Xiaoyaosan promotes neurotransmitter transmission and alleviates CUMS-induced depression by regulating the expression of Oct1 and Oct3 in astrocytes of the prefrontal cortex.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription for the treatment of liver depression and qi stagnation, and pharmacological studies have shown that XYS has great potential to reverse depression. However, anti-depression targets and the mechanism of XYS are still not entirely clear. AIM OF THE STUDY: The present study aims to explore and verify the anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant effect of XYS was assessed in rats with depression induced by chronic unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in different brain regions were measured using ELISA. The expression of organic cation transporters (Octs) were detected by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the correlation between Octs and depression-like behavior. Then, the effects of XYS on the behavior, neurotransmitter concentration, and Octs expression in D22-induced rats were examined. Finally, primary astrocytes were used to verify the mechanism of XYS exerting anti-depressant activity by regulating Octs. RESULTS: The result showed that XYS had a significant positive impact on the behavior of depression rats induced by CUMS. XYS also improved the secretion of 5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 expression in the PFC. These results suggest that XYS has the potential to alleviate depression by enhancing the secretion of neurotransmitters. This may be related to XYS regulation of Oct's expression. When the expression of Octs was inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was able to reverse this behavior, indicating that Octs play a significant role in the development of depression and XYS may exert its antidepressant effects through the regulation of Octs. Furthermore, the study also found that dopamine uptake decreased after inhibiting the expression of Octs, and XYS-containing serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant effects by promoting dopamine uptake to improve neurotransmitter transport by regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: The antidepressant effect of XYS may be attributed to its ability to regulate the expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting neurotransmitter transport.

Revealing active constituents within traditional Chinese Medicine used for treating bacterial pneumonia, with emphasis on the mechanism of baicalein against multi-drug resistant Klebsiella pneumoniae.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence of antibiotic-resistant bacteria has rendered it more challenging to treat bacterial pneumonia. Traditional Chinese medicine (TCM) has superior efficacy in the treatment of pneumonia, and it has the unique advantage of antibacterial resistance against multi-drug resistant (MDR) bacteria, but the medication rule and pharmacological mechanism of its antibacterial activity are not clear. AIM OF THE STUDY: This study aims to reveal Chinese medication patterns in treating bacterial pneumonia to select bioactive constituents in core herbs, predict their pharmacological mechanisms and further explore their antibacterial ability against clinically isolated MDR Klebsiella pneumoniae (KP) and their antibacterial mechanisms. MATERIALS AND METHODS: The high-frequency medicinal herbs to treat lung diseases were first screened from Pharmacopoeia of the People's Republic of China (ChP.), and then bioactive compounds in core herbs and targets for compounds and disease were collected. Potential targets, signaling pathways, and drugs' core components were determined by constructing protein-protein interaction network, enrichment analysis and "component-target-pathway-disease" network were mapped by Cytoscape 3.8.2, and the potential therapeutic value of selected core components was verified by comparing the disease targets in the GEO database with the herbal component targets in the ITCM database. The clinically isolated KP were screened by drug sensitivity tests with meropenem (MEM), polymyxin E (PE), and tigecycline and biofilm-forming assay; broth microdilution, chessboard methods and biofilm morphology and permeability experiments were employed to determine the antibacterial, bactericidal and biofilm inhibition ability of selected bioactive constituents alone and in combination with antibiotics; The mechanism of bioactive components on quorum sensing (QS) genes LuxS and LuxR was predicted by molecular docking and tested by RT-PCR. RESULTS: The 13 core Chinese medicines were obtained by mining ChP., and 615 potential targets of core herbal medicine were screened, and the PI3K-Akt signaling pathway might play crucial roles in the therapeutic process. In-vitro experiments revealed that the selected core compounds, including forsythoside B, baicalin, baicalein, and forsythin, all have antibacterial activity, in which baicalein had the strongest ability and a synergistic effect in combination with MEM or PE. Their synergy exhibited a stronger effect on biofilms of MDR KP, inhibiting biofilm formation, disrupting formed biofilms, and removing the residual structures of dead bacteria. Baicalein was predicted to have stable binding capacity to LuxS and LuxR genes by molecular docking, and RT-PCR results verified that the combination of baicalein with MEM or PE was effective in inhibiting the expression of QS genes (LuxS and LuxR) and consequently suppressing biofilm formation. CONCLUSION: The core Chinese herbal medicine in the ChP. to treat lung diseases has a multi-component, multi-target, and multi-pathway synergy to improve bacterial pneumonia. Experimental studies have confirmed that the bioactive compound baicalein was able to combat MDR KP alone and synergistic with MEM or PE, inhibited and disrupted biofilms via regulating LuxS and LuxR genes, and further disturbed quorum sensing system to promote the therapeutic efficacy, which provides a new pathway and rationale for treating MDR KP-induced bacterial pneumonia.

