Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation.

Background and purpose: The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in patients based on clinical observations. Although multi-component and multi-target characteristics are important attributes of BYD treatment, its pharmacological effect on asthma and the underlying mechanism of action remain unclear. Method: Network pharmacology: the asthma-related genes were retrieved from the GeneCards and OMIM database. The active constituents of BYD and their corresponding target genes were collected from the TCMSP database. The underlying pathways associated with overlapping targets between BYD and asthma were identified through GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Experimental validation: pulmonary function tests, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson's trichrome stainings were conducted to validate the efficacy of BYD in ameliorating airway inflammation in allergic asthma mice. Western blot (WB) and molecular docking were performed to confirm the involvement of the underlying pathway in BYD treatment of asthma. Results: The results of animal experiments demonstrated that BYD may improve airway responsiveness and suppress airway inflammation in allergic asthma mice. The network pharmacological analysis revealed the involvement of 11 potentially key active components, 9 potential key targets, and the phosphatidylinositol3 kinase-RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway in the mechanism of action of BYD for asthma treatment. Our findings have confirmed that BYD effectively alleviated airway inflammation by targeting interleukin 6 (IL-6), epidermal growth factor receptor (EGFR), and hypoxia inducible factor 1 alpha (HIF1A), with quercetin, kaempferol, and luteolin performing as the pivotal active constituents. BYD may potentially reduce inflammatory cell infiltration in lung tissues by regulating the PI3K/AKT signaling pathway. Conclusion: In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM's "bushenyiqi" therapy in asthma management, as corroborated by contemporary medical technology.

Shengxian decoction improves lung function in rats with bleomycin-induced idiopathic pulmonary fibrosis through the inhibition of PANoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. MATERIALS AND METHODS: Fifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1ß, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. RESULTS: SXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. CONCLUSION: Bleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.

miR-122-3p targets UBE2I to regulate the immunosuppression of liver cancer and the intervention of Liujunzi formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Liujunzi formula has been used to treat liver cancer in China for many years, but its underlying mechanism remains unclear. We previously found that decreased expression of miR-122-3p was associated with liver cancer. In this study, we aimed to explore the target of miR-122-3p and the effect of the Liujunzi formula on miR-122-3p and its downstream events in liver cancer. MATERIAL AND METHODS: Bioinformatics pinpointed potential targets of miR-122-3p. The actual target was confirmed by miRNA mimic/inhibitor transfections and a dual-luciferase reporter assay. RNA-seq looked at downstream genes impacted by this target. Flow cytometry checked for changes in T cell apoptosis levels after exposing them to liver cancer cells. Gene expression was measured by RT-qPCR, western blotting, and immunofluorescence staining. RESULTS: Cell experiments found the Liujunzi extract (LJZ) upregulated miR-122-3p and in a dose-dependent manner. Bioinformatics analysis found UBE2I was a potential target of miR-122-3p, which was validated through experiments using miRNA mimics/inhibitors and a dual-luciferase reporter assay. RNA-seq data implicated the NF-κB pathway as being downstream of the miR-122-3p/UBE2I axis, further confirmed by forcing overexpression of UBE2I. Bioinformatic evidence suggested a link between UBE2I and T cell infiltration in liver cancer. Given that the NF-κB pathway drives PD-L1 expression, which can inhibit T cell infiltration, we investigated whether PD-L1 is a downstream effector of miR-122-3p/UBE2I. This was corroborated through mining public databases, UBE2I overexpression studies, and tumor-T cell co-culture assays. In addition, we also confirmed that LJZ downregulates UBE2I and NF-κB/PD-L1 pathways through miR-122-3p. LJZ also suppressed SUMOylation in liver cancer cells and protected PD-1+ T cells from apoptosis induced by co-culture with tumor cells. Strikingly, a miR-122-3p inhibitor abrogated LJZ's effects on UBE2I and PD-L1, and UBE2I overexpression rescued the LJZ-mediated effects on NF-κB and PD-L1. CONCLUSIONS: miR-122-3p targets UBE2I, thereby suppressing the NF-κB signaling cascade and downregulating PD-L1 expression, which potentiates anti-tumor immune responses. LJZ bolsters anti-tumor immunity by modulating the miR-122-3p/UBE2I/NF-κB/PD-L1 axis in liver cancer cells.

