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INTRODUCTION: The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 µL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). CONCLUSION: Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.
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Circadian rhythms regulate physiological processes in approximately 24 h cycles, and their disruption is associated with various diseases. Inflammation may perturb circadian rhythms, though these interactions remain unclear. This study examined whether systemic inflammation induced by an intraperitoneal injection of lipopolysaccharide (LPS) could alter central and peripheral circadian rhythms and diurnal neuroimmune dynamics. Mice were randomly assigned to two groups: the saline control group and the LPS group. The diurnal expression of circadian clock genes and inflammatory cytokines were measured in the hypothalamus, hippocampus, and liver. Diurnal dynamic behaviors of microglia were also assessed. Our results revealed that the LPS perturbed circadian gene oscillations in the hypothalamus, hippocampus, and liver. Furthermore, systemic inflammation induced by the LPS could trigger neuroinflammation and perturb the diurnal dynamic behavior of microglia in the hippocampus. These findings shed light on the intricate link between inflammation and circadian disruption, underscoring their significance in relation to neurodegenerative diseases.
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Ritmo Circadiano , Inflamação , Lipopolissacarídeos , Animais , Camundongos , Masculino , Microglia/metabolismo , Microglia/imunologia , Hipotálamo/metabolismo , Hipotálamo/imunologia , Hipocampo/metabolismo , Citocinas/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/imunologia , Camundongos Endogâmicos C57BL , Relógios Circadianos/genética , NeuroimunomodulaçãoRESUMO
Selenium (Se) is an essential micronutrient for human and animals. It plays an important role in antioxidative stress, selenoenzymes regulation and immunomodulation. In this study, two common immunostimulants chitosan (CTS) and Se were used to synthesize nanoparticles (CTS-SeNP). Immunomodulation of CTS-SeNP were explored in wild-type zebrafish (Danio rerio). Dietary supplementation of CTS-SeNP enhanced lysozyme activity, phagocytic respiratory burst as well as splenocytes proliferation stimulated by LPS and ConA. CTS-SeNP showed immunomodulation effect from 5 to 20⯵g/g but the best outcome was observed at 10⯵g/g. Immunomodulation effect were rapidly induced after 3-9d and can sustain to 60. The zebrafish fed with 10⯵g/g CTS-SeNP also showed 26.7% higher survival rate than the control after intraperitoneal injection of common bacterium Aeromonas hydrophila. Our results suggested that CTS-SeNP is an effective immunostimulant to fish and has potential application in aquaculture.
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Quitosana/metabolismo , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , Nanopartículas , Selênio/metabolismo , Peixe-Zebra/imunologia , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Quitosana/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Infecções por Bactérias Gram-Negativas/imunologia , Nanopartículas/administração & dosagem , Selênio/administração & dosagemRESUMO
Selenium (Se) is an essential element and its biological activity is related to its speciation. It is also well-known that in excess it can cause teratogenesis in fish and birds. In this study we compared dietary toxicity of elemental selenium nanoparticles (SeNPs) with selenite and selenomethionine (Se-Met). Japanese medaka (Oryzias latipes) was used as a laboratory model to determine Se effects on adults and their offspring. Adult females were individually exposed using a dry diet fortified with 0, 10 or 20⯵g/g of the three Se species for 7 days and then allowed to breed for 3 days. Fertilization rate and the proportion of malformed offspring were examined. The three Se diets led to significant increase in maternal tissue Se concentration in the order of Se-Met >>selenite > SeNP. However, in terms of proportion of malformed offspring, the effect of Se-Met = selenite > SeNP. The malformations included pericardial edema and craniofacial changes, which were typical for Se toxicity. The mismatch of maternal ovary Se concentration and proportion of malformed offspring suggested total Se concentration is a poor predictor of toxicity and teratogenesis. Comparing expression of four genes related to oxidative stress in maternal tissue also showed that there were significant differences in expression patterns between three Se diets in the order of selenite = SeNP > Se-Met. Our results showed that SeNPs cause similar toxicity as other Se species but require further study to elucidate the underlying mechanism.
