Chitosan-coated soybean protein isolate/lecithin nanoparticles for enhancing the stability and bioaccessibility of phytosterol.

BACKGROUND: Phytosterols (PS) have various beneficial effects on human health, especially the property of reducing blood cholesterol. However, the low solubility and bioaccessibility of PS have greatly limited their application in functional food ingredients. RESULTS: To improve the bioaccessibility and stability of PS, chitosan-coated PS nanoparticles (CS-PNP) were successfully prepared by self-assembly. The properties of CS-PNP, including size, zeta potential, encapsulation efficiency (EE) and loading amount (LA) were characterised. The optimisation of CS concentration (0.4 mg mL-1) and pH (3.5) resulted in the formation of CS-PNP with an EE of over 90% and a particle size of 187.7 nm. Due to the special properties of CS chitosan, the interaction between CS and soybean protein isolate (SPI)/lecithin (SL) led to the formation of a soluble complex. CS-PNP exhibited good stability to temperature variations but was more sensitive to salt ions. During in vitro digestion, CS efficiently maintained the stability of nanoparticles against the hydrolysis of SPI by pepsin under acidic conditions. However, these nanoparticles tended to aggregate in a neutral intestinal environment. After 3 h of in vitro digestion, the bioaccessibility of PS increased from 18.2% of free PS to 63.5% of CS-PNP. CONCLUSION: Overall, these results highlight the potential of chitosan-coated nanoparticles as effective carriers for the oral administration of PS. This multilayer construction may serve as a promising for applications in food products as delivery vehicles for nutraceuticals. © 2024 Society of Chemical Industry.

A New Calculation Model for Calcium Requirements After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

OBJECTIVES: We aimed to develop a new calculation model for calcium requirements in dialysis patients following parathyroidectomy. METHODS: A total of 98 patients with secondary hyperparathyroidism receiving parathyroidectomy from January 2014 to January 2022 were enrolled in this study. Among these patients, 78 were randomly selected for construction of the calcium requirement calculation model, and the remaining 20 patients were selected for model validation. The calcium requirement model estimated the total calcium supplementation for 1 week after surgery using variables with significant relationships in the derivation group by stepwise multiple linear regression analysis. Bias, precision, and accuracy were measured in the validation group to determine the performance of the model. RESULTS: The model was as follows: calcium requirement for 1 week after surgery=33.798-8.929×immediate postoperative calcium+0.190×C-reactive protein-0.125×age+0.002×preoperative intact parathyroid hormone+0.003×preoperative alkaline phosphatase (R2=0.8). The model was successfully validated. CONCLUSION: We generated a novel model to guide calcium supplementation. This model can assist in stabilizing the serum calcium levels of patients during the early postoperative period. Furthermore, it contributes to the individualized and precise treatment of hypocalcemia in patients following parathyroidectomy.

Effects of ß-carotene supplementation in the diet of laying breeder hens on the growth performance and liver development of offspring chicks.

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.

Transcutaneous electrical acupoint stimulation for suspected laryngopharyngeal reflux disease.

PURPOSE: To determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with proton pump inhibitor (PPI) therapy on symptoms and signs of patients with suspected laryngopharyngeal reflux disease (LPRD). METHODS: This was a prospective randomized controlled study. Seventy patients with reflux symptom index (RSI) > 13 and reflux finding score (RFS) > 7 were recruited and received PPI alone (control group) or TEAS combined with PPI (experimental group) for 12 weeks. Patients in the experimental group received TEAS at Tiantu (RN22), Renying (ST9), and Neiguan (PC6) once a day, five times a week. RSI, RFS, throat pain visual analog score (VAS), and LPR-health-related quality-of-life (LPR-HRQL) scores were evaluated at baseline and after 4 and 12 weeks. RESULTS: The decreases in total RSI and RFS, along with several subscores, were significantly higher in the experimental group than in the control group after 12 weeks (P < 0.05). The throat pain VAS and LPR-HRQL scores decreased significantly at 4 and 12 weeks after treatment in both groups, with significant differences between the groups (P < 0.001). No severe adverse events occurred, and the rates of adverse events were similar between the two groups. CONCLUSION: Compared with PPI alone, TEAS combined with PPI showed a significantly greater improvement in symptoms, signs, and quality of life in the treatment of LPRD without increasing the occurrence of adverse effects. Therefore, TEAS could serve as a useful and safe treatment method for LPRD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046755.

