Effect of traditional Chinese medicine on metabolism disturbance in ischemic heart diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic heart diseases (IHD), characterized by metabolic dysregulation, contributes majorly to the global morbidity and mortality. Glucose, lipid and amino acid metabolism are critical energy production for cardiomyocytes, and disturbances of these metabolism lead to the cardiac injury. Traditional Chinese medicine (TCM), widely used for treating IHD, have been demonstrated to effectively and safely regulate the cardiac metabolism reprogramming. AIM OF THE REVIEW: This study discussed and analyzed the disturbed cardiac metabolism induced by IHD and development of formulas, extracts, single herb, bioactive compounds of TCM ameliorating IHD injury via metabolism regulation, with the aim of providing a basis for the development of clinical application of therapeutic strategies for TCM in IHD. MATERIALS AND METHODS: With "ischemic heart disease", "myocardial infarction", "myocardial ischemia", "metabolomics", "Chinese medicine", "herb", "extracts" "medicinal plants", "glucose", "lipid metabolism", "amino acid" as the main keywords, PubMed, Web of Science, and other online search engines were used for literature retrieval. RESULTS: IHD exhibits a close association with metabolism disorders, including but not limited to glycolysis, the TCA cycle, oxidative phosphorylation, branched-chain amino acids, fatty acid ß-oxidation, ketone body metabolism, sphingolipid and glycerol-phospholipid metabolism. The therapeutic potential of TCM lies in its ability to regulate these disturbed cardiac metabolisms. Additionally, the active ingredients of TCM have depicted wonderful effects in cardiac metabolism reprogramming in IHD. CONCLUSION: Drawing from the principles of TCM, we have pinpointed specific herbal remedies for the treatment of IHD, and leveraged advanced metabolomics technologies to uncover the effect of these TCMs on metabolomics alteration. In the future, further clinical experimental studies should be included to explore whether more TCM medicines can play a therapeutic role in IHD by reversing cardiac metabolism disorders; multi-omics would be conducted to explore more pathways and genes targeting such metabolism reprogramming by TCMs, and to seek more TCM therapies for IHD.

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

Main Control Factors of Fracture Propagation in Reservoir: A Review.

The fracture distribution and internal control factors after the fracturing of unconventional oil and gas reservoirs determine the reservoir reforming effect to a large extent. Based on the research of global scholars on the influencing factors of fracture propagation, comprehensive theoretical model, and numerical simulation, this Review systematically discusses the influence of internal geological factors and external engineering factors of unconventional oil and gas reservoir on fracture propagation behavior and summarizes the current problems and development trends in fracture research. The results show the following: (1) The fracture propagation is a comprehensive process constrained by lithology and mineral composition, water saturation, nonhomogeneity, natural weak surface, and ground stress. (2) External engineering factors have a meaningful control effect on fracture propagation; the type and temperature of fracturing fluids can also change the mechanical properties of different rocks, thus affecting the fracture propagation pattern. (3) The existing fracture propagation models have certain limitations, and their computational reliability still needs to be further verified. (4) Numerical simulation can break through the limitations of physical simulation, but different simulation methods have different shortcomings and applicability. In the future, we should focus on: (1) finding parameters to quantitatively characterize heterogeneity at the 3D level, which is an important direction to study the effect of heterogeneity on fracture propagation; (2) introducing computerized methods to establish a geological model that considers multiple factors and combining it with numerical simulation software to study fracture propagation; (3) considering the characteristics of fluid-liquid-solid phase comprehensively, establishing a suitable THL coupling equation; (4) how the interaction mode of fracturing fracture is combined with the natural fracture geometry, and how the fracture is affected by fracturing engineering parameters such as fluid injection rate and viscosity of fracturing fluid; and (5) geology-engineering dynamic integration, which is an important direction to be carried out in the future.

Trimethylamine N-oxide promotes abdominal aortic aneurysm by inducing vascular inflammation and vascular smooth muscle cell phenotypic switching.