[Correlation between rhizosphere environment and content of medicinal components of Arnebia euchroma].

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of ß,ß'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.

Evaluation of the efficacy and safety of percutaneous transforaminal endoscopic discectomy for multi-segmental lumbar disc herniation.

Objective: To investigate the clinical efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of multi-segmental lumbar disc herniation (msLDH). Methods: From January 2021 to December 2021, 75 patients with msLDH admitted to Baoding No.1 Hospital of Traditional Chinese Medicine were selected and divided into PTED group (n=40) and posterior lumbar interbody fusion (PLIF) group (n=35) according to different surgical methods. The operative time, intraoperative blood loss, surgical complications, Oswestry disability index (ODI) and Japanese Orthopedic Association score (JOA) scores were compared between the two groups. Results: In the PTED group, the average operation time was 57.45±12.01minutes, and the average intraoperative blood loss was 50.57±16.69ml. There were three patients with surgical complications, including one case of hematoma, one case of aggravation of neurological symptoms and one case of new onset of neurological symptoms. In the PLIF group, there were 12 cases undergoing single-segment operation, 15 cases undergoing double-segment operation and 8 cases undergoing three-segment operation, the average operation time was 137.26±34.64minutes, and the average intraoperative blood loss was 456.06±33.06ml, there were four cases of wound fat liquefaction or delayed healing, two cases of hematoma, and three cases of exacerbation of original neurological symptoms or new neurological symptoms. At one month, six months, and one year of postoperative, the ODI and JOA scores of the two groups were significantly improved compared with those preoperative, and the ODI scores of the PTED group were better than those of the PLIF group (t=3.131, 2.263, 3.768, all P<0.05). Conclusion: The surgical effect of PTED in the treatment of LDH is similar to that of PLIF. However, PTED has the advantages of short operation time, less blood loss, fewer surgical complications, and high surgical safety. It is worthy of clinical promotion.

