Buyang huanwu decoction promotes remyelination via miR-760-3p/GPR17 axis after intracerebral hemorrhage.

ETHNOPHARMACOLOGICAL RELEVANCE: The repairment of myelin sheaths is crucial for mitigating neurological impairments of intracerebral hemorrhage (ICH). However, the current research on remyelination processes in ICH remains limited. A representative traditional Chinese medicine, Buyang Huanwu decoction (BYHWD), shows a promising therapeutic strategy for ICH treatment. AIM OF THE STUDY: To investigate the pro-remyelination effects of BYHWD on ICH and explore the underlying mechanisms. MATERIALS AND METHODS: The collagenase-induced mice ICH model was created for investigation. BYHWD's protective effects were assessed by behavioral tests and histological staining. Transmission electron microscopy was used for displaying the structure of myelin sheaths. The remyelination and oligodendrocyte differentiation were evaluated by the expressions of myelin proteolipid protein (PLP), myelin basic protein (MBP), MBP/TAU, Olig2/CC1, and PDGFRα/proliferating cell nuclear antigen (PCNA) through RT-qPCR and immunofluorescence. Transcriptomics integrated with disease database analysis and experiments in vivo and in vitro revealed the microRNA-related underlying mechanisms. RESULTS: Here, we reported that BYHWD promoted the neurological function of ICH mice and improved remyelination by increasing PLP, MBP, and TAU, as well as restoring myelin structure. Besides, we showed that BYHWD promoted remyelination by boosting the differentiation of PDGFRα+ oligodendrocyte precursor cells into olig2+/CC1+ oligodendrocytes. Additionally, we demonstrated that the remyelination effects of BYHWD worked by inhibiting G protein-coupled receptor 17 (GPR17). miRNA sequencing integrated with miRNA database prediction screened potential miRNAs targeting GPR17. By applying immunofluorescence, RNA in situ hybridization and dual luciferase reporter gene assay, we confirmed that BYHWD suppressed GPR17 and improved remyelination by increasing miR-760-3p. CONCLUSIONS: BYHWD improves remyelination and neurological function in ICH mice by targeting miR-760-3p to inhibit GPR17. This study may shed light on the orchestration of remyelination mechanisms after ICH, thus providing novel insights for developing innovative prescriptions with brain-protective properties.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Spatial amine metabolomics and histopathology reveal localized brain alterations in subacute traumatic brain injury and the underlying mechanism of herbal treatment.

INTRODUCTION: Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment. METHODS: A newly developed liquid microjunction surface sampling-tandem mass tag-ultra performance liquid chromatography-mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact-induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI. RESULTS: Besides the hippocampus and cortex, the thalamus, caudate-putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L-leucine and L-isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys-Phe/Phe-Lys and dopamine. Also, XFZYD enhances post-TBI angiogenesis in the hippocampus and the thalamus. CONCLUSION: This study reveals the local amine-metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.

Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson's disease.

BACKGROUND: Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson's disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. METHODS: Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and "Compound-Disease-Target" (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. RESULTS: In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. CONCLUSION: Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

Short-term effect of internet-delivered mindfulness-based stress reduction on mental health, self-efficacy, and body image among women with breast cancer during the COVID-19 pandemic.

Background and aim: During the COVID-19 pandemic, an Internet-Mindfulness-Based Stress Reduction (iMBSR) program was delivered and may be better than an in-person approach. Our study evaluated the effects of iMBSR intervention on mental health, self-efficacy, and body image in women with breast cancer in Taiwan. Materials and methods: Sixty-seven women with breast cancer were allocated to a 6-week iMBSR (n = 41) program or a waitlist control group (n = 26), without heterogeneity between group characteristics. Patients from both groups were measured at baseline and postintervention using three scales: Depression, Anxiety, and Stress Scale (DASS-21), General self-efficacy scale, and Body Image Scale. Descriptive dataset analysis, paired t-test, and Student's t-test were used to evaluate the data. Results: Although iMBSR did not significantly improve depression and stress between groups, iMBSR could improve anxiety (Δmean: -2.0 vs. -0.4, p = 0.041) with medium effect sizes. Significant benefits were found for body image (Δmean: -3.6 vs. 0.9, p = 0.003) and self-efficacy (Δmean: 4.2 vs. 1.5, p = 0.004), with large effect sizes (Cohen's d = 0.73). Conclusion: Our preliminary study supports iMBSR as a program that can improve mental health, body image, and self-efficacy in women with breast cancer. During the COVID-19 pandemic, medical professionals can use Internet-based clinical health education.

