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1.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37798251

RESUMO

Natural products have successfully treated several diseases using a multi-component, multi-target mechanism. However, a precise mechanism of action (MOA) has not been identified. Systems pharmacology methods have been used to overcome these challenges. However, there is a limitation as those similar mechanisms of similar components cannot be identified. In this study, comparisons of physicochemical descriptors, molecular docking analysis and RNA-seq analysis were performed to compare the MOA of similar compounds and to confirm the changes observed when similar compounds were mixed and used. Various analyses have confirmed that compounds with similar structures share similar MOA. We propose an advanced method for in silico experiments in herbal medicine research based on the results. Our study has three novel findings. First, an advanced network pharmacology research method was suggested by partially presenting a solution to the difficulty in identifying multi-component mechanisms. Second, a new natural product analysis method was proposed using large-scale molecular docking analysis. Finally, various biological data and analysis methods were used, such as in silico system pharmacology, docking analysis and drug response RNA-seq. The results of this study are meaningful in that they suggest an analysis strategy that can improve existing systems pharmacology research analysis methods by showing that natural product-derived compounds with the same scaffold have the same mechanism.


Assuntos
Produtos Biológicos , Medicamentos de Ervas Chinesas , Plantas Medicinais , Simulação de Acoplamento Molecular , Transcriptoma , Produtos Biológicos/farmacologia , Extratos Vegetais , Medicina Tradicional Chinesa
2.
Gastroenterology ; 165(1): 104-120, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36933623

RESUMO

BACKGROUND & AIMS: Dysbiosis of gut microbiota is linked to the development of colorectal cancer (CRC). However, microbiota-based stratification of CRC tissue and how this relates to clinicomolecular characteristics and prognosis remains to be clarified. METHODS: Tumor and normal mucosa from 423 patients with stage I to IV CRC were profiled by bacterial 16S rRNA gene sequencing. Tumors were characterized for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), APC, BRAF, KRAS, PIK3CA, FBXW7, SMAD4, and TP53 mutations, subsets for chromosome instability (CIN), mutation signatures, and consensus molecular subtypes (CMS). Microbial clusters were validated in an independent cohort of 293 stage II/III tumors. RESULTS: Tumors reproducibly stratified into 3 oncomicrobial community subtypes (OCSs) with distinguishing features: OCS1 (Fusobacterium/oral pathogens, proteolytic, 21%), right-sided, high-grade, MSI-high, CIMP-positive, CMS1, BRAF V600E, and FBXW7 mutated; OCS2 (Firmicutes/Bacteroidetes, saccharolytic, 44%), and OCS3 (Escherichia/Pseudescherichia/Shigella, fatty acid ß-oxidation, 35%) both left-sided and exhibiting CIN. OCS1 was associated with MSI-related mutation signatures (SBS15, SBS20, ID2, and ID7) and OCS2 and OCS3 with SBS18 related to damage by reactive oxygen species. Among stage II/III patients, OCS1 and OCS3 both had poorer overall survival compared with OCS2 for microsatellite stable tumors (multivariate hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.15-2.99; P = .012; and HR, 1.52; 95% CI 1.01-2.29; P = .044, respectively) and left-sided tumors (multivariate HR, 2.66; 95% CI, 1.45-4.86; P = .002; and HR, 1.76; 95% CI, 1.03-3.02; P = .039, respectively). CONCLUSIONS: OCS classification stratified CRCs into 3 distinct subgroups with different clinicomolecular features and outcomes. Our findings provide a framework for a microbiota-based stratification of CRC to refine prognostication and to inform the development of microbiota-targeted interventions.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Humanos , Prognóstico , Proteína 7 com Repetições F-Box-WD/genética , Proteínas Proto-Oncogênicas B-raf/genética , RNA Ribossômico 16S , Metilação de DNA , Mutação , Instabilidade de Microssatélites , Instabilidade Cromossômica , Fenótipo , Neoplasias Colorretais/patologia , Ilhas de CpG
3.
J Med Virol ; 96(5): e29648, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727032

RESUMO

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transtornos Cerebrovasculares , Vacinação , Humanos , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Idoso , Vacinação/estatística & dados numéricos , Sobreviventes/estatística & dados numéricos , Adulto , SARS-CoV-2/imunologia , Fatores de Risco , Modelos de Riscos Proporcionais
4.
J Med Virol ; 96(4): e29549, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38563352

RESUMO

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.