Trophic relationships between protists and bacteria and fungi drive the biogeography of rhizosphere soil microbial community and impact plant physiological and ecological functions.

Rhizosphere microorganisms play a vital role in enhancing plant health, productivity, and the accumulation of secondary metabolites. Currently, there is a limited understanding of the ecological processes that control the assembly of community. To address the role of microbial interactions in assembly and for functioning of the rhizosphere soil microbiota, we collected rhizosphere soil samples from Anisodus tanguticus on the Tibetan Plateau spanning 1500 kilometers, and sequenced the bacteria, fungi, archaea, and protist communities. We observed a significant but weak distance-decay relationship in the microbial communities of rhizosphere soil. Our comprehensive analysis of spatial, abiotic, and biotic factors showed that trophic relationships between protists and bacteria and fungi predominantly influenced the alpha and beta diversity of bacterial, fungal, and protistan communities, while abiotic factors had a greater impact on archaeal communities, including soil pH, available phosphorus, total phosphorus and mean annual temperature. Importantly, microbial interactions had a more significant influence on Anisodus tanguticus physiological and ecological functions compared to individual microorganisms. Network analyses revealed that bacteria occupy a central position of the co-occurrence network and play a crucial role of connector within this community. The addition of protists increased the stability of bacterial, fungal, and archaeal networks. Overall, our findings indicate that trophic relationships play an important role in assembly and for functioning of the rhizosphere soil microbiota. Bacterial communities serve as a crucial link between different kingdoms of microorganisms in the rhizosphere community. These findings help us to fully harness the beneficial functions of rhizosphere microorganisms for plants and achieve sustainable use of biological resources.

Adsorption of phosphate onto agricultural waste biochars with ferrite/manganese modified-ball-milled treatment and its reuse in saline soil.

Agricultural waste biochar was widely used to absorb phosphorus (P) from eutrophicated water and soil remediation. However, the research on the reuse of the sorbed P on biochar in infertile saline soil is insufficient. Biochars derived from four kinds of agricultural wastes (cotton straws from two origins, maize stalk, and rice husk) were modified and applied to adsorb phosphate in waste water and then be reused in saline soil in this study. The co-modified method combining ball milling and metal coated treatment obtained the higher specific surface area (SSA) of ferrite/manganese modified-ball-milled biochars (Fe/Mn-BMBCs) (226.5-331.5 m2 g-1) than that of pristine biochars (14.02-30.35 m2 g-1) and ferrite/manganese modified biochar (Fe/Mn-BC) (223.7 m2 g-1), which could improve the pore structure of metal modified biochar. The phosphate adsorption capacity (qmax) of Fe/Mn-BMBCs with rich functional groups and high SSA were 44.0-53.8 mg g-1, which was 4.47-5.82 times higher than that of pristine biochars. Fe/Mn-BMBCs showed efficiently adsorption performance at low pH and high temperature. The application of BC to saline soil could promote the availability of P in saline soil. P-loaded biochars could afford P as a nutrient to promote the growth of lettuce (Lactuca sativa L.) in saline soil. The lettuce fresh weight in Fe/Mn-BMBC-P2 treated soil was 8.21 times higher than that grew in control check (CK) treatment. As a P element provider, P-loaded biochars not only improve saline soil fertility and crop productivity, but also convert the agricultural wastes and P in eutrophicated waters to the sustainable resource.

Unraveling the mechanisms behind sodium persulphate-induced changes in petroleum-contaminated aquifers' biogeochemical parameters and microbial communities.

Sodium persulphate (PS) is a highly effective oxidising agent widely used in groundwater remediation and wastewater treatment. Although numerous studies have examined the impact of PS with respect to the removal efficiency of organic pollutants, the residual effects of PS exposure on the biogeochemical parameters and microbial ecosystems of contaminated aquifers are not well understood. This study investigates the effects of exposure to different concentrations of PS on the biogeochemical parameters of petroleum-contaminated aquifers using microcosm batch experiments. The results demonstrate that PS exposure increases the oxidation-reduction potential (ORP) and electrical conductivity (EC), while decreasing total organic carbon (TOC), dehydrogenase (DE), and polyphenol oxidase (PO) in the aquifer. Three-dimensional excitation-emission matrix (3D-EEM) analysis indicates PS is effective at reducing fulvic acid-like and humic acid-like substances and promoting microbial metabolic activity. In addition, PS exposure reduces the abundance of bacterial community species and the diversity index of evolutionary distance, with a more pronounced effect at high PS concentrations (31.25 mmol/L). Long-term (90 d) PS exposure results in an increase in the abundance of microorganisms with environmental resistance, organic matter degradation, and the ability to promote functional genes related to biological processes such as basal metabolism, transmission of genetic information, and cell motility of microorganisms. Structural equation modeling (SEM) further confirms that ORP and TOC are important drivers of change in the abundance of dominant phyla and functional genes. These results suggest exposure to different concentrations of PS has both direct and indirect effects on the dominant phyla and functional genes by influencing the geochemical parameters and enzymatic activity of the aquifer. This study provides a valuable reference for the application of PS in ecological engineering.

