Effects of Tai Chi on depression of middle-aged and older adults: an updated systematic review and meta-analysis.

AIM: The objective of this study was to evaluate the efficacy of Tai Chi, a mind-body movement therapy originating from China, on depression in middle-aged and older adults. METHODS: A systematic search was conducted in seven databases (Embase, Cochrane, Medline, Wanfang, SinoMed, Weipu date, CNKI) for Randomized Controlled Trials (RCTs) published until Apr 16, 2023. The quality assessment, heterogeneity analysis, subgroup analysis, and sensitivity analysis of 12 RCTs selected from the literature were performed. Meta-analyses were conducted using RevMan 5.4 software. RESULTS: The study included 12 trials comprising 731 participants that met the inclusion criteria. The findings revealed that Tai Chi significantly improved depression in middle-aged and older adults [SMD = -1.21, 95% CI (-1.59, -0.83), I2 = 87.6%, P < 0.001]. Subgroup analysis revealed that the number of exercise weeks within the specified range, the total duration of exercise, and Tai Chi maneuvers had the greatest benefits on depression in middle-aged and elderly people. The results demonstrated that interventions lasting more than 24 weeks were more effective [SMD = -1.66, 95% CI (-2.28, -1.04), P < 0.05] than those lasting only 12 weeks [SMD = -0.73, 95% CI (-1.08, -0.38), P < 0.05]. The effect size was more significant when the total duration of the intervention was more than 2400 min [SMD = -1.31, 95% CI (-1.71, -0.92), P < 0.001], and when the 24-style Tai Chi exercise was selected [SMD = -1.06, 95% CI (-1.37, -0.75), P < 0.001], the difference was also statistically significant. Funnel plots combined with sensitivity analyses, Begg's and Egger's tests indicated no publication bias. CONCLUSION: The study suggests that Tai Chi can be an alternative therapy for reducing depression in middle-aged and older adults. It is recommended to prolong the Tai Chi exercise period to more than 24 weeks, with a total exercise duration of more than 2400 min, and 24-style Tai Chi should be selected to achieve the best therapeutic effect in middle-aged and older adults with depression. It should be noted that there may be lower-quality studies in the RCT literature analyzed, which may limit the general applicability and credibility of the conclusions.

Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings.

RUVBL proteins are involved in plant gametophyte development.

The proper development of male and female gametophytes is critical for successful sexual reproduction and requires a carefully regulated series of events orchestrated by a suite of various proteins. RUVBL1 and RUVBL2, plant orthologues of human Pontin and Reptin, respectively, belong to the evolutionarily highly conserved AAA+ family linked to a wide range of cellular processes. Previously, we found that RUVBL1 and RUVBL2A mutations are homozygous lethal in Arabidopsis. Here, we report that RUVBL1 and RUVBL2A play roles in reproductive development. We show that mutant plants produce embryo sacs with an abnormal structure or with various numbers of nuclei. Although pollen grains of heterozygous mutant plants exhibit reduced viability and reduced pollen tube growth in vitro, some of the ruvbl pollen tubes are capable of targeting ovules in vivo. Similarly, some ruvbl ovules retain the ability to attract wild-type pollen tubes but fail to develop further. The activity of the RUVBL1 and RUVBL2A promoters was observed in the embryo sac, pollen grains, and tapetum cells and, for RUVBL2A, also in developing ovules. In summary, we show that the RUVBL proteins are essential for the proper development of both male and particularly female gametophytes in Arabidopsis.

Clinical Characteristics and Treatment Overview in Hand-Foot-and-Mouth Disease Using Real-World Evidence Based on Hospital Information System.

