Network Pharmacology and Experimental Verification Reveal the Regulatory Mechanism of Chuanbeimu in Treating Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches. Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments. Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2. Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.

Masson Pine pollen (Pinus massoniana) activate HD11 chicken macrophages invitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Masson Pine pollen (Pinus massoniana; MP) are used in Traditional Chinese Medicine to treat gut conditions. Early in vivo work supports this claim and suggests interaction of the material with the gastrointestinal immune system. AIM OF THE STUDY: The present study tested if and how MP material activates HD11 chicken macrophages in vitro using material from different production sites and harvest years. MATERIAL & METHODS: We applied twelve batches of MP from different Chinese production sites and harvest years. Materials were subjected to LAL tests (endotoxic activity), GC-MS (fatty acid analysis), and plate techniques (microbiological background, antimicrobial activity). Furthermore, HD11 chicken macrophages were challenged (6 h, 37 °C) with MP or LPS (E. coli O111:B4), respectively, to quantify nitric oxide (NO) production and immune gene expression (RT-qPCR). RESULTS: MP material promoted strong signals in LAL tests and contained significant amounts of 3-hydroxydodecanoic acid and 3-hydroxymyristic acid, irrespective of processing, harvest year, or origin. The pollen material activated HD11 chicken macrophages, which was confirmed by spikes of NO release and k-means cluster analysis of TLR-signaling pathway gene expression data. Response of NO production to Log2-titration of MP and LPS-treated media was in any case linear and significant. The response was reduced by polymyxin-B (PMB) and the inhibition was twice as strong for LPS than MP. No or minor microbiological background was detected on the majority of MP samples. Three samples showed presence of spoilage microorganisms and Gram-negative bacteria, but this did not correlate to LAL data or bacterial DNA counts. No antimicrobial activity of MP was evident. CONCLUSION: Pollen of the Masson Pine activated HD11 chicken macrophages in vitro, which is likely partially due to a background of bacterial LPS associated with the pollen material. However, as most of the effect (appr. 80%) could not be blocked by PMB this is certainly due to other stimuli. We hypothesize that polysaccharides and oligosaccharides of the pollen matrix have the potential to interact with certain immune receptors presented on the plasma membrane of chicken macrophages.

Formononetin promotes fatty acid ß-oxidation to treat non-alcoholic steatohepatitis through SIRT1/PGC-1α/PPARα pathway.

BACKGROUND: Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), carries a high risk of cirrhosis and hepatocellular carcinoma. With the increasing incidence of NASH, the accompanying medical burden is also increasing rapidly, so the development of safe and reliable drugs is urgent. Formononetin (FMNT) has a variety of pharmacological effects such as antioxidant and anti-inflammation, and plays a major role in regulating lipid metabolism, reducing hepatic steatosis and so on, but the mechanism for alleviating NASH is unclear. MATERIALS AND METHODS: We firstly established a mouse model on NASH through methionine-choline deficient (MCD) diet to investigate the improvement of FMNT as well as the effects of fatty acid ß oxidation and SIRT1/PGC-1α/PPARα pathway. Then, we explored the mechanisms of FMNT regulation in SIRT1/PGC-1α/PPARα pathway and fatty acid ß oxidation based on genes silencing of SIRT1 and PGC1A. In addition, SIRT1 agonist (SRT1720) and inhibitor (EX527) were used to verify the mechanism of FMNT on improvement of NASH. RESULTS: Our study found that after FMNT intervention, activities of ALT and AST and TG level were improved, and liver function and hepatocellular steatosis on NASH mice were significantly improved. The detection of ß oxidation related indicators showed that FMNT intervention up-regulated FAO capacity, level of carnitine, and the levels of ACADM and CPT1A. The detection of factors related to the SIRT1/PGC-1α/PPARα pathway showed that FMNT activated and promoted the expression of SIRT1/PGC-1α/PPARα pathway, including up-regulating the expression level of SIRT1, improving the activity of SIRT1, promoting the deacetylation of PGC-1α, and promoting the transcriptional activity of PPARα. Furthermore, after genes silencing of SIRT1 and PGC1A, we found that FMNT intervention could not alleviate NASH, including improvement of hepatocellular steatosis, enhancement of ß oxidation, and regulation of SIRT1/PGC-1α/PPARα pathway. Afterwards, we used SRT1720 as a positive control, and the results indicated that FMNT and SRT1720 intervention had no significant difference on improving hepatocellular steatosis and promoting fatty acid ß oxidation. Besides, we found that when EX527 intervention inhibited expression of SIRT1, the improvement of FMNT on NASH was weakened or even disappeared. CONCLUSION: In summary, our results demonstrated that FMNT intervention activated SIRT1/PGC-1α/PPARα pathway to promote fatty acid ß oxidation and regulate lipid metabolism in liver, ultimately improved hepatocellular steatosis on NASH mice.

