x 10(7) were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received standard medical therapy served as control. Baseline and follow up evaluations included complete clinical evaluations, plasma BNP, ANP, ET-1 measurements, echocardiography, PET, and Holter monitoring. RESULTS: Baseline characteristics were similar between the 2 groups. There were no major periprocedural complications. One patient developed ventricular premature contractions during cell infusion for several seconds and recovered spontaneously. Compared to pre-transplantation, plasma BNP and ET-1 significantly decreased and plasma ANP significantly increased at 7 days post transplantation; 6 minutes walking distance increased from (72.1 +/- 31.5) to (201.6 +/- 23.3) m (P < 0.01), LVEF increased 9.9% (P < 0.001) and FDG-PET revealed vital myocardium area increased (10.3 +/- 3.4)% (P < 0.01) at 3 months after BM-MNCs transplantation. At 6 months follow up, the NYHA class improved from (3.4 +/- 0.1 to 2.4 +/- 0.2, P < 0.001) and no patient died and 1 patient rehospitalized due to lower extremities edema. In control group, LVEF decreased 7.2% compared to baseline (P < 0.001) and was significantly lower than transplantation group at 3 months (P < 0.001). At 6 months follow up, the NYHA class increased from (3.5 +/- 0.1 to 3.9 +/- 0.1, P < 0.05), 2 patients died and 10 patients rehospitalized due to aggravated heart failure. CONCLUSION: Present study demonstrates that intracoronary transplantation of autologous BM-MNCs is safe and effective for treating patients with RIHF after myocardial infarction.