Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Design, synthesis and biological evaluation of bakuchiol derivatives as multi-target agents for the treatment of Alzheimer's disease.

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.

[Quality analysis of Rosae Radix et Rhizoma].

Rosae Radix et Rhizoma is a herbal medicine in a variety of famous Chinese patent medicines, while the quality standard for this medicine remains to be developed due to the insufficient research on the quality of Rosae Radix et Rhizoma from different sources. Therefore, this study comprehensively analyzed the components in Rosae Radix et Rhizoma of different sources from the aspects of extract, component category content, identification based on thin-lay chromatography, active component content determination, and fingerprint, so as to improve the quality control. The results showed that the content of chemical components varied in the samples of different sources, while there was little difference in the chemical composition among the samples. The content of components in the roots of Rosa laevigata was higher than that in the other two species, and the content of components in the roots was higher than that in the stems. The fingerprints of triterpenoids and non-triterpenoids were established, and the content of five main triterpenoids including multiflorin, rosamultin, myrianthic acid, rosolic acid, and tormentic acid in Rosae Radix et Rhizoma was determined. The results were consistent with those of major component categories. In conclusion, the quality of Rosae Radix et Rhizoma is associated with the plant species, producing area, and medicinal parts. The method established in this study lays a foundation for improving the quality standard of Rosae Radix et Rhizoma and provides data support for the rational use of the stem.

Mediating effect of mindfulness level on the relationship between marital quality and postpartum depression among primiparas.

BACKGROUND: Postpartum depression refers to a depressive episode or depressive symptoms up to 12 mo after delivery. Trait mindfulness has presented a protective factor for postpartum depressive symptoms and proved efficient in improving relationship satisfaction among couples. AIM: To investigate the correlations among mindfulness, marital quality, anxiety, and depression in a large city in western China during the post-corona virus infectious disease-2019 era and determine whether trait mindfulness mediates the relationship between marital quality and postpartum anxiety and depression among primiparas. METHODS: A cross-sectional study was conducted. The self-administered questionnaire was submitted online through smartphones. The levels of mindfulness, anxiety, depression, and marital quality were respectively investigated by the mindful attention awareness scale (MAAS), the self-rating anxiety scale (SAS), the self-rating depression scale (SDS), and the marriage perception scale (MPS) in these enrolled Han and Tujia primiparas. RESULTS: No statistical significance was observed in the prevalence of postpartum anxiety and depression, nor scores of MAAS and MPS-Total in different regions or ethnicities (P > 0.05). However, MPS-Marital interaction (P < 0.05), MPS-Family relationship (MPS-FR) (P < 0.01), and MPS-Marital conflict (MPS-MC) (P < 0.01) scores of urban primiparas were higher than those of rural primiparas. The MPS-MC score of Han primiparas was higher than that of Tujia primiparas (P < 0.05). Negative correlations were observed between MAAS and SAS (r = -0.457, P < 0.01), and MAAS and SDS (r = -0.439, P < 0.01). SAS has revealed a highly positive correlation with SDS (r = 0.720, P < 0.01) and a weak negative correlation with MPS (r = -0.200, P < 0.05). Besides, a weak negative correlation was observed between MAAS and MPS-MC (r = -0.184, P < 0.05), and a weak positive correlation was noticed between SAS and MPS-MC (r = -0.225, P < 0.01). Mediation analysis demonstrated a full mediation effect of mindfulness level on the relationship between MPS-FR and postpartum anxiety (P < 0.05, 95%CI: -0.384 to 0.033), MPS-MC and postpartum anxiety (P < 0.01, 95%CI: 0.027-0.193), MPS-FR and postpartum depression (P < 0.05, 95%CI: -0.365 to 0.031), and MPS-MC and postpartum depression (P < 0.01, 95%CI: 0.022-0.206). CONCLUSION: Mindfulness demonstrates negative correlations with marital conflict, postpartum anxiety and depression, and it may have cross-ethnic and trans-regional characteristics. Although the mindfulness levels have revealed no significant mediating effect between the total score of marital quality and postpartum depression in this study, it demonstrates a full mediation effect on the relationships between family relationships, marital conflict, and postpartum anxiety and depression.

Fabrication of whey protein/pectin double layer microcapsules for improving survival of Lacticaseibacillus rhamnosus ZFM231.