Black ginseng protects against Western diet-induced nonalcoholic steatohepatitis by modulating the TLR4/NF-κB signaling pathway in mice.

Black ginseng (BG) shows beneficial effects on liver injury, but the related mechanism has not been fully revealed. This study attempted to investigate the protective effects and associated mechanisms of BG against nonalcoholic steatohepatitis (NASH). Twelve ginsenosides in BG were annotated by ultrahigh performance liquid chromatography combined with high resolution mass spectrometry (UHPLC-HRMS). The Western diet (WD) together with the low-dose CCl4 was given to mice to create the NASH model. Histopathological examination and liver/serum biochemical analysis revealed that the NASH mice displayed severe steatosis and liver damage compared with control mice. After BG administration, the serum and liver triglycerides (TG) concentrations and the serum level of low-density lipoprotein (LDL) were dramatically reduced. Besides, the BG treatment greatly decreased the serum values of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and the hepatic expression of fibrotic-related genes, such as alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1). We further discovered that BG administration could block the protein expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65), indicating that BG exerted a liver protective effect via regulating the TLR4/NF-κB pathway. This study demonstrated the therapeutic efficacy and the associated mechanism of BG in the treatment of NASH, giving evidence for BG as a potential functional food to prevent NASH. PRACTICAL APPLICATIONS: BG is a type of processed ginseng product that has been used as diet supplementation and has shown favorable effects on liver injury. However, the pharmacological impact of BG on NASH has not been studied in depth. The present study showed that BG could effectively reduce WD-induced liver fibrosis and inflammation through the TLR4/NF-κB axis, which indicated that BG has the potential to be utilized as a functional herb to attenuate liver injury.

Exploring the Therapeutic Effects of Black Ginseng on Non-Alcoholic Fatty Liver Disease by Using Network Pharmacology and Molecular Docking.

This study aimed to investigate the therapeutic effect of black ginseng (BG) on non-alcoholic fatty liver disease (NAFLD) using network pharmacology combined with the molecular docking strategy. The saponin composition of BG was analyzed by liquid chromatography-mass spectrometry (LC/MS) instrument. Then the network pharmacology was applied to explore the potential targets and related mechanisms of BG in the treatment of NAFLD. After screening out key targets, molecular docking was used to predict the binding modes between ginsenoside and target. Finally, a methionine and choline deficiency (MCD) diet-induced NAFLD mice model was established to further confirm the therapeutic effect of BG on NAFLD. Twenty-four ginsenosides were annotated based on the MS and tandem MS information. Ten proteins were screened out as key targets closely related to BG treatment of NAFLD. The molecular docking showed that most of the ginsenosides had good binding affinities with AKT1. The validation experiment revealed that BG administration could reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the MCD diet-induced histological changes in liver tissue. Moreover, BG could upregulate the phosphorylation level of AKT in the liver of NAFLD mice, thereby exerting the therapeutic effect on NAFLD. Further studies on the active ginsenosides as well as their synergistic action on NAFLD will be required to reveal the underlying mechanisms in-depth. This study demonstrates that network pharmacological prediction in conjunction with molecular docking is a viable technique for screening the active chemicals and related targets of BG, which can be applied to other herbal medicines.

Cholecalciferol supplementation effectively improved tertiary hyperparathyroidism, FGF23 resistance and lowered coronary calcification score: a prospective study.

Introduction: Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation. Materials and methods: Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23-KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients. Results: Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion: Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

Protective Effect of Salvianolic Acid A against N-Methyl-N-Nitrosourea-Induced Retinal Degeneration.