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Anormalidades Induzidas por Medicamentos , Exposição Dietética , Exposição Materna , Nanopartículas , Selênio/toxicidade , Anormalidades Induzidas por Medicamentos/genética , Anormalidades Induzidas por Medicamentos/metabolismo , Animais , Feminino , Oryzias/genética , Oryzias/metabolismo , Estresse Oxidativo , Ácido Selenioso/toxicidade , Selenometionina/toxicidadeRESUMO
BACKGROUND AND OBJECTIVE: The tuberculin skin test (TST), T-Spot.TB (T-Spot) and QuantiFERON-TB Gold-In Tube (QFT) were compared in diagnosing latent tuberculosis infection (LTBI) among human immunodeficiency virus (HIV)-infected persons. METHODS: Human immunodeficiency virus-infected persons without previous history of tuberculosis or LTBI were simultaneously tested by TST, T-Spot and QFT annually and followed up for tuberculosis. RESULTS: Among 110 HIV-infected subjects with 85% previous TST screening coverage, 75% on anti-retroviral therapy, well-preserved median CD4 count (414/µL) and low median viral load (<75/µL), baseline TST, T-Spot and QFT were positive in 5.5%, 5.6% and 4.9%, respectively, with almost complete discordance of positive results. Among 91 (83%), 66 (60%) and 26 (24%) subjects successfully undergoing the first, second and third annual retesting, TST, T-Spot and QFT were, respectively, positive in 11/123 (8.9%), 13/173 (7.5%) and 21/182 (11.5%) on retesting, with similar discordance of positive results. There was no significant association with the concurrent CD4 count or viral load. Conversion occurred in 11/123 (8.9%), 8/160 (5.0%) and 18/168 (10.7%) of TST, T-Spot and QFT, respectively, and none was associated with changes in CD4 count or viral load. More than half of the positive T-SPOT and QFT results reverted to negative on follow-up. None of these tests picked up the single case of culture-confirmed tuberculosis observed after 798 person-years of follow-up. CONCLUSION: Major discordance in positive results, high reversion rates and low tuberculosis incidence among test-positive subjects cast serious doubt on the utility of the currently available LTBI tests in the annual screening of HIV-infected persons in an intermediate tuberculosis burden area.
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Infecções por HIV/complicações , Tuberculose Latente/diagnóstico , Adulto , Idoso , Contagem de Linfócito CD4 , Testes Diagnósticos de Rotina , Feminino , Infecções por HIV/microbiologia , Hong Kong , Humanos , Incidência , Tuberculose Latente/epidemiologia , Tuberculose Latente/virologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Teste Tuberculínico , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Worldwide, Hepatitis C (HCV) infection has been increasingly recognized in HIV-positive men who have sex with men (MSM). The objective of this study was to characterize the transmission dynamics of acute HCV infection in HIV-positive MSM in Hong Kong using a molecular approach. FINDINGS: We retrospectively examined 24 HIV-positive MSM with acute HCV infection diagnosed between 2009 and 2014 in Hong Kong. Detection and molecular characterization of HCV was successfully performed in 22 (91.7 %) patients. Genotype 3a was the most prevalent as identified in 14 (63.6 %) MSM, followed by 1a in 4 (18.2 %), 6a in 2 (9.1 %), and 1each (4.5 %) for 1b and 2a. The high prevalence of genotype 3a in MSM was in stark contrast to its rarity among HCV infected injection drug users (IDU) in Hong Kong. Phylogenetic analyses revealed a monophyletic HCV-3a cluster composing of MSM without injection history, and a homologous pair with HCV-6a genotype. There was otherwise no temporal or genetic clustering of the corresponding HIV sequences. CONCLUSIONS: The origin of sexually acquired acute HCV infections in HIV-positive MSM was diverse and not directly linked with local IDU. The transmission dynamics of HIV and HCV infections in MSM in Hong Kong were evidently unrelated.
