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Clinicopathological characteristics of myelodysplastic syndromes with del(5q) in Taiwan

Yang CF, Hsu CY, Hsiao LT, Chen SW, Chuang SS

Malays J Pathol, 2023 Dec;45(3):405-416.
PMID: 38155382

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce.
MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]).
RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05).
CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).
Fulltext CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

Sun Y, Wu G, Cheng KS, Chen A, Neoh KH, Chen S, et al.

EBioMedicine, 2019 Aug;46:133-149.
PMID: 31375425 DOI: 10.1016/j.ebiom.2019.07.044

BACKGROUND: The evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients.
METHODS: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.
FINDINGS: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC 
A Compassionate Self Is a True Self? Self-Compassion Promotes Subjective Authenticity

Zhang JW, Chen S, Tomova Shakur TK, Bilgin B, Chai WJ, Ramis T, et al.

Pers Soc Psychol Bull, 2019 09;45(9):1323-1337.
PMID: 30658553 DOI: 10.1177/0146167218820914

Theory and research converge to suggest that authenticity predicts positive psychological adjustment. Given these benefits of authenticity, there is a surprising dearth of research on the factors that foster authenticity. Five studies help fill this gap by testing whether self-compassion promotes subjective authenticity. Study 1 found a positive association between trait self-compassion and authenticity. Study 2 demonstrated that on days when people felt more self-compassionate, they also felt more authentic. Study 3 discovered that people experimentally induced to be self-compassionate reported greater state authenticity relative to control participants. Studies 4 and 5 recruited samples from multiple cultures and used a cross-sectional and a longitudinal design, respectively, and found that self-compassion predicts greater authenticity through reduced fear of negative evaluation (Study 4) and heightened optimism (Study 5). Across studies, self-compassion's effects on authenticity could not be accounted for by self-esteem. Overall, the results suggest that self-compassion can help cultivate subjective authenticity.
Parasitological and molecular detection of human fascioliasis in a young man from Guizhou, China

Chen MX, Zhang RL, Xu XN, Yu Q, Huang DN, Liu W, et al.

Trop Biomed, 2020 Mar 01;37(1):50-57.
PMID: 33612717

A 24-year-old man born in Guizhou province was diagnosed with obstructive jaundice and bile duct stones in 2013. Four living trematodes were found during laparotomy and cholecystectomy. Based on the morphology and molecular genetics analysis of internal transcribed spacer and pcox1 genes of the flatworm specimens, the trematodes from the patient were confirmed to be Fasciola hepatica. This report provided the clinical and molecular diagnosis information on human fascioliasis, which is an emerging sanitary problem still ignored in China. Human fascioliasis constantly occurs due to climatic changes and frequency of human travel. Therefore, it deserves more attention from physicians working in both developing and developed countries.
microRNAs expression profiles in Schistosoma japonicum of different sex 14 and 28 days post-infection

Ai L, Hu W, Zhang RL, Huang DN, Chen SH, Xu B, et al.

Trop Biomed, 2020 Dec 01;37(4):947-962.
PMID: 33612748 DOI: 10.47665/tb.37.4.947

Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode's growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.
How does biochar aging affect NH3 volatilization and GHGs emissions from agricultural soils?

Feng Y, Feng Y, Liu Q, Chen S, Hou P, Poinern G, et al.

Environ Pollut, 2022 Feb 01;294:118598.
PMID: 34861331 DOI: 10.1016/j.envpol.2021.118598

Biochar has been considered as a potential tool to mitigate soil ammonia (NH3) volatilization and greenhouse gases (GHGs) emissions in recent years. However, the aging effect of biochar on soils remains elusive, which introduces uncertainty on the effectiveness of biochar to mitigate global warming in a long term. Here, a meta-analysis of 22 published works of literature with 217 observations was conducted to systematically explore the aging effect of biochar on soil NH3 and GHGs emissions. The results show that, in comparison with the fresh biochar, the aging makes biochar more effective to decrease soil NH3 volatilization by 7% and less risk to contribute CH4 emissions by 11%. However, the mitigation effect of biochar on soil N2O emissions is decreased by 15% due to aging. Additionally, aging leads to a promotion effect on soil CO2 emissions by 25% than fresh biochar. Our findings suggest that along with aging, particularly the effect of artificial aging, biochar could further benefit the alleviation of soil NH3 volatilization, whereas its potential role to mitigate global warming may decrease. This study provides a systematic assessment of the aging effect of biochar to mitigate soil NH3 and GHGs, which can provide a scientific basis for the sustainable green development of biochar application.
Fulltext Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management

Yang J, Chen S, Duan F, Wang X, Zhang X, Lian B, et al.