OBJECTIVE: Inflammation and vascular smooth muscle cell (VSMC) phenotypic switching are implicated in the pathogenesis of abdominal aortic aneurysm (AAA). Trimethylamine N-oxide (TMAO) has emerged as a crucial risk factor in cardiovascular diseases, inducing vascular inflammation and calcification. We aimed to evaluate the effect of TMAO on the formation of AAA. APPROACH AND RESULTS: Here, we showed that TMAO was elevated in plasma from AAA patients compared with nonaneurysmal subjects by liquid chromatography‒mass spectrometry (LC‒MS) detection. Functional studies revealed that increased TMAO induced by feeding a choline-supplemented diet promoted Ang II-induced AAA formation. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analyses revealed that TMAO induced macrophage infiltration and inflammatory factor release. Conversely, inhibition of TMAO by supplementation with DMB suppressed AAA formation and the inflammatory response. Molecular studies revealed that TMAO regulated VSMC phenotypic switching. Flow cytometry analyses showed that TMAO induces macrophage M1-type polarization. Furthermore, pharmacological intervention experiments suggested that the nuclear factor-κB (NF-κB) signaling pathway was critical for TMAO to trigger AAA formation. CONCLUSIONS: TMAO promotes AAA formation by inducing vascular inflammation and VSMC phenotypic switching through activation of the NF-κB signaling pathway. Thus, TMAO is a prospective therapeutic AAA target.

Critical Signaling Transduction Pathways and Intestinal Barrier: Implications for Pathophysiology and Therapeutics.

The intestinal barrier is a sum of the functions and structures consisting of the intestinal mucosal epithelium, mucus, intestinal flora, secretory immunoglobulins, and digestive juices. It is the first-line defense mechanism that resists nonspecific infections with powerful functions that include physical, endocrine, and immune defenses. Health and physiological homeostasis are greatly dependent on the sturdiness of the intestinal barrier shield, whose dysfunction can contribute to the progression of numerous types of intestinal diseases. Disorders of internal homeostasis may also induce barrier impairment and form vicious cycles during the response to diseases. Therefore, the identification of the underlying mechanisms involved in intestinal barrier function and the development of effective drugs targeting its damage have become popular research topics. Evidence has shown that multiple signaling pathways and corresponding critical molecules are extensively involved in the regulation of the barrier pathophysiological state. Ectopic expression or activation of signaling pathways plays an essential role in the process of shield destruction. Although some drugs, such as molecular or signaling inhibitors, are currently used for the treatment of intestinal diseases, their efficacy cannot meet current medical requirements. In this review, we summarize the current achievements in research on the relationships between the intestinal barrier and signaling pathways. The limitations and future perspectives are also discussed to provide new horizons for targeted therapies for restoring intestinal barrier function that have translational potential.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A-induced hepatotoxicity via inhibition of ferroptosis in mice.

The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.

Artemisia argyi H.Lév. & Vaniot essential oil induces ferroptosis in pancreatic cancer cells via up-regulation of TFR1 and depletion of γ-glutamyl cycle.

Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicine with a history spanning over two millennia, has been extensively used in folk medicine to treat dysmenorrhea, uterine bleeding and inflammation. Recent studies have demonstrated that the essential oil extracted from Artemisia argyi H.Lév. & Vaniot, known as AAEO, exhibits significant anti-tumor properties against liver and lung cancers. There is a scarcity of research on the potential impact of AAEO on pancreatic cancer (PC) cells. In this study, UPLC-MS/MS-based metabolomics method was established to evaluate the effect of AAEO on the proliferation of PC cells. The differential compounds included 5-oxoproline, glutamate, γ-glutamylcysteine, glutathione, arachidonic acid, adrenal acid and linoleic acid were detected by metabolomics, enriching in the γ-glutamyl cycle and polyunsaturated fatty acid metabolism, which were closely related to ferroptosis. Meanwhile, AAEO dramatically increased the levels of intracellular iron ion via up-regulation of TFR1, augmented reactive oxygen species and malondialdehyde in a dose-dependent manner by down-regulation of γ-glutamyl cycle through decreasing expressions of SLC7A11. Additionally, ß-caryophyllene oxide, one of the main components of AAEO, could covalently bind to Cys in SW1990 cells to form a conjugate Cpo-Cys, resulting in the inhibition of glutathione synthesis. Importantly, the ferroptosis inhibitor deferoxamine significantly blocked the inhibitory effect of AAEO on SW1990 cells. Meanwhile, ß-caryophyllene oxide, dihydro-ß-ionone and α-bisabolol had strong binding force with GPX4, SLC7A11 and TFR1, respectively. These findings showed that AAEO induced ferroptosis via regulation of γ-glutamyl cycle by SLC7A11 and iron disorders by TFR1. Our study discovered AAEO as a potential therapeutic approach to induce ferroptosis to prevent or treat PC.

[Modified acupuncture at sphenopalatine ganglion for allergic rhinitis: a randomized controlled trial].