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Coinfecção , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/transmissão , Homossexualidade Masculina , Adulto , Genótipo , HIV-1 , Hepacivirus/classificação , Hepatite C/virologia , Hong Kong/epidemiologia , Humanos , Masculino , Filogenia , Proteínas não Estruturais Virais/genéticaRESUMO
BACKGROUND: The availability of HIV antiretroviral therapy (ART) has been associated with the development of transmitted drug resistance-associated mutations (TDRM). TDRM can compromise treatment effectiveness in patients initiating ART and the prevalence can vary in different clinical settings. In this study, we investigated the proportion of TDRM in treatment-naïve, recently infected HIV-positive individuals sampled from four urban locations across Asia between 2007-2010. METHODS: Patients enrolled in the TREAT Asia Studies to Evaluate Resistance - Surveillance Study (TASER-S) were genotyped prior to ART initiation, with resulting resistance mutations analysed according to the WHO 2009 list. RESULTS: Proportions of TDRM from recently infected individuals from TASER-S ranged from 0% to 8.7% - Hong Kong: 3/88 (3.4%, 95% CI (0.71%-9.64%)); Thailand: Bangkok: 13/277 (4.7%, 95% CI (2.5%-7.9%)), Chiang Mai: 0/17 (0%, 97.5% CI (0%-19.5%)); and the Philippines: 6/69 (8.7%, 95% CI (3.3%-18.0%)). There was no significant increase in TDRM over time across all four clinical settings. CONCLUSIONS: The observed proportion of TDRM in TASER-S patients from Hong Kong, Thailand and the Philippines was low to moderate during the study period. Regular monitoring of TDRM should be encouraged, especially with the scale-up of ART at higher CD4 levels.
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Both human immunodeficiency virus (HIV) and viral hepatitis constitute major disease burden globally. As with other parts of the world, the HIV epidemic in Asia impacts mainly on men who have sex with men, one of the at-risk populations for sexually transmitted viral hepatitis. With the increasing availability of effective antiretroviral therapy, HIV-related mortality of people living with HIV has markedly reduced. Liver disease has become an important cause of mortality and morbidity in the HIV-infected population. With the improvement of socioeconomic conditions and availability of healthcare in Asian countries in recent years, the epidemiology of sexually transmitted viral hepatitis among HIV-positive men who have sex with men has also evolved. This review updates the epidemiology of different types of sexually transmitted viral hepatitis in this defined population in Asia.
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Soropositividade para HIV/complicações , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/transmissão , Homossexualidade Masculina , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Ásia/epidemiologia , Hepatite Viral Humana/classificação , Humanos , Masculino , Fatores de RiscoRESUMO
Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. Therefore, it is of great importance to develop chemosensitizing agents to cisplatin. In the present study, we demonstrated the strategy to use methylseleninic acid (MeSe) as a synergistic agent of cisplatin and elucidated their action mechanisms. The combination of MeSe and cisplatin exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cell and normal cell. By inducing intracellular oxidative stress, MeSe potentiated cisplatin-induced DNA damage and led to enhanced p53 phosphorylation, followed by increased activation of both mitochondrial and death receptor pathway. Down-regulation of phosphorylated AKT and ERK also played important roles in the synergistic effects of MeSe and cisplatin. Our results suggested that the strategy to apply MeSe as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by targeting the intracellular redox system. MeSe might be a candidate for clinical application as a chemosensitizer to cisplatin-based therapy for cancer treatments, especially for hepatocellular carcinoma.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Compostos Organosselênicos/farmacologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/fisiologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Fosforilação , Transdução de SinaisRESUMO
Lithium chloride (LiCl) has been used in signalling and molecular studies of animals, plants, and yeast. However, information on its roles in basidiomycetous fungi is still limited. In this study, we used RNA-Seq to study the effects of LiCl on Coprinopsis cinerea. LiCl enhanced mycelial growth and inhibited fruiting body formation in C. cinerea. RNA-Seq of the LiCl-treated C. cinerea resulted in a total of 14,128 genes. There were 1199 differentially expressed genes (DEGs) between the LiCl-treated samples and control samples in the mycelium stage (the first time point), and 1391 DEGs were detected when the control samples were forming hyphal knots while the treated samples were still in the mycelium (the second time point). Pathway enrichment analysis of the DEGs revealed a significant association between enhanced mycelium growth in the LiCl-treated C. cinerea and metabolic pathways. In addition, the DEGs involved in cellular process pathways, including "cell cycle-yeast" and "meiosis-yeast", were identified in suppressed C. cinerea fruiting body formation by LiCl under favourable environmental conditions. As LiCl can predominantly inhibit the activity of glycogen synthase kinase3 (GSK3), our findings suggest that LiCl affects the expression of genes involved in fruiting body initiation and cellular processes by inhibiting GSK3 activity which is essential for fruiting body formation.