Objectives: To describe the epidemiological characteristics and medication overview of HFMD in Guangzhou and analyze the factors of length of stay (LOS) based on TCM usage. Method: From January 1, 2014, to June 30, 2019, clinical data of HFMD (ICD-10 B08.401) as the initial diagnosis, based on HIS of five medical institutions for outpatient and inpatient cases, was collected. The inpatient cases of the five hospitals in Guangzhou were utilized for hospitalization analysis. Information extracted from the warehouse was standardized. Descriptive analysis was used for baseline characteristics, medication usage, and inpatient characteristics. Potential factors were analyzed by bivariate analysis. COX regression analysis and Kaplan-Meier analysis for calculating HRs and 95% CIs were adopted to determine the predictors of LOS. Stratified COX regression was applied to analyze the relationship between predictors and LOS and to calculate interaction. Results: A total of 14172 patients with HFMD were included. It showed that HFMD would occur in males, infants, and summer. Cause and symptoms are the two aspects of conventional Western medicine treatments, while TCM treatment of HFMD took clearing heat and detoxification as the basic principle. Inpatients with HFMD were divided into two groups by the use ratio of TCM. Age, season, and disease severity were possible correlated factors of LOS, extrapolating from their disparity in distribution. By stratified Cox regression, three factors following presented as possible contributions to shortening LOS, including TCM ≥ 0.1 (HR = 1.79, 95% CI (1.67-1.92), P < 0.01), winter (HR = 1.28, 95% CI (1.12-1.47)), P < 0.01), mild HFMD (HR = 1.93, 95% CI (1.69-2.22), P < 0.01). Additive interaction of TCM use and disease severity was significant (RERI = 1.014 (0.493-1.534), P < 0.01). Conclusion: Young children and high temperature were the risk factors of HFMD infection, which suggests that increasing surveillance for susceptible particular-age individuals and season is indispensable. Favorable factors to decrease LOS included a higher proportion of TCM use, mild HFMD, and onset in winter. The proportion of TCM use had additive interaction with disease severity, indicating that TCM may have antiviral and other biological effects on HFMD. Increasing the proportion of TCM use was probably beneficial to shortening LOS.

Synthesis and antibacterial activity studies in vitro of indirubin-3'-monoximes.

Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3'-monoximes 5a-5z and 5aa-5ad displayed good potency against S. aureus ATCC25923 (MIC = 0.4-25.6 µg mL-1). Among them, we found that the 5-F, 5-Cl and 7-CF3 substituted indirubin-3'-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for S. aureus (MICs up to 0.4 µg mL-1) than the prototype natural product indirubin (MIC = 32 µg mL-1). More importantly, indirubin-3'-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant S. aureus (fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating S. aureus with indirubin-3'-monoxime 5aa, and the results revealed that indirubin-3'-monoximes could increase the cell membrane permeability of S. aureus. Although indirubin-3'-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 µg mL-1 had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.

Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development.

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body's innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.

Effects of composite materials and revegetation on soil nutrients, chemical and microbial properties in rare earth tailings.

The mining of ionic rare earth elements in Ganzhou left large area of barren tailings with severe vegetation destruction in pressing needs of remediation. However, the remediating effects of soil additives combined with revegetation on the preservation of nutrients in the tailings and microbial communities were rarely studied. For this purpose, pilot experiments were implemented in a field, with the control group (CK) only cultivating plants without adding materials, and three treatments including peanut straw biochar composite (T1), phosphorus­magnesium composite (T2) and modified zeolite composite (T3) along with the cultivation of Medicago sativa L., Paspalum vaginatum Sw. and Lolium perenne L. Soil pH and organic matter in CK significantly decreased from 4.90 to 4.17 and from 6.62 g/kg to 3.87 g/kg after six months, respectively (p ≤ 0.05), while all the treatments could effectively buffer soil acidification (over 5.74) and delay the loss of soil organic matter. Soil cation exchange capacity was still below the detection limit in all the groups except T2. The results of rainfall runoff monitoring indicated that compared with CK, only T2 could significantly reduce the runoff loss of soil NO3- and SO42- by 45.61 %-75.78 % and 64.03 %-76.12 %, respectively (p ≤ 0.05). Compared with CK, the bacterial diversity in T2 and T3 significantly increased 21.18 % and 28.15 %, respectively (p ≤ 0.05), while T1 didn't change the bacterial or fungal diversity (p > 0.05). Co-occurrence network analysis showed that compared with CK, the whole microbial communities interacted more closely in the three treatments. Functional prediction of the microbial communities revealed all the treatments were dominated by carbon transforming bacteria and saprotrophic fungi except T2. This study demonstrated that the composite materials combined with revegetation couldn't retain soil nitrogen compounds and sulfate in rare earth tailings in the long term.