OBJECTIVE: To observe the effect of modified acupuncture at sphenopalatine ganglion for allergic rhinitis (AR). METHODS: A total of 80 patients with AR were randomly divided into an observation group and a control group, 40 cases in each group. In the observation group, modified acupuncture at sphenopalatine ganglion was given, 30 min each time, 2 times a week and with an interval of 3-4 days. In the control group, budesonide nasal spray was given. Both groups were treated for 4 weeks. The total nasal symptom score (TNSS) and total non-nasal symptom score (TNNSS) were observed before treatment, after first treatment, after last treatment and 4 weeks after treatment; the scores of visual analogue scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were observed before treatment, after last treatment and 4 weeks after treatment; the recurrence condition was evaluated 4 weeks after treatment; the clinical efficacy was evaluated after last treatment in the two groups. RESULTS: Compared with before treatment, the total scores and each score of TNSS, TNNSS scores after first treatment, after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01, P<0.05). After first treatment, the total score, stuffy nose score, itchy nose score of TNSS and TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). After last treatment, the total score, stuffy nose score, itchy nose score of TNSS in the observation group were lower than the control group (P<0.01). Four weeks after treatment, the total score and each score of TNSS, TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). Compared with before treatment, the scores of VAS and RQLQ after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). The recurrence rate was 13.5% (5/37) in the observation group, which was lower than 44.8% (13/29) in the control group (P<0.01). The total effective rate was 92.5% (37/40) in the observation group, which was higher than 72.5% (29/40) in the control group (P<0.05). CONCLUSION: Modified acupuncture at sphenopalatine ganglion could effectively improve symptoms and quality of life in patients with AR, and the recurrence rate is lower.

Effects of electroacupuncture on liver function in mice with chronic alcoholic liver injury: visual display by in vivo fluorescence imaging.

OBJECTIVE: Acupuncture can improve the symptoms of alcohol-induced bodily injury and has been accepted by the World Health Organization. In this study, in vivo fluorescence imaging (IVFI) was applied to display and evaluate the effect of electroacupuncture (EA) on liver function (LF) in mice with chronic alcoholic liver injury (cALI). METHODS: IVFI of the Cy5.5-galactosylated polylysine (Cy5.5-GP) probe targeting the liver asialoglycoprotein receptor (ASGPR) and liver indocyanine green (ICG) clearance was performed to visually evaluate the effect of EA at ST36 and BL18 on liver reserve function and hepatic metabolism in mice with cALI. In addition, changes in ASGPR expression, serum indexes of LF, and hepatic morphology were observed. RESULTS: After EA at ST36 and BL18, the ASGPR-targeted fluorescence signals (FS) in the liver increased significantly in cALI mice (p < 0.05) and exhibited relationships with liver ASGPR expression, liver ICG clearance, liver histology, and serum marker levels of LF in cALI mice undergoing EA intervention. CONCLUSIONS: As displayed by IVFI, EA at ST36 and BL18 appears to improve liver reserve function and inhibit the development of liver injury in mice with cALI. EA may have potential as a treatment strategy to protect against ALI.

Modified acupuncture at sphenopalatine ganglion for allergic rhinitis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of modified acupuncture at sphenopalatine ganglion for allergic rhinitis (AR).@*METHODS@#A total of 80 patients with AR were randomly divided into an observation group and a control group, 40 cases in each group. In the observation group, modified acupuncture at sphenopalatine ganglion was given, 30 min each time, 2 times a week and with an interval of 3-4 days. In the control group, budesonide nasal spray was given. Both groups were treated for 4 weeks. The total nasal symptom score (TNSS) and total non-nasal symptom score (TNNSS) were observed before treatment, after first treatment, after last treatment and 4 weeks after treatment; the scores of visual analogue scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were observed before treatment, after last treatment and 4 weeks after treatment; the recurrence condition was evaluated 4 weeks after treatment; the clinical efficacy was evaluated after last treatment in the two groups.@*RESULTS@#Compared with before treatment, the total scores and each score of TNSS, TNNSS scores after first treatment, after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01, P<0.05). After first treatment, the total score, stuffy nose score, itchy nose score of TNSS and TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). After last treatment, the total score, stuffy nose score, itchy nose score of TNSS in the observation group were lower than the control group (P<0.01). Four weeks after treatment, the total score and each score of TNSS, TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). Compared with before treatment, the scores of VAS and RQLQ after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). The recurrence rate was 13.5% (5/37) in the observation group, which was lower than 44.8% (13/29) in the control group (P<0.01). The total effective rate was 92.5% (37/40) in the observation group, which was higher than 72.5% (29/40) in the control group (P<0.05).@*CONCLUSION@#Modified acupuncture at sphenopalatine ganglion could effectively improve symptoms and quality of life in patients with AR, and the recurrence rate is lower.

