Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7.

Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (Ki) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (Ki) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb-drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7.

Glucuronidation of aurantio-obtusin: identification of human UDP-glucuronosyltransferases and species differences.

1. The aurantio-obtusin's glucuronide was detected when aurantio-obtusin was incubated with human liver microsomes (HLMs). Recombinant UGT isoforms screening experiment showed that UGT1A8 was the major isoform contributed to the glucuronidation. 2. The metabolic profiles for aurantio-obtusin in liver microsomes from different species were similar, however, the intrinsic clearance values (Vmax/Km) among the species were: Monkey > Human > Rat > Rabbit > Dog > Pig > Mouse > Guinea pig.

Preparation of Polyimide/Ionic Liquid Hybrid Membrane for CO2/CH4 Separation.

Imidazole ionic liquids (ILs) have good affinity and good solubility for carbon dioxide (CO2). Such ionic liquids, combined with polyimide membrane materials, can solve the problem that, today, CO2 is difficult to separate and recover. In this study, the ionic liquid (IL) of 1-ethyl-3-methylimidazolium tetrafluoroborate (IL1), 1-pentyl-3-methylimidazolium tetrafluoroborate (IL2), 1-octyl-3-methylimidazolium tetrafluoroborate (IL3), and 1-dodecylimidazolium tetrafluoroborate (IL4) with different contents were added to a polyimide matrix, and a series of polyimide membranes blended with ionic liquid were prepared using a high-speed mixer. The mechanical properties and gas separation permeability of the membranes were investigated. Among them, the selectivity of the PI/IL3 membrane for CO2/CH4 was 180.55, which was 2.5 times higher than the PI membrane, and its CO2 permeability was 16.25 Barrer, which exceeded the Robeson curve in 2008; the separation performance of the membrane was the best in this work.

Advanced biomass-based Janus materials: Classification, preparation and application: A review.

In contrast to conventional particles characterized by isotropic surfaces, Janus particles possess anisotropic surfaces, resulting in unique physicochemical properties and functional attributes. In recent times, there has been a surge in interest regarding the synthesis of Janus particles using biological macromolecules. Various synthesis techniques have been developed for the fabrication of Janus materials derived from biomass. These methods include electrospinning, freeze-drying, secondary casting film formation, self-assembly technology, and other approaches. In the realm of Janus composite materials, those derived from biomass have found extensive applications in diverse domains including oil-water separation, sensors, photocatalysis, and medical materials. This article provides a systematic introduction to the classification of Janus materials, with a specific focus on various types of biomass-based Janus materials (mainly cellulose-based Janus materials, lignin-based Janus materials and protein-based Janus materials) and the methods used for their preparation. This work will not only deepen the understanding of biomass-based Janus materials, but also contribute to the development of new methods for designing biomass-based Janus structures to optimize biomass utilization.

Preparation and Separation Properties of Electrospinning Modified Membrane with Ionic Liquid Terminating Polyimide/Polyvinylpyrrolidone@Polydopamine.

In this paper, superhydrophilic polyimide (PI) membranes were prepared using the electrostatic spinning method, capped with a hydrophilic ionic liquid (IL), and blended with polyvinylpyrrolidone (PVP). Using this preparation, the surface of the fiber membranes was coated in polydopamine (PDA) by means of an in-growth method. Scanning electron micrographs showed prepared blend films can form continuous fibers, for whom the distributions of diameter and pore were uniform. Post-modification (carried out by adding hydrophilic substances), the ability of the membrane surface to adhere to water was also significantly improved. The water contact angle was reduced from 128.97 ± 3.86° in unmodified PI to 30.26 ± 2.16°. In addition, they displayed a good separation effect on emulsified oil/water mixtures. The membrane flux reached a maximum value of 290 L·m-2·h-1, with a maximum separation efficiency reached of more than 99%. After being recycled 10 times, the separation efficiency maintained a level exceeding 95%. The purpose of this study is to demonstrate the simplicity and efficiency of this experiment, thereby providing new ideas for the future application of membrane separation technology in wastewater treatment.

Preparation of Butadiene-Bridged Polymethylsiloxane/Ethylcellulose/1-Carboxymethyl-3-methylimidazolium Chloride Ternary Composite Membranes for Gas Separation.