[Influence of electroacupuncture of "Dazhui"（GV14） and "Mingmen" （GV4） on expressions of NL1 and NF-200 in spinal cord injury rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on activities of A2 type astrocytes(A2s)and A1 type astrocytes (A1s) , expressions of neurofilament protein 200 (NF-200, a marker of axon regeneration), nexin 1(NL1, a marker of synaptic regeneration), and regeneration of Nissl bodies in rats with spinal cord injury (SCI), so as to explore its mechanisms underlying improvement of SCI. METHODS: A total of 75 male SD rats were rando-mized into sham operation, model, antibody neutralizing (AN), EA and EA+AN groups, with 15 rats in each group. The SCI model was established by using an infinite field impactor to deliver an about 200 k dyne weight onto the exposed spinal cord after making a dorsal laminectomy at vertebral level T10. EA (2 Hz, 1 mA) was applied to"Dazhui"(GV14) and "Mingmen"(GV4) for 20 min, once daily for 28 days. After modeling, intraspinal injection of neutralizing antibodies IL-1α, TNF-α and complement 1q (C1q, 2 µL) to the injured spinal locus for inhibition of A1 type astrocytes (A1s) was conducted on the 1st, 7th , 14th and 21st day for rats of AN and EA+AN groups. BBB rating scale was used to evaluate hindlimb locomotor function on day 1, 7, 14, 21 and 28 after modeling. The activation of A2s (its specific marker S100a10), astrocyte (its specific marker glial fibrillary acidic protein, GFAP), and A1s (its specific marker C3) in the spinal cord was detected by immunofluorescence, and the protein expressions of NF-200 and NL1 in the spinal cord detected by Western blot and immunohistochemistry, separately, and the neuronal regeneration was observed after Nissl staining. RESULTS: After SCI, the BBB scores at 1 , 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200 were significantly decreased (P<0.01), and the fluorescence intensity of double labelled S100a10 (A2s)/GFAP and C3, and the expression of NF-200 were considerably increased in the model group (P<0.05, P<0.01). In contrast to the model group, the BBB scores at 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200, and the fluorescence intensity of A2s/GFAP in the AN, EA and AN+EA groups, and the expressions of NL1 in the EA and AN+EA groups, and expression of NF-200 protein in the AN+EA group were evidently increased (P<0.05, P<0.01), and the fluorescence intensity of C3 was strikingly decreased in the EA group (P<0.01). The effect of AN+EA was significantly superior to that of single AN and EA in increasing BBB scores at 14, 21 and 28 day, and in up-regulating the immunoactivity of NF-200(P<0.01, P<0.05). Nissl staining showed damaged structure of the gray matter of the spinal cord, atrophy of the Nissl body, and pyknosis of neurons, which was milder in the AN and EA groups, particularly in the AN+EA group. CONCLUSION: EA at GV14 and GV4 may promote activation of A2s and promote regeneration of axons and synapses in SCI model rats.

[Remediation of Petroleum-contaminated Soil by Highly Efficient Oil-degrading Bacteria and Analysis of Its Enhancement Mechanism].

A 120-day in situ remediation of oil-contaminated soil was carried out by using highly efficient oil-degrading bacteria. The effects of bio-enhanced remediation and changes in soil physicochemical properties and enzyme activities were investigated. Combined with metagenomic sequencing and bioinformatics analysis, the strengthening mechanism was revealed. The results showed that compared with the blank control group (Ctrl), the degradation rate of total petroleum hydrocarbons in the bioremediation group (Exp-BT) was significantly increased, reaching 81.23%. During enhanced bioremediation by highly efficient oil-degrading bacteria, the pH of the soil was stable, the oxidation capacity of the system was improved, and the electrical conductivity was in the range suitable for agricultural activities. Lipase and dehydrogenase maintained high activity during repair. In addition, the analysis of the initial contaminated soil (B0), the highly efficient oil-degrading bacteria obtained from domestication (GZ), and the soil samples after bioremediation (BT) in the obtained samples showed that, at the phylum level, the total proportion of Proteobacteria and Actinobacteria increased by 17.1%. At the genus level, the abundance of Nocardioides, Achromobacter, Gordonia, and Rhodococcus increased significantly. The species and function contribution analysis of COG and KEGG proved that the above bacterial genera had important contributions to the degradation of petroleum hydrocarbons. A high abundance of petroleum hydrocarbon-related metabolic enzymes and five petroleum hydrocarbon-related degradation genes was found in the soil after remediation:alkM, tamA, rubB, ladA, and alkB. The analysis showed that the introduction of the exogenous petroleum hydrocarbon-degrading bacteria group enhanced the metabolic activity of microorganism-related enzymes and the expression of corresponding functional genes.

[Effects of shading intensity on growth and quality of Artemisia stolonifera].

