A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure.

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

An interesting dynamic retrograde His bundle potential during the transventricular-septal process for left bundle branch pacing in a patient with right bundle branch block: A case report.

A 67-year-old male presented with symptomatic bradycardia caused by atrial fibrillation and underwent His bundle pacing (HBP) and left bundle branch pacing (LBBP). Electrocardiography (ECG) revealed a complete right bundle branch block (RBBB). John Jiang's connecting cable was used during the transventricular septal process. An interesting dynamic retrograde His bundle potential (RHP) was recorded with uninterrupted lead screws.

Umbilical therapy for promoting transdermal delivery of topical formulations: Enhanced effect and underlying mechanism.

Umbilical paste therapy is a promising method to promote transdermal drug delivery of topical formulations. This work investigated the effect and mechanism of transdermal drug delivery through the umbilical skin. The transdermal permeation studies showed the phenomenon of higher cumulative penetration and faster penetration rates for drug through the umbilical skin compared with non-umbilical skin, namely umbilical pro-permeability. This special transdermal permeability of drugs is influenced by their molecular weight, logP value, ability to form hydrogen bonds, and molecular volume. The underlying mechanism of umbilical pro-permeability was elucidated from unique structure and regulation the effect of drugs on microcirculation in the umbilical skin. Mechanistic studies revealed that this phenomenon was not only associated with the structural and physiological properties of the skin but also to the interactions between drugs and different skin layers. The umbilical pro-permeation is attributed to the thinner stratum corneum layer, differences in stratum corneum lipid composition and keratin structure, and lower levels of intercellular tight junction proteins in the viable epidermis and dermis layer of the skin. Our research indicated that umbilical paste therapy enhanced the transdermal delivery and absorption of drugs by stimulating local blood flow through mast cell activation. Surprisingly, skin temperature modulation and calcitonin gene-related peptide and substance P levels did not appear to significantly affect this process. In conclusion, umbilical drug administration, as a straightforward and non-invasive approach to enhance transdermal drug delivery, presents novel concepts for continued investigation and practical implementation of transdermal drug delivery systems.

Biomacromolecule assembly of soy glycinin-potato starch complexes: Focus on structure, function, and applications.

The effect of the cross-linking mechanism and functional properties of soy glycinin (11S)-potato starch (PS) complexes was investigated in this study. The results showed that the binding effecting and spatial network structure of 11S-PS complexes via heated-induced cross-linking were adjusted by biopolymer ratios. In particular, 11S-PS complexes with the biopolymer ratios of 2:15, had a strongest intermolecular interaction through hydrogen bonds and hydrophobic force. Moreover, 11S-PS complexes at the biopolymer ratios of 2:15 exhibited a finer three-dimensional network structure, which was used as film-forming solution to enhance the barrier performance and mitigate the exposure to the environment. In addition, the 11S-PS complexes coating was effective in moderating the loss of nutrients, thereby extending their storage life in truss tomato preservation experiments. This study provides helpful to insights into the cross-linking mechanism of the 11S-PS complexes and the potential application of food-grade biopolymer composite coatings in food preservation.

Unification of medicines and excipients: The roles of natural excipients for promoting drug delivery.

INTRODUCTION: Drug delivery systems (DDSs) formed by natural active compounds be instrumental in developing new green excipients and novel DDS from natural active compounds (NACs). 'Unification of medicines and excipients'(UME), the special inherent nature of the natural active compounds, provides the inspiration and conduction to achieve this goal. AREAS COVERED: This review summarizes the typical types of NACs from herbal medicine, such as saponins, flavonoids, polysaccharides, etc. that act as excipients and their main application in DDS. The comparison of the drug delivery systems formed by NACs and common materials and the primary formation mechanisms of these NACs are also introduced to provide a deepened understanding of their performance in DDS. EXPERT OPINION: Many natural bioactive compounds, such as saponins, polysaccharides, etc. have been used in DDS. Diversity of structure and pharmacological effects of NACs turn out the unique advantages in improving the performance of DDSs like targeting ability, adhesion, encapsulation efficiency(EE), etc. and enhancing the bioavailability of loaded drugs.

pH-Shifting combined with ultrasound treatment of emulsion-filled ß-conglycinin gels as ß-carotene carriers: Effect of emulsion concentration on gel properties.