Objective: Retinal degeneration (RD) is a serious, irreversible, and blinding eye disease, which seriously affects the visual function and quality of life of patients. At present, there is no effective method to treat RD. The final outcome of its development is photoreceptor cell oxidation and apoptosis. Therefore, looking for safe, convenient, and effective antioxidant therapy is still the key research field of Rd. In this study, the mice model of RD was induced by N-methyl-N-nitrosourea (MNU) in vivo to explore the therapeutic effect and mechanism of salvianolic acids (Sal A) on RD. In vitro, the protective effect of Sal A on MNU injured 661 W cell line of mouse retina photoreceptor cone cells was investigated preliminarily. Methods: Male C57BL/6 mice (7-8 weeks old) received a single intraperitoneal injection (ip) of 60 mg/kg MNU or vehicle control. Treatment groups then received Sal-A 0.5 mg/kg and 1.0 mg/kg via daily intravenous injections. On day 7, functional and morphological examinations were performed, including photopic and scotopic electroretinography (ERG) and hematological analyses to observe functional changes and damage to the outer nuclear layer (ONL). On the 3rd and 7th days, the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined. The expression of retinal Bax, Bcl-2, and caspase-3 was quantified by Western blot and RT-PCR assays. 661 W strain of mice retinal photoreceptor cone cells were cultured in vitro and treated with 1 µm MNU. The cells in the treatment group were given 50 µM Sal A as an intervention. The growth of 661 W cells was observed and recorded under an inverted light microscope, and the activity of cells was detected by the MTT method. Results: Sal A treatment was effective against MNU-induced RD in mice at both 0.5 mg/kg/d and 1.0 mg/kg/d doses, and the protective effect was dose-dependent. Sal A can alleviate MNU-mediated alterations to retinal ERG activity and can support maintenance of the thickness of the ONL layer. Sal A treatment increases the expression of retinal SOD and reduces the lipid peroxidation product MDA, suggesting that its protective effect is related to the oxidation resistance. It can offset changes to the expression of apoptotic factors in the retina caused by MNU treatment. Sal A mitigates MNU-mediated damage to cultured mice photoreceptor cone cells 661 W in vitro. Conclusion: Sal A alleviates the damage caused by MNU to retinal photoreceptor cells in vivo and in vivo, and its protective effect is related to its antioxidant and antiapoptotic activities.

Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. METHODS: This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. DISCUSSION: This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.

Putrescine is involved in root cell wall phosphorus remobilization in a nitric oxide dependent manner.

Phosphorus (P) deficiency is a key limited factor to affect the crop production in rice (Oryza sativa). Recently, accumulating evidences have shown that root cell wall P reutilization could be released to the cytoplasm to alleviate the P starvation and a set of plant hormone and signal molecules have been identified to be involved in it. However, the role of putrescine (Put) in this process is still unknown. In this study, we found that Put with a concentration of 0.001 mM, 0.01 mM and 0.1 mM increased the root and shoot biomass in Nipponbare (Nip) and Kasalath (Kas) under P deficiency, although only 0.1 mM Put could significantly elevated the root and shoot soluble P concentration in Nip. Exogenous 0.1 mM Put treatment reduced the root cell wall P content through increasing the pectin content and pectin methylesterase (PME) activity, indicating that Put can be involved in the root cell wall P reutilization under P starvation. In addition, Put treatment also stimulated the root-to-shoot translocation of P through upregulating the expression of PHOSPHORUS TRANSPORTER 2 (OsPT2) and OsPT8 that responsible for the long-distance transport. Put under P-deficient condition significantly enhanced the Nitric Oxide (NO) accumulation in root and the application of NO inhibitor carboxy-PTIO (cPTIO) could reverse the Put-alleviated P-deficient phenotype, suggesting this process is mediated by NO. In conclusion, our results demonstrated that Put acts upstream of NO to activate the root cell wall P remobilization in rice.

Liquiritin Alleviates Depression-Like Behavior in CUMS Mice by Inhibiting Oxidative Stress and NLRP3 Inflammasome in Hippocampus.