Effects of Zhuang medicine compound Xiancao Granule on diabetic kidney disease: A multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the mechanisms underlying the action of CXCG in DKD remain unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics. MATERIALS AND METHODS: The chemical compounds of CXCG were identified using ultra-high- performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was performed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes. RESULTS: A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella, Oscillibacter, Anaeroplasma, Anaerotruncus, and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes. CONCLUSION: This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD.

Volatile oil of Angelica sinensis Radix improves cognitive function by inhibiting miR-301a-3p targeting Ppp2ca in cerebral ischemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica Sinensis Radix (ASR) is a commonly used Chinese medicine known for its effects on tonifying blood, promoting blood circulation, and alleviating pain associated with menstrual regulation. Additionally, it has been used in the treatment of vascular cognitive impairment (VCI). The primary pharmacodynamic agent within ASR is volatile oil of Angelica Sinensis Radix (VOASR), which has demonstrated efficacy in combating cognitive impairment, although its mechanism remains unclear. OBJECTIVE: This study aimed to elucidate the potential molecular mechanisms underlying VOASR's improvement of cognitive function in cerebral ischemic mice. METHODS: A model of cerebral ischemic mice was established through unilateral common carotid artery occlusion (UCCAO) surgery, followed by intervention with VOASR. Cognitive function was assessed using the Morris water maze (MWM) test, while RT-qPCR was utilized to measure the differential expression of miR-301a-3p in the hippocampus. To evaluate cognitive function and hippocampal protein differences, wild-type mice and miR-301a-3p knockout mice were subjected to the MWM test and iTRAQ protein profiling. The relationship between miR-301a-3p and potential target genes was validated through a Dual-Luciferase Reporter experiment. RT-qPCR and Western blot were employed to determine the differential expression of Ppp2ca and synaptic plasticity-related proteins in the mouse hippocampus. RESULTS: Intervention with VOASR significantly improved cognitive impairment in cerebral ischemic mice and reduced the expression of miR-301a-3p in the hippocampus. Our findings suggest that miR-301a-3p may regulate cognitive function by targeting Ppp2ca. Furthermore, VOASR intervention led to an increase in the expression of Ppp2ca and synaptic plasticity-related proteins. CONCLUSION: Our study indicates that VOASR may be involved in regulating cognitive function by inhibiting miR-301a-3p, consequently increasing the expression of Ppp2ca and synaptic plasticity proteins. These results provide a new target and direction for the treatment of cognitive dysfunction.

[Effect and mechanism of Zexie Decoction in promoting white adipose tissue browning/brown adipose tissue activation based on GLP-1R/cAMP/PKA/CREB pathway].

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1ß, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.

Analysis of the Value of Flexible Ureteroscopy in the Treatment of Renal Calculi.