Polluting characteristics, sources, cancer risk, and cellular toxicity of PAHs bound in atmospheric particulates sampled from an economic transformation demonstration area of Dongguan in the Pearl River Delta, China.

The Songshan Lake Science and Technology Industrial Park is a national economic transition demonstration area, which centers at a traditional industrial region, in Dongguan, China. We were interested in the involved atmospheric particulates-bound PAHs regarding their sources, cancer risk, and related cellular toxicity for those in other areas under comparable conditions. In this study, the daily concentrations of TSP, PM10, and PM2.5 were averaged 127.95, 95.91, and 67.62 µg/m3, and the bound PAHs were averaged 1.31, 1.22, and 0.77 ng/m3 in summer and 12.72, 20.51 and 40.27 ng/m3 in winter, respectively. The dominant PAHs were those with 5-6 rings, and 4-6 rings in summer and winter, respectively. The incremental lifetime cancer risk (ILCR) (90th percentile probability) of total PAHs was above 1.00E-06 in each age group, particularly high in adolescents. Sensitivity analysis indicated that slope factor and body weight had greater impact than exposure duration and inhalation rate on the ILCR. Moreover, treatment of human bronchial epithelial BEAS-2B cells with mixed five indicative PAHs increased the formation of ROS, DNA damage (elevation in γ-H2AX), and protein levels of CAR, PXR, CYP1A1, 1A2, 1B1, while reduced the AhR protein, with the winter mixture more potent than summer. For the sources of PAHs, the stable carbon isotope ratio analysis and diagnostic ratios consistently pointed to petroleum and fossil fuel combustion as major sources. In conclusion, our findings suggest that particulates-bound PAHs deserve serious concerns for a cancer risk in such environment, and the development of new power sources for reducing fossil fuel combustion is highly encouraged.

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

Systematic analysis of tRNA-derived small RNAs reveals therapeutic targets of Xuefu Zhuyu decoction in the cortexes of experimental traumatic brain injury.

BACKGROUND: Xuefu Zhuyu Decoction (XFZYD), a well-known traditional Chinese medicine prescription, has been widely used to treat traumatic brain injury (TBI). However, the underlying mechanisms involved in XFZYD therapy remain unclear. AIM OF THE STUDY: We explored new therapeutic targets of XFZYD in TBI by the tsRNA-sequencing (tsRNA-seq) method. MATERIAL AND METHODS: High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to assess the quality of XFZYD. Male Sprague-Dawley rats were randomly categorized into three groups: sham, TBI, and XFZYD. The protective effects of XFZYD were investigated in vivo by using the Morris water maze (MWM), modified neurological severity score (mNSS) tests, hematoxylin-eosin (H&E) staining, and Nissl staining. tsRNA-seq was applied to analyze the expression of tsRNAs in the rat cortex. Four tsRNAs were validated by qRT-PCR. The biological function of putative tsRNAs was investigated using bioinformatics techniques. The functions of tsRNAs targeting mRNAs were verified in vitro. RESULTS: The mNSS and MWM indicated that XFZYD notably improved neurological deficits and cognitive function after TBI (p < 0.05). H&E staining and Nissl staining demonstrated that XFZYD suppressed damage and neuronal loss in the TBI rat cortex. We evaluated the dysregulated expression of 732 tsRNAs (128 tsRNAs were significantly altered in the TBI/sham group (fold change > 2 and p < 0.05), and 97 tsRNAs were dysregulated in the XFZYD/TBI group (fold change > 2 and p < 0.05)) in the TBI rat cortex. Interestingly, 41 tsRNAs were distinctly regulated by XFZYD. The qRT-PCR results of the four randomly chosen tsRNAs (tRF-54-75-Glu-TTC-2, tRF-55-75-Gln-CTG-2-M2, tRF-55-76-Val-TAC-1, tRF-64-85-Leu-AAG-1-M4) exhibited trends similar to those of the tsRNA-seq data. We certified the possible targets of tsRNAs and suggested the crosscurrent in the expression trend of the target genes. Bioinformatics analysis showed that XFZYD-related tsRNAs could contribute to regulating insulin resistance, the calcium signaling pathway, autophagy, and axon guidance. CONCLUSIONS: The current research implies that tsRNAs are putative therapeutic targets of XFYZD for TBI treatment. This research provides new insight into the therapeutic targets of XFZYD in treating TBI.