Assuntos
Infecções por Papillomavirus , Gravidez , Feminino , Humanos , Recém-Nascido , Adulto , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Pesquisa , Taiwan/epidemiologia , Fatores de Risco
5.
Chemistry ; 30(3): e202303211, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37909248

RESUMO

Aqueous zinc-ion batteries (AZIBs) have attracted considerable attention. However, due to the uneven distribution of charge density at Zn anode-electrolyte interface, severe dendrites and corrosion are generated during cycling. In this work, a facile and scalable strategy to address the above-mentioned issues has been proposed through regulating the charge density at Zn anode-electrolyte interface. As a proof of concept, amidinothiourea (ATU) with abundant lone-pair electrons is employed as an interfacial charge modifier for Zn anode-electrolyte interface. The uniform and increased interfacial charge distribution on Zn anode-electrolyte interface has been obtained. Moreover, the unique Zn-bond constructed between N atoms and Zn2+ as well as the hydrogen bonds are formed among ATU and Ac- anion/active H2 O, which promote the migration and desolvation behavior of Zn2+ at anode-electrolyte interface. Accordingly, at a trace concentration of 0.01 mg mL-1 ATU, these features endow Zn anode with a long cycling life (more than 800 h), and a high average Columbic efficiency (99.52 %) for Zn||Cu batteries. When pairing with I2 cathode, the improved cycling ability (5000 cycles) with capacity retention of 77.9 % is achieved. The fundamental understanding on the regulation of charge density at anode-electrolyte interface can facilitate the development of AZIBs.

6.
Pancreatology ; 24(2): 211-219, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302312

RESUMO

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.


Assuntos
Pancreatite Crônica , Esteatorreia , Humanos , Estudos Transversais , Qualidade de Vida , Prevalência , China/epidemiologia , Fatores de Risco , Pancreatite Crônica/complicações , Pancreatite Crônica/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologia , Dor , Inquéritos e Questionários
7.
Eur Radiol ; 34(3): 1411-1421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37646808

RESUMO

OBJECTIVES: This study evaluated the collateral map's ability to predict lesion growth and penumbra after acute anterior circulation ischemic strokes. METHODS: This was a retrospective analysis of selected data from a prospectively collected database. The lesion growth ratio was the ratio of the follow-up lesion volume to the baseline lesion volume on diffusion-weighted imaging (DWI). The time-to-maximum (Tmax)/DWI ratio was the ratio of the baseline Tmax > 6 s volume to the baseline lesion volume. The collateral ratio was the ratio of the hypoperfused lesion volume of the phase_FU (phase with the hypoperfused lesions most approximate to the follow-up DWI lesion) to the hypoperfused lesion volume of the phase_baseline of the collateral map. Multiple logistic regression analyses were conducted to identify independent predictors of lesion growth. The concordance correlation coefficients of Tmax/DWI ratio and collateral ratio for lesion growth ratio were analyzed. RESULTS: Fifty-two patients, including twenty-six males (mean age, 74 years), were included. Intermediate (OR, 1234.5; p < 0.001) and poor collateral perfusion grades (OR, 664.7; p = 0.006) were independently associated with lesion growth. Phase_FUs were immediately preceded phases of the phase_baselines in intermediate or poor collateral perfusion grades. The concordance correlation coefficients of the Tmax/DWI ratio and collateral ratio for the lesion growth ratio were 0.28 (95% CI, 0.17-0.38) and 0.88 (95% CI, 0.82-0.92), respectively. CONCLUSION: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. Further studies are needed to generalize the findings of this study. CLINICAL RELEVANCE STATEMENT: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. KEY POINTS: • Cell viability in cerebral ischemia due to proximal arterial steno-occlusion mainly depends on the collateral circulation. • The collateral map shows salvageable brain extent, which can survive by recanalization treatments after acute anterior circulation ischemic stroke. • Precise estimation of salvageable brain makes it possible to make patient-specific treatment decision.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , AVC Isquêmico/complicações , AVC Isquêmico/patologia , Estudos Retrospectivos , Isquemia Encefálica/complicações , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Circulação Colateral , Circulação Cerebrovascular
8.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731856

RESUMO

We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds.


Assuntos
Simulação de Acoplamento Molecular , Terpenos , Transcriptoma , Terpenos/farmacologia , Terpenos/química , Transcriptoma/efeitos dos fármacos , Humanos , Wolfiporia/química , Perfilação da Expressão Gênica/métodos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Microglia/efeitos dos fármacos , Microglia/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Biologia Computacional/métodos , Animais
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 365-370, 2024 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-38660900

RESUMO

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.