Potential to Reduce Chemical Fertilizer Application in Tea Plantations at Various Spatial Scales.

Tea is the main commercial crop grown in China, and excessive application of chemical fertilizers in tea plantations is common. However, the potential to reduce chemical fertilizer use in tea plantations is unclear. In this study, Zhejiang Province was selected as the research object to systematically analyze the potential for tea plantation chemical-fertilizer reduction at different spatial scales. The geographic information system-based analytic hierarchy process method and Soil and Water Assessment Tool model were used to determine the chemical fertilizer reduction potential at the province scale and watershed scale, respectively. At the field scale, two consecutive years of field experiments were conducted on a tea plantation. Province-level analysis showed that 51.7% of the area had an average total fertilization intensity greater than 350 kg/hm2 and a high reduction potential. Watershed analysis revealed that chemical fertilizer reduction had better potential in reducing total nitrogen and total phosphorus inputs to runoff in the short term, whereas 50% organic fertilizer substitution was the best strategy to achieve long-term effects. The field experiments further proved that organic fertilizer substitution balanced tea growth and environmental protection. This study provides a useful method to investigate strategies to reduce chemical fertilizer use in tea-growing areas.

Engineering zinc oxide hybrid selenium nanoparticles for synergetic anti-tuberculosis treatment by combining Mycobacterium tuberculosis killings and host cell immunological inhibition.

Introduction: As a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. Methods: Here, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. Results: The obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. Discussion: These ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy.

Montreal Cognitive Assessment: Seeking a Single Cutoff Score May Not Be Optimal.

BACKGROUND: Cutoff scores of the Montreal cognitive assessment (MoCA) for screening mild cognitive impairment in older adults differ across the world and within the Chinese culture. It is argued that to seek a cutoff score is essential to classify test participants. It was unknown how taking a classifying approach might reveal the cutoff score for identifying mildly cognitively impaired older adults. METHODS: Participants, selected from 13 communities in Wuhan, China, were tested with the Chinese version of MoCA and rated with the Activities of Daily Living and the Clinical Dementia Rating scales. Mixture modeling was applied to the data with certain covariates and MoCA sum scores as the outcome of the latent class. Models with different numbers of classes were compared in terms of information criteria, likelihood ratio test, entropy, and interpretability. RESULTS: A 3-class model (normal, mildly impaired, and severely impaired) was found to fit the data best. The normal class averaged a MoCA score of 24, while the severely impaired class averaged a score below 18. For those cases with MoCA scores above 18 and below 24, it is not certain if they are in the normal or the severely impaired classes. CONCLUSION: Latent variable classification modeling provides another option to identify MCI in older adults. Some categorically different cases of MCI cannot be captured with any single MoCA sum score. A range of 18-24 MoCA scores might serve as a better screening criterion of MCI. Older adults who scored within this gray zone should be monitored for potential interventions.

Defects in meiotic chromosome segregation lead to unreduced male gametes in Arabidopsis SMC5/6 complex mutants.

Structural maintenance of chromosome 5/6 (SMC5/6) complex is a crucial factor for preserving genome stability. Here, we show that mutants for several Arabidopsis (Arabidopsis thaliana) SMC5/6 complex subunits produce triploid offspring. This phenotype is caused by a meiotic defect leading to the production of unreduced male gametes. The SMC5/6 complex mutants show an absence of chromosome segregation during the first and/or the second meiotic division, as well as a partially disorganized microtubule network. Importantly, although the SMC5/6 complex is partly required for the repair of SPO11-induced DNA double-strand breaks, the nonreduction described here is SPO11-independent. The measured high rate of ovule abortion suggests that, if produced, such defects are maternally lethal. Upon fertilization with an unreduced pollen, the unbalanced maternal and paternal genome dosage in the endosperm most likely causes seed abortion observed in several SMC5/6 complex mutants. In conclusion, we describe the function of the SMC5/6 complex in the maintenance of gametophytic ploidy in Arabidopsis.

Does dual reduction in chemical fertilizer and pesticides improve nutrient loss and tea yield and quality? A pilot study in a green tea garden in Shaoxing, Zhejiang Province, China.