Objective: Kidney stones (renal calculi) are a prevalent medical condition, causing significant pain and discomfort to patients. The existing treatment options for kidney stones include extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and flexible ureteroscopy. It is crucial to evaluate the effectiveness of different treatment modalities, including flexible ureteroscopy, to ensure optimal patient outcomes. This study aims to assess the effectiveness of flexible ureteroscopy in treating renal calculi and determine its value in managing this condition. Methods: The study involved a total of 106 patients with kidney stones admitted to the hospital. The patients were divided into an experimental group and a control group. In the control group, percutaneous nephrolithotomy was performed on the patients. The procedure involved placing the patient in the lithotomy position, making an opening at the urethra, inserting a ureteral catheter retrograde to the affected side, and performing puncture under ultrasound guidance. Postoperative anti-infection treatment was given and the results were evaluated through imaging.In the experimental group, ureteral lithotripsy was performed with the patient under general anesthesia. The procedure included dilating the patient's ureter, exploring the location of the kidney stone, using a laser lithotripter to crush the stone, and clearing the fragments. A double J tube was placed at the end of the procedure, and the patient received appropriate antibiotics. Treatment and care continued until the patients were discharged. Clinical efficacy, clinical indicators, renal function, coagulation function, complications, and other factors were observed and recorded. Results: The experimental group showed higher rates of treatment effectiveness (98.11%) and significance (79.25%) compared to the control group, while the treatment failure rate (1.89%) was lower in the experimental group (P < .05). In terms of surgical outcomes, the experimental group had lower intraoperative bleeding volume, catheter removal time, hospitalization time, and postoperative activity time compared to the control group. The time to get out of bed after surgery and drainage tube removal time were also lower in the experimental group. However, the operation time was longer in the experimental group (P < .05). Regarding postoperative indicators, the experimental group exhibited lower levels of KIM-1, Cys-c, and NGAL compared to the control group (P < .05). The experimental group also had lower MA and α values, but higher R and K values during the postoperative period compared to the control group (P < .05). Overall, the experimental group had a significantly lower complication rate (11.32%) compared to the control group (28.30%) (P < .05). Conclusion: The use of ureteroscopic lithotripsy in the treatment of kidney stones can effectively improve the efficiency of patient treatment, with better intraoperative conditions and better prognosis, and less impact on the patient's renal function and coagulation function, as well as reducing the occurrence of postoperative complications in patients, which is worthy of wide application and promotion in clinical practice.

Reconstitution of Natural Killer cells after allogeneic hematopoietic stem cell transplantation is facilitated by Huiyang-Guben decoction through activating the Smad7/Stat3 signal pathway.

Natural Killer (NK) cell is the first batch of re-constructed cell populations after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and its delayed reconstitution inevitably causes poor outcome. The traditional Chinese medicine Huiyang-Guben decoction (HYGB) has been clinically used in patients undergoing allo-HSCT, but its effect on NK cell reconstruction is still unclear. 40 patients with allo-HSCT therapy were randomly divided into the control group and the HYGB group, and were given oral administration of normal saline or HYGB for 4 weeks before allo-HSCT, respectively. NK cells were cultured and treated with transforming growth factor ß (TGF-ß) and HYGB in vitro, and cell viability, cell apoptosis, and the function of NK cells were evaluated. Functional verification experiments were performed by knocking down signal transduction molecule 7 (Smad7) in NK cells before TGF-ß and HYGB treatment. Clinical data suggested that HYGB intervention decreased the incidence of acute graft-versus-host disease after allo-HSCT, and increased the proportion of NK cell population. Meanwhile, HYGB improved cell viability, restrained apoptotic cell death, and enhanced cell killing activity of NK cells in patients with allo-HSCT. Notably, we found that HYGB significantly increased the expression level of Smad7 and the phosphorylation level of signal transducer and activator of transcription 3 (Stat3) in NK cells from patients with allo-HSCT. Moreover, HYGB alleviated TGF-ß-induced NK cell impairment and re-activated the Smad7/Stat3 signaling in vitro, while silencing Smad7 reversed the protective effect of HYGB on TGF-ß-treated NK cells. HYGB promotes NK cell reconstruction and improves NK cell function after allo-HSCT through activating the Smad7/Stat3 signaling pathway.

Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

Unraveling a Combined Inactivation Mechanism of Cytochrome P450s by Genipin, the Major Reactive Aglycone Derived from Gardeniae Fructus.

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.

Aqueous extract of Polygala japonica Houtt. ameliorated nonalcoholic steatohepatitis in mice through restoring the gut microbiota disorders and affecting the metabolites in feces and liver.

BACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear. PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism. MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics. RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites. CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.

Anti-cancer potential of selenium-chitosan-polyethylene glycol-carvacrol nanocomposites in multiple myeloma U266 cells.