OBJECTIVE: Central inflammation is generally accepted to be involved in the pathology of depression. We investigated whether liquiritin exerts antidepressant effects by inhibiting central NLRP3 inflammasomes. RESULTS: The behavioral despair model and chronic unpredictable mild stress (CUMS) model in mice were established to evaluate the antidepressant action of liquiritin. In the despair model study, liquiritin (40 mg/kg) administration reduced immobility time in tail suspension test (TST) and forced swimming test (FST) without affecting locomotion activity. In CUMS model study, liquiritin (40 mg/kg, once daily for 4 weeks) significantly increased sucrose consumption and body weight of CUMS mice. The behavioral experiment results showed that liquiritin reduced the immobile time of CUMS mice in TST and FST, respectively, and increased the time spent and open arm entries in the elevated plus-maze (EPM) test. Further, the hippocampal superoxide dismutase (SOD) activity was increased in liquiritin-treated group, while malonaldehyde (MDA) decreased. Additionally, the hippocampal cytokines interleukin-18 (IL-18) and interleukin-1 beta (IL-1ß) contents were reduced in the liquiritin-treated group. Further, liquiritin downregulated the expression of NLRP3 in the hippocampus of CUMS mice rather than TLR4. Besides, NLRP3 inflammasome-associated proteins caspase-1 and ASC were also downregulated. However, liquiritin did not alter the thermal stability of NLRP3 in the cellular thermal shift assay (CETSA), suggesting that its inhibition of NLPR3 was not by direct targeting of NLRP3 protein. CONCLUSIONS: Liquiritin attenuates depression-like behavior of CUMS mice and inhibited cytokines levels triggered by NLRP3 inflammasome, suggesting the antidepressant action is, at least partially, associated with antioxidant stress and inhibition of NLRP3 inflammasome activation.

Jasmonic acid is involved in root cell wall phosphorus remobilization through the nitric oxide dependent pathway in rice.

Jasmonic acid (JA) is involved in phosphorus (P) stress in plants, but its underlying molecular mechanisms are still elusive. In this study, we found root endogenous JA content in rice increased under P deficiency (-P), suggesting that JA might participate in P homeostasis in plants. This hypothesis was further confirmed through the addition of exogenous JA (+JA), as this could increase both the root and shoot soluble P content through regulating root cell wall P reutilization. In addition, -P+JA treatment significantly induced the expression of P transporter gene OsPT2, together with increased xylem P content, implying that JA is also important for P translocation from the root to the shoot in P-deficient rice. Furthermore, the accumulation of the molecular signal nitric oxide (NO) was enhanced under -P+JA treatment when compared with -P treatment alone, while the addition of c-PTIO, a scavenger of NO, could reverse the P-deficient phenotype alleviated by JA. Taken together, our results reveal a JA-NO-cell wall P reutilization pathway under P deficiency in rice.

Leaf-root-soil N:P stoichiometry of ephemeral plants in a temperate desert in Central Asia.

Ephemeral plants are a crucial vegetation component in temperate deserts of Central Asia, and play an important role in biogeochemical cycle and biodiversity maintenance in desert ecosystems. However, the nitrogen (N) and phosphorus (P) status and interrelations of leaf-root-soil of ephemeral plants remain unclear. A total of 194 leaf-root-soil samples of eight ephemeral species at 37 sites in the Gurbantunggut Desert, China were collected, and then the corresponding N and P concentrations, and the N:P ratio were measured. Results showed that soil parameters presented no significant difference among the eight species. The total soil N:P was only 0.116 (geomean), indicating limited soil N, while the available soil N:P (4.896, geomean) was significantly larger than the total N:P. The leaf N (averagely 30.995 mg g-1) and P (averagely 1.523 mg g-1) concentrations were 2.64-8.46 and 0.93-3.99 times higher than the root N (averagely 8.014 mg g-1) and P (averagely 0.802 mg g-1) concentrations, respectively. Thus, leaf N:P (averagely 21.499) was 1.410-2.957 times higher than root N:P (averagely 11.803). Meanwhile, significant interspecific differences existed in plant stoichiometric traits. At the across-species level, N content scaled as the 3/4-power of P content in both leaves and roots. Leaf and root N:P ratios were mainly influenced by P; however, the leaf-to-root N or P ratio was dominated by roots. Leaf and root N, P contents and N:P were generally unrelated to soil nutrients, and the former presented lower variation than the latter, indicating a strong stoichiometric homeostasis for ephemerals. These results demonstrate that regardless of soil nutrient supply capacity in this region, the fast-growing ephemeral plants have formed a specific leaf-root-soil stoichiometric relation and nutrient use strategy adapting to the extreme desert environment.