In this work, emulsion-filled gels were prepared from natural and pH-shifting combined with ultrasound ß-conglycinin (7S) as emulsifiers. The emulsifier modification and emulsion concentrations (5, 10, 15, 20 wt%) were evaluated on the structural and ß-carotene release properties of the gels. Compared to the 7S hydrogel, the emulsion-filled gels exhibited better water-holding and textural properties. The 7S modification and the increase in emulsion concentration resulted in altered water distribution and improved microstructure and rheological properties of the emulsion-filled gels. The dense and homogeneous gel network was formed at an emulsion content of 15 wt%. The gels were regulated by different release kinetics in a simulated gastrointestinal environment. M-15 showed the highest bioaccessibility and chemical stability (72.25% and 89.87%) with good slow-release properties of ß-carotene. These results will guide the development of encapsulated delivery systems for gel food products.

Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis.

Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are usually asymptomatic during early stages and have a high degree of malignancy, along with a high rate of recurrence and metastasis, thereby increasing the risk of mortality. Studies have shown that ferroptosis regulates cell proliferation and tumour growth and reduces drug resistance. Hence, ferroptosis could play a role in preventing and treating cancers. Wogonin is a flavonoid with anticancer activity against various cancers, including pancreatic cancer. It is extracted from the root of Scutellaria baicalensis Georgi. In this study, we show that wogonin inhibits the survival and proliferation of human pancreatic cancer cell lines and induces cell death. We performed RNA-sequencing and analysed the differentially expressed gene and potential molecular mechanism to determine if wogonin reduced cell survival via ferroptosis. Our results showed that wogonin upregulates the levels of Fe2+, lipid peroxidation and superoxide and decreases the protein expression levels of ferroptosis suppressor genes, and downregulates level of glutathione in pancreatic cancer cells. In addition, ferroptosis inhibitors rescue the ferroptosis-related events induced by wogonin, thereby confirming the role of ferroptosis. A significant increase in ferroptosis-related events was observed after treatment with both wogonin and ferroptosis inducer. These results show that wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosis via the Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer.

Physical treatment synergized with natural surfactant for improving gas-water interfacial behavior and foam characteristics of α-lactalbumin.

The purpose of this study was to investigate effect of physical treatment (ultrasound, U/high pressure homogenization, H/combined treatment, UH or HU) and surfactant (Mogroside V, Mog) on air/water interface adsorption and foaming properties of α-lactalbumin (ALa). Firstly, the binding of Mog and all physical-treated ALa was a static quenching process. Mog had the greatest binding affinity for HU-ALa among all treated samples. U or H treatment could change surface hydrophobicity of ALa/Mog complex. Secondly, at the molar ratio (ALa:Mog) of 1:50, foaming ability (FA) of all ALa samples got the maximum. The sequence of FA in ALa and ALa/Mog complex was listed as follow: HU > U > H > UH. Moreover, foaming stability (FS) of HU-ALa was the highest, followed by H-ALa, U-ALa and UH-ALa. Meanwhile, low concentration Mog increased FS of ALa or UH-ALa, but it reduced FS of H-ALa, U-ALa and HU-ALa. Quartz crystal microbalance with dissipation monitoring (QCM-D) experiment indicated that ALa/Mog complex after U or H treatment was quickly absorbed at air/water interface, compared with the treated ALa, and HU-ALa/Mog had the largest frequency shift. In addition, HU-ALa had the thickest bubble membrane and the highest dissipation shift in all samples, indicating that the absorbed membrane thickness and viscoelasticity of samples was correlated with foam stability. Therefore, U and H treatment synergism with Mog was an effective approach to enhance foam properties of ALa, which indicated that HU-treated ALa/Mog complex could be viewed as the safe and efficient foaming agent applied in food processing.

Microbial Diversity and Flavor Regularity of Soy Milk Fermented Using Kombucha.