Efficacy and Safety of Complementary Therapy With Jing Si Herbal Tea in Patients With Mild-To-Moderate COVID-19: A Prospective Cohort Study.

Background: Since late 2019, there has been a global COVID-19 pandemic. To preserve medical capacity and decrease adverse health effects, preventing the progression of COVID-19 to severe status is essential. Jing-Si Herbal Tea (JSHT), a novel traditional Chinese medicine formula was developed to treat COVID-19. This study examined the clinical efficacy and safety of JSHT in patients with mild-to-moderate COVID-19. Methods: In this prospective cohort study, we enrolled 260 patients with mild-to-moderate COVID-19. The enrolled patients were divided into the JSHT (n = 117) and control (n = 143) groups. Both groups received standard management. The JSHT group was treated with JSHT as a complementary therapy. Results: Compared with standard management alone, JSHT combined with standard management more effectively improved the reverse transcription-polymerase chain reaction cycle threshold value, C-reactive protein level, and Brixia score in the adult patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). The results revealed that the patients treated with JSHT combined with standard management had 51, 70, and 100% lower risks of intubation, Medisave Care Unit admission, and mortality compared with those receiving standard management only. Conclusions: JSHT combined with standard management more effectively reduced the SARS-CoV-2 viral load and systemic inflammation and alleviated lung infiltrates in the patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). JSHT combined with standard management may prevent critical status and mortality in patients with mild-to-moderate COVID-19. JSHT is a promising complementary therapy for patients with mild-to-moderate COVID-19.

[Comparison of effects of Xuebijing injection and its component hydroxysafflor yellow A on coagulation and survival rates of septic rats].

OBJECTIVE: To explore the effects of Xuebijing injection and its component hydroxysafflor yellow A on coagulation and survival rates of septic rats. METHODS: (1) Assessment of coagulation: 144 male Sprague-Dawley (SD) rats were divided into four groups by random number table: sham group, cecal ligation and puncture (CLP) induced sepsis model group (CLP group), CLP+Xuebijing group, and CLP+hydroxysafflor yellow A group, with 36 rats in each group. CLP was used for reproducing septic models. The cecum of the rats in the sham group was exposed by laparotomy and then returned to the abdominal cavity without CLP, while the other steps were the same as those in the CLP group. Rats in the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group were injected with Xuebijing (4 mL/kg, twice a day) or hydroxysafflor yellow A solution (0.378 g/L, 298 µg each time, twice a day) through caudal vein after operation. Levels of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and D-dimer in peripheral blood were measured by automatic coagulation analyzer at 6, 12, 24 hours after operation. The enzyme linked immunosorbent assay (ELISA) was applied to determine levels of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin (sTM) in peripheral blood. (2) Analysis of survival rates: 120 rats were divided into four groups by random number table (the same groups with those in the section of assessment of coagulation), with 30 rats in each group. The Kaplan-Meier survival curve was plotted, and the cumulative survival rates were observed and recorded for 7 days after CLP surgery. RESULTS: (1) Results of coagulation assessment: compared with the sham group, septic rats in the CLP group showed significant dysfunction in coagulation early, as evidenced by prolonged PT at 6 hours after CLP (s: 8.9±0.2 vs. 8.4±0.4, P < 0.01), and significantly increased levels of Fib, D-dimer, TFPI and sTM [Fib (g/L): 2.8±0.3 vs. 2.3±0.1, D-dimer (ng/L): 1.8±0.2 vs. 1.5±0.1, TFPI (ng/L): 131.1±10.9 vs. 102.8±10.5, sTM (µg/L): 27.2±1.2 vs. 19.8±2.9, all P < 0.01]. The coagulation dysfunction became more and more serious at 12 hours after operation, and further deteriorated with time. The use of both Xuebijing and hydroxysafflor yellow A revealed significant improvement in coagulation of septic rats at 6 hours, as shown by shortened PT (s: 8.3±0.2, 8.3±0.1 vs. 8.9±0.2, both P < 0.01), and decreased Fib, D-dimer, TFPI and sTM as compared with those in the CLP group [Fib (g/L): 2.3±0.1, 2.3±0.2 vs. 2.8±0.3; D-dimer (ng/L): 1.5±0.1, 1.5±0.2 vs. 1.8±0.2; TFPI (ng/L): 109.5±10.2, 91.5±5.0 vs. 131.1±10.9; sTM (µg/L): 22.3±1.5, 21.1±1.8 vs. 27.2±1.2; all P < 0.01]. However, there was no significant difference in coagulation function between the two intervention groups. (2) Results of survival rates analysis: the rats in the sham group all survived 7 days after operation. The 7-day cumulative survival rate of the CLP group was only 36.67% (11/30). Compared with the CLP group, the cumulative survival rates were significantly increased in rats of the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group [66.67% (20/30), 66.67% (20/30) vs. 36.67% (11/30), both P < 0.05], but no significant difference was found between the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group. CONCLUSIONS: Both Xuebijing and its component hydroxysafflor yellow A appear to be capable of alleviating coagulation disorders and improving survival rates of septic rats effectively, and the effects show no significant difference between them.