The purpose of this study was to analyze the effects of shading intensity on the growth, yield, and quality of Artemisia stolonifera so as to provide references for the artificial cultivation of A. stolonifera. The seedlings of A. stolonifera with consistent growth underwent shading treatment at four shading intensity levels(0, 55%, 85%, and 95%) with different layers of black shading nets. The agronomic indexes, yield, moxa yield, total ash, quality characteristics of moxa during combustion and pyrolysis, main volatile components, flavonoids, and phenolic acids were measured. The results showed that under shading conditions, the stem diameter, leaf width, 5-leaf spacing, branch number, and yield of A. stolonifera decreased significantly, while the plant height, leaf length, leaf number, chlorophyll content, and moxa yield increased first and then decreased with the increase in shading intensity. The burning performance of moxa under natural light was better than that under moderate and severe shading conditions. The content of eucalyptol first increased and then decreased with the increase in shading intensity. The humulene content was negatively correlated with shading intensity. Other major volatile components showed no significant difference under various shading conditions. The content of neochlorogenic acid, cryptochlorogenic acid, isoschaftoside, and isochlorogenic acid B was positively correlated with shading intensity, while the content of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C decreased first and then increased with the increase in shading intensity. To sum up, A. stolonifera is a light-loving plant, and shading can greatly reduce the yield, the content of internal components, and the burning performance of moxa. It is the main reason why A. stolonifera is mainly distributed in the forest edge, open forest, roadside, and wasteland grass in the middle and high mountains in the wild. For artificial domestication and cultivation of A. stolonifera, it is better to select plots with sufficient light.

[Comparison of growth and quality of wild and cultivated Artemisia stolonifera].

This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.

[Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes].

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

Identification of Radix Bupleuri From Different Geographic Origins Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Support Vector Machine Algorithm.

BACKGROUND: The geographic origin of Radix bupleuri is an important factor affecting its efficacy, which needs to be effectively identified. OBJECTIVE: The goal is to enrich and develop the intelligent recognition technology applicable to the identification of the origin of traditional Chinese medicine. METHOD: This article establishes an identification method of Radix bupleuri geographic origin based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and support vector machine (SVM) algorithm. The Euclidean distance method is used to measure the similarity between Radix bupleuri samples, and the quality control chart method is applied to quantitatively describe their quality fluctuation. RESULTS: It is found that the samples from the same origin are relatively similar and mainly fluctuate within the control limit, but the fluctuation range is large, and it is impossible to distinguish the samples from different origins. The SVM algorithm can effectively eliminate the impact of intensity fluctuations and huge data dimensions by combining the normalization of MALDI-TOF MS data and the dimensionality reduction of principal components, and finally achieve efficient identification of the origin of Radix bupleuri, with an average recognition rate of 98.5%. CONCLUSIONS: This newly established approach for identification of the geographic origin of Radix bupleuri has been realized, and it has the advantages of objectivity and intelligence, which can be used as a reference for other medical and food-related research. HIGHLIGHTS: A new intelligent recognition method of medicinal material origin based on MALDI-TOF MS and SVM has been established.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. METHODS: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. RESULTS: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. CONCLUSION: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Research progress on acupuncture treatment in central nervous system diseases based on NLRP3 inflammasome in animal models.

Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer's disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.

Phytoestrogens, novel dietary supplements for breast cancer.

While endocrine therapy is considered as an effective way to treat breast cancer, it still faces many challenges, such as drug resistance and individual discrepancy. Therefore, novel preventive and therapeutic modalities are still in great demand to decrease the incidence and mortality rate of breast cancer. Numerous studies suggested that G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor, is a potential target for breast cancer prevention and treatment. It was also shown that not only endogenous estrogens can activate GPERs, but many phytoestrogens can also function as selective estrogen receptor modulators (SERMs) to interact GPERs. In this review, we discussed the possible mechanisms of GPERs pathways and shed a light of developing novel phytoestrogens based dietary supplements against breast cancers.

The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics.

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the "Metabolite-Target-Component" interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.

Synthesis, Characterization of Low Molecular Weight Chitosan Selenium Nanoparticles and Its Effect on DSS-Induced Ulcerative Colitis in Mice.

