[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Cryptochrome PtCPF1 regulates high temperature acclimation of marine diatoms through coordination of iron and phosphorus uptake.

Increasing ocean temperatures threaten the productivity and species composition of marine diatoms. High temperature response and regulation are important for the acclimation of marine diatoms to such environments. However, the molecular mechanisms behind their acclimation to high temperature are still largely unknown. In this study, the abundance of PtCPF1 homologs (a member of the cryptochrome-photolyase family in the model diatom Phaeodactylum tricornutum) transcripts in marine phytoplankton is shown to increase with rising temperature based on Tara Oceans datasets. Moreover, the expression of PtCPF1 in P. tricornutum at high temperature (26 °C) was much higher than that at optimum temperature (20 °C). Deletion of PtCPF1 in P. tricornutum disrupted the expression of genes encoding two phytotransferrins (ISIP2A and ISIP1) and two Na+/P co-transporters (PHATRDRAFT_47667 and PHATRDRAFT_40433) at 26 °C. This further impacted the uptake of Fe and P, and eventually caused the arrest of cell division. Gene expression, Fe and P uptake, and cell division were restored by rescue with the native PtCPF1 gene. Furthermore, PtCPF1 interacts with two putative transcription factors (BolA and TF IIA) that potentially regulate the expression of genes encoding phytotransferrins and Na+/P co-transporters. To the best of our knowledge, this is the first study to reveal PtCPF1 as an essential regulator in the acclimation of marine diatoms to high temperature through the coordination of Fe and P uptake. Therefore, these findings help elucidate how marine diatoms acclimate to high temperature.

Biphasic Rapid Culture in Differential Diagnosis of Tuberculosis.

Context: Early intervention and treatment are key measures for tuberculosis (TB) prevention and control, making early, rapid, and accurate diagnostic methods crucial. The Liquid-solid (Biphasic) rapid cultures is a novel tool for the differential diagnosis of tuberculosis. Objective: The study intended to evaluate the value of the biphasic cultures by comparing it to the acid-fast staining and liquid cultures, which have been the traditional gold-standard technology, to determine its value in the diagnosis of TB. Design: The research team conducted an experimental study. Setting: The study took place at the Affiliated Wuxi Fifth Hospital of Jiangnan University in Wuxi, China. Participants: Participants were 221 patients with suspected pulmonary tuberculosis who had been admitted to the hospital between July 2020 and December 2021. Outcome Measures: Using three methods-liquid-solid (biphasic) culture, acid-fast staining, and mycobacterial growth indicator tube (MGIT) 960 liquid culture, the research team tested participants' sputum samples: (1) for sensitivity; (2) for time to positive culture results, and (3) for differential diagnosis. Results: The biphasic culture's sensitivity was significantly higher than that of acid-fast staining, (P = .0003), and no significant difference existed between it and the MGIT 960 liquid cultures. The biphasic cultures's mean time to positivity was significantly shorter than that of the MGIT 960 liquid culture at the intervals 11-20 d (P < .0001) and 21-35 days (P = .0001). Moreover, the biphasic cultures could preliminarily differentiate nontuberculous mycobacteria (NTM) from mycobacterium tuberculosis (MTB), which is a significant advantage in tuberculosis diagnosis. Conclusions: This study highlights the potential of a biphasic culture as a reliable tool for the rapid differential diagnosis of tuberculosis, with a faster detection cycle and a higher sensitivity than conventional methods. The biphasic cultures is a valuable addition to the tuberculosis diagnostic armamentarium and can help improve patients' outcomes by enabling earlier diagnosis and treatments.

The protein kinase A signaling pathway mediates the effect of electroacupuncture on excessive contraction of the bladder detrusor in a rat model of neurogenic bladder.

BACKGROUND: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. AIMS: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. METHODS: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. RESULTS: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. CONCLUSION: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB.

Comparative effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with chronic low back pain.