Phosphate deficiency responsive TaSPX3 is involved in the regulation of shoot phosphorus in Arabidopsis plants.

SPX (SYG/PHO81/XPR1) domain genes have been reported to play vital roles in the Phosphorus (Pi) signaling network in Arabidopsis thaliana and rice. However, the functions of SPX proteins in wheat remain largely unknown. In this study, the full-length cDNA sequence of the TaSPX3 gene was cloned from the common wheat variety Zhengmai9023. The expression of TaSPX3 was up-regulated in eight different genotypes of wheat under low phosphorus (LP) stress, indicating that TaSPX3 responds to Pi limitation in multiple wheat genotypes. The transcription level of TaSPX3 was also detected in the absence of seven different elements, showing certain specificity for Pi deficiency in wheat. Over expressing TaSPX3 in Arabidopsis can alleviate Pi deficiency symptoms at the seedling stage and promote the growth of plant, and advance the flowering period at the adult stage. The expression of 7 genes associated with the Pi starvation signal pathways was analyzed using qRT-PCR. The results showed that TaSPX3, along with AtSPX1, AtRNS1, AtIPS1, AtPAP2, AtPAP17 and AtAT4, were all induced by Pi deficiency. This study reveals that the TaSPX3 gene in wheat is involved in the response to phosphorus stress and may affect shoot phosphorus levels through AT4 or PAPs-related pathways. Overall, our study provides new insights into the regulation of plant response under LP conditions and the molecular mechanism underlying the role of the wheat SPX gene in coping with LP stress.

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.

Electroacupuncture ameliorates AOM/DSS-induced mice colorectal cancer by inhibiting inflammation and promoting autophagy via the SIRT1/miR-215/Atg14 axis.

Colorectal cancer (CRC) is one of the most common tumors of the digestive tract, with the third-highest incidence and the second-highest mortality rate among all malignant tumors worldwide. However, treatment options for CRC remain limited. As a complementary therapy, acupuncture or electro-acupuncture (EA) has been widely applied in the treatment of various inflammation-related diseases, such as obesity, ulcerative colitis and tumors. Although numerous pre-clinical and clinical studies have investigated the beneficial effects of acupuncture on CRC, the mechanism underlying the therapeutic action of EA is largely unknown. Evidence from previous studies has revealed that SIRT1 participates in CRC progression by activating autophagy-related miRNAs. Using azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colorectal cancer model in mice, we explored whether EA treatment can inhibit inflammation and promote autophagy via the SIRT1/miR-215/Atg14 axis. Our results showed that EA notably alleviated the CRC in mice, by decreasing the tumor number and DAI scores, inflammation, and increasing body weight of mice. Besides, EA increased the expression of SIRT1 and autophagy. Further experiments showed that SIRT1 overexpression downregulated miR-215, and promoted the expression of Atg14, whereas SIRT1 knockdown induced opposite results. In conclusion, EA can ameliorate AOM/DSS-induced CRC through regulating the SIRT1-mediated miR-215/Atg14 axis by suppressing inflammation and promoting autophagy in mice. These findings reveal a potential molecular mechanism underlying the anti-CRC effect of EA indicating that EA is a promising therapeutic candidate for CRC.

Herba Patriniae and its component Isovitexin show anti-colorectal cancer effects by inducing apoptosis and cell-cycle arrest via p53 activation.