Selenium nanoparticles have attracted extensive attention due to their good bioavailability and activity. In the present study, a new form of selenium nanoparticle (Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs)) were synthesized in a system of sodium selenite and acetic acid. The size, element state, morphology and elementary composition of LCS-SeNPs were characterized by using various spectroscopic and microscopic measurements. The protection of LCS-SeNPs against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction and the inherent mechanisms of this process were investigated. The results showed that LCS-SeNPs, with an average diameter of 198 nm, zero-valent and orange-red relatively uniform spherical particles were prepared. LCS-SeNPs were mainly composed of C, N, O and Se elements, of which Se accounted for 39.03% of the four elements C, N, O and Se. LCS-SeNPs reduced colon injury and inflammation symptoms and improved intestinal barrier dysfunction. LCS-SeNPs significantly reduced serum and colonic inflammatory cytokines TNF-α and IL-6 levels. Moreover, LCS-SeNPs remarkably increased antioxidant enzyme GSH-Px levels in serum and colonic tissue. Further studies on inflammatory pathways showed that LCS-SeNPs alleviated DSS-induced colitis through the NF-κB signaling pathway, and relieved inflammatory associated oxidative stress through the Nrf2 signaling pathway. Our findings suggested that LCS-SeNPs are a promising selenium species with potential applications in the treatment of oxidative stress related inflammatory intestinal diseases.

[Therapeutic effect of Jingfang Granules on CCl_4-induced liver fibrosis in mice and its mechanism].

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1ß(IL-1ß) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-ß(TGF-ß), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1ß in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-ß, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-ß/Smad4 signaling pathway.

Does acupuncture therapy affect peripheral inflammatory cytokines of major depressive disorder? A protocol for the systematic review and meta-analysis.

Background: Acupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis. Methods and analysis: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD. Discussion: Acupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD. Systematic review registration: [PROSPERO], identifier [CRD42021289207 on 04 December 2021].

Vinegar-baked Radix Bupleuri enhances the liver-targeting effect of rhein on liver injury rats by regulating transporters.

OBJECTIVE: This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury. METHODS: The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays. KEY FINDING: VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein. CONCLUSION: VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.

Dual immunological and proliferative regulation of immune checkpoint FGL1 in lung adenocarcinoma: The pivotal role of the YY1-FGL1-MYH9 axis.

Rational: Lung cancer is the most common tumor worldwide, with the highest mortality rate and second highest incidence. Immunotherapy is one of the most important treatments for lung adenocarcinoma (LUAD); however, it has relatively low response rate and high incidence of adverse events. Herein, we explored the therapeutic potential of fibrinogen-like protein 1 (FGL1) for LUAD. Methods: Data from GEPIA and ACLBI databases were assessed to explore gene-gene correlations and tumor immune infiltration patterns. A total of 200 patients with LUAD were recruited. FGL1 levels in the serum and cellular supernatant were determined by enzyme-linked immunosorbent assay. In vitro and in vivo experiments were performed to assess the effect FGL1 on the proliferation of LUAD cells. Cocultures were performed to explore the effect of FGL1 knockdown in lung cancer cells on T cells, concerning cytokine secretion and viability. PROMO and hTFtarget databases were used for transcription factor prediction. Quantitative polymerase chain reaction (qPCR), chromatin immunoprecipitation, and dual luciferase reporter assays were performed to validate the identified transcription factor of FGL1. Immunoprecipitation, mass spectrometry and gene ontology analysis were performed to explore the downstream partners of FGL1. Results: FGL1 expression in LUAD was positively associated with PDL1, but not for PD1 expression. Moreover, FGL1 was positively associated with the CD3D expression and negatively associated with FOXP3, S100A9, and TPSB2 within the tumor site. FGL1 promotes the secretion of interleukin-2 by T cells in vitro, simultaneously inducing their apoptosis. Indeed, YY1 is the upstream molecule of FGL1 was found to be transcriptionally regulated by YY1 and to directly by to MYH9 to promote the proliferation of LUAD cells in vitro and in vivo. Conclusions: FGL1 is involved in the immunological and proliferative regulation of LUAD cells by controlling the secretion of important immune-related cytokines via the YY1-FGL1-MYH9 axis. Hence, targeting FGL1 in LUAD may pave the way for the development of new immunotherapies for tackling this malignancy.