Prevention of Dexmedetomidine on Postoperative Delirium and Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Thoracoscopic Lobectomy.

Objective: To investigate the effect of dexmedetomidine on postoperative cognitive function and delirium in elderly patients undergoing thoracoscopic lobectomy. Methods: 109 elderly patients (age is more than 65 years) who underwent thoracoscopic lobectomy in our hospital from June 2020 to Feb 2022 were randomly divided into the dexmedetomidine (DEX) group (n = 54) and the control group (n = 55). The patients in the experimental group were given dexmedetomidine by intravenous pump, intravenous pump 0.5 µg/kg within 10 minutes, and maintained the speed of 0.5 µg/(kg. h) to 30 min before the operation was ended. The control group was given the same amount of normal saline. Delirium assessment-severity (CAM-S) assessment and Mini-Cog were used to assess the severity levels of POD and POCD 24 h before, 6 hours after, one day after the operation, three days after the operation, and 1 week after the operation. Serum TNF-αα and NSE levels were assessed by using enzyme-linked immunosorbent assay. NRS pain marks were assessed in the DEX group at postanesthesia care unit (PACU) and 24 postoperation. Surgical pierhysmographic index (SPI) evaluation was performed at five time points. Results: The Mini-Cog scores in the DEX group were markedly enhanced compared with those in the saline group 6 and 24 hours after the operation. The SPI values in the DEX group were markedly reduced within 2 min after intubation and at surgical sutures. Moreover, the CAM scores in the DEX group were markedly reduced 24 hours after the operation. Tumor necrosis factor-α (TNF-α) and neuron-specific enolase (NSE) levels were significantly decreased in the DEX group at T1∼T3. Conclusion: The use of dexmedetomidine in the thoracoscopic lobectomy in elderly patients could reduce the occurrence and severity of postoperative cognitive dysfunction and delirium.

[Mechanism of acupuncture and moxibustion in treatment of chronic fatigue syndrome from perspective of intestinal flora].

Intestinal flora dysbiosis may play an important role in the occurrence and development of chronic fatigue syndrome (CFS), which may induce the inflammatory response and metabolic disturbance of patients with CFS. Acupuncture and moxibustion may achieve anti-fatigue effect by affecting the diversity and quantity of intestinal flora, improving intestinal barrier function, and regulating brain-gut peptides.

Network pharmacology and bioinformatics analysis identified essential genes of Jingulian in the treatment of rheumatoid arthritis and COVID-19.

Background: Patients with rheumatoid arthritis (RA) may be more susceptible to infection by coronavirus disease-19 (COVID-19) due to immune system dysfunction. However, there are still insufficient treatment strategies for patients with RA and COVID-19. Since Jingulian is a traditional Chinese medicine (TCM) with anti-viral and immune regulatory functions, our study aims to explore the detailed mechanisms of Jingulian in treating patients with RA and COVID-19. Methods: All the components of Jingulian were retrieved from pharmacology databases. Then, a series of network pharmacology-based analyses and molecular docking were used to understand the molecular functions, core targets, related pathways, and potential therapeutic targets of Jingulian in patients with RA/COVID-19. Results: A total of 93 genes were identified according to the disease-compound-target network. We investigated that the main targets, signaling pathways, and biological functions of Jingulian in RA and COVID-19. Our results indicated that Jingulian may treat patients with RA/COVID-19 through immune processes and viral processes. Moreover, the results of molecular docking revealed that tormentic acid was one of the top compounds of Jingulian, which had high affinity with Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR) in patients with RA/COVID-19. Furthermore, 5 core targets of Jingulian were also identified, including JAK1, Janus kinase 2 (JAK2), STAT3, lymphocyte specific protein tyrosine kinase (LCK), and EGFR. Conclusions: Tormentic acid in Jingulian may regulate JAK1, STAT3, and EGFR, and might play a critical role in RA/COVID-19.

Environmental cadmium exposure during gestation impairs fetal brain and cognitive function of adult offspring via reducing placenta-derived E2 level.