Cells, 2022 Nov 06;11(21).
PMID: 36359908 DOI: 10.3390/cells11213511

Mitochondrial cardiomyopathy (MCM) is characterized by abnormal heart-muscle structure and function, caused by mutations in the nuclear genome or mitochondrial DNA. The heterogeneity of gene mutations and various clinical presentations in patients with cardiomyopathy make its diagnosis, molecular mechanism, and therapeutics great challenges. This review describes the molecular epidemiology of MCM and its clinical features, reviews the promising diagnostic tests applied for mitochondrial diseases and cardiomyopathies, and details the animal and cellular models used for modeling cardiomyopathy and to investigate disease pathogenesis in a controlled in vitro environment. It also discusses the emerging therapeutics tested in pre-clinical and clinical studies of cardiac regeneration.
Quality control of Ganoderma lucidum by using C, H, O, and N stable isotopes and C and N contents for geographical traceability

Zhang Y, Jiang K, Chen S, Wang L, Zhang X, Xu W, et al.

Front Plant Sci, 2023;14:1234729.
PMID: 37885663 DOI: 10.3389/fpls.2023.1234729

RATIONALE: Ganoderma lucidum (G. lucidum) is a popular medicinal fungus that has been used in traditional medicine for decades, with its provenance influencing its medicinal and commercial worth. The amount of active ingredients and the price of G. lucidum from different origins vary significantly; hence, fraudulent labeling is common. Reliable techniques for G. lucidum geographic verification are urgently required to safeguard the interests of consumers, producers, and honest dealers. A stable isotope is widely acknowledged as a useful traceability technique and could be developed to confirm the geographical origin of G. lucidum.
METHODS: G. lucidum samples from various sources and in varying stages were identified by using δ 13C, δD, δ 18O, δ 15N, C, and N contents combined with chemometric tools. Chemometric approaches, including PCA, OPLS-DA, PLS, and FLDA models, were applied to the obtained data. The established models were used to trace the origin of G. lucidum from various sources or track various stages of G. lucidum.
RESULTS: In the stage model, the δ 13C, δD, δ 18O, δ 15N, C, and N contents were considered meaningful variables to identify various stages of G. lucidum (bud development, growth, and maturing) using PCA and OPLS-DA and the findings were validated by the PLS model rather than by only four variables (δ 13C, δD, δ 18O, and δ 15N). In the origin model, only four variables, namely δ 13C, δD, δ 18O, and δ 15N, were used. PCA divided G. lucidum samples into four clusters: A (Zhejiang), B (Anhui), C (Jilin), and D (Fujian). The OPLS-DA model could be used to classify the origin of G. lucidum. The model was validated by other test samples (Pseudostellaria heterophylla), and the external test (G. lucidum) by PLS and FLDA models demonstrated external verification accuracy of up to 100%.
CONCLUSION: C, H, O, and N stable isotopes and C and N contents combined with chemometric techniques demonstrated considerable potential in the geographic authentication of G. lucidum, providing a promising method to identify stages of G. lucidum.
Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells

Sweeney S, Leo BF, Chen S, Abraham-Thomas N, Thorley AJ, Gow A, et al.

Colloids Surf B Biointerfaces, 2016 Sep 01;145:167-75.
PMID: 27182651 DOI: 10.1016/j.colsurfb.2016.04.040

Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
Fulltext Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

Botelho DJ, Leo BF, Massa CB, Sarkar S, Tetley TD, Chung KF, et al.

Nanotoxicology, 2016;10(1):118-27.
PMID: 26152688 DOI: 10.3109/17435390.2015.1038330

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.
Prevalence and Risk of Mild Cognitive Impairment in Low and Middle-Income Countries: A Systematic Review

McGrattan AM, Zhu Y, Richardson CD, Mohan D, Soh YC, Sajjad A, et al.