Tea tree (Camellia sinensis) is a valuable and popular cash crop widely planted in tropical and subtropical areas of China. To increase tea yield and quality, high rates of chemical fertilizer and pesticide application have generally been used; however, increasing usage of fertilizers and pesticides does not always proportionally increase tea yield. Indeed, excessive nutrient inputs may cause serious agricultural non-point source pollution. A pilot study on dual reduction in fertilizers and pesticides was conducted in a green tea plantation in Shaoxing, Zhejiang Province, to explore the environmental effects of different fertilizer and pesticide managements (e.g., changes in soil properties and nutrient accumulation, nutrient inputs in runoff water) and to reveal the potential effects of the interaction of these two managements on tea yield and quality. Traditional formulas and rates of chemical fertilizers and pesticides were used as the baselines (100% usage); replacement with different proportions of organic fertilizer (i.e., 20%, 50% and 80%) and direct pesticide reductions of 30%, 50%, and 80% were tested. The results showed that proper management with organic fertilizer replacement can effectively mitigate soil acidification and nutrient deficiency in tea plantations, increase soil organic matter (OM) and ammonium nitrogen (NH4-N) contents, and promote tea yield and quality. Moreover, managements with organic fertilizer replacement can markedly reduce the inputs of ammonium nitrogen (NH4-N), nitrate nitrogen (NO3-N), total phosphorus (TP), and total potassium (TK) in runoff water. Soil nutrient accumulation was the highest while the runoff nutrient input was the lowest at 20% organic fertilizer replacement. Experimental spraying of bifenthrin and chlorfenapyr revealed that these pesticides were mainly trapped by the tea leaves and rarely entered the soil or water bodies. Although pesticide reduction treatments can effectively decrease pesticide residues in tea leaves, differences in pesticide residue between various treatments were not obvious due to the rapid degradation of pesticides. Multivariate analysis of variance showed that 50% of the variation in tea yield, bud density, polyphenols, and caffeine can be explained by interactions between fertilizers and pesticides. Combinations of 20% or 50% organic fertilizer replacement and 30% or 50% pesticide application reduction are appropriate for both mitigating nutrient loss and balancing tea yield and quality, especially the combination of 50% organic fertilizer replacement and 50% pesticide reduction, which produced the best results. This study demonstrates the feasibility of dual reductions in fertilizers and pesticides for mitigating environmental hazards while maintaining the yield and quality of tea.

Improvement of glucocorticoid-impaired thymus function by dihydromyricetin via up-regulation of PPARγ-associated fatty acid metabolism.

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vß TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.

Atomic force microscopy technique used for assessment of the anti-arthritic effect of licochalcone A via suppressing NF-κB activation.

Atomic force microscopy (AFM) is appropriately applied to the examination of hard surfaces and soft samples with extremely high resolution and ultrasensitive force, which cannot be obtained by other imaging techniques, including optical and electron microscopy. In the current study, AFM was employed to evaluate the anti-arthritic effect of licochalcone A (LCA), a flavonoid isolated from the root of Chinese medicinal herb Glycyrrhiza inflate, on rheumatoid arthritis synovial fibroblasts (RASFs) at the nanoscale for the first time. The morphology, ultrastructure and stiffness of RASFs was modified by LCA as determined by AFM, suggesting that LCA most likely exerts an anti-arthritic effect based on the key role of RASFs in the progression of RA. Further studies showed that the inhibitory effect of LCA on IκBα phosphorylation and degradation as well as on p65 nuclear translocation and phosphorylation contributed to altering the morphology, ultrastructure and stiffness of the RASF membrane. Interestingly, IKKß phosphorylation was not detectable in RASFs, indicating that LCA altered the morphology, ultrastructure and stiffness of the RASF membrane by inhibiting NF-κB activation independent of IKKß phosphorylation. Antigen-induced arthritis (AIA) was established in Sprague Dawley (SD) rats to validate the anti-arthritic effect of LCA, and LCA significantly decreased both the arthritis scores and paw swelling in the AIA rats, suggesting that LCA inhibits the progression and development of arthritis in vivo. Collectively, AFM provides evidence at the nanoscale to predict the anti-arthritic effect of drugs on RASFs, and LCA should be further investigated as a candidate agent for the treatment of arthritis.

Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function.