Early-life exposure to environmental cadmium (Cd) is known to cause developmental disorders, yet the effect and mechanism of gestational exposure to Cd on the offspring's cognitive function remains unclear. Placenta as a well-established target organ for Cd-impaired fetal development, its role in estrogen regulation and offspring cognitive function is unknown. Our in vivo experiments found that gestational Cd exposure impaired cognitive function in adult male offspring, accompanied with lowered 17ß-estradiol (E2) level in the male fetal brain upon Cd exposure. Correspondingly, the expression of synapse-associated proteins including brain-derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95) and synapsin-1 were downregulated, which were reversed when supplemented with E2 hormone during gestation. Further observation showed placental estrogen synthesis inhibition and general control non-derepressible 2 (GCN2) signaling activation upon Cd exposure, whereas placental estrogen synthesis could be restored through inhibiting GCN2 activity. Based on ovariectomy (OVX) of pregnant mice, we confirmed that Cd exposure reduced E2 level in fetal brain via inhibiting placenta-derived estrogen synthesis. The aforementioned Cd-induced fetal brain injury and cognitive impairment in adult offspring were significantly alleviated when pregnant dams were supplemented with anti-stress agent N-Acetyl-l-cysteine. In summary, Cd disrupted placenta-derived estrogen synthesis via activating GCN2 signaling, and thereby caused cognitive impairment in adult offspring mice. Our findings suggest that placenta-derived estrogen may be an effect marker of environmental toxicants-evoked cognitive dysfunction in adult offspring and suggest that environmental toxicants may affect the fetal brain development via placenta-fetal-brain axis.

Mechanical Study of Jian-Gan-Xiao-Zhi Decoction on Nonalcoholic Fatty Liver Disease Based on Integrated Network Pharmacology and Untargeted Metabolomics.

Jian-Gan-Xiao-Zhi decoction (JGXZ) has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms by which JGXZ improve NAFLD are still unclear. Methods. In this study, we first used a high-fat diet (HFD) to establish a NAFLD rat model to clarify the therapeutic effect of JGXZ on NAFLD. Secondly, we used network pharmacology to predict the potential targets of JGXZ on NAFLD, and then the key targets obtained from network pharmacology were verified. Finally, we used untargeted metabolomics to study the metabolic regulatory mechanism of JGXZ. Results. JGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and oil red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells in the liver. In addition, network pharmacology research found that the potential targets of JGXZ on NAFLD pathway were mainly associated with improving oxidative stress, apoptosis, inflammation, lipid metabolism disorders, and insulin resistance. Further experimental verification confirmed that JGXZ could inhibit inflammation and improve oxidative stress, insulin resistance, and lipid metabolism disorders. Serum untargeted metabolomics analyses indicated that the JGXZ in the treatment of NAFLD may work through the linoleic acid metabolism, alpha-linolenic acid metabolism, tryptophan metabolism, and glycerophospholipid metabolism pathways. Conclusions. In conclusion, this study found that JGXZ has an ameliorative effect on NAFLD, and JGXZ alleviates the inflammatory response and oxidative stress and lipid metabolism disorders in NAFLD rats. The mechanism of action of JGXZ in the treatment of NAFLD may be related to the regulation of linoleic acid metabolism, tryptophan metabolism, alpha-linolenic acid metabolism, and glycerophospholipid metabolism.

[Research practice and strategy of resource utilization of residues for edible medicinal plants under background of Big Health].

In recent years, with the acceleration of population aging in China, the frequent occurrence of chronic diseases, and the increase in the number of sub-health groups, people began to seek ways to maintain health in line with the laws of nature. Healthy China has become a national strategy, and the Big Health industry has ushered in a golden period of development. In this context, the concept of medicine and food homology and edible medicinal substances which have guided Chinese people to pursue health since ancient times have ushered in significant and favorable development opportunities, and the industrial scale has gradually expanded. The development and utilization of edible medicinal plants have also become an important research direction. In the industrialization process of modern health care and edible medicinal products, a large number of drug residues are often abandoned due to ineffective utilization, resulting in a huge waste of resources and increasing the pressure on the ecological environment. Under the guidance of the homology theory of medicine and food, based on the recycling strategy of Chinese medicine resources, this paper analyzed the inherent common characteristics such as physical and chemical properties and biological activity of Chinese medicine residues of edible medicinal plants and put forward some suitable resource utilization strategies and suggestions in combination with the current situation of resource development and utilization of Chinese medicine residues of edible medicinal plants, in order to promote the high-value development and utilization of medicinal and edible resources, and extend the industrial chain of edible medicinal resources, thereby empowering Big Health industry and facilitating Healthy China.

Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension.

Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.

Effectiveness and safety of KunXian capsule for the treatment of IgA nephropathy.

BACKGROUND: Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown. METHODS: Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline. RESULTS: At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea. CONCLUSION: KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.