Plant-based milk is considered a healthy and environmentally sustainable option. However, due to the low protein content of most plant-based milk and the difficulty of gaining flavor acceptance by consumers, its production scale is usually limited. Soy milk is a kind of food with comprehensive nutrition and high protein content. In addition, kombucha is naturally fermented by acetic acid bacteria (AAB), yeast, lactic acid bacteria (LAB), and other microorganisms, and the microorganisms in its system can improve the flavor characteristics of food. In the present study, LAB (commercially purchased) and kombucha were used as fermenting agents for soybean, which was used as a raw material to produce soy milk. A variety of characterization methods were used to study the relationship between the microbial composition and flavor regularity of soy milk produced with different proportions of fermenting agents and different fermentation times. In soy milk produced at 32 °C with a mass ratio of LAB to kombucha of 1:1 and a fermentation time of 42 h, the concentrations of LAB, yeast, and acetic acid bacteria in the milk were optimal at 7.48, 6.68, and 6.83 log CFU/mL, respectively. In fermented soy milk produced with kombucha and LAB, the dominant bacterial genera were Lactobacillus (41.58%) and Acetobacter (42.39%), while the dominant fungal genera were Zygosaccharomyces (38.89%) and Saccharomyces (35.86%). After 42 h, the content of hexanol in the fermentation system of kombucha and LAB decreased from 30.16% to 8.74%, while flavor substances such as 2,5-dimethylbenzaldehyde and linalool were produced. Soy milk fermented with kombucha offers the opportunity to explore the mechanisms associated with flavor formation in multi-strain co-fermentation systems and to develop commercial plant-based fermentation products.

Right subclavian vein approach for selective left bundle branch pacing: A case report.

We reported a 65-year-old man with symptomatic bradycardia caused by chronic atrial fibrillation who underwent pacemaker implantation by left bundle branch pacing (LBBP) via right subclavian vein (RSV) approach. A tricuspid valve annulus (TVA) angiography was performed, and a different connecting cable that can monitor electrocardiograms (ECG) and intracardiac electrograms (EGM) in real time was used during the process. By TVA angiography, we could easily find the ideal location of LBBP; a new connecting cable helped us avoid perforation and guide effective endpoint without the need to stop pacing. The case showed that it was feasible and safe to use the new method for LBBP through RSV route.

Construction of the small intestine on molecular dynamics simulation and preliminary exploration of drug intestinal absorption prediction.

In this study, molecular dynamics simulation was applied to the construction of the small intestinal epithelial cell membrane and prediction of drug absorption. First, we constructed a system of a small intestinal epithelial cell membrane that was close to the real proportion and investigated the effects of temperature, water layer thickness, and ionic strength on membrane properties to optimize environmental parameters. Next, three drugs with different absorptivity, including Ephedrine (EPH), Quercetin (QUE), and Baicalin (BAI), were selected as model drugs to study the ability of drugs through the membrane by the free diffusion and umbrella sampling simulation, and the drug permeation ability was characterized by the free diffusion coefficient D and free energy barrier (△G) in the processes. The results showed that the free diffusion coefficient D and △G orders of the three drugs were consistent with the classical experimental absorption order, indicating that these two parameters could be used to jointly characterize the membrane permeability of the drugs.

Co-precipitates proteins prepared by soy and wheat: Structural characterisation and functional properties.

Co-precipitation was a novel method for improving the functional properties of pure proteins. To investigate the mechanism of this effect, different protein proportions of soy-wheat co-precipitated protein were extracted by isoelectric point co-precipitation. Soy protein isolate (SPI) was mainly linked to wheat protein (WP) through non-covalent forces and disulfide bonds as determined by circular dichroism spectroscopy, disulfide bond, protein fraction extraction, interaction, and molecular modeling. Amino acid analysis indicated that co-precipitation could increase wheat lysine content. Furthermore, co-precipitation improved multiple functional properties of pure protein, and the emulsifying and foaming properties of the composite system with a mass ratio of 7:3 outperformed those of other systems. At the same time, correlation analysis revealed that protein structure and intermolecular forces significantly affected its functional properties. This study provided some useful and interesting information for the development and application of protein-protein systems with diverse functional properties.

Diammonium Glycyrrhizinate-Based Micelles for Improving the Hepatoprotective Effect of Baicalin: Characterization and Biopharmaceutical Study.

Saponins are an important class of surface-active substances. When formulated as an active ingredient or co-used with other drugs, the effect of their surface activity on efficacy or safety must be considered. In this paper, diammonium glycyrrhizinate (DG), a clinical hepatoprotective drug that has long been used as a biosurfactant, was taken as the research object to study its combined hepatoprotective effect with baicalin (BAI). Animal experiments proved that the preparation of DG and BAI integrated into micelles (BAI-DG Ms) had a better protective effect on acute liver injury caused by carbon tetrachloride than the direct combined use of the two. From the perspective of biopharmaceutics, the synergistic mechanism of BAI-DG Ms was further explored. The results showed that after forming BAI-DG Ms with DG, the solubility of BAI increased by 4.75 to 6.25 times, and the cumulative percentage release in the gastrointestinal tract also increased by 2.42 times. In addition, the negatively charged BAI-DG Ms were more likely to penetrate the mucus layer and be absorbed by endocytosis. These findings provide support for the rational application of glycyrrhizin, and other saponins.