Colorectal cancer (CRC) is the most prevalent cancer of the digestive tract. Herba Patriniae (also known as Bai Jiang Cao, HP) have been widely used to manage diarrhea, ulcerative colitis, and several cancers, including CRC. Nonetheless, the molecular mechanisms underlying the pharmacological action of HP on CRC remain unclear. This study investigated the underlying mechanisms of HP against CRC using network pharmacology analysis and in vitro and in vivo experiments. The results revealed nine bioactive compounds of HP. Furthermore, 3460 CRC-related targets of the identified active compounds were predicted from the Gene Expression Omnibus (GEO) database. Furthermore, 65 common targets were identified through the intersection of two related targets. Moreover, ten hub genes, including CDK4, CDK2, CDK1, CCND1, CCNB1, CCNA2, MYC, E2F1, CHEK1, and CDKN1A were identified through the topological analysis. Meanwhile, the GO and KEGG pathway analysis revealed that the core target genes were majorly enriched in the p53 and HIF-1 signaling pathways. Moreover, HP promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway in a dose-dependent manner, while a similar effect was observed for Isovitexin (the primary component of HP). Overall, this study provides valuable insights into the underlying mechanisms of HP and its component Isovitexin against CRC, providing a theoretical foundation for additional experimental verification of its clinical application.

Novel Nitric Oxide Donor-Azole Conjugation Strategy for Efficient Treatment of Cryptococcus neoformans Infections.

Invasive fungal infections (IFIs) such as cryptococcal meningitis (CM) remain a serious health issue worldwide due to drug resistance closely related to biofilm formation. Unfortunately, available antifungal drugs with ideal safety and promising potency are still lacking; thus, the research of new candidate and therapeutic approach is urgently needed. As an important gas messenger molecule, nitric oxide (NO) shows vital inhibition on various microorganism biofilms. Hence, three series of novel NO-donating azole derivatives were designed and synthesized, and the in vitro antifungal activity as well as the mechanism of action was investigated. Among them, 3a and 3e displayed excellent antifungal activity against Cryptococcus neoformans and biofilm depending on the release of NO. Moreover, a more stable analogue 3h of 3a demonstrated markedly anti-CM effects via intranasal dropping, avoiding the first-pass effects and possessing a better brain permeability bypass blood-brain barrier. These results present a promising antifungal candidate and intranasal dropping approach for the treatment of CM, warranting further studies.

Effect of fermented dandelion on productive performance, meat quality, immune function, and intestinal microbiota of broiler chickens.

BACKGROUND: Dandelion has a great potential to be used as feed additive. Using microbial fermentation technology to degrade cell walls is conducive to enable better release of bioactive compounds of dandelion. This study intended to explore the effect of fermented dandelion (FD) on production performance, meat quality, immune function, and intestinal microbiota of broiler chickens. One-hundred and twenty 1-day-old male Arbor Acres broiler chickens were randomly allotted into three treatments: CON (basal diet, control), LFD and HFD (basal diet with 500 and 1000 mg/kg FD, respectively), with five replicates of eight birds each. The experiment lasted for 42 days. RESULTS: The results showed that birds in HFD group had increased ADG during 1-21 days (P < 0.05). On day 21, the bursa of Fabricius index of birds in LFD group was higher (P < 0.05), while the serum contents of IFN-γ and TNF-ɑ were lower in HFD group (P < 0.05). FD supplementation decreased the observed_species, shannon, chao1 and ace indexes (P < 0.05) as well as the abundance of Bacteroidota, Bacteroides, and Alistipes (P < 0.05). Birds in HFD group had higher abundance of Firmicutes and lower abundance of Verrucomicrobiota (P < 0.05). LFD group had lower abundance of unidentified_bacteria (P < 0.05). On day 42, the abdominal fat yield of HFD group was decreased (P < 0.05). Birds in LFD group had lower L* and b* values of breast muscle (P < 0.05), while higher spleen index. The CAT activities of breast muscle of FD groups were higher (P < 0.05). CONCLUSION: In summary, dietary FD supplementation at 1000 mg/kg improved production performance and immune function and modulated microbiota composition in ileum of broiler chickens. FD can be supplemented in the diet to enhance performance and health of broiler chickens, of which 1000 mg/kg FD is more effective.

The effects of carbon nitrogen ratio and salinity on the treatment of swine digestion effluent simultaneously producing bioenergy by microalgae biofilm.