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Food products simultaneously containing both food contaminants and emulsifiers are common in baked products, coffee and chocolate. Little is known regarding how food contaminants and emulsifiers interact and alter toxicity. Recent studies have shown that while emulsifiers themselves have little toxicity, they could cause changes in the gut microenvironment and lead to issues such as increased uptake of allergens. This study examined toxic effect of two common process contaminants acrylamide (AA) and benzo [a]pyrene (BAP) combined with food emulsifiers polyoxyethylene sorbitan monooleate (TW) or glycerol monostearate (G). In liver cell line HepG2 and gastrointestinal cell lines HIEC6 and Caco-2, toxicities of AA and BAP were increased by TW but not by G as indicated by decrease in IC50 values. Addition of TW also exacerbated gene expression changes caused by AA or BAP. Cellular uptake and cell membrane permeability were enhanced by TW but not by G, but tight junction proteins of Caco-2 monolayer was impacted by both emulsifiers. These results suggested that TW could increase toxicity of AA and BAP through increasing cell permeability thus chemical uptake and potentially through other interactions. The study is to draw the attention of regulators on the potential synergistic interaction of co-occurring chemicals in food.
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Chocolate , Alimentos , Humanos , Células CACO-2 , Café , Transporte Biológico , Acrilamida/toxicidade , Benzo(a)pirenoRESUMO
BACKGROUND: Selenium (Se) pollution poses serious threats to terrestrial ecosystems. Mushrooms are important sources of Se with the potential for bioremediation. Pre-eminent Se resources must possess the ability to tolerate high levels of Se. To obtain Se-accumulating fungi, we isolated selenite-tolerance-enhanced Ganoderma lucidum JNUSE-200 through adaptive evolution. METHODS: The molecular mechanism responsible for selenite tolerance and accumulation was explored in G. lucidum JNUSE-200 by comparing it with the original strain, G. lucidum CGMCC 5.26, using a combination of physiological and transcriptomic approaches. RESULTS: G. lucidum JNUSE-200 demonstrated tolerance to 200 mg/kg selenite in liquid culture and exhibited normal growth, whereas G. lucidum CGMCC 5.26 experienced reduced growth, red coloration, and an unpleasant odor as a result of exposure to selenite at the same concentration. In this study, G. lucidum JNUSE-200 developed a triple defense mechanism against high-level selenite toxicity, and the key genes responsible for improved selenite tolerance were identified. CONCLUSIONS: The present study offers novel insights into the molecular responses of fungi towards selenite, providing theoretical guidance for the breeding and cultivation of Se-accumulating varieties. Moreover, it significantly enhances the capacity of the bio-manufacturing industry and contributes to the development of beneficial applications in environmental biotechnology through fungal selenite transformation bioprocesses.