OBJECTIVES: Chronic low back pain (CLBP) can seriously impair the quality of life of patients and has a remarkable comorbidity with psychological symptoms, which, in turn, can further exacerbate the symptoms of CLBP. Psychological treatments are critical and nonnegligent for the management of CLBP, and thus, should attract sufficient attention. However, current evidence does not suggest the superiority and effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with CLBP.Thus, this study was designed to compare the effectiveness of nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP and to recommend preferred strategies for attenuating psychological symptoms in clinical practice. METHODS: In this systematic review and network meta-analysis (NMA), PubMed, Embase Database, Web of Science, and Cochrane Library were searched from database inception until March 2022. Randomized clinical trials (RCTs) that compare different nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP were eligible. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was used. Four reviewers in pairs and divided into two groups independently performed literature selection, data extraction, and risk of bias, and certainty of evidence assessments. This NMA was conducted with a random effects model under a frequentist framework. The major outcomes were depression, anxiety, and mental health presented as the standardized mean difference (SMD) with the corresponding 95% CI. RESULTS: A total of 66 RCTs that randomized 4806 patients with CLBP met the inclusion criteria. The quality of evidence was typically low or some risks of bias (47 out of 66 trials, 71.3%), and the precision of summary estimates for effectiveness varied substantially. In addition, 7 categories of interventions with 26 specific treatments were evaluated. For depression, mind body therapy (pooled SMD = -1.20, 95% CI: -1.63 to -0.78), biopsychosocial approach (pooled SMD = -0.41, 95% CI: -0.70 to -0.12), and physical therapy (pooled SMD = -0.26, 95% CI: -0.50 to -0.02) exhibited remarkable effectiveness in reducing depression compared with the control group. For managing anxiety, mind body therapy (pooled SMD = -1.35, 95% CI: -1.90 to -0.80), multicomponent intervention (pooled SMD = -0.47, 95% CI: -0.88 to -0.06), and a biopsychosocial approach (pooled SMD = -0.46, 95% CI: -0.79 to -0.14) were substantially superior to the control group. For improving mental health, multicomponent intervention (pooled SMD = 0.77, 95% CI: 0.14 to 1.39), exercise (pooled SMD = 0.60, 95% CI: 0.08 to 1.11), and physical therapy (pooled SMD = 0.47, 95% CI: 0.02-0.92) demonstrated statistically substantial effectiveness compared with the control group. The rank probability indicated that mind body therapy achieved the highest effectiveness in reducing depression and anxiety among patients with CLBP. Besides, the combined results should be interpreted cautiously based on the results of analyses evaluating the inconsistency and certainty of the evidence. CONCLUSION: This systemic review and NMA suggested that nonpharmacological interventions show promise for reducing psychological symptoms among patients with CLBP. In particular, mind body therapy and a biopsychosocial approach show considerable promise, and mind body therapy can be considered a priority choice in reducing depression and anxiety. These findings can aid clinicians in assessing the potential risks and benefits of available treatments for CLBP comorbidity with psychological symptoms and provide evidence for selecting interventions in clinical practice. More RCTs involving different interventions with rigorous methodology and an adequate sample size should be conducted in future research.

[hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine].

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.

[Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis].

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.

The effect of TENS on sleep: A pilot study.

BACKGROUND: Insomnia is the second most common neuropsychiatric disorder, but the current treatments are not very effective. There is therefore an urgent need to develop better treatments. Transcutaneous electrical nerve stimulation (TENS) may be a promising means of treating insomnia. OBJECTIVE: This work aims to explore whether and how TENS modulate sleep and the effect of stimulation waveforms on sleep. METHODS: Forty-five healthy subjects participated in this study. Electroencephalography (EEG) data were recorded before and after four mode low-frequency (1 Hz) TENS with different waveforms, which were formed by superimposing sine waves of different high frequencies (60-210 Hz) and low frequencies (1-6 Hz). The four waveform modes are formed by combining sine waves of varying frequencies. Mode 1 (M1) consists of a combination of high frequencies (60-110 Hz) and low frequencies (1-6 Hz). Mode 2 (M2) is made up of high frequencies (60-210 Hz) and low frequencies (1-6 Hz). Mode 3 (M3) consists of high frequencies (110-160 Hz) and low frequencies (1-6 Hz), while mode 4 (M4) is composed of high frequencies (160-210 Hz) and low frequencies (1-6 Hz). For M1, M3 and M4, the high frequency portions of the stimulus waveforms account for 50%, while for M2, the high frequency portion of the waveform accounts for 65%. For each mode, the current intensities ranged from 4 mA to 7 mA, with values for each participant adjusted according to individual tolerance. During stimulation, the subjects were stimulated at the greater occipital nerve by the four mode TENS. RESULTS: M1, M3, and M4 slowed down the frequency of neural activity, broadened the distribution of theta waves, and caused a decrease in activity in wakefulness-related regions and an increase in activity in sleep-related regions. However, M2 has the opposite modulation effect. CONCLUSION: These results indicated that low-frequency TENS (1 Hz) may facilitate sleep in a waveform-specific manner. Our findings provide new insights into the mechanisms of sleep modulation by TENS and the design of effective insomnia treatments.

The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: Sodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. METHODS: All analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). RESULTS: The meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. CONCLUSION: SF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

A multi-target protective effect of Danggui-Shaoyao-San on the vascular endothelium of atherosclerotic mice.