Assuntos
Sarcoma de Ewing , Humanos , Sarcoma de Ewing/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Feminino , Masculino , Criança , Adolescente , Pré-Escolar , Lactente , Estudos Retrospectivos , Neoplasias Ósseas/terapia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Prognóstico , Resultado do Tratamento
10.
Pediatr Blood Cancer ; 70(12): e30680, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37715719

RESUMO

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

11.
BMC Gastroenterol ; 23(1): 360, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853330

RESUMO

Pancreatic stones are the result of pathophysiologic changes in chronic pancreatitis with an incidence of more than 90%. At present, pancreatic extracorporeal shock wave lithotripsy (P-ESWL) can be used as the first-line treatment for large or complex stones. Although a large number of studies have proven the safety and effectiveness of P-ESWL, we should also pay attention to postoperative adverse events, mainly due to the scattering of shock waves in the conduction pathway. Adverse events can be classified as either complications or transient adverse events according to the severity. Because the anatomic location of organs along the shock wave conducting pathway differs greatly, adverse events after P-ESWL are varied and difficult to predict. This paper outlines the mechanism, definition, classification, management and risk factors for adverse events related to P-ESWL. It also discusses the technique of P-ESWL, indications and contraindications of P-ESWL, and adverse events in special populations.


Assuntos
Cálculos , Litotripsia , Pancreatopatias , Humanos , Pancreatopatias/terapia , Pancreatopatias/etiologia , Ductos Pancreáticos , Resultado do Tratamento , Litotripsia/efeitos adversos , Litotripsia/métodos , Cálculos/terapia
12.
Acta Pharmacol Sin ; 44(1): 81-91, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35732708

RESUMO

Organic anion transporter 1 (OAT1) plays a major role in mediating the absorption, distribution and excretion of drugs and other xenobiotics in the human body. In this study we explored the OAT1 status in rheumatoid arthritis (RA) patients and arthritic animals and its role in regulating the anti-arthritic activity of methotrexate (MTX). We showed that OAT1 expression was significantly downregulated in synovial tissues from RA patients compared with that in the control patients. In collagen-induced arthritis (CIA) rats, synovial OAT1 expression was significantly decreased compared with the control rats. In synoviocytes isolated from CIA rats, PGE2 (0.003-1.75 µM) dose-dependently downregulated OAT1 expression, resulting in decreased absorption of MTX. Silencing OAT1 in synoviocytes caused a 43.7% reduction in the uptake of MTX. Furthermore, knockdown of OAT1 impaired MTX-induced inhibitory effects on the viability and migration of synoviocytes isolated from CIA rats. Moreover, injection of OAT1-shRNA into articular cavity of CIA rats significantly decreased synovial OAT1 expression and impaired the anti-arthritic action of MTX, while injection of lentivirus containing OAT1 sequences led to the opposite results. Interestingly, we found that paeoniflorin-6'-O-benzene sulfonate (CP-25) upregulated OAT1 expression both in vitro and in vivo and promoted MTX uptake by synoviocytes via regulating OAT1 expression and function. Taken together, OAT1 plays a major role in regulating MTX uptake by synoviocytes and the anti-arthritic activity of MTX. OAT1 is downregulated in RA and CIA rats, which can be improved by CP-25.


Assuntos
Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Ratos , Humanos , Animais , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Membrana Sinovial , Articulações , Artrite Reumatoide/tratamento farmacológico
13.
BMC Biol ; 20(1): 103, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549698

RESUMO

BACKGROUND: The coral-Symbiodiniaceae symbiosis is fundamental for the coral reef ecosystem. Corals provide various inorganic nutrients to their algal symbionts in exchange for the photosynthates to meet their metabolic demands. When becoming symbionts, Symbiodiniaceae cells show a reduced proliferation rate and a different life history. While it is generally believed that the animal hosts play critical roles in regulating these processes, far less is known about the molecular underpinnings that allow the corals to induce the changes in their symbionts. RESULTS: We tested symbiont cell proliferation and life stage changes in vitro in response to different nutrient-limiting conditions to determine the key nutrients and to compare the respective symbiont transcriptomic profiles to cells in hospite. We then examined the effects of nutrient repletion on symbiont proliferation in coral hosts and quantified life stage transitions in vitro using time-lapse confocal imaging. Here, we show that symbionts in hospite share gene expression and pathway activation profiles with free-living cells under nitrogen-limited conditions, strongly suggesting that symbiont proliferation in symbiosis is limited by nitrogen availability. CONCLUSIONS: We demonstrate that nitrogen limitation not only suppresses cell proliferation but also life stage transition to maintain symbionts in the immobile coccoid stage. Nutrient repletion experiments in corals further confirmed that nitrogen availability is the major factor limiting symbiont density in hospite. Our study emphasizes the importance of nitrogen in coral-algae interactions and, more importantly, sheds light on the crucial role of nitrogen in symbiont life history regulation.