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Food emulsifiers like glycerol monostearate (G) and Tween 80 (TW) are commonly used to help formation and maintain stability of emulsions. However, certain food contaminants and emulsifiers often co-occur in the same food item due to food culture and cooking methods. For this reason, the present study investigated interaction of toxic effect of emulsifiers (G and TW) and process contaminants (acrylamide (AA) and benzo [a]pyrene (BAP)) on zebrafish. Adult zebrafish were exposed to emulsifiers, food contaminants, or the combination through diet for 2 h and 7 days. Oxidative stress and inflammation caused by food contaminants were increased when food emulsifiers were present. These combined treatments also induced more severe morphological changes than the contaminant alone treatments. In the gut, disruption of villi structure and increased number of goblet cells was observed and in the liver there were increased lipid deposition, infiltration of immune cells, glycogen depletion and focal necrosis. Increased accumulation of AA and BAP in the liver and gut were detected after addition of emulsifiers, suggesting that emulsifiers can enhance absorption of diet-borne contaminants. Our results showed food emulsifiers and contaminants can interact synergistically and increase risk.
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Emulsificantes , Contaminação de Alimentos , Inflamação , Estresse Oxidativo , Peixe-Zebra , Animais , Estresse Oxidativo/efeitos dos fármacos , Emulsificantes/toxicidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Contaminação de Alimentos/análise , Benzo(a)pireno/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Acrilamida/toxicidade , Polissorbatos/toxicidadeRESUMO
Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.
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Cárie Dentária , Microbiota , Probióticos , Simbióticos , Feminino , Humanos , Prebióticos , Cárie Dentária/prevenção & controle , Probióticos/uso terapêutico , BocaRESUMO
This study aimed to conduct a comprehensive analysis of the primary and secondary metabolites of water spinach (Ipomoea aquatica) using hydrophilic interaction liquid chromatography coupled with Orbitrap high-resolution mass spectrometry (HILIC-Orbitrap-HRMS). Certified samples from two cultivars, Green stem water spinach (G) and White stem water spinach (W) cultivated using organic and conventional farming methods, were collected from the Hong Kong market. Multivariate analysis was used to differentiate water spinach of different cultivars and farming methods. We identified 12 metabolites to distinguish between G and W, 26 metabolites to identify G from organic farming and 8 metabolites to identify W from organic farming. Then, two metabolites, isorhamnetin and jasmonic acid, have been proposed to serve as biomarkers for organic farming (in both G and W). Our foodomics findings provide useful tools for improving the crop performance of water spinach under abiotic/biotic stressesand authentication of organic produce.
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Ipomoea , Agricultura Orgânica , Ipomoea/química , Ipomoea/metabolismo , Ipomoea/crescimento & desenvolvimento , Espectrometria de Massas , Metabolômica , Cromatografia Líquida de Alta PressãoRESUMO
Microparticle-enhanced cultivation was used to enhance the production of exopolysaccharides (EPSs) from Antrodia cinnamomea. The structure and antibacterial activity of two EPSs produced by A. cinnamomea treated with Al2O3 [EPS-Al (crude) and EPS-Al-p (purified)] and without Al2O3 [EPS-C (crude) and EPS-C-p (purified)] were compared. It was observed that the addition of 4 g/L Al2O3 at 0 h resulted in the highest EPS yield of 1.46 g/L, possible attributed to the enhanced permeability of the cell membrane. The structural analysis revealed that EPS-C-p and EPS-Al-p had different structures. EPS-C-p was hyperbranched and spherical with a Mw of 10.8 kDa, while EPS-Al-p was irregular and linear with a Mw of 12.5 kDa. The proportion of Man in EPS-Al-p decreased, while those of Gal and Glc increased when compared to EPS-C-p. The total molar ratios of 6-Glcp and 4-Glcp in EPS-Al-p are 1.45 times that of EPS-C-p. Moreover, EPSs could alter bacterial cell morphology, causing intracellular substance leakage and growth inhibition, with EPS-Al having a stronger antibacterial activity than EPS-C. In conclusion, A. cinnamomea treated with Al2O3 could produce more EPSs, changing monosaccharide composition and glycosidic linkage profile, which could exert stronger antibacterial activity than that produced by untreated A. cinnamomea.