BACKGROUND: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. METHODS: ApoE-/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5ß1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. RESULTS: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5ß1/ c-Abl/YAP in the aortic vessels. CONCLUSIONS: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

Curcumin combined with arsenic trioxide in the treatment of acute myeloid leukemia: network pharmacology analysis and experimental validation.

PURPOSE: This study aimed to evaluate the effects of curcumin by co-administration of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) treatment, using network pharmacology and experimental validation. METHODS: Using Pubchem database, Traditional Chinese Medicine Information Database (TCMID) database, and Swiss target prediction database to predict compound-related targets, AML-associated targets were determined using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. We identify overlapping common targets by comparing Compounds-related and AML-associated targets and using these targets to perform GO and KEGG functional enrichment analyses. Subsequently, these targets were input into the STRING database, and we used Cytoscape to construct protein-protein interaction (PPI) network. Finally, we used KG1-a cells and the AML mouse model to measure the anti-leukemia effects of curcumin and As2O3 and their combination. RESULTS: Compounds and targets screening hinted that 85 intersection targets were predicted in the curcumin treatment of AML, 75 targets in the As2O3 treatment of AML, and 48 targets in the curcumin combined with the As2O3 treatment of AML. GO and KEGG analyses indicated that the top 10 enriched biological processes and top 20 pathways implicated in the therapeutic effects of curcumin and As2O3 on AML, respectively. In addition, network pharmacology screening revealed STAT3, TP53, EP300, MAPK1, and PIK3CA as the top five genes in PPI network of curcumin treatment of AML and TP53, MAPK3, MAPK1, STAT3, and SRC as the top five genes in PPI network of As2O3 treatment of AML. Moreover, the in vitro experiment demonstrated that curcumin combined with As2O3 inhibited proliferation and induced apoptosis in KG1-a cells, and this effect is more substantial than curcumin or As2O3 alone. Mechanistically, the curcumin combined with As2O3 significantly down-regulated the protein expression of JAK2, STAT3, and Bcl-2, and up-regulated the levels of P53, P27, and Bax. In the mouse model, the survival time of mice in each administration group was drawn out to varying degrees, with the most significant prolongation in the curcumin combined with the As2O3 group. CONCLUSION: Our results suggested that curcumin and As2O3 combination therapy exerts more significant anti-leukemia effects in the treatment of AML than curcumin or As2O3 monotherapy by up-regulating p53 pathway and down-regulating the JAK2/STAT3 pathway.

IL-17A Promotes Epithelial ADAM9 Expression in Cigarette Smoke-Related COPD.

Background: It has been reported that a disintegrin and metalloproteinase 9 (ADAM9) is involved in the pathogenesis of cigarette smoke (CS)-associated chronic obstructive pulmonary disease (COPD). But how CS exposure leads to upregulation of ADAM9 remains unknown. Methods: Patients who underwent lobectomy for a solitary pulmonary nodule were enrolled and divided into three groups: non-smokers with normal lung function, smokers without COPD and smoker patients with COPD. Immunoreactivity of interleukin (IL)-17A and ADAM9 in small airways and alveolar walls was measured by immunohistochemistry. Wild-type and Il17a -/- C57BL/6 mice were exposed to CS for six months, and ADAM9 expression in the airway epithelia was measured by immunoreactivity. In addition, the protein and mRNA expression levels of IL-17A and ADAM9 were assessed in CS extract (CSE) and/or IL-17A-treated human bronchial epithelial (HBE) cells. Results: The immunoreactivity of ADAM9 was increased in the airway epithelia and alveolar walls of patients with COPD compared to that of the controls. The expression of IL-17A was also upregulated in airway epithelial cells of patients with COPD and correlated positively with the level of ADAM9. The results from the animal model showed that Il17a -/- mice were protected from emphysema induced by CS exposure, together with a reduced level of ADAM9 expression in the airway epithelia, suggesting a possible link between ADAM9 and IL-17A. Consistently, our in vitro cell model showed that CSE stimulated the expression of ADAM9 and IL-17A in HBE cells in a dose- and time-dependent manner. Recombinant IL-17A induced ADAM9 upregulation in HBE cells and had a synergistic effect with CSE, whereas blocking IL-17A inhibited CSE-induced ADAM9 expression. Further analysis revealed that IL-17A induced c-Jun N-terminal kinase (JNK) phosphorylation, thereby increasing ADAM9 expression. Conclusion: Our results revealed a novel role of IL-17A in CS-related COPD, where IL-17A contributes to ADAM9 expression by activating JNK signaling.

