Enhanced uranium removal from aqueous solution by core-shell Fe0@Fe3O4: Insight into the synergistic effect of Fe0 and Fe3O4.

In this study, Fe0@Fe3O4 was synthesized and used to remove U(VI) from groundwater. Different experimental conditions and cycling experiments were used to investigate the performance of Fe0@Fe3O4 in the U(VI) removal, and the XRD, TEM, XPS and XANES techniques were employed to characterize the Fe0@Fe3O4. The results showed that the U(VI) removal efficiency of Fe0@Fe3O4 was 48.5 mg/g that was higher than the sum of removal efficiency of Fe0 and Fe3O4. The uranium on the surface of Fe0@Fe3O4 mainly existed as U(IV), followed by U(VI) and U(V). The Fe0 content decreased after reaction, while the Fe3O4 content increased. Based on the results of experiments and characterization, the enhanced removal efficiency of Fe0@Fe3O4 was attributed to the synergistic effect of Fe0 and Fe3O4 in which Fe3O4 accelerated the Fe0 corrosion that promoted the progressively formation of Fe(II) that promoted the reduction of adsorbed U(VI) to U(IV) and incorporated U(VI) to U(V). The performance of Fe0@Fe3O4 at near-neutrality condition was better than at acidic and alkalic conditions. The chloride ions, sulfate ions and nitrate ions showed minor effect on the Fe0@Fe3O4 performance, while carbonate ions exhibited significant inhibition. The metal cations showed different effect on the Fe0@Fe3O4 performance. The removal efficiency of Fe0@Fe3O4 decreased with the number of cycling experiment. Ionizing radiation could regenerate the used Fe0@Fe3O4. This study provides insight into the U(VI) removal by Fe0@Fe3O4 in aqueous solution.

Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Cross-reaction mediated by distinct key amino acid combinations in the complementary-determining region (CDR) of a monoclonal antibody.

In immunology, cross-reaction between antigens and antibodies are commonly observed. Prior research has shown that various monoclonal antibodies (mAbs) can recognize a broad spectrum of epitopes related to influenza viruses. However, existing theories on cross-reactions fall short in explaining the phenomena observed. This study explored the interaction characteristics of H1-74 mAb with three peptides: two natural peptides, LVLWGIHHP and LPFQNI, derived from the hemagglutinin (HA) antigen of the H1N1 influenza virus, and one synthetic peptide, WPFQNY. Our findings indicate that the complementarity-determining region (CDR) of H1-74 mAb comprised five antigen-binding sites, containing eight key amino acid residues from the light chain variable region and 16 from the heavy chain variable region. These critical residues formed distinct hydrophobic or hydrophilic clusters and functional groups within the binding sites, facilitating interaction with antigen epitopes through hydrogen bonding, salt bridge formation, and π-π stacking. The study revealed that the formation of the antibody molecule led to the creation of binding groups and small units in the CDR, allowing the antibody to attach to a variety of antigen epitopes through diverse combinations of these small units and functional groups. This unique ability of the antibody to bind with antigen epitopes provides a new molecular basis for explaining the phenomenon of antibody cross-reaction.

The role of Ginkgo Folium on antitumor: Bioactive constituents and the potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.

Effects of DHA on cognitive dysfunction in aging and Alzheimer's disease: The mediating roles of ApoE.

The prevalence of Alzheimer's disease (AD) continues to rise due to the increasing aging population. Among the various genetic factors associated with AD, apolipoprotein E (ApoE), a lipid transporter, stands out as the primary genetic risk factor. Specifically, individuals carrying the ApoE4 allele exhibit a significantly higher risk. However, emerging research indicates that dietary factors play a prominent role in modifying the risk of AD. Docosahexaenoic acid (DHA), a prominent ω-3 fatty acid, has garnered considerable attention for its potential to ameliorate cognitive function. The intricate interplay between DHA and the ApoE genotype within the brain, which may influence DHA's utilization and functionality, warrants further investigation. This review meticulously examines experimental and clinical studies exploring the effects of DHA on cognitive decline. Special emphasis is placed on elucidating the role of ApoE gene polymorphism and the underlying mechanisms are discussed. These studies suggest that early DHA supplementation may confer benefits to cognitively normal older adults carrying the ApoE4 gene. However, once AD develops, ApoE4 non-carriers may experience greater benefits compared to ApoE4 carriers, although the overall effectiveness of DHA supplementation at this stage is limited. Potential mechanisms underlying these differential effects may include accelerated DHA catabolism in ApoE4 carriers, impaired transport across the blood-brain barrier (BBB), and compromised lipidation and circulatory function in ApoE4 carriers. Thus, the supplementation of DHA may represent a potential intervention strategy aimed at compensating for these deficiencies in ApoE4 carriers prior to the onset of AD.