Assuntos
Antozoários , Dinoflagellida , Animais , Antozoários/fisiologia , Proliferação de Células , Dinoflagellida/genética , Ecossistema , Nitrogênio , Simbiose/fisiologia
14.
Immunopharmacol Immunotoxicol ; 45(1): 16-25, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35850595

RESUMO

BACKGROUND: The first-line anti-rheumatic drug methotrexate (MTX) is used in the combination. Because of the unpredictable adverse reactions, optimization of relevant regimens is necessary and meaningful. This study aimed to study the possible interaction between Securidaca inappendiculate Hassk. Derived xanthones and MTX. METHODS: We established adjuvant-induced arthritis (AIA) model, which was treated with MTX and MTX + xanthone-rich fraction (XRF). The clinical efficacy was evaluated by histopathological examination, and LC-MS was used to monitor the blood concentration of MTX. Western blotting and immunohistochemistry were used to detect protein expression. In vitro, we assessed the activity of related transporters by cellular uptake assay based on HEK-293T cells. RESULTS: Compared with MTX-treated rats, inflammation in the immunized rats in the MTX + XRF group was obvious, indicating that XRF antagonized the anti-rheumatic effect of MTX. Meanwhile, XRF reduced liver and kidney injuries caused by MTX in addition to MTX. Results from immunohistochemical and nappendiculat assays suggested that XRF may reduce uptake of MTX by down-regulating reduced folate carrier 1 (RFC1). CONCLUSION: This study indicated that XRF could reduce the plasma concentration of MTX by inhibiting the expression of RFC1, antagonize the therapeutic effect of MTX on AIA rats, and reduce its oral bioavailability. The combination of S. inappendiculate and MTX should be further optimized to achieve the goal of increasing efficiency and reducing toxicity.


Assuntos
Antirreumáticos , Securidaca , Xantonas , Ratos , Animais , Metotrexato/farmacologia , Securidaca/metabolismo , Proteína Carregadora de Folato Reduzido , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Xantonas/farmacologia
15.
Plant Dis ; 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36995768

RESUMO

Bougainvilleas (Bougainvillea spp.) are popular ornamentals commonly grown as bushes, vines, or trees worldwide (Kobayashi et al. 2007). Leaf spot symptoms were observed on a bougainvillea hedge located in North District, Taichung, Taiwan during August of 2022. The lesions were brown, necrotic and had yellow halos (Fig. S1). All the plants at the location showed similar symptoms. Leaf samples were collected from five plants and symptomatic tissues were minced in 10 mM MgCl2. The samples were streaked onto nutrient agar (NA) and after culturing at 28°C for 2 days, small, round, creamy white colonies were consistently isolated from all the samples. A total of five strains (BA1 to BA5) were obtained; each of them was isolated from a different plant. All five strains induced hypersensitive response in tobacco leaves. Amplification and sequencing of the isolated strains' 16S rDNA using primers 27F and 1492R (Lane 1991) revealed that all five strains shared identical sequences (GenBank accession no. OQ053015) with Robbsia andropogonis LMG 2129T (formerly Burkholderia andropogonis and Pseudomonas andropogonis; GenBank accession no. NR104960; 1,393/1,393 bp). Further testing of BA1 to BA5's DNA samples using the pathogen's species-specific primers Pf (5'-AAGTCGAACGGTAACAGGGA-3') and Pr (5'-AAAGGATATTAGCCCTCGCC-3'; Bagsic et al. 1995) successfully amplified the expected 410-bp amplicon in all five samples; the sequences of the PCR products completely matched to those of BA1 to BA5's 16S rDNA. Strains BA1 to BA5 also tested negative for arginine dihydrolase and oxidase activity, and failed to grow at 40°C, all of which are consistent with descriptions of R. andropogonis (Schaad et al. 2001). Pathogenicity of the isolated bacteria was confirmed by spray inoculation. Three representative