In order to remove high concentrations of ammonia nitrogen (NH4+-N) and refractory sulfamethazine (SM2) from swine digestion effluent, different carbon/nitrogen (C/N) ratios and salinity were used to determine the effects of pollutants removal in the microalgae biofilm system. Microalgae biofilm treatment under optimal environmental conditions in synthetic swine digestion effluent were C/N ratio of 20 and salinity of 140 mM. In order to make the actual swine digestion effluent discharge up to the standard, three different two-cycle treatments (suspended microalgae, microalgae biofilm, microalgae biofilm under the optimal conditions) were studied. The results showed that after two-cycle treatment with microalgae biofilm under the optimal conditions, the actual swine digestion effluent levels of total nitrogen (TN), NH4+-N, total phosphorus (TP), chemical oxygen demand (COD), SM2 were 22.65, 9.32, 4.11, 367.28, and 0.99 mg L-1, respectively, which could satisfy the discharge standards for livestock and poultry wastewater in China. At the same time, first-order kinetic simulation equations suggested a degradation half-life of 4.85 d for SM2 under optimal conditions in microalgae biofilm, and microbial community analysis indicated that the dominant genus was Halomonas. Furthermore, 35.66% of lipid, 32.56% of protein and 18.44% of polysaccharides were harvested after two-cycle in microalgae biofilm treatment under optimal environmental conditions. These results indicated that the regulation of C/N and salinity in microalgae biofilm for the treatment of swine digestion effluent was a high-efficiency strategy to simultaneously achieve wastewater treatment and bioenergy production.

Discovery of Pyrazolone Carbothioamide Derivatives as Inhibitors of the Pdr1-KIX Interaction for Combinational Treatment of Azole-Resistant Candidiasis.

Candida glabrata has emerged as an important opportunistic pathogen of invasive candidiasis due to increasing drug resistance. Targeting Pdr1-KIX interactions with small molecules represents a potential strategy for treating drug-resistant candidiasis. However, effective Pdr1-KIX inhibitors are rather limited, hindering the validation of target druggability. Here, new Pdr1-KIX inhibitors were designed and assayed. Particularly, compound B8 possessed a new chemical scaffold and exhibited potent KIX binding affinity, leading to enhanced synergistic efficacy with fluconazole to treat resistant C. glabrata infection (FICI = 0.28). Compound B8 acted by inhibiting the efflux pump and down-regulating resistance-associated genes through blocking the Pdr1-KIX interaction. Compound B8 exhibited excellent in vitro and in vivo antifungal potency in combination with fluconazole against azole-resistant C. glabrata. It also had direct antifungal effect to treat C. glabrata infection, suggesting new mechanisms of action independent of Pdr1-KIX inhibition. Therefore, compound B8 represents a promising lead compound for antifungal drug development.

Mollugin activates GLP-1R to improve cognitive dysfunction in type 2 diabetic mice.

AIMS: The incidence of diabetic cognitive dysfunction is increasing year by year, and it has gradually become a research hot spot. Studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can improve cognitive dysfunction in diabetic patients. This study focuses on whether small molecule GLP-1R agonists from traditional Chinese medicine (TCM) can improve the diabetic cognitive dysfunction. MATERIALS AND METHODS: The small molecules from TCM were screened by cell membrane chromatography (CMC) with GLP-1R-HEK293 cell membrane column. MTT assay, flow cytometry, immunofluorescence cytochemistry and other methods were used to determine the effects of mollugin on the apoptosis rate and reactive oxygen species (ROS) level of high glucose (HG)/hydrogen peroxide (H2O2) induced PC12 cells. Real-Time PCR was used to detect mRNA expression in mouse cerebral cortex. Water maze test was further used to confirm the effect of mollugin on cognitive dysfunction in T2DM mice. KEY FINDINGS: Mollugin bound to GLP-1R, promoted Ca2+ influx, increased insulin secretion and cAMP content in ß-TC-6 cells. Mollugin enhanced the cell viability, ameliorated apoptosis, reduced intracellular ROS levels in HG/H2O2-injured PC12 cells. Mollugin reduced the T2DM mice's escape latency, improved neuronal cell damage, decreased the expression of Pik3ca, Akt1 and Mapk1 mRNA in the cerebral cortex tissue. SIGNIFICANCE: The results suggest that mollugin could improve cognitive dysfunction in T2DM mice through activating GLP-1R/cAMP/PKA signal pathway.