To improve the viability of Lacticaseibacillus rhamnosus ZFM231 strain in the gastrointestinal tract and exhibit better probiotic effect, an internal emulsification/gelation technique was employed to encapsulate this strain using whey protein and pectin as wall materials to fabricate the double layer microcapsules. Four key factors affecting the encapsulation process were optimized using single factor analysis and response surface methodology. Encapsulation efficiency of L. rhamnosus ZFM231 reached 89.46 ± 0.82 %, the microcapsules possessed a particle size of 172 ± 1.80 µm and ζ-potential of -18.36 mV. The characters of the microcapsules were assessed using optical microscope, SEM, FT-IR and XRD analysis. It was found that after exposure to simulated gastric fluid, the bacterial count (log (CFU g-1)) of the microcapsules only lost 1.96 units, the bacteria were released readily in simulated intestinal fluid, reaching 86.56 % after 90 min. After stored at 4 °C for 28 days and 25 °C for 14 days, bacterial count of the dry microcapsules decreased from 10.59 to 9.02 and 10.49 to 8.70 log (CFU g-1), respectively. The double layered microcapsules could significantly increase the storage and thermal abilities of bacteria. Such L. rhamnosus ZFM231 microcapsules could find applications as ingredient of the functional foods and the dairy products.

[Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target].

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

Tongguanteng injection reverses paclitaxel resistance via upregulation of TAB1 expression in ovarian cancer in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mg⋅mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.

Quality analysis of Rosae Radix et Rhizoma / 中国中药杂志

Rosae Radix et Rhizoma is a herbal medicine in a variety of famous Chinese patent medicines, while the quality standard for this medicine remains to be developed due to the insufficient research on the quality of Rosae Radix et Rhizoma from different sources. Therefore, this study comprehensively analyzed the components in Rosae Radix et Rhizoma of different sources from the aspects of extract, component category content, identification based on thin-lay chromatography, active component content determination, and fingerprint, so as to improve the quality control. The results showed that the content of chemical components varied in the samples of different sources, while there was little difference in the chemical composition among the samples. The content of components in the roots of Rosa laevigata was higher than that in the other two species, and the content of components in the roots was higher than that in the stems. The fingerprints of triterpenoids and non-triterpenoids were established, and the content of five main triterpenoids including multiflorin, rosamultin, myrianthic acid, rosolic acid, and tormentic acid in Rosae Radix et Rhizoma was determined. The results were consistent with those of major component categories. In conclusion, the quality of Rosae Radix et Rhizoma is associated with the plant species, producing area, and medicinal parts. The method established in this study lays a foundation for improving the quality standard of Rosae Radix et Rhizoma and provides data support for the rational use of the stem.

Transcutaneous electrical acupoint stimulation combined with electroacupuncture for rapid recovery after abdominal surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with electroacupuncture (EA) on rehabilitation after abdominal surgery.@*METHODS@#A total of 320 patients undergoing abdominal surgery were randomly divided into a combination group (80 cases), a TEAS group (80 cases, 1 case discontinued), an EA group (80 cases, 1 case discontinued) and a control group (80 cases, 1 case discontinued). The patients in the control group received enhance recovery after surgery (ERAS) standardized perioperative management. On the basis of the treatment in the control group, the TEAS group was treated with TEAS at Liangmen (ST 21) and Daheng (SP 15); the EA group was treated with EA at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39); the combination group was treated with TEAS combined with EA, with continuous wave, 2-5 Hz in frequency, and the intensity was tolerable to the patients, 30 min each time, once a day, from the first day after surgery, until the anus resumed spontaneous defecation and the oral intake of solid food was tolerated. The gastrointestinal-2 (GI-2) time, first exhaust time, first defecation time, first tolerance of oral intake of solid food time, time of first get out of bed and hospital stay were observed in all the groups; the pain visual analogue scale (VAS) score and incidence rates of nausea and vomiting 1, 2, 3 days after surgery were compared in all the groups; after treatment, the acceptability of each treatment was evaluated by patients in each group.@*RESULTS@#Compared with the control group, the GI-2 time, first exhaust time, first defecation time, first tolerance of oral intake of solid food time were shortened (P<0.05), the VAS scores 2, 3 days after surgery were decreased (P<0.05) in the combination group, the TEAS group and the EA group; those in the combination group were shorter and lower than the TEAS group and the EA group (P<0.05). Compared with the control group, the time of hospital stay in the combination group, the TEAS group and the EA group were shortened (P<0.05), and that in the combination group was shorter than the TEAS group (P<0.05).@*CONCLUSION@#TEAS combined with EA can accelerate the recovery of gastrointestinal function in patients after abdominal surgery, relieve postoperative pain, and shorten hospital stay.

Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target / 中国中药杂志

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults.

Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18-65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. "The Clinical Memory Test", the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of "The Clinical Memory Test" as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults.

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism.

CONTEXT: Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. OBJECTIVE: To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. RESULTS: The t1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·µg/mL) and t1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 µmol/L for CYP2C8, and 27.31, 7.57, and 4.59 µmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. DISCUSSION AND CONCLUSIONS: The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.

Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity.

This study aimed to assess the effects of total flavonoid extracts (TFDG) and the monomers of Daphne genkwa on the CYP2C8 activity in vitro and in vivo.The 50% inhibitory concentration (IC50) values were used to determine the inhibitory effect of TFDG and its four monomers for the CYP2C8 activity by recombinant human CYP2C8 (RHCYP2C8) yeast microsome system in vitro, and the volume per dose index (VDI) was predicted the potential inhibition in vivo. The effects of multiple-dose administration of TFDG on the pharmacokinetic parameters of rosiglitazone in rats were evaluated.The IC50 values of apigenin, luteolin, hydroxy-genkwanin, genkwanin, and TFDG were 7.27 µmol/L, 11.9 µmol/L, 28.1 µmol/L, 127 µmol/L, and 13.4 µg/mL, respectively. The VDI values of apigenin and TFDG were 2.15 L and 6.60 L. In vivo study, compared with the control group, the elimination phase half-life and mean residence time in the TFDG treatment group were significantly increased by 96.9% and 106.8% (p <.05), respectively.Apigenin showed a moderate inhibitory effect on the CYP2C8 activity in vitro, while the other three monomers were weak inhibitors. TFDG had a strong inhibitory effect on CYP2C8 in vitro and in vivo, and also inhibited the metabolism of rosiglitazone in rats.

Postoperative ileus after laparotomy for gastrointestinal cancer treated with electroacupuncture: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on postoperative ileus after laparotomy for gastrointestinal cancer.@*METHODS@#A total of 90 patients with postoperative ileus after laparotomy for gastrointestinal cancer were randomized into an EA group and a conventional treatment group, 45 cases in each one. In the conventional treatment group, the postoperative fast track surgical regimen was accepted. In the EA group, on the base of the treatment as the conventional treatment group, acupuncture was applied to Zusanli (ST 36), Shangjuxu (ST 37), Yinlingquan (SP 9) and Taichong (LR 3) and electric stimulation was attached on Zusanli (ST 36) and Yinlingquan (SP 9), with continuous wave, 2 Hz in frequency and 3-5 mA in intensity. Acupuncture was provided once daily till the onset of postoperative exhaust and defecation. The first postoperative exhaust time, the first postoperative defecation time, the postoperative hospital stay and the wound pain under standing on the next morning after entering group were compared in the patients between the two groups. The impact of the EA expectation was analyzed on the first postoperative exhaust time, the first postoperative defecation time and the postoperative hospital stay separately.@*RESULTS@#The first postoperative exhaust time and the first postoperative defecation time in the EA group were earlier than the conventional treatment group (P<0.05), the postoperative hospital stay was shorter than the conventional treatment group (P<0.05), and the rate of wound pain in the postoperative standing was lower than the conventional treatment group (P<0.05). EA expectation had no obvious correlation with the clinical therapeutic effect (P>0.05).@*CONCLUSION@#EA can relieve postoperative ileus symptoms, alleviate pain and shorten hospital stay in the patients after laparotomy for gastrointestinal cancer.

Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling.