Mechanistic insights into the health benefits of fish-oil supplementation against fine particulate matter air pollution: a randomized controlled trial.

BACKGROUND: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects. METHODS: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups. RESULTS: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. CONCLUSION: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov (NCT03255187).

Baicalin Attenuates Continuous Activation of ß-Catenin Induced by Lipopolysaccharide (LPS) and Depression Complicated by Infertility in Male Rats.

Background: Baicalin (BA) is a potential candidate drug to inhibit depressive behavior. However, the mechanism of BA's role on depression complicated with male infertility (DCMI) is still unclear. This study aimed to investigate the role of BA in alleviating inflammatory factor-induced DCMI by regulating ß-catenin. Methods: Firstly, we performed sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST) in the chronic unpredictable mild stress (CUMS) + lipopolysaccharide (LPS) model rats to study the effect of BA on depressive behavior. The levels of neuropeptide Y (NPY), testosterone (T), and IL-1ß, IL-6, TNF-α, IL-10, and IL-4 in the peripheral blood plasma of normal people, patients with depression, and patients with DCMI were measured. Then, the levels of IL-1ß, IL-6, TNF-α, IL-10, IL-4, ß-catenin in rat testis and peripheral blood and ANXA2, APP, SEMG1, and SEMG2 in seminal plasma proteins were examined. Moreover, the level of ß-catenin in the testicular tissue was detected. LPS was used to treat Sertoli cells, and the level of ß-catenin was detected. Finally, we evaluated the reproductive phenotype and sperm motility of rats. Results: BA (especially 100 mg/kg) could notably ameliorate depression-like behavior induced by CUMS + LPS. The levels of IL-4, IL-10, T, and NPY in depression patients, DCMI patients, and CUMS + LPS model rats elevated, while the levels of IL-1ß, IL-6, and TNF-α were reduced. However, BA alleviated the changes in these factors. Moreover, BA alleviated male rat depression induced by CUMS + LPS. LPS upregulated ß-catenin (NP) but could not adjust ß-catenin (TP) level in rat Sertoli cells. BA relieved the symptoms of DCMI by regulating ß-catenin. Furthermore, BA ameliorated the reproductive ability of depressed rats. Conclusion: BA modulated ß-catenin in the relief of inflammatory factor-induced DCMI.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis.

Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 µM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc- inhibitor erastin (10 µM), and the effect of the 40 µM dose of PD was more obvious than that of ferrostatin-1 (1 µM) and deferoxamine (DFO, 100 µM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc--GSH-GPx4 axis and iron metabolism.

A comparison of directed functional connectivity among fist-related brain activities during movement imagery, movement execution, and movement observation.

Brain-computer interface (BCI) has been widely used in sports training and rehabilitation training. It is primarily based on action simulation, including movement imagery (MI) and movement observation (MO). However, the development of BCI technology is limited due to the challenge of getting an in-depth understanding of brain networks involved in MI, MO, and movement execution (ME). To better understand the brain activity changes and the communications across various brain regions under MO, ME, and MI, this study conducted the fist experiment under MO, ME, and MI. We recorded 64-channel electroencephalography (EEG) from 39 healthy subjects (25 males, 14 females, all right-handed) during fist tasks, obtained intensities and locations of sources using EEG source imaging (ESI), computed source activation modes, and finally investigated the brain networks using spectral Granger causality (GC). The brain regions involved in the three motor conditions are similar, but the degree of participation of each brain region and the network connections among the brain regions are different. MO, ME, and MI did not recruit shared brain connectivity networks. In addition, both source activation modes and brain network connectivity had lateralization advantages.

Cytotoxic new caged-polyprenylated xanthonoids from Garcinia oligantha.

Caged-polyprenylated xanthonoids represent a rare class of natural products. This type of compounds is mainly isolated from Genus Garcinia. Phytochemical studies on the leaves and twigs of Garcinia oligantha led to the isolation of four new caged-polyprenylated xanthonoids, oliganthone CF (1-4), and two new simple xanthones (5-6), oliganthaxanthone D and oliganthaxanthone E. Eight known other polyprenylated xanthones (7-14) including five caged-polyprenylated xanthonoids (7-11) were also isolated. Their structures were elucidated based on the analyses of extensive spectroscopic data. All the isolated compounds except for 5, 6 and 14 showed cell viability reducing effect against human lung cancer A549 cells. Compounds 1-3 were proved to be potential apoptosis inducing agents.

Network Pharmacology and Molecular Docking Study of Zhishi-Baizhu Herb Pair in the Treatment of Gastric Cancer.