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Antrodia , Polyporales , Humanos , Polyporales/metabolismo , Monossacarídeos/análise , Antrodia/química , Polissacarídeos Bacterianos/químicaRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by continuous and selective degeneration or death of dopamine neurons in the midbrain, leading to dysfunction of the nigrostriatal neural circuits. Current clinical treatments for PD include drug treatment and surgery, which provide short-term relief of symptoms but are associated with many side effects and cannot reverse the progression of PD. Pluripotent/multipotent stem cells possess a self-renewal capacity and the potential to differentiate into dopaminergic neurons. Transplantation of pluripotent/multipotent stem cells or dopaminergic neurons derived from these cells is a promising strategy for the complete repair of damaged neural circuits in PD. This article reviews and summarizes the current preclinical/clinical treatments for PD, their efficacies, and the advantages/disadvantages of various stem cells, including pluripotent and multipotent stem cells, to provide a detailed overview of how these cells can be applied in the treatment of PD, as well as the challenges and bottlenecks that need to be overcome in future translational studies.
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BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.
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Motilidade Gastrointestinal , Naftalenos , Doença de Parkinson , Receptores de Detecção de Cálcio , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Esvaziamento Gástrico/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Receptores de Detecção de Cálcio/antagonistas & inibidores , Receptores de Detecção de Cálcio/metabolismoRESUMO
The aim of this study was to investigate the structural characteristics and in vitro fermentation patterns of polysaccharides from Boletus mushrooms. Polysaccharides were solubilized from fruit bodies of selected mushrooms Boletus auripes, B. bicolor, and B. griseus using subcritical water extraction. Boletus polysaccharides were characterized for their general physicochemical pattern, constituent monosaccharides and molecular weight. A simulated in vitro fermentation model was used to study the utilization of Boletus polysaccharides by the gut microbiota and their consequent modulation of microbial communities. Results showed that the main constituent monosaccharides of Boletus polysaccharides were glucose, galactose and mannose, followed by fucose, xylose and rhamnose, with glucose being the most abundant. The polysaccharides from B. bicolor and B. griseus exhibited a relatively high proportion of galactose and mannose, respectively. Boletus polysaccharides exhibited a wide range of molecular weights (5 kDa to 2000 kDa), which covered multiple polysaccharide populations, but the proportions of these populations varied among the samples. Boletus polysaccharides were gradually utilized by the human fecal microbiota, promoting the production of SCFAs. Boletus polysaccharides contributed to a healthier gut microbiota composition by increasing the relative abundance of beneficial bacterial genera such as Bacteroides and Faecalibacterium and reducing the relative abundance of harmful bacterial genera such as Sutterella and Escherichia-Shigella. B. bicolor polysaccharides showed better fermentability and prebiotic effects than the other Boletus polysaccharide groups. Therefore, the consumption of select Boletus mushrooms, particularly B. bicolor, could be a potential approach to obtain polysaccharides for microbiota modulation and to support gut health.
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Agaricales , Humanos , Fermentação , Galactose , Manose , Polissacarídeos/química , Monossacarídeos , Glucose , Ácidos Graxos VoláteisRESUMO
With WHO announcing COVID-19 no longer as a public health emergency of international concern (PHEIC) on May 5, 2023, coupled with the fact that the majority of the countries of the world have dropped strict city lockdown or border closure, this perhaps signals the end of the COVID-19 crisis caused by the SARS-CoV-2 virus. However, the COVID-19 pandemic has resulted in far-reaching effects affecting nearly every aspect of our lives and society. Notably, the food industry including agriculture, food manufacturers, food logistics, distributors and retailers have all felt the profound impact and had experienced significant stress during the pandemic. Therefore, it is essential to retrospect the lessons that can be learned from this pandemic for the food industry. This short review aims to address the food safety issues related to the COVID-19 pandemic by focusing on its foodborne transmission potential, innovations of virus detection strategies suitable for food industry; development of phathogenicaidal methods and devices to inactivate SARS-CoV-2 virus (particularly in industrial scale); and the set-up of related food regulations and guidelines as preventive and control measures for preventing the spread of SARS-CoV-2 virus through the food supply chain during the pandemic. This article may provide useful references for the food industry to minimize the food safety impact of COVID-19 (as well as other respiratory virus) and allows them to better prepare for similar future challenges.