The Layered Encapsulation of Vitamin B2 and ß-Carotene in Multilayer Alginate/Chitosan Gel Microspheres: Improving the Bioaccessibility of Vitamin B2 and ß-Carotene.

This research underlines the potential of alginate multilayered gel microspheres for the layered encapsulation and the simultaneous delivery of vitamin B2 (VB) and ß-carotene (BC). Chitosan was used to improve the stability and controlled release ability of alginate-based gel microspheres. It was shown that a clear multilayered structure possessed the characteristics of pH response, and excellent thermal stability. The sodium alginate concentration and the number of layers had notable effects on mechanical properties and particle size of gel microspheres. Fourier-transform infrared spectroscopy and X-ray diffraction analyses further proved that VB and BC were encapsulated within the gel microspheres. Compared with the three-layer VB-loaded gel microspheres, the total release of VB from the three-layer VB and BC-loaded gel decreased from 93.23% to 85.58%. The total release of BC from the three-layer VB and BC-loaded gel increased from 66.11% to 69.24% compared with three-layer BC-loaded gel. The simultaneous encapsulation of VB and BC in multilayered gel microspheres can markedly improve their bioaccessibility and bioavailability. These results showed the multilayer gel microspheres synthesized herein have potential for applications in the layered encapsulation and simultaneous delivery of various bioactive substances to the intestinal tract.

A case control study on family history as a risk factor for herpes zoster and associated outcomes, Beijing, China.

BACKGROUND: Hospital-based case control studies have found family history of herpes zoster (HZ) was associated with risk of HZ, but the role of family history is not fully examined for other HZ-associated outcomes such as recurrent HZ, occurrence of postherpetic neuralgia (PHN), and HZ with different pain severities. METHODS: We conducted a population-based matched case control study. HZ cases that occurred during December 1, 2011 to November 30, 2012 were identified by face-to-face interview with all residents of eight selected communities/villages from three districts of Beijing, China. Medical records were reviewed for those who sought healthcare for HZ. For each case-patient, three, age-matched controls (±5 years) without HZ were enrolled from the same community/village of the matched case. Data on family history of HZ were collected by interview and only defined among first-degree relatives. RESULTS: A total of 227 case-patients and 678 matched controls were enrolled. Case-patients were more likely to report a family history of HZ [odds ratio (OR) =2.4, P = 0.002]. Compared with controls, association of family history decreased from HZ with PHN to HZ without PHN (OR = 6.0 and 2.3, respectively; P = 0.002 for trend), from recurrent HZ to primary HZ (OR = 9.4 and 2.2, respectively; P = 0.005 for trend), and from HZ with moderate or severe pain to HZ with mild or no pain (OR = 3.2 and 0.8, respectively; P < 0.001 for trend). CONCLUSIONS: Family history of HZ was associated with HZ occurrence and was more likely in HZ case-patients with PHN, recurrences, and painful HZ.

Clinical outcomes of bridging therapy with fondaparinux versus low-molecular-weight heparin in patients undergoing atrial fibrillation ablation.

OBJECTIVE: To compare the efficacy and safety of bridging therapy with fondaparinux versus low-molecular-weight heparin (LMWH) in patients undergoing radiofrequency ablation for atrial fibrillation (AF). METHODS: AF patients undergoing radiofrequency ablation between January, 2009 and June, 2013 in Nanfang Hospital were analyzed. The patients received subcutaneous injection of either fondaparinux or LMWH as a bridging therapy during warfarin discontinuation 5 days before the ablation until a post-ablation international normalized ratio (INR) of 2.0-3.0 was achieved. Anticoagulant-related complications, identified and classified as thromboembolic and bleeding events, were compared between the two groups. RESULTS: A total of 465 patients (68% male; mean age 52.3∓15 years, range 25 to 80 years) were enrolled in the study, including 265 in fondaparinux group and 200 in LMWH group. Anticoagulation-related complications were observed in 3 patients in fondaparinux group, as compared with 13 in LMWH group (P=0.002), but the thromboembolic rate did not differ significantly between the two groups (P=0.111). Two patients in fondaparinux group and 8 in LMWH group showed bleeding complications (P=0.039). No cardiovascular death occurred in these patients during a mean follow-up period of 3 months. CONCLUSIONS: Fondaparinux as the bridging therapy during catheter ablation for AF does not increase the risk of thromboembolic complications but slightly reduces the risk of bleeding compared to LMWH, suggesting its safety and effectiveness for periprocedural anticoagulation management in AF patients undergoing radiofrequency ablation.