J Alzheimers Dis, 2021;79(2):743-762.
PMID: 33361599 DOI: 10.3233/JAD-201043

BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state associated with increased risk of dementia. Little research on MCI exists from low-and middle-income countries (LMICs), despite high prevalence of dementia in these settings.
OBJECTIVE: This systematic review aimed to review epidemiological reports to determine the prevalence of MCI and its associated risk factors in LMICs.
METHODS: Medline, Embase, and PsycINFO were searched from inception until November 2019. Eligible articles reported on MCI in population or community-based studies from LMICs and were included as long as MCI was clearly defined.
RESULTS: 5,568 articles were screened, and 78 retained. In total, n = 23 different LMICs were represented; mostly from China (n = 55 studies). Few studies were from countries defined as lower-middle income (n = 14), low income (n = 4), or from population representative samples (n = 4). There was large heterogeneity in how MCI was diagnosed; with Petersen criteria the most commonly applied (n = 26). Prevalence of amnesic MCI (aMCI) (Petersen criteria) ranged from 0.6%to 22.3%. Similar variability existed across studies using the International Working Group Criteria for aMCI (range 4.5%to 18.3%) and all-MCI (range 6.1%to 30.4%). Risk of MCI was associated with demographic (e.g., age), health (e.g., cardio-metabolic disease), and lifestyle (e.g., social isolation, smoking, diet and physical activity) factors.
CONCLUSION: Outside of China, few MCI studies have been conducted in LMIC settings. There is an urgent need for population representative epidemiological studies to determine MCI prevalence in LMICs. MCI diagnostic methodology also needs to be standardized. This will allow for cross-study comparison and future resource planning.
Fulltext Effect of silver nanospheres and nanowires on human airway smooth muscle cells: role of sulfidation

Michaeloudes C, Seiffert J, Chen S, Ruenraroengsak P, Bey L, Theodorou IG, et al.

Nanoscale Adv, 2020 Dec 15;2(12):5635-5647.
PMID: 34381958 DOI: 10.1039/d0na00745e

Background: The toxicity of inhaled silver nanoparticles on contractile and pro-inflammatory airway smooth muscle cells (ASMCs) that control airway calibre is unknown. We explored the oxidative activities and sulfidation processes of the toxic-inflammatory response. Method: Silver nanospheres (AgNSs) of 20 nm and 50 nm diameter and silver nanowires (AgNWs), short S-AgNWs, 1.5 μm and long L-AgNWs, 10 μm, both 72 nm in diameter were manufactured. We measured their effects on cell proliferation, mitochondrial reactive oxygen species (ROS) release and membrane potential, and also performed electron microscopic studies. Main results and findings: The greatest effects were observed for the smallest particles with the highest specific surface area and greatest solubility that were avidly internalised. ASMCs exposed to 20 nm AgNSs (25 μg mL-1) for 72 hours exhibited a significant decrease in DNA incorporation (-72.4%; p < 0.05), whereas neither the 50 nm AgNSs nor the s-AgNWs altered DNA synthesis or viability. There was a small reduction in ASMC proliferation for the smaller AgNS, although Ag+ at 25 μL mL-1 reduced DNA synthesis by 93.3% (p < 0.001). Mitochondrial potential was reduced by both Ag+ (25 μg mL-1) by 47.1% and 20 nm Ag NSs (25 μg mL-1) by 40.1% (*both at p < 0.05), but was not affected by 50 nm AgNSs and the AgNWs. None of the samples showed a change in ROS toxicity. However, malondialdehyde release, associated with greater total ROS, was observed for all AgNPs, to an extent following the geometric size (20 nm AgNS: 213%, p < 0.01; 50 nm AgNS: 179.5%, p < 0.01 and L-AgNWs by 156.2%, p < 0.05). The antioxidant, N-acetylcysteine, prevented the reduction in mitochondrial potential caused by 20 nm AgNSs. The smaller nanostructures were internalised and dissolved within the ASMCs with the formation of non-reactive silver sulphide (Ag2S) on their surface, but with very little uptake of L-AgNWs. When ASMCs were incubated with H2S-producing enzyme inhibitors, the spatial extent of Ag2S formation was much greater. Conclusion: The intracellular toxicity of AgNPs in ASMCs is determined by the solubility of Ag+ released and the sulfidation process, effects related to particle size and geometry. Passivation through sulfidation driven by biogenic H2S can outcompete dissolution, thus reducing the toxicity of the smaller intracellular Ag nanostructures.
Fulltext Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

Botelho D, Leo BF, Massa C, Sarkar S, Tetley T, Chung KF, et al.

Front Pharmacol, 2018;9:213.
PMID: 29632485 DOI: 10.3389/fphar.2018.00213

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.
Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia

Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.

Mol Biol Evol, 2022 Feb 03;39(2).
PMID: 34940850 DOI: 10.1093/molbev/msab361

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
Fulltext Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes

Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, et al.