Multiple myeloma (MM) is an incurable cancer that is characterized by malignant plasma cell proliferation. Approximately 10% of all blood cancers are MM, and there is no standard curative therapy. In this work, we intended to synthesize, characterize, and assess the anticancer effects of selenium/chitosan/polyethylene glycol-carvacrol nanocomposites (SCP-Car-NCs) on MM U266 cells in vitro. Various characterization techniques were used to characterize the synthesized SCP-Car-NCs. Several in vitro free radical scavenging experiments were conducted to test the ability of synthesized SCP-Car-NCs to scavenge the different free radicals. The cytotoxicity of SCP-Car-NCs was assessed on Vero and U266 cells using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. By using various fluorescence staining techniques, the amount of reactive oxygen species (ROS) generation, MMP, and apoptosis were measured. Using commercial test kits, the levels of oxidative stress and apoptotic biomarkers in control and treated U266 cells were assessed. The highest peak in the UV spectral analysis was found to be at 271 nm, demonstrating the development of SCP-Car-NCs. Fourier transform infrared analysis showed that the synthesized SCP-Car-NCs contained a variety of stretching and bonding. The X-ray diffraction study confirmed the crystallinity of SCP-Car-NCs. The dynamic light scattering analysis showed that the SCP-Car-NCs had an average size of 171 nm. The different free radicals, such as the 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, and peroxyl radicals, were significantly scavenged by the SCP-Car-NCs. According to the MTT assay results, the SCP-Car-NCs decreased the viability of U266 cells while having no impact on the proliferation of Vero cells. The SCP-Car-NCs significantly boosted ROS production, decreased the MMP level, and promoted apoptosis, as evidenced by the fluorescence staining experiments. In U266 cells treated with SCP-Car-NCs, the level of thiobarbituric acid reactive substances increased while superoxide dismutases and glutathione levels were reduced. In the SCP-Car-NCs treated U266 cells, it was found that the Bax, caspase-3, and -9 activities had increased while the Bcl-2 level had decreased. In conclusion, our findings show that SCP-Car-NCs treatment reduced the viability and increased apoptosis in the U266 cells, providing a new insight on SCP-Car-NCs' potential for usage in the future to treat MM.

Dengzhan Shengmai capsule attenuates cardiac fibrosis in post-myocardial infarction rats by regulating LTBP2 and TGF-ß1/Smad3 pathway.

BACKGROUND: Cardiac fibrosis contributes to myocardial remodeling after myocardial infarction (MI), which may facilitate the progression to end-stage heart failure. Dengzhan Shengmai capsule (DZSMC), a traditional Chinese formula derived from Shen-mai powder, has shown remarkable therapeutic effects against cardiovascular diseases. However, the effect of DZSMC on cardiac fibrosis and its potential mechanism are ill-defined. PURPOSE: To evaluate the effects of DZSMC on cardiac fibrosis after myocardial infarction (MI) and investigate its underlying mechanism. METHOD: In vivo, MI rat models were established by permanently ligation of left anterior descending coronary arteries (LAD) and then were intragastrically treated with DZSMC or captopril for 5 weeks. Ex vivo, an everted intestinal sac model was used to study the intestinal absorption components of DZSMC, which were further identified through an ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. In vitro, a myocardium fibrotic model was constructed by stimulating primary cardiac fibroblasts (CFs) with 1 µM Ang II. Subsequently, the absorbent solution of DZSMC from the intestinal sac was performed on the cell models to further elucidate its anti-fibrotic effects and underling mechanism. RESULTS: In vivo results showed that DZSMC significantly improved cardiac function and inhibited pathological myocardial fibrosis in post-MI rats in a dose dependent manner. Histological analysis and western blot results demonstrated that DZSMC treatment significantly reduced the expression of extracellular matrix (ECM)-related proteins, including LTBP2, TGF-ßR1, Smad3 and pSmad3, in myocardial tissue of MI rats. Ex vivo results showed that 18 absorbed components were identified, mainly consisting of phenolic acids, flavonoids and lignans, which may be responsible for the anti-fibrotic effects. Further in vitro results validated that DZSMC attenuated myocardial fibrosis by suppressing the expression of LTBP2, TGF-ß1 and pSmad3. CONCLUSION: DZSMC ameliorates cardiac function and alleviates cardiac fibrosis, which may be mediated by inhibition of CFs activation and reduction of excessive ECM deposition via LTBP2 and TGF-ß1/Smad3 pathways.

Ornamental plants associated with Buddhist figures in China.