Efficacy of medication directed by home-monitoring cardiac resynchronization therapy in chronic heart failure patients.

PATIENTS with chronic heart failure (CHF) have a high incidence of atrial/ventricular arrhythmias which seriously affect life span and quality of life. Cardiac re-synchronization therapy (CRT) can improve cardiac function and reverse myocardial remodeling, therefore improving the quality of life and reducing mortality. CRT with Home-Monitoring (HM) can be used to monitor cardiac arrhythmias and other heart physiological indexes such as intrathoracic impedance and hemodynamics. Through wireless satellites, the data from the patients are sent to a monitor center for analysis. Doctors can identify emergent information and make a rapid diagnosis based on the information stored in the monitor center. CRT with HM has been verified as a valid method to optimize drug treatment according to individual parameters.

[Effects of soil, climate, and their interaction on some neutral volatile aroma components in flue-cured tobacco leaves from high quality tobacco planting regions of Hunan Province].

A pot experiment with the soils from Yongzhou, Liuyang, and Sangzhi, the high-quality tobacco planting regions of Hunan Province, was conducted to study the effects of climate, soil, and their interaction on some neutral volatile aroma components in flue-cured tobacco leaves. The contents of test neutral volatile aroma components in the flue-cured tobacco leaves were of medium variation, and the variation intensity was decreased in the order of dihydroactinolide, damascenone, furfural, total megastigmatrienone, and beta-ionone. Climate, soil, and their interaction affected the neutral volatile aroma components in different degrees. The furfural content was most affected by climate, the damascenone content was most affected by climate and by soil, the total megastigmatrienone and beta-ionone contents were most affected by the interaction of soil and climate, while the dihydroactinolide content was less affected by soil, climate, and their interaction. The contribution of climate, soil, and their interaction to the contents of the five aroma components was 40.82%, 20.67%, and 38.51%, respectively. During different growth periods of tobacco, different climate factors had different effects on the neutral volatile aroma components. The rainfall, cloudiness, and mean air temperature at rooting stage, the diurnal temperature amplitude, sunshine time, and evaporation at vigorous growth stage, and the rainfall, evaporation, and mean air temperature at maturing stage were the top three climate factors affecting the contents of the neutral volatile aroma components in flue-tobacco leaves. For the soil factors, the available potassium, available phosphorus, and pH were the top three factors affecting the contents of the five components.

[Ecological reasons for the difference in nicotine content of flue-cured tobacco planted in different regions of Hunan Province].

Aimed to explore the ecological reasons for the difference in nicotine content of flue-cured tobacco planted in different regions of Hunan Province, field experiments were conducted in Sangzhi, Liuyang, and Yongzhou counties, the three typical tobacco regions of Hunan Province, taking tobacco variety K326 as the test object. Simultaneously, pot experiments with local soils and guest soils were carried out. The nicotine content of mid position tobacco leaves was analyzed at harvest time. Field experiments showed that the average nicotine content of tobacco leaves differed significantly among test sites, with that in Sangzhi being the highest, followed by Liuyang, and Yongzhou. Pot experiments showed that climate had significant effects on the average nicotine content of tobacco leaves, while soil and its interaction with climate had less effects. The contribution rate of climate, soil, and their interaction on the variance of the average nicotine content was 60.0%, 12.8% and 27.2%, respectively. The main sub-ecological factors closely related to the average nicotine content of flue-cured tobacco planted in different regions of Hunan Province were in turn the cloud cover at maturing stage, the relative humidity, sunshine hours, diurnal temperature variance, and rainfall at root-extending stage, and the average air temperature at vigorous growth stage. Generally, climate was the main ecological factor that led to the nicotine content difference of flue-cured tobacco planted in different regions of Hunan Province.