Sci Rep, 2017 03 02;7:42871.
PMID: 28251989 DOI: 10.1038/srep42871

Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson's disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.
Fulltext Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, et al.

Cell Death Dis, 2022 Jul 04;13(7):580.
PMID: 35787632 DOI: 10.1038/s41419-022-05034-x

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
Data Resource Profile: The Global School-based Student Health Survey-behavioural risk and protective factors among adolescents

Bischops AC, Radev ST, Köthe U, Chen S, Geldsetzer P, Sarker M, et al.

Int J Epidemiol, 2023 Apr 19;52(2):e102-e109.
PMID: 36350584 DOI: 10.1093/ije/dyac208
Heat stress reduces brown adipose tissue activity by exacerbating mitochondrial damage in type 2 diabetic mice

Lai P, Zhang L, Qiu Y, Ren J, Sun X, Zhang T, et al.

J Therm Biol, 2024 Jan;119:103799.
PMID: 38342042 DOI: 10.1016/j.jtherbio.2024.103799

Epidemiological evidence shows that diabetic patients are susceptible to high temperature weather, and brown adipose tissue (BAT) activity is closely related to type 2 diabetes (T2DM). Activation of BAT under cold stress helps improve T2DM. However, the impact of high temperature on the activity of BAT is still unclear. The study aimed to investigate the impact of heat stress on glucose and lipid metabolism in T2DM mice by influencing BAT activity. High-fat feeding and injecting streptozotocin (STZ) induced model of T2DM mice. All mice were randomly divided into three groups: a normal(N) group, a diabetes (DM) group and a heat stress diabetes (DMHS) group. The DMHS group received heat stress intervention for 3 days. Fasting blood glucose, fasting serum insulin and blood lipids were measured in all three groups. The activity of BAT was assessed by using quantitative real-time PCR (qRT-PCR), electron microscopy, and PET CT. Furthermore, the UHPLC-Q-TOF MS technique was employed to perform metabolomics analysis of BAT on both DM group and DMHS group. The results of this study indicated that heat stress aggravated the dysregulation of glucose and lipid metabolism, exacerbated mitochondrial dysfunction in BAT and reduced the activity of BAT in T2DM mice. This may be related to the abnormal accumulation of branched-chain amino acids (BCAAs) in the mitochondria of BAT.
Fulltext Improvement of chicken plasma protein hydrolysate angiotensin I-converting enzyme inhibitory activity by optimizing plastein reaction

Gao D, Guo P, Cao X, Ge L, Ma H, Cheng H, et al.

Food Sci Nutr, 2020 Jun;8(6):2798-2808.
PMID: 32566197 DOI: 10.1002/fsn3.1572

Chicken plasma protein hydrolysate (CPPH) was prepared by trypsin with angiotensin I-converting enzyme (ACE) inhibitory activity of 53.5% ± 0.14% and the degree of hydrolysis (DH) of 16.22% ± 0.21% at 1 mg·ml-1; then, five proteases, including pepsin, trypsin, papain, alcalase, and neutrase, were employed to improve ACE inhibitory ability by catalyzing plastein reaction. The results indicated that trypsin-catalyzed plastein reaction showed the highest ACE inhibitory activity. The exogenous amino acids of leucine, histidine, tyrosine, valine, and cysteine were selected to modify the CPPH. The leucine-modified plastein reaction released the highest ACE inhibitory activity. The effects of four reaction parameters on plastein reaction were studied, and the optimal conditions with the purpose of obtaining the most powerful ACE inhibitory peptides from modified products were obtained by response surface methodology (RSM). The maximum ACE inhibition rate of the modified hydrolysate reached 82.07% ± 0.03% prepared at concentration of hydrolysates of 30%, reaction time of 4.9 hr, pH value of 8.0, temperature of 40°C, and E/S ratio of 5,681.62 U·g-1. The results indicated that trypsin-catalyzed plastein reaction increased ACE inhibitory activity of chicken plasma protein hydrolysates by 28.57%.
Fulltext Modulation of Human Macrophage Responses to Mycobacterium tuberculosis by Silver Nanoparticles of Different Size and Surface Modification

Sarkar S, Leo BF, Carranza C, Chen S, Rivas-Santiago C, Porter AE, et al.

PLoS One, 2015;10(11):e0143077.
PMID: 26580078 DOI: 10.1371/journal.pone.0143077

Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.

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