Excessive CO2 emissions have resulted in global warming and are a serious threat to the life of people, various strategies have been implemented to cut carbon emissions, and one of them is the use of a gas separation membrane to capture CO2 effectively. In this experiment, the butadiene-bridged polymethylsiloxane (BBPMS)/ethyl cellulose (EC)/ionic liquid (IL) ternary composite membranes were prepared by EC as a substrate, BBPMS, and IL as additives in tetrahydrofuran under high-speed stirring and coated on the membrane. The membrane structure was characterized by a Fourier transform infrared spectrometer and scanning electron microscope, and the membrane properties were tested by a membrane tensile strength tester, thermal weight loss analyzer, and gas permeability meter. The results show that the surface of the ternary composite membrane is dense and flat with a uniform distribution, and the membrane formation, heat resistance, and mechanical properties are good. The permeability coefficient of the ternary composite membrane for CO2 reached 1806.03 Barrer, which is 20.00 times higher than that of the EC/IL hybrid matrix membrane. The permeability coefficient of O2 reached 321.01 Barrer, which is 19.21 times higher than that of the EC/IL membrane. When the doping amount of BBPMS is 70-80%, the O2/N2 gas permeation separation of the BBPMS/EC/IL ternary composite membrane is close to the Robertson 2008 curve. It is always known that in the gas separation process the membrane material is the most crucial factor. The success of this experiment points to a new direction for the preparation of new membrane materials.

Substrate-dependent modulation of the catalytic activity of CYP3A by erlotinib.

AIM: To ascertain the effects of erlotinib on CYP3A, to investigate the amplitude and kinetics of erlotinib-mediated inhibition of seven major CYP isoforms in human liver microsomes (HLMs) for evaluating the magnitude of erlotinib in drug-drug interaction in vivo. METHODS: The activities of 7 major CYP isoforms (CYP1A2, CYP2A6, CYP3A, CYP2C9, CYP2D6, CYP2C8, and CYP2E1) were assessed in HLMs using HPLC or UFLC analysis. A two-step incubation method was used to examine the time-dependent inhibition of erlotinib on CYP3A. RESULTS: The activity of CYP2C8 was inhibited with an IC(50) value of 6.17±2.0 µmol/L. Erlotinib stimulated the midazolam 1'-hydroxy reaction, but inhibited the formation of 6ß-hydroxytestosterone and oxidized nifedipine. Inhibition of CYP3A by erlotinib was substrate-dependent: the IC(50) values for inhibiting testosterone 6ß-hydroxylation and nifedipine metabolism were 31.3±8.0 and 20.5±5.3 µmol/L, respectively. Erlotinib also exhibited the time-dependent inhibition on CYP3A, regardless of the probe substrate used: the value of K(I) and k(inact) were 6.3 µmol/L and 0.035 min(-1) for midazolam; 9.0 µmol/L and 0.045 min(-1) for testosterone; and 10.1 µmol/L and 0.058 min(-1) for nifedipine. CONCLUSION: The inhibition of CYP3A by erlotinib was substrate-dependent, while its time-dependent inhibition on CYP3A was substrate-independent. The time-dependent inhibition of CYP3A may be a possible cause of drug-drug interaction, suggesting that attention should be paid to the evaluation of erlotinib's safety, especially in the context of combination therapy.

Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol.

Diethylstilbestrol (DES), a synthetic estrogen clinically used to treat threatened abortion between the 1940s and the 1970s, has been restricted to treat certain cases of prostatic and breast cancer due to its adverse drug responses such as teratogenicity and carcinogenicity. Some reports have demonstrated that the addition of DES to docetaxel could modify tubulin composition and improve response of prostate cancer to chemotherapy. Given that DES might be co-administered with other drugs such as docetaxel, the present study focused on CYP-based drug-drug interaction (DDI). In vitro inhibitory effects of DES on CYP isoforms were investigated, and the results showed that DES could competitively inhibit CYP3A4, CYP2C8, CYP2C9 and CYP2E1. The inhibition constants (Ki) were calculated to be 4.4 microM, 3.0 microM, 5.0 microM and 8.0 microM for CYP3A4, CYP2C9, CYP2E1 and CYP2C8, respectively. Based on peak serum DES level after drip influsion of 500 mg of fosfestrol (DES diphosphate) in patients, [I]/Ki was calculated to be 4.3, 6.2, 3.7 and 2.3 for CYP3A4, CYP2C9, CYP2E1 and CYP2C8, which suggested that DES was likely to induce in vivo DDI through inhibition of these four major CYP isoforms. These results collectively demonstrate that adverse drug responses might exist when DES is co-administered with other drugs.

Clinical analysis of total endoscopic thyroidectomy via breast areola approach in early differentiated thyroid cancer.