Herbal medicine derived carbon dots: synthesis and applications in therapeutics, bioimaging and sensing.

Since the number of raw material selections for the synthesis of carbon dots (CDs) has grown extensively, herbal medicine as a precursor receives an increasing amount of attention. Compared with other biomass precursors, CDs derived from herbal medicine (HM-CDs) have become the most recent incomer in the family of CDs. In recent ten years, a great many studies have revealed that HM-CDs tend to be good at theranostics without drug loading. However, the relevant development and research results are not systematically reviewed. Herein, the origin and history of HM-CDs are outlined, especially their functional performances in medical diagnosis and treatment. Besides, we sort out the herbal medicine precursors, and analyze the primary synthetic methods and the key characteristics. In terms of the applications of HM-CDs, medical therapeutics, ion and molecular detection, bioimaging, as well as pH sensing are summarized. Finally, we discuss the crucial challenges and future prospects.

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Spatiotemporal dynamics of succession and growth limitation of phytoplankton for nutrients and light in a large shallow lake.

Understanding the limiting factors of phytoplankton growth and competition is crucial for the restoration of aquatic ecosystems. However, the role and synergistic effect of co-varying environmental conditions, such as nutrients and light on the succession of phytoplankton community remains unclear. In this study, a hydrodynamic-ecological modeling approach was developed to explore phytoplankton growth and succession under co-varying environmental conditions (nutrients, total suspended solids (TSS) and variable N:P ratios) in a large shallow lake called Lake Chagan, in Northeast China. A phytoplankton bloom model was nested in the ecological modeling approach. In contrast to the traditonal ecological modeling, competition between phytoplankton species in our study was modeled at both the species/functional group and phenotype levels. Six phytoplankton functional groups, namely diatoms, green algae, Anabaena, Microcystis, Aphanizomenon and Oscillatoria and each of them with three limitation types (i.e., light-limitation, nitrogen-limitation and phosphorus-limitation) were included in the bloom model. Our results demonstrated that the average biomass proportion of the three limitation types (light-limitation, nitrogen-limitation and phosphorus-limitation) in the six phytoplankton function groups accounted for approximately 50%, 37% and 23% of the total phytoplankton biomass, respectively. TSS suppressed the growth of diatoms and green algae, but favored the dominance of cyanobacteria in Lake Chagan, especially in the turbid water phase (TSS ≥ 60 mg/L). In addition, it was reported that the potential of either N-fixing or non-N-fixing cyanobacterial blooming along the gradients of N:P ratios could exist under the influence of the co-environmental factors in the lake. The proportion of non-N-fixing cyanobacteria (i.e., Microcystis and Oscillatoria) exceeded the proportion of N-fixing cyanobacteria (i.e., Anabaena and Aphanizomenon) when the N:P ratios exceeded 20. Non-N-fixing cyanobacteria would become dominant at higher TSS concentrations and lower light intensities in the turbid water. N-fixing cyanobacteria favored lower N:P ratios and higher light intensities in the clearwater phase (where TSS ≤ 60 mg/L). To sustain a good ecological status in the lake, our results suggest that nutrient and TSS levels in the lake should be maintained at or below the thresholds (TN ≤ 1.5 mg/L; TP ≤ 0.1 mg/L; N:P ratios between 15 and 20; and TSS ≤ 60 mg/L). These findings can help improve water quality management practices to restore aquatic ecosystems.

Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy.