BACKGROUND: In China, many ornamental plants associated with Buddhist figures, including the Sakyamuni, Bodhisattva, and Arhat, were grown and worshiped because of their cultural and religious significance. However, the systematic collation and ethnobotanical information about these culturally important plants have yet to be fully understood. METHODS: Online information was collected from 93 e-commercial platforms for ornamental plants all over China. Field sampling was conducted in 16 ornamental markets and 163 Buddhist temples using key informant interviews and participatory observation with traders, tourists, and local disciples. The types, distributions, and associated characteristics of the screened plants were summarized and the evolving characteristics of these ornamental plants were analyzed. RESULTS: A total of 60 ornamental plants, including six varieties and one subspecies, were screened, of which 43 species were associated with Sakyamuni, 13 with Bodhisattva, and four with Arhat. Among the 60 species, three were regarded as the Asoka tree related to Buddha's birth, ten as the Bodhi tree connected to Buddha's enlightenment, three as the Sal tree associated with Buddha's nirvana, nine were related to Buddha's head, belly, or hand, and 18 were connected with Buddha as lotus throne, bamboo monastery, or Bodhi beads. The evolving characteristics of these ornamental plants primarily constituted the substitution of the original plants by similar native plant species, followed by the introduced species with comparable morphology to the Buddhist figures. CONCLUSIONS: People grow ornamental plants associated with Buddhist figures to reflect their love and praise for plants and Buddha. The association between the ornamental plants and Buddhist figures will aid the inheritance of Buddhist culture and promote ornamental plants in the commercial market. Thus, the ethnobotany of ornamental plants associated with Buddhist figures can serve as a basis for future investigation of modern Buddhist culture.

EMDR versus waiting list in individuals at clinical high risk for psychosis with post-traumatic stress symptoms: A randomized controlled trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in the individuals at clinical-high risk for psychosis (CHR). The aim of this study was to examine the efficacy and safety of Eye Movement Desensitization and Reprocessing (EMDR) in individuals at CHR with comorbid PTSD or subthreshold PTSD in a randomized controlled trial. METHODS: Fifty-seven individuals at CHR with PTSD or subthreshold PTSD formed the study sample. The eligible participants were randomly assigned to a 12 weeks EMDR treatment (N = 28) or a waiting list condition (WL, N = 29). The structured interview for psychosis risk syndrome (SIPS), the clinician administered post-traumatic stress disorder scale (CAPS) and a battery of self-rating inventories covering depressive, anxiety and suicidal symptoms were administered. RESULTS: Twenty-six participants in the EMDR group and all the participants in the WL group completed the study. The analyses of covariance revealed greater reduction of the mean scores on CAPS (F = 23.2, Partial η2 = 0.3, P < 0.001), SIPS positive scales (F = 17.8, Partial η2 = 0.25, P < 0.001) and all the self-rating inventories in the EMDR group than in the WL group. Participants in the EMDR group were more likely to achieve remission of CHR compared to those in the WL group at endpoint (60.7 % vs. 31 %, P = 0.025). CONCLUSIONS: EMDR treatment not only effectively improved traumatic symptoms, but also significantly reduced the attenuated psychotic symptoms and resulted in a higher remission rate of CHR. This study highlighted the necessity of adding a trauma-focused component to the present approach of early intervention in psychosis.