Genetically engineered probiotics for an optical imaging-guided tumor photothermal therapy/immunotherapy.

Bacteria-based cancer therapy (BCT) has been extensively investigated because of the tumor targeting and antitumor immunity activating abilities of bacteria over traditional nanodrugs, but their potential systemic toxicity poses a challenge. Therefore, it is important to visualize the precise localization and real-time distribution of bacteria in vivo to guide the treatment. Herein, biogenetically engineered Escherichia coli Nissle 1917 (EcN) were constructed to highly express tyrosinase to intracellularly generate cyanine 5-labeled melanin-like polymers (Cy5-Mel), thus endowing them with a bright fluorescence and an excellent photothermal performance upon NIR laser irradiation, thereby inducing the intense immunogenic death of tumor cells and release of tumor-associated antigens. Acting as adjuvants, bacteria can greatly stimulate the maturation of dendritic (DC) cells. The in vivo behaviors of these bacteria was monitored via noninvasive optical imaging when they were intravenously administrated to tumor-bearing mice. From this, NIR exposure on tumor sites was carried out at an appropriate time point to induce the damage to tumor cells and for the modulation of tumor immune microenvironments. Thus, via a simple bioengineering strategy, a promising bacteria-based theranostic platform was constructed for tumor treatment.

Electroacupuncture stimulation to modulate neural oscillations in promoting neurological rehabilitation.

Electroacupuncture (EA) stimulation is a modern neuromodulation technique that integrates traditional Chinese acupuncture therapy with contemporary electrical stimulation. It involves the application of electrical currents to specific acupoints on the body following acupuncture. EA has been widely used in the treatment of various neurological disorders, including epilepsy, stroke, Parkinson's disease, and Alzheimer's disease. Recent research suggests that EA stimulation may modulate neural oscillations, correcting abnormal brain electrical activity, therefore promoting brain function and aiding in neurological rehabilitation. This paper conducted a comprehensive search in databases such as PubMed, Web of Science, and CNKI using keywords like "electroacupuncture," "neural oscillations," and "neurorehabilitation", covering the period from year 1980 to 2023. We provide a detailed overview of how electroacupuncture stimulation modulates neural oscillations, including maintaining neural activity homeostasis, influencing neurotransmitter release, improving cerebral hemodynamics, and enhancing specific neural functional networks. The paper also discusses the current state of research, limitations of electroacupuncture-induced neural oscillation techniques, and explores prospects for their combined application, aiming to offer broader insights for both basic and clinical research.

Identification and analysis of differential miRNA-mRNA interactions in coronary heart disease: an experimental screening approach.

Objective: This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway. Methods: Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis. Results: The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P < 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P < 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P < 0.0001). Conclusion: The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.

Antidepressant effect of bright light therapy on patients with Alzheimer's disease and their caregivers.

Background: As a non-pharmacologic treatment, bright light therapy (BLT) is often used to improve affective disorders and memory function. In this study, we aimed to determine the effect of BLT on depression and electrophysiological features of the brain in patients with Alzheimer's disease (AD) and their caregivers using a light-emitting diode device of 14000 lux. Methods: A 4-week case-control trial was conducted. Neuropsychiatric and electroencephalogram (EEG) examination were evaluated at baseline and after 4 weeks. EEG power in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) bands was calculated for our main analysis. Demographic and clinical variables were analyzed using Student's t test and the chi-square test. Pearson's correlation was used to determine the correlation between electrophysiological features, blood biochemical indicators, and cognitive assessment scale scores. Results: In this study, 22 in-patients with AD and 23 caregivers were recruited. After BLT, the Hamilton depression scale score decreased in the fourth week. Compared with the age-matched controls of their caregivers, a higher spectral power at the lower delta and theta frequencies was observed in the AD group. After BLT, the EEG power of the delta and theta frequencies in the AD group decreased. No change was observed in blood amyloid concentrations before and after BLT. Conclusion: In conclusion, a 4-week course of BLT significantly suppressed depression in patients with AD and their caregivers. Moreover, changes in EEG power were also significant in both groups.

[Effects of electroacupuncture on the secretion function of ovarian cells and kisspeptin/kiss1r system in rats with polycystic ovarian syndrome].

OBJECTIVE: To observe the effects of electroacupuncture （EA） on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome （PCOS）, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats. METHODS: Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole （0.1 mg/mL, 10 mL•kg-1•d-1）. In the EA group, EA （2 Hz, 2 mA） was used to stimulate "Guanyuan" （CV4） for 20 min each time. In the flutamide group, flutamide solution （50 mg•kg-1•d-1） was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone （T）, luteinizing hormone （LH） and estradiol （E2） in serum, the contents of E2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot. RESULTS: Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was decreased （P<0.01） in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was increased （P<0.05, P<0.01）. CONCLUSION: EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.

Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation.

Fangji Huangqi Tang (FHT) is a well-known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT-herb-active compound-target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein-protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS-like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt-qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti-SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS-related autoantibodies (anti-SSA and anti-SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt-qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

[Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial].

OBJECTIVE: To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA). METHODS: A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups. RESULTS: After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05). CONCLUSION: Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.

Effects of Conventional Speech Therapy with Liuzijue Qigong, a Traditional Chinese Method of Breath Training, in 70 Patients with Post-Stroke Spastic Dysarthria.

BACKGROUND Post-stroke spastic dysarthria (PSSD) is a motor speech impairment that impacts patient communication and quality of life. Liuzijue Qigong (LQG), a traditional Chinese method of breath training, could serve as an effective treatment for PSSD. This study compared the effects of conventional speech therapy and conventional speech therapy combined with LQG in patients with PSSD. MATERIAL AND METHODS Seventy patients with PSSD were randomly divided into a control group (conventional speech therapy, n=35, 77.14% cerebral infarction, 22.86% cerebral hemorrhage) and experimental group (LQG combined with conventional speech therapy, n=35, 85.71% cerebral infarction, 14.29% cerebral hemorrhage). Conventional speech therapy included relaxation, breath control, organ articulation, and pronunciation training. LQG involved producing 6 different sounds (Xu, He, Hu, Si, Chui, and Xi) accompanied by breathing and body movements. Patients were treated once a day, 5 times a week, for 4 weeks. The Frenchay Dysarthria Assessment scale (FDA), speech articulation, maximum phonation time (MPT), loudness, and Montreal Cognitive Assessment scale (MoCA) were evaluated. RESULTS At 4 weeks, the experimental group showed significant improvements compared with the control group in the change of FDA (13.26±6.84 vs 18.03±5.32, P=0.028), speech articulation (63.17±22.40 vs 76.51±15.28, P=0.024), MPT (1.34±1.30 vs 3.89±3.98, P<0.001), loudness (3.46±2.74 vs 7.14±2.56, P=0.009), MoCA (19.40±3.72 vs 22.20±5.30, P=0.020), total effective rate (68.57% vs 88.57%, P=0.041). CONCLUSIONS LQG, when combined with conventional speech therapy, enhanced the comprehensive speech ability of patients with PSSD compared with conventional treatment alone.

Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells.

This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 µM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.

[Mechanisms of traditional Chinese medicine formulas and active ingredients in regulation of macrophage subsets involved in inflammation and repair of coronary heart disease].

Coronary artery disease(CAD) caused by atherosclerosis(AS) is a major contributor to the global burden of disease. The pathogenesis of CAD is complex, and the subset and function of cardiac macrophages are important factors affecting the occurrence and development of AS and the prognosis of CAD. Recent studies have shown that some traditional Chinese medicine(TCM) formulas and active ingredients can regulate macrophage subsets involved in the inflammation, injury, and repair process of CAD. This paper summarized the significant role of macrophages in AS and myocardial infarction. Based on the plasticity of macrophages, this paper elaborated that traditional Chinese medicine prevented and attenuated AS by regulating macrophage subsets, reducing the level of inflammatory factors, and promoting macrophage autophagy.Traditional Chinese medicine participated in the cardiac repair process after myocardial infarction by accelerating the recruitment of M2 macrophages, inhibiting the polarization of M1 macrophages mediated by glycolysis, inhibiting M1 macrophage-mediated cardiac nerve remodeling, and promoting M2 macrophage-mediated angiogenesis. In addition, in vitro studies on the regulation of macrophage subsets by the active ingredients of traditional Chinese medicine were also reviewed. It was pointed out that nuclear factor kappa B(NF-κB), adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt), chemokine(C-C motif) ligand 2/C-C chemokine receptor type 2(CCL2/CCR2) were the key targets and pathways for the regulation of macrophages by TCM.

Metal-organic framework-encapsulated dihydroartemisinin nanoparticles induces apoptotic cell death in ovarian cancer by blocking ROMO1-mediated ROS production.

Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

[Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology].

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

[Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification].

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.

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.

Cistanche tubulosa alleviates ischemic stroke-induced blood-brain barrier damage by modulating microglia-mediated neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. AIM OF THE STUDY: This study aimed to identify CT's curative effect on IS and explore its underlying mechanism. MATERIALS AND METHODS: IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mg/kg/day was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. RESULTS: According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. CONCLUSION: These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.