Intravitreous delivery of melatonin affects the retinal neuron survival and visual signal transmission: in vivo and ex vivo study.

Intravitreal delivery can maximize the intensity of therapeutic agents and extend their residence time within ocular tissue. Melatonin is a lipophilic molecule that crosses freely biological barriers and cell membranes. This study intends to investigate the effects of intravitreally delivered melatonin on mouse retina. The visual function of administered mice is assessed by electrophysiological and behavior examinations three weeks after intravitreal delivery. Moreover, multi-electrode array (MEA) was used to assess the electrical activities of retinal ganglion cells (RGCs). We found that intravitreal delivery of high dosage melatonin (400-500 µg/kg) destroyed the retinal architecture and impaired the visual function of mice. Conversely, the melatonin administration at low dose (100-300 µg/kg) did not have any significant effects on the photoreceptor survival or visual function. As shown in the MEA recording, the photoreceptors activity of the central region was more severely disturbed by the high dose melatonin. A pronounced augment of the spontaneous firing frequency was recorded in these mice received high dosage melatonin, indicating that intravitreal delivery of high dosage melatonin would affect the electrical activity of RGCs. Immunostaining assay showed that the vitality of cone photoreceptor was impaired by high dose melatonin. These findings suggest that intravitreal melatonin is not always beneficial for ocular tissues, especially when it is administered at high dosage. These data add new perspectives to current knowledge about melatonin delivery at the ocular level. Further therapeutic strategies should take into consideration of these risks that caused by delivery approach.

[Evaluation of therapeutic effects of the ultramicro needle knife combined with cervical spine fine adjusting on youth cervical curvature abnormality case].

OBJECTIVE: To study the therapeutic effects of the ultramicro needle-knife combine with cervical spine fine adjusting on youth cervical curvature abnormality case. METHODS: From November 2016 to October 2018, 88 young patients with abnormal curvature of cervical spine were treated. Due to loss of follow up, 86 cases were actually completely including 37 males and 49 females, ranging in age from 20 to 40 years old, with an average of (30.55±5.21) years old, and the course of disease ranged from 1 to 42 months, with a mean of (14.21±7.38) months. All the patients were divided into two groups:treatment group (44 cases) and control group (42 cases). The patients in the treatment group were treated with ultramicro needle-knife and cervical spine fine adjusting, and the patients in the control group were treated with conventional acupuncture and manipulation. The treatments were done 1 time per week in the treatment group while 3 times per week in control group every week, with a duration of 3 weeks for both groups. Before treatment, 3 weeks after treatment, and at the end of 1 month follow-up, the score of neck pain questionnaire(NPQ), range of the motion(ROM) in the cervical region and the D values of cervical physiological curvature were recorded. The efficacy at the end of treatment and in the follow up was evaluated. During the treatment, the patients were also required to correct the bad posture in daily life, to sleep in a low pillow position, and put a moderately columnar pillow behind the neck for 0.5 hours every morning and evening. RESULTS: Two patients in the control group were dropped out after 3 weeks treatment. No adverse reactions were found in the 2 groups during the treatment period. Compared with those before treatment, all scores at all the observation time points were significantly improved between two groups after treatment(all P<0.05). The NPQ scores of cervical symptoms were different significantly between two groups(all P<0.05). The changing range of the the NPQ score of cervical symptoms and cervical spine alignment curve of the treatment group were better than those of the control group (P<0.05).There was statistical difference in NPQ scores between different time points, in the other words, there was time effect(F=203.63, P=0.000). There was interaction between time factor and group factor(F=4.964, P=0.012). There was no statistical difference in the changing range of the ROM score between two groups (all P>0.05). There was statistical difference in ROM scores between different time points, there was time effect (F=240.32), P=0.000). There was no interaction between time factor and group factor (F=0.311, P=0.734). The effective rate of the treatment group and control group were 90.91%(40 / 44) and 80.95%(34 / 42) respectively, the treatment group was more effective than the control group (P<0.05). During the follow-up period, the effective rate of the treatment group and the control group were 84.09%(37 / 44) and 76.19%(32 / 42) respectively. Obviously, the difference of total effective rate between two groups had no statistical signification(P>0.05) in the follow-up duration. CONCLUSION: The method of needle knife combined with cervical spine fine adjusting has a better therapeutic efficiency than conventional acupuncturecombined with manipulation in treating youth cervical curvature abnormality patients. Because this novel method can recover the cervical curvature, relieve the neck pain, and improve cervical mobility.