Efficacy of mind-body therapies for sleep disturbance in patients with early-stage cancer: A systematic review and network meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy of different mind-body therapies (MBTs) for sleep disturbance in patients with early-stage cancer. METHODS: Randomised controlled trials that included patients (aged ≥18 years) with early stage cancer who underwent MBTs (mindfulness, hypnosis, relaxation, yoga, and qigong) were searched in the CINAHL via the EBSCO Host, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed, and Scopus databases, from the date of database inception to October 2022. The outcomes were subjective sleep disturbance and objective sleep efficiency. Network meta-analysis (NMA) and comparative effects ranking were performed using STATA (v14.0; STATACorp, College Station, TX, USA). RESULTS: Forty-seven studies investigating five MBTs were included in the NMA. For cancer patients receiving active treatment, mindfulness demonstrated the largest effect size in reducing subjective sleep disturbance (standardised mean difference [SMD]: 0.85; 95% confidence intervals [CI]: 0.20-1.50; Grading of Recommendations Assessment, Development, and Evaluation assessment: moderate), and had the highest cumulative probability compared to usual care or waitlist. For cancer patients who had completed active treatment, qigong demonstrated the largest effect size in reducing subjective sleep disturbance (SMD: 0.99; 95% CI: 0.35-1.63; GRADE: low), followed by hypnosis (SMD: 0.87; 95% CI: 0.32-1.42; GRADE: moderate), and mindfulness (SMD: 0.42; 95% CI: 0.24-0.59; GRADE: moderate). Qigong also demonstrated the largest effect size in improving objective sleep efficiency (weighted mean differences: 10.76; 95% CI: 2.01-19.50; GRADE: low); however, the effect of qigong was tested in only one study in this NMA. Among the eight different treatment conditions, cognitive behavioral therapy (CBT) showed the highest cumulative probability (surface under the cumulative ranking curve: 96.3%) in reducing subjective sleep disturbance and the second highest cumulative probability (SUCRA: 83.3%) in improving objective sleep efficiency. CONCLUSION: There is no evidence supporting the use of MBTs to replace or be comparable to CBT. Mindfulness can be recommended as an optional treatment for reducing sleep disturbance in patients with early-stage cancer. Some support was observed for qigong and hypnosis in reducing sleep disturbances in patients with early-stage cancer who had completed active treatment. More rigorous trials are warranted to confirm whether different forms of MBTs have different effects on sleep in patients with cancer.

Application of instantaneous nebulization dispersive liquid-phase microextraction combined with HPLC for the determination of chalcone and isoflavone in traditional Chinese medicines.

A simple and rapid instantaneous nebulization dispersive liquid-phase microextraction method was developed, and combined with high-performance liquid chromatography for determination of the contents of seven analytes in traditional Chinese medicines. In this study, using the sprinkler device to achieve instantaneous synchronous dispersion and extraction, only one spray can rapidly achieve the concentration and enrichment of seven kinds of chalcone and isoflavones. The key factors affecting the extraction efficiency were optimized including the type and volume of extractant, the pH and salt concentration of the sample phase, and the number of dispersion. Under the optimal conditions, the enrichment factor of the target analytes ranged from 103.1 to 180.9, with good linearity and correlation coefficients above 0.9970. The limits of detection ranged from 0.02 to 0.15 ng/mL, with good accuracy (recoveries 91.1 to 108.9%) and precision (relative standard deviations 1.5-7.1%). This method has short extraction time (2 s), low organic solvent consumption and high enrichment effect, so it has a wide application prospects.

Natural compound So-2 suppresses triple-negative breast cancer through inducing ferroptosis via downregulating transcription factor E2F7.