Although diabetic encephalopathy (DE) is a major late complication of diabetes, the pathophysiology of postural instability in DE remains poorly understood. Prior studies have suggested that neuronal apoptosis is closely associated with cognitive function, but the mechanism remains to be elucidated. Green tea, which is a non­fermented tea, contains a number of tea polyphenols, alkaloids, amino acids, polysaccharides and other components. Some studies have found that drinking green tea can reduce the incidence of neurodegenerative diseases and improve cognitive dysfunction. We previously found that myosin light chain kinase (MLCK) regulates apoptosis in high glucose­induced hippocampal neurons. In neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, activation of the JNK signaling pathway promotes neuronal apoptosis. However, the relationship between JNK and MLCK remains to be elucidated. Green tea serum was obtained using seropharmacological methods and applied to hippocampal neurons. In addition, a type 1 diabetes rat model was established and green tea extract was administered, and the Morris water maze test, Cell Counting Kit­8 assays, flow cytometry, western blotting and terminal deoxynucleotidyl transferase­mediated dUTP nick end­labelling assays were used to examine the effects of green tea on hippocampal neuronal apoptosis in diabetic rats. The results demonstrated that green tea can protect against hippocampal neuronal apoptosis by inhibiting the JNK/MLCK pathway and ultimately improves cognitive function in diabetic rats. The present study provided novel insights into the neuroprotective effects of green tea.

Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate.

SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. In neurons, imaging documented mouse SARM1 activation preceded vincristine-induced axonal degeneration by hours. Library screening identified a derivative of nisoldipine (NSDP) as a covalent inhibitor of SARM1 that reacted with the cysteines, especially Cys311 in its ARM domain and blocked its NMN-activation, protecting axons from degeneration. The Cryo-EM structure showed that SARM1 was locked into an inactive conformation by the inhibitor, uncovering a potential neuroprotective mechanism of dihydropyridines.

Metabolomics analysis reveals the responses of tea plants to excessive calcium.

BACKGROUND: The proper growth and development of tea plants requires moderately acidic soils and relatively low calcium levels, and excessive calcium at high pH can damage tea plant roots. To reveal the effects of calcium on the responses of tea plant to three pH levels (3.5, 5.0 and 6.5), a repeated test of two factors was designed. RESULTS: Root growth and elemental analysis indicated that excessive calcium improved the growth of tea roots at low pH conditions, whereas it did not harm the growth of tea roots under normal and high pH conditions, especially at pH 6.5. Excessive calcium antagonized the absorption and utilization of magnesium by tea plants. Gas chromatography-mass spectrometry results showed that the addition of Ca2+ resulted in the primary metabolism in roots being more active at a low pH level. By contrast, it had obvious adverse effects on the accumulation of root metabolites with high calcium treatment at normal or high pH. Differential metabolites identified using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry indicated that flavonoids demonstrated the largest number of changes, and their biosynthesis was partially enriched with excessive calcium at low and high pH conditions, whereas it was down-regulated under normal pH conditions. Kaempferol 3-(2'-rhamnosyl-6'-acetylgalactoside) 7-rhamnoside, quercetin 3-(6'-sinapoylsophorotrioside) and delphinidin 3-(3'-p-coumaroylglucoside) showed the greatest increase. The results of gene expression related to root growth and calcium regulation were consistent with root growth and root metabolism. CONCLUSION: The overall results demonstrated that high Ca concentrations further aggravate the detrimental effects of high pH to tea roots. However, it is interesting that excessive calcium reduced the harm of a low pH on tea root growth to some extent. © 2021 Society of Chemical Industry.

Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis.

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 µg·kg-1·d-1) induced the occurrence of cholestasis in female Wistar rats, as evidenced by increased serum levels of γ-glutamyl transpeptidase (γ-GGT), alkaline phosphatase (ALP) and hepatic total bile acids (TBAs). In addition, the heptocyte polarity associated with the strcture of tight junctions (TJs) was disrupted in both rats and sandwich-cultured primary hepatocytes. Immunoblotting revealed decreased expression of the TJ-associated proteins occludin, claudin-1, and zonula occludens protein (ZO-1), and downregulated mRNA levels of these TJs was also detected by real-time PCR. An immunofluorescence analysis showed abnormal subcellular localization of occludin, claudin-1 and ZO-1, which was also confirmed by transmission electron microscopy. Moreover, the concentration of FITC-dextran, a marker of paracellular penetration, was found to increase rapidly in bile increased rapidly (within 6 minutes) after treatment with TP, which indicated the functional impairment of TJs. Taken together, these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver, and the increased paracellular permeability might play an important role in these pathological changes.

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection.

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer's Disease Based on Network Pharmacology and Molecular Docking.

Alzheimer's disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer's disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of "drug-active ingredient-ingredient target." A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer's disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer's signal pathway, thus reducing the production of Aß, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.