Research Progress on Multi-material and Multi-process Processing of Aconiti Radix / 中国实验方剂学杂志

Aconiti Radix is a kind of medicinal material with great toxicity, which has more than 2 000 years of clinical application history, in the folk, there are often poisoning accidents caused by improper processing. The main processing purpose of Aconiti Radix in the early period was to reduce the toxicity with simple procedure and single excipient. Since the Song dynasty, with the deepening of physicians' cognition of processing and the theory of medicinal properties, the application of procedures and materials in the processing of Aconiti Radix began to become complicated, and the scope of clinical application was further expanded. In modern times, the processing technology of Aconiti Radix is mainly based on steaming and boiling, which is quite different from the traditional processing method with multiple materials and multiple processes. Based on the characteristics of many kinds of materials and processes, this paper discusses the change in processing methods of Aconiti Radix from the perspective of excipients and processes, as well as modern processing research, in order to lay a scientific foundation for exploring the effects of many kinds of materials and processes on the quality of Aconiti Radix and revealing its processing mechanism, and provide basis and reference for establishing a more reasonable and scientific processing method for Aconiti Radix in the future.

Research and Practice of " Three Suitability" Theory in Processing of Traditional Chinese Medicine / 中国实验方剂学杂志

As an important part of clinical medication, the main function of processing of traditional Chinese medicine (TCM) is to reduce toxicity and increase efficiency. The key to the best clinical efficacy of TCM after processing lies in three aspects of moderation, adaptation and timeliness, namely " three suitability" theory. In recent years, scholars have done a lot of research under the guide of " three suitability" theory, fully explaining the scientific connotation of the theory, which greatly promoted the inheritance and innovation of TCM processing. In this paper, the basic connotation of " three suitability" theory was summarized, combining with a large number of modern research reports, the pharmacodynamics and composition changes of processed drugs were analyzed and discussed under the guide of " three suitability" theory. At the end of the paper, the authors proposed that we should not only systematize the traditional processing theories, but also use modern advanced technologies to explain the essence of traditional processing theories, and to innovate and develop new processing theories, promote the development of TCM processing discipline and the progress of TCM processing industry.

TCM-ADMEpred: A novel strategy for poly-pharmacokinetics prediction of traditional Chinese medicine based on single constituent pharmacokinetics, structural similarity, and mathematical modeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanhu Zhitong prescription (YZP) is a commonly used and relatively simple clinical herb preparation recorded in the China Pharmacopoeia. It contains Corydalis yanhusuo (Chinese name, Yanhusuo [YH]) and Angelica dahurica (Hoffm.) (Chinese name, Baizhi [BZ]), and has a long history of use in traditional Chinese medicine (TCM) for the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea. AIM OF THE STUDY: A TCM-ADMEpred method is developed for novel strategy for poly-pharmacokinetics prediction of TCM. To predict the pharmacokinetic characteristics of the main YZP constituents in rat plasma using in silico models, based on the theory that structurally similar constituents show similar pharmacokinetic properties. This approach may facilitate in silico prediction of the pharmacokinetics of TCM. MATERIALS AND METHODS: A robust platform using ultra-performance liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for simultaneous determination of seven active YZP constituents in rat plasma. These seven compounds were divided into two structural classes, alkaloids and coumarins. The correlation between AUC profiles within a structural class was expressed as Γ+, and this variable was used to develop two novel in silico models to predict constituent AUC values. The pharmacokinetics of tetrahydropalmatine, tetrahydroberberine, and corydaline following YZP administration were predicted using the Γ+-values of α-allocryptopine observed following YH administration, while those of imperatorin and isoimperatorin following BZ administration were predicted using the Γ+-values of byakangelicin observed following YZP administration. RESULTS: The UPLC-ESI-MS/MS method was successfully used to evaluate pharmacokinetic parameters after oral YZP, YH, or BZ administration. Our findings showed that co-administration of YH and BZ increased the AUC of four alkaloid constituents and reduced the AUC of three coumarin constituents, which might provide a scientific rationale for co-administering these herbs clinically as a YZP preparation, thus increasing their efficacy and reducing toxicity. The AUC values of imperatorin and isoimperatorin were predicted 3 h after oral BZ administration, with the bias ratios between the theoretical values and the observed experimental values ranging from 0.61% to 11.4%, and average bias ratios of 5.8% and 8.0%, respectively. The AUC values of tetrahydropalmatine, tetrahydroberberine, and corydaline were predicted 3 h after oral YZP administration, with bias ratios ranging from 3.7% to 46.4%, and average bias ratios of 23.8%, 15.4%, and 25.8%, respectively. CONCLUSION: The UPLC-ESI-MS/MS method was successfully applied to pharmacokinetic evaluations after oral administration of YZP, YH, and BZ to rats. The Γ+ variable was used to express the correlation between the AUC profiles of structurally similar compounds. This facilitated the development of an in silico model that was used to predict the AUC of three alkaloids in YZP and of two coumarins in BZ. Calculation of the bias ratios between the predicted and experimental values suggested that this in silico model provided a viable approach for the prediction of TCM pharmacokinetics.