Matrine, as a natural alkaloid isolated from the traditional herb medicine sophora flavescens, has been proved to possess excellent biological activities, including anticancer effects. Now, this research aims to assess the anticancer activities and the mechanism of matrine against esophageal cancer cells, we investigated the proliferative inhibition, apoptosis induction, as well as the underlying mechanism of matrine on esophageal cancer KYSE-150 cells. It was found that matrine could suppress KYSE-150 cell proliferation and significantly mediate cell apoptosis in a dose-dependent relation by increasing intracellular reactive oxygen species level and triggering mitochondrial membrane potential disruption. More precise mechanism studies demonstrated that matrine could up-regulate the expression of Bax proteins and down-regulate the expression of Bcl-2 proteins, as well as the activation about caspase-3, 8 and 9 in KYSE-150 cells. The morphological analysis of KYSE-150 cells exhibited that matrine could destroy the F-actin and nuclei structures and induce morphological damage with increased surface height distribution and roughness of cell membrane. These results not only demonstrated the potential anticancer activity mechanism of matrine at nanoscale, but also provide preliminary guidance for the treatment of esophageal cancer using matrine.

GE11 peptide conjugated selenium nanoparticles for EGFR targeted oridonin delivery to achieve enhanced anticancer efficacy by inhibiting EGFR-mediated PI3K/AKT and Ras/Raf/MEK/ERK pathways.

Selenium nanoparticles (Se NPs) have attracted increasing interest in recent decades because of their anticancer, immunoregulation, and drug carrier functions. In this study, GE11 peptide-conjugated Se NPs (GE11-Se NPs), a nanosystem targeting EGFR over-expressed cancer cells, were synthesized for oridonin delivery to achieve enhanced anticancer efficacy. Oridonin loaded and GE11 peptide conjugated Se NPs (GE11-Ori-Se NPs) were found to show enhanced cellular uptake in cancer cells, which resulted in enhanced cancer inhibition against cancer cells and reduced toxicity against normal cells. After accumulation into the lysosomes of cancer cells and increase of oridonin release under acid condition, GE11-Ori-Se NPs were further transported into cytoplasm after the damage of lysosomal membrane integrity. GE11-Ori-Se NPs were found to induce cancer cell apoptosis by inducting reactive oxygen species (ROS) production, activating mitochondria-dependent pathway, inhibiting EGFR-mediated PI3K/AKT and inhibiting Ras/Raf/MEK/ERK pathways. GE11-Se NPs were also found to show active targeting effects against the tumor tissue in esophageal cancer bearing mice. And in nude mice xenograft model, GE11-Ori-Se NPs significantly inhibited the tumor growth via inhibition of tumor angiogenesis by reducing the angiogenesis-marker CD31 and activation of the immune system by enhancing IL-2 and TNF-α production. The selenium contents in mice were found to accumulate into liver, tumor, and kidney, but showed no significant toxicity against liver and kidney. This cancer-targeted design of Se NPs provides a new strategy for synergistic treating of cancer with higher efficacy and reduced side effects, introducing GE11-Ori-Se NPs as a candidate for further evaluation as a chemotherapeutic agent for EGFR over-expressed esophageal cancers.

Calycosin suppresses expression of pro-inflammatory cytokines via the activation of p62/Nrf2-linked heme oxygenase 1 in rheumatoid arthritis synovial fibroblasts.

The activation of synovial fibroblasts (SFs) and the subsequent production and expression of pro-inflammatory cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). In the current study, rheumatoid arthritis synovial fibroblasts (RASFs) isolated from the joint of the patients were used to evaluate the suppressive effects of calycosin (CAL), a compound derived from the Chinese medicinal herb Radix Astragali, on the expression of pro-inflammatory cytokines in RASFs. The results demonstrated that increased mRNA expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-25 (IL-25), interleukin-33(IL-33) were significantly inhibited by CAL. Furthermore, the compound obviously suppressed IL-6 and IL-33 secretion. The key inflammatory mediator, cyclooxygenase-2 (COX-2) was significantly attenuated by CAL. A mechanistic study showed that the antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1(NQO1) and Nrf2 of RASFs were markedly activated by CAL. Furthermore, CAL potentiated the accumulation of sequestosome 1 (SQSTM1, p62) and the degradation of Kelch-like ECH-associated protein 1 (Keap1), thereby inducing Nrf2 translocation from the cytoplasm to the nucleus. Thus, CAL suppresses the expression of pro-inflammatory cytokines via p62/Nrf2-linked HO-1 induction in RASFs, which suggests that the compound should be further investigated as a candidate anti-inflammatory and anti-arthritic agent.