Autophagy plays an essential role in the defense against many microbial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, motility-associated killing factor A (MakA). pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 (herein referring to MAP1LC3B) lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex, required for LC3 lipidation at the membranous aggregate, resulted in an inhibition of both canonical autophagy and autophagy-related processes, including the unconventional secretion of interleukin-1ß (IL-1ß). These findings identify a novel mechanism of host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.

Mechanism of Xuefu Zhuyu Decoction in treatment of myocardial infarction based on network pharmacology and molecular docking / 中国中药杂志

To explore the action mechanism of Xuefu Zhuyu Decoction in treating myocardial infarction based on network pharmaco-logy and molecular docking. Active components and corresponding targets of Xuefu Zhuyu Decoction were obtained through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and related targets of myocardial infarction were obtained through GeneCards, DisGeNET, and OMIM databases. Then the intersection targets were obtained by integrating the drug targets and disease targets. The "active component-target" network was constructed by Cytoscape software, and protein-protein interaction(PPI) network was drawn using STRING platform. Protein cluster analysis was carried out using MCODE. GO enrichment analysis and KEGG pathway analysis were carried out using DAVID database and ClueGO, and molecular docking was carried out using Autodock Vina and Pymol. Finally, 226 active components of Xuefu Zhuyu Decoction were obtained, 257 corresponding targets, 1 340 targets of myocardial infarction, and 109 drug and disease intersection targets were obtained. From GO enrichment analysis, 208 biological process terms, 38 molecular function terms, and 33 cellular component terms were obtained. From KEGG pathway analysis, NF-κB signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, and other related pathways were obtained. The molecular docking results showed that the main active components(quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol and baicalein) of Xuefu Zhuyu Decoction in the treatment of myocardial infarction had good binding properties with the core proteins IL6, ALB, VEGFA, TNF, MAPK3 and CASP3. The results suggested that Xuefu Zhuyu Decoction may play a role in the treatment of myocardial infarction by reducing the inflammatory response, reducing oxidative stress, inhibiting cell apoptosis, and promoting angiogenesis.

Metabolomics Deciphers Potential Targets of Xuefu Zhuyu Decoction Against Traumatic Brain Injury in Rat.

Xuefu Zhuyu decoction (XFZYD) performs multiple functions for traumatic brain injury (TBI) treatment. However, its clinical application is limited by the incomplete exploration of targets and inadequate discussion of mechanisms. We aimed to investigate the metabolic alterations of XFZYD in acute and chronic stages of TBI. Sprague-Dawley rats were randomly divided into the sham, controlled cortical impact (CCI) and XFZYD group. Behavioral and histopathological tests were used to evaluate the neuroprotective effects. Coagulation assays were performed to assess safety. Moreover, we analyzed the metabolomic profiling of hippocampal samples with different time intervals after CCI by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differential metabolites were screened by multivariate data analysis. To further uncover the association between candidate metabolites and biological interaction networks, we applied bioinformatics analysis using MetaboAnalyst 4.0, STITCH 5.0 and TCMSP. The potential mechanism was verified by ELISA and Western blot. XFZYD ameliorated neurological deficiencies post-CCI without impairing blood coagulation in the rat's model. Seventeen and fourteen metabolites were filtered on d 3 and 21, respectively. Eleven of potential metabolites were common at these time points, involving two significant pathways (arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis). Gamma-aminobutyric acid (GABA) and the related pathways were specifically affected by XFZYD at the acute phase of TBI, while biosynthesis of amino acids was the major pathway influenced at the chronic phase. This study provides broad insights into the therapeutic effects of XFZYD in treating TBI through the whole phases.

The predominant role of pectin in binding Cd in the root cell wall of a high Cd accumulating rice line (Oryza sativa L.).

Cell wall (CW) plays an important role in Cd accumulation in roots of metal-tolerant plants, including rice. The role of CW polysaccharides, especially pectin, in binding Cd in roots of a high Cd accumulating (HA) rice line of Lu527-8 and a non-high Cd accumulating (NHA) rice line of Lu527-4 was investigated in this study. About 59%-63% of Cd in roots of the two rice lines was bound to CWs, indicating that CW was the main site for Cd accumulation in roots of the two rice lines. Cd adsorbed on the root CWs of the HA was 1.1-1.2 times more than that of the NHA, demonstrating the root CWs of the HA showed greater Cd binding ability. Cd exposure induced more Cd accumulation in pectin and hemicellulose in the HA. In particular, up to 65% of Cd accumulation in root CWs of the HA was observed in pectin. The removal of pectin lead to a 50% decrease for the amounts of Cd adsorption on root CWs of the HA, indicating that pectin was the major binding site for Cd in root CWs of the HA. The HA showed greater pectin methylesterase activities, resulting in lower degree of pectin methylesterification along with more low-methylesterified pectins in root CWs than the NHA. The more accumulation of low-methylesterified pectins in CWs induced by Cd contributed greatly to the high Cd accumulation in roots of the HA rice line of Lu527-8.