NLRP3 mediates the neuroprotective effects of SVHRSP derived from scorpion venom in rotenone-induced experimental Parkinson's disease model.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, scorpion is used to treat diseases with symptoms such as trembling, convulsion and dementia. Our laboratory employs patented technology to extract and purify the active single component from scorpion venom. We then utilize mass spectrometry to determine the amino acid sequence of the polypeptide and synthesize it artificially to acquire the polypeptide with a purity of 99.3%, named SVHRSP (Scorpion Venom Heat-Resistant Peptide). SVHRSP has been demonstrated to display potent neuroprotective efficacy in Parkinson's disease. AIM OF THE STUDY: To explore the molecular mechanisms and potential molecular targets of SVHRSP-afforded neuroprotection in PD mouse models, as well as to investigate the role of NLRP3 in SVHRSP-mediated neuroprotection. MATERIALS AND METHODS: The PD mouse model was induced by rotenone and the neuroprotective role of SVHRSP on the PD mouse model was measured using the gait test, rotarod test, the number of dopaminergic neurons, and the activation of microglia. RNA sequencing and GSEA analysis were performed to find the differentially biological pathways regulated by SVHRSP. Primary mid-brain neuron-glial cultures and NLRP3-/- mice were applied to verify the role of NLRP3 by using qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA) and immunostaining. RESULTS: SVHRSP-afforded dopaminergic neuroprotection was accompanied with inhibition of microglia-mediated neuroinflammatory pathways. Importantly, depletion of microglia markedly reduced the neuroprotective efficacy of SVHRSP against rotenone-induced dopaminergic neurotoxicity in vitro. SVHRSP inhibited microglial NOD-like receptor pathway, mRNA expression and protein level of NLRP3 in rotenone PD mice. SVHRSP also reduced rotenone-induced caspse-1 activation and IL-1ß maturation, indicating that SVHRSP mitigated activation of NLRP3 inflammasome. Moreover, inactivation of NLRP3 inflammasome by MCC950 or genetic deletion of NLRP3 almost abolished SVHRSP-afforded anti-inflammatory, neuroprotective effects and improvement of motor performance in response to rotenone. CONCLUSIONS: NLRP3 mediated the neuroprotective effects of SVHRSP in rotenone-induced experimental PD model, providing additional evidence for the mechanisms of SVHRSP-afforded anti-inflammatory and neuroprotective effects in PD.

Antifungal alkaloids from Mahonia fortunei against pathogens of postharvest fruit.

Postharvest pathogens can affect a wide range of fresh fruit and vegetables, including grapes, resulting in significant profit loss. Isoquinoline alkaloids of Mahonia fortunei, a Chinese herbal medicine, have been used to treat infectious microbes, which might be effective against postharvest pathogens. The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids, of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum. The antifungal alkaloids could change the mycelium morphology, the total lipid content, and leak the cell contents of B. cinerea. Furthermore, the two most potent antifungal alkaloids, berberine (13) completely inhibited effect on gray mold of table grape at 512 mg L-1, while jatrorrhizine (18) exhibited an inhibition rate > 90% on grape rot at the same concentration, with lower cytotoxicity and residue than chlorothalonil, which suggested that ingredients of M. fortunei might be a low-toxicity, low-residue, eco-friendly botanical fungicide against postharvest pathogens.

Activation of the brain during motor imagination task with auditory stimulation.

Introduction: Auditory stimulation is one of the most important influence factors in the cognitive process. It is an important guiding role in cognitive motor process. However, previous studies on auditory stimuli mainly focused on the cognitive effects of auditory stimuli on the cortex, while the role of auditory stimuli in motor imagery tasks is still unclear. Methods: In order to explore the role of auditory stimuli in motor imagery tasks, we studied the EEG power spectrum distribution characteristics, frontal parietal mismatch negative (MMN) wave characteristics, and the Inter trial phase locking consistency (ITPC) characteristics of the prefrontal cognitive cortex and parietal motor cortex. In this study, 18 subjects were hired to complete the motor imagery tasks, induced by auditory stimuli of task related verbs and task independent nouns. Results: EEG power spectrum analysis showed that the activity of the contralateral motor cortex was significantly increased under the stimulation of verbs, and the amplitude of mismatch negative wave was also significantly increased. ITPC is mainly concentrated in µ, α, and γ bands in the process of motor imagery task guided by the auditory stimulus of verbs, while it is mainly concentrated in the ß band under the nouns stimulation. This difference may be due to the impact of auditory cognitive process on motor imagery. Discussion: We speculate that there may be a more complex mechanism for the effect of auditory stimulation on the inter test phase lock consistency. When the stimulus sound has the corresponding meaning to the motor action, the parietal motor cortex may be more affected by the cognitive prefrontal cortex, thus changing its normal response mode. This mode change is due to the joint action of motor imagination, cognitive and auditory stimuli. This study provides new insight into the neural mechanism of motor imagery task guided by auditory stimuli, and provides more information on the activity characteristics of the brain network in motor imagery task by cognitive auditory stimulation.

Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis.

BACKGROUND: Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored. OBJECTIVES: We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP). METHODS: Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing. RESULTS: Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1ß, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis. CONCLUSIONS: Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.

Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.