Taurine protected As2O3-induced the activation of hepatic stellate cells through inhibiting PPARα-autophagy pathway.

The activation of hepatic stellate cells (HSCs) is a key event in the development of hepatic fibrosis caused by arsenic. However, it is unclear how arsenic induces the activation of HSCs. In the present study, we found that arsenic trioxide (As2O3) induced liver tissue damage, stimulated autophagy and HSCs activation, and increased collagen accumulation in the liver of mice. Supplemented with taurine (Tau) attenuated the changes mentioned above caused by As2O3. In human hepatic stellate cell line LX-2 cells, we found that As2O3-induced activation of HSCs was autophagy-dependent, and we found that peroxisome proliferator activated receptors alpha (PPARα) played an important role in arsenic-induced HSCs activation. In addition, inhibiting autophagy and PPARα alleviated the activation of HSCs and lipid droplet loss induced by As2O3. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy and PPARα expression, and activation of the HSCs. Our results indicated that autophagy was regulated by PPARα and was involved in lipid droplet loss during the activation of HSCs. Tau alleviated As2O3-induced HSCs activation by inhibiting the PPARα/autophagy pathway. These findings give an innovative insight into the association of PPARα, autophagy, the activation of HSCs and hepatic fibrosis induced by As2O3.

Inorganic arsenic induces pyroptosis and pancreatic ß cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine.

Low-level inorganic arsenic (iAs) in drinking water is a risk factor for ß cells dysfunction. Taurine (Tau) is a kind of semi-essential ß amino acid, and beneficial for ß cell function. However, the effects of Tau on arsenic trioxide (As2O3) induced ß cells dysfunction and related mechanisms are still uncertain. Here, we found that Tau relieved As2O3-induced endoplasmic reticulum (ER) stress, inflammation and pyroptosis in rat pancreas. In INS-1 cells, with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inhibitor pretreatment, As2O3-induced activation of pyroptosis was decreased; with tumor necrosis factor-α (TNF-α) inhibitor pretreatment, As2O3-induced activation of NLRP3 inflammasome and pyroptosis were decreased; further, with the inositol-requiring enzyme 1 alpha (IRE1α) inhibitor, As2O3-induced induction of TNF-α was decreased. Tau markedly protected As2O3-induced ß cells dysfunction by reducing the phosphorylation of IRE1α, production of TNF-α, activation of NLRP3 inflammasome and pyroptosis. Our results revealed that ER stress dependent inflammation and pyroptosis are critical pathogenic components of As2O3-induced ß cell dysfunction. Moreover, TNF-α was a critical signaling node that linked As2O3-induced ER stress and pyroptosis. Tau was an effective supplement against As2O3-induced ß cells dysfunction through the pathway as mentioned above.