Effects of titanium dioxide nanoparticles on nutrient absorption and metabolism in rats: distinguishing the susceptibility of amino acids, metal elements, and glucose.

Food grade titanium dioxide (TiO2) containing nanofractions, is commonly applied to whiten and brighten food products, which put consumers under health risks of ingesting TiO2 nanoparticles (NPs). Although the oral toxicity of TiO2-NPs has been evaluated in several studies, gaps in knowledge exist regarding interactions between NPs and food components. Therefore, this study aimed to estimate the influence of TiO2-NPs on nutrient absorption and metabolism through an in situ intestinal loop experiment which conducted on adult Sprague Dawley (SD) rats after 30-d gastrointestinal exposure to TiO2-NPs of two different sizes (N-TiO2 and M-TiO2). Results showed that exposure to TiO2-NPs caused flat apical membranes with sparse and short microvilli and inflammatory infiltration in small intestine. Both particles were absorbed into small intestinal cells, but N-TiO2 with smaller size could more easily be transported through gut and raise the blood titanium (Ti) levels. Changes in serum levels of amino acid were also different after exposure to these two particles. After injecting mixed solution of nutrients into in situ intestinal loop, the N-TiO2 exposure groups displayed significant absorption inhibition of the added histidine (His) and metabolism disorder of some non-added amino acid. However, no influence was observed on metal elements or glucose levels. This study identified TiO2-NPs with small sizes could affect nutrient absorption and metabolism by inducing intestinal epithelium injury, and amino acids were more susceptible than metal elements and glucose. These findings suggested that foods supplemented with TiO2-NPs should be carefully consumed by people with high protein requirements, such as children, the elderly, and patients with high metabolic disease or intestinal inflammation.

Complementary multiple hydrogen-bond-based magnetic composite microspheres for high coverage and efficient phosphopeptide enrichment in bio-samples.

Due to the number of phosphorylation sites, mono- and multiple-phosphopeptides exhibit significantly different biological effects. Therefore, comprehensive profiles of mono- and multiple-phosphopeptides are vital for the analysis of these biological and pathological processes. However, the most commonly used affinity materials based on metal oxide affinity chromatography (MOAC) show stronger selectivity toward mono-phosphopeptides, thus losing most information on multiple-phosphopeptides. Herein, we report polymer functionalized magnetic nanocomposite microspheres as an ideal platform to efficiently enrich both mono- and multiple-phosphopeptides from complex biological samples. Driven by complementary multiple hydrogen bonding interactions, the composite microspheres exhibited remarkable performance for phosphopeptide enrichment from model proteins and real bio-samples. Excellent selectivity (the molar ratio of nonphosphopeptides/phosphopeptides was 5000 : 1), high enrichment sensitivity (2 fmol) and coverage, as well as high capture rates of multiple-phosphopeptides revealed their great potential in comprehensive phosphoproteomics studies. More importantly, we successfully captured the cancer related phosphopeptides (from the phosphoprotein Stathmin-1) and identified their relevant phosphorylation sites from oral carcinoma patients' saliva and tissue lysate, demonstrating the potential of this material for phosphorylated disease marker detection and discovery.

Therapeutic effects and mechanisms of actions of Descurainia sophia.

Descurainia sophia Webb ex Prantl has been used in traditional medicine globally. It has been shown that Descurainia sophia, together with many other bioactive compounds, can modulate the biological functions of various genes. We have viewed the clinical benefits and mechanisms of action of Descurainia sophia associated with its current uses and outlined potential further applications. There are many studies documenting its numerous clinical effects in cancer, respiratory, gastrointestinal, and cardiac systems. Further, Descurainia sophia has been shown to exhibit anti-inflammatory, anti-oxidative, and anthelmintic activities. The clinical studies did not indicate any significant adverse effects of Descurainia sophia, demonstrating that it is a safe and effective herbal medicine. However, more clinical studies demonstrating the therapeutic effects of Descurainia sophia are still warranted.