Triple-negative breast cancer (TNBC), accounting for about 15∼18% of all breast cancers, is notorious for its poor prognosis, high rate of relapse and short overall survival. Because of lacking effective therapeutic targets or drugs, treatment of TNBC in clinical encounters great obstacle. Siegesbeckiaorientalis L. have been used as a traditional Chinese medicine "Xi-Xian-Cao" for centuries with multiple medicinal benefits including cancerous treatment. We have reported the isolation of twenty-seven germacranolides including So-2 from the aerial parts of S. orientalis with potent cytotoxicity against breast cancer cells. The studyaims to verified the anti-TNBC function of the natural compound So-2 both in vitro and vivo and uncover the underlying mechanism. The results showed that So-2 caused cell cycle arrest and suppress TNBC cell proliferation and migration. Also, So-2 was first identified to be a bona fide ferroptosis inducer in TNBC cells. So-2 effectively suppressed tumor growth of TNBC by using an orthotopic transplantation tumor model. We also characterized the oncogenic role of the transcription factor E2F7 in TNBC. E2F7 was demonstrated to be involved in the ferroptosis-inducing and tumor suppression effect of So-2. Altogether, So-2 exhibits inhibitory effect on TNBC both in vitro and vivo by inducing TNBC ferroptosis via downregulating the expression of E2F7. These findings provide valuable insight into the pathogenesis of TNBC. The natural compound So-2, isolated from Chinese traditional medicine, might be a prospective drug candidate in TNBC therapy.

Schisandrin B, a potential GLP-1R agonist, exerts anti-diabetic effects by stimulating insulin secretion.

Diabetes mellitus is a metabolic disease that is characterized by elevated blood sugar. Although glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood glucose in a glucose-dependent manner, most of them are macromolecule polypeptides. Macromolecular peptides are relatively expensive and inconvenient compared with small molecules. Therefore, this study sought to identify the small molecules binding to GLP-1R via cell membrane chromatography (CMC), confirm their agonistic activity, and further study its beneficial effects in a mouse model of type 2 diabetes mellitus (T2DM) induced by a combination of high-fat diet and streptozotocin. We used CMC, calcium imaging and molecular docking techniques to screen and identify the potential small molecule Schisandrin B (Sch B), which exhibits a strong binding effect to GLP-1R, from the small molecule library of traditional Chinese medicine. Through in-vitro experiments, we found that Sch B stimulated insulin secretion in ß-TC-6 cells, while GLP-1R antagonist Exendin9-39, adenylate cyclase inhibitor SQ22536, and protein kinase A (PKA) inhibitor H89 could significantly inhibit the insulin secretion induced by Sch B. In vivo, Sch B significantly improved fasting blood glucose levels, intraperitoneal glucose tolerance test damage, and the status of pancreatic tissue damage, and reduced serum insulin levels, total cholesterol, triglyceride and low density lipoprotein in T2DM mice. These results indicate that Sch B alleviates T2DM by promoting insulin release through the GLP-1R/cAMP/PKA signaling pathway, suggesting that Sch B may be a potential GLP-1RA, which is expected to provide a new therapeutic strategy for the prevention and treatment of T2DM.

Hyperthermic Intraperitoneal Chemotherapy May Damage Renal Function and Cause Serum Electrolyte Disturbance: A Retrospective Observational Study.

OBJECTIVE: The objective of this study was to evaluate the efficacy of postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) on bone marrow hematopoiesis, liver and kidney function, and serum electrolytes for patients who underwent open radical gastrectomy, and investigate the variation tendency of above indicators. MATERIALS AND METHODS: The clinical data of 153 patients who underwent open radical gastrectomy were retrospectively analyzed and were divided into HIPEC group (n=83) and control group (n=70). Repeated analysis of variance was used to analyze the variation tendency of bone marrow hematopoiesis, liver and kidney function, and serum electrolytes in the HIPEC and control group, respectively, and then made a comparison between the 2 groups. RESULTS: There were statistical differences in alanine aminotransferase ( P =0.034), phosphorus ( P+ ) ( P <0.05), potassium (K + ) ( P =0.023), sodium (Na + ) ( P <0.001), and chloride (Cl - ) ( P =0.008) between HIPEC and control group. All outcome indicators changed significantly over time ( P <0.05). No significant difference was found in hemoglobin, white blood cell, platelet, aspartate aminotransferase, total bilirubin, or uric acid between the 2 treatment groups at each time point. On the next day after HIPEC treatment, the levels of blood urea nitrogen, creatinine, and P+ were higher in the HIPEC group, whereas the calcium (Ca + ), magnesium (Mg + ), and K + levels of HIPEC group tended to be lower. However, the effects of HIPEC on alanine aminotransferase, Na + , and Cl - levels needed to be further explored. CONCLUSIONS: HIPEC treatment after open radical gastrectomy has no significant effect on hematopoietic bone marrow and liver function but may damage renal function; reduce Ca + , Mg + , K + levels; and increase P+ level.