PURPOSE: The purpose of this study was to explore the efficacy and safety of total endoscopic thyroidectomy (TET) via breast areola approach in the treatment of early differentiated thyroid cancer. METHODS: The clinical data of 134 patients with early differentiated thyroid cancer were retrospectively analyzed. The patients underwent different treatments, including TET via breast areola approach in endoscope group (n=67), and conventional small incision open surgery in control group (n=67). The surgery-related indexes, complications, postoperative incision recovery, visual analogue scale (VAS) pain score, postoperative patients' satisfaction, tumor recurrence and survival conditions were compared between the two groups. RESULTS: Compared with control group, the endoscope group showed significantly longer operation time, smaller intraoperative bleeding, less postoperative drainage, shorter duration of postoperative catheter indwelling and shorter postoperative length of stay. Meanwhile, in the endoscope group, the postoperative VAS pain score was markedly lower than that in control group, and the postoperative patients' satisfaction was higher than that in control group. The neurological severity score (NSS) had statistically significant differences between the two groups at 3 months and 6 months after operation. Moreover, no tumor recurrence and metastasis were found during the follow-up period. CONCLUSIONS: TET via breast areola approach is safe and effective in the treatment of early differentiated thyroid cancer, and it can achieve a better cosmetic effect and high satisfaction of patients, which is worthy of clinical application.

Optimization of a MOF Blended with Modified Polyimide Membrane for High-Performance Gas Separation.

The preparation, characterization and gas separation properties of mixed matrix membranes (MMMs) were obtained from polyimide capped with ionic liquid and blended with metal-organic frameworks (MOFs). The synthesized MOF was amine functionalized to produce UiO-66-NH2, and its amino group has a higher affinity for CO2. Mixed matrix membranes exhibited good membrane forming ability, heat resistance and mechanical properties. The polyimide membrane exclusively capped by ionic liquid exhibited good permselectivity of 74.1 for CO2/CH4, which was 6.2 times that of the pure polyimide membrane. It is worth noting that MMM blended with UiO-66-NH2 demonstrated the highest ideal selectivity for CO2/CH4 (95.1) with a CO2 permeability of 7.61 Barrer, which is close to the 2008 Robeson upper bound. The addition of UiO-66-NH2 and ionic liquid enhanced the permselectivity of MMMs, which may be one of the promising technologies for high performance CO2/CH4 gas separation.

Expression levels of ARHI and Beclin1 in thyroid cancer and their relationship with clinical pathology and prognosis.

Expression levels of autophagy-related genes ARHI and Beclin1 in thyroid cancer and their relationship with clinical pathology and prognosis were investigated. The expression levels of ARHI and Beclin1 proteins in 80 cases of thyroid cancer and adjacent tissues were detected by western blot analysis. According to the expression levels of ARHI and Beclin1, low- and high-expression groups were determined and the relationship of the expression levels with the pathological parameters and prognosis in thyroid cancer was compared between the two groups. The correlation between the ARHI and Beclin1 protein expression level was analyzed by Pearsons correlation analysis. The levels of ARHI and Beclin1 proteins in thyroid cancer tissues were significantly lower than those in adjacent tissues (P<0.05). There was a significant difference in the expression levels of ARHI and Beclin1 in terms of pathological stage and differentiation degree of cancer tissues (P<0.001); however, there was no significant difference in the expression levels of ARHI and Beclin1 for different types of cancer tissues (P>0 05). There was a positive correlation between the expression levels of Beclin1 and ARHI (r=0.5187, P<0.001). The 3-year survival rates of patients with low-expression level of ARHI and Beclin1 proteins were significantly lower than those of patients with high expression (P<0.05). In conclusion, the expression levels of Beclin1 and ARHI were low in thyroid cancer, and were significantly associated with the pathological stage, differentiation degree and prognosis in thyroid cancer. Beclin1 and ARHI can be used as predictors for the development and prognosis of thyroid cancer.

Multiple bone brown tumor secondary to primary hyperparathyroidism: a case report and literature review.

Bone brown tumors secondary to primary hyperparathyroidism (PHPT) are rare and only around 2-5% of PHPT patients have multiple bone brown tumor lesions, which are also uncommon in literatures. We found a female patient who got misdiagnosis of multiple malignant bone tumors in our clinical work, she was eventually diagnosed as a brown tumor secondary to hyperparathyroidism. This article records the diagnosis and treatment process, and summarizes similar case reports in the past decade to provide experience in diagnosis and treatment of similar cases that may occur in the future.

Onset of cooperation between layered networks.

Functionalities of a variety of complex systems involve cooperations among multiple components; for example, a transportation system provides convenient transfers among airlines, railways, roads, and shipping lines. A layered model with interacting networks can facilitate the description and analysis of such systems. In this paper we propose a model of traffic dynamics and reveal a transition at the onset of cooperation between layered networks. The cooperation strength, treated as an order parameter, changes from zero to positive at the transition point. Numerical results on artificial networks as well as two real networks, Chinese and European railway-airline transportation networks, agree well with our analysis.