OBJECTIVE: This study aimed to investigate the possible mechanism of the Zhishi and Baizhu herb pair in the treatment of gastric cancer by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating gastric cancer. METHODS: The main active chemical components of Zhishi and Baizhu were screened through Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and selected by using the thresholds of oral bioavailability ≥30% and drug-likeness ≥18%. The targets of Zhishi and Baizhu were obtained from TCMSP, Therapeutic Targets Database (TTD), and the DrugBank database. The corresponding genes of the targets were retrieved from the UniProt database, and the gastric cancer targets were obtained from the GeneCards database and TTD. Subsequently, the networks were built between the main drug components, drug targets, and gastric cancer targets. Then, the enrichment analyses of GO and KEGG were applied to predict the potential roles of gastric cancer pathogenesis via the R package clusterProfiler. Finally, molecular docking was used to determine the affinity between the targets and components. RESULTS: Twenty-seven main active components were predicted from the Zhishi-Baizhu herb pair, and a total of 120 intersection genes were screened from 303 potential medicine genes and 1,839 disease genes. The enrichment included the PI3K-Akt and IL-17 signaling pathways, and the network analysis showed that the Zhishi-Baizhu herb pair acted on seven key targets, namely, AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2 (where they played a role in treating gastric cancer). Molecular docking showed that luteolin and naringenin could stably bind to the targets. CONCLUSION: The possible mechanisms of the components of the Zhishi-Baizhu herb pair in treating gastric cancer might be related to luteolin and naringenin, which intervened with the targets AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2, and are linked with the PI3K-Akt and IL-17 signaling pathways. This knowledge will lay a solid foundation for further experimental and clinical studies.

Natural Language Processing Algorithms for Normalizing Expressions of Synonymous Symptoms in Traditional Chinese Medicine.

BACKGROUND: The modernization of traditional Chinese medicine (TCM) demands systematic data mining using medical records. However, this process is hindered by the fact that many TCM symptoms have the same meaning but different literal expressions (i.e., TCM synonymous symptoms). This problem can be solved by using natural language processing algorithms to construct a high-quality TCM symptom normalization model for normalizing TCM synonymous symptoms to unified literal expressions. METHODS: Four types of TCM symptom normalization models, based on natural language processing, were constructed to find a high-quality one: (1) a text sequence generation model based on a bidirectional long short-term memory (Bi-LSTM) neural network with an encoder-decoder structure; (2) a text classification model based on a Bi-LSTM neural network and sigmoid function; (3) a text sequence generation model based on bidirectional encoder representation from transformers (BERT) with sequence-to-sequence training method of unified language model (BERT-UniLM); (4) a text classification model based on BERT and sigmoid function (BERT-Classification). The performance of the models was compared using four metrics: accuracy, recall, precision, and F1-score. RESULTS: The BERT-Classification model outperformed the models based on Bi-LSTM and BERT-UniLM with respect to the four metrics. CONCLUSIONS: The BERT-Classification model has superior performance in normalizing expressions of TCM synonymous symptoms.

Effects of a Chlorogenic Acid-Containing Herbal Medicine (LASNB) on Colon Cancer.

BACKGROUND: Plant polyphenols, which contain phenolic acids such as chlorogenic acid (CGA), can be used for the treatment of gastrointestinal cancer and have gained increasing attention in recent years. In this study, we explored a novel CGA-containing herbal medicine named LASNB, which was extracted from Lonicera japonica Thunb., Agrimonia eupatoria L., and Scutellaria barbata D.Don. METHODS: CGA in LASNB was analyzed using high-performance liquid chromatography (HPLC). The biological functions and molecular mechanisms of LASNB were investigated in colon cancer cell lines (HCT116, HCT15, and CT26), a normal colon cell line (NCM460), and a CT26 xenograft model. To assess safety, hematological toxicity and pathology of the liver, kidney, and lung were evaluated. RESULTS: LASNB suppressed HCT116, HCT15, and CT26 colon cancer progression by inhibiting proliferation capacity, promoting cell apoptosis, and suppressing cell migration both in vitro and in vivo. Investigation into the underlying molecular mechanism indicated that LASNB suppressed the activation of receptor tyrosine kinase- (RTK-) MEK-ERK and NF-κB pathways. With regard to safety, slight interstitial vascular congestion in the lung was observed, but no severe pathological or hematological toxicity was detected. CONCLUSIONS: We found that LASNB suppressed the progression of colon cancer via the RTK-MEK-ERK and NF-κB pathways, with no severe toxicity observed. Therefore, LASNB has the potential to be used as a supplementary herbal medicine for the treatment of colon cancer.