Immunomodulatory effects of polysaccharide compounds in macrophages revealed by high resolution AFM.

Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by atomic force microscopy (AFM). By high resolution AFM imaging, PCs-1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 were also proved to increase the particle size and roughness of resting RAW264.7 macrophages, which suggested that PCs could activate resting RAW264.7 macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse the surface particle size and roughness decrease of peritoneal macrophages isolated from cyclophosphamide induced immunosuppressive mice, suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health. SCANNING 38:792-801, 2016. © 2016 Wiley Periodicals, Inc.

[Effects of lead stress on net photosynthetic rate, SPAD value and ginsenoside production in Ginseng (Panax ginseng)].

The paper aimed to evaluate the effects of lead stress on photosynthetic performance and ginsenoside content in ginseng (Panax ginseng). To accomplish this, three years old ginseng were cultivated in pot and in phytotron with different concentrations of lead, ranging from 0 to 1000 mg x kg(-1) soil for a whole growth period (about 150 days). The photosynthetic parameters in leaves and ginsenoside content in roots of ginseng were determined in green fruit stage and before withering stage, respectively. In comparison with the control, net photosynthetic rate and SPAD value in ginseng leaves cultivated with 100 and 250 mg x kg(-1) of lead changed insignificantly, however, ginseng supplied with 500 and 1 000 mg x kg(-1) of lead showed a noticeably decline in the net rate of photosynthesis and SPAD value (P < 0.05), the lowest net photosynthetic rate and SPAD value showed in the treatment supplied with 1 000 mg x kg(-1) of lead, with decline of 57.8%,11.0%, respectively. Total content of ginsenoside in ginseng roots cultivated with 100 mg x kg(-1) of lead showed insignificantly change compared to the control, but the content increased remarkably in treatments supplied with 250, 500, 1 000 mg x kg(-1) of lead (P < 0.05), and highest content appeared in these ginsengs exposed to 1000 mg x kg(-1) of lead. The net photosynthetic rate and SPAD value in leaves of ginseng both showed significantly negative linear correlations with lead stress level (P < 0.01), and significant positive linear correlations between total content of ginsenoside and lead concentration was also observed (P < 0.05). These results strongly indicate that exposing to high level of lead negatively affects photosynthetic performance in ginseng leaves, but benefits for accumulation of secondary metabolism (total content of ginsenoside) in ginseng root.

Selenium nanoparticles induced membrane bio-mechanical property changes in MCF-7 cells by disturbing membrane molecules and F-actin.

Selenium nanoparticles (Se NPs) have been served as promising materials for biomedical applications, especially for cancer treatment. The anti-cancer effects of Se NPs against cancer cells have been widely studied in recent years, but whether Se NPs can induce the changes of cell membrane bio-mechanical properties in cancer cells still remain unexplored. In this Letter, we prepared Se NPs for investigating the intracellular localization of Se NPs in MCF-7 cells and determined the effects of Se NPs on apoptosis and necrosis in MCF-7 cells. Especially, we reported for the first time about the effects of Se NPs on the bio-mechanical properties of cancer cells and found that Se NPs could remarkably decrease the adhesion force and Young's modulus of MCF-7 cells. To further understand the potential mechanisms about how Se NPs affect the bio-mechanical properties of MCF-7 cells, we also investigated the expression of CD44 molecules, the structure and the amounts of F-actin. The results indicated that the decreased adhesion force between AFM tip and cell membrane was partially due to the changes of membrane molecules induced by Se NPs, such as the down-regulation of trans-membrane CD44 molecules. Additionally, the decrease of Young's modulus of MCF-7 cells was due to the dis-organization and down-regulation of F-actin induced by Se NPs. These results collectively suggested that cell membrane was of vital importance in Se NPs induced toxicity in cancer cells, which could be served as a potential target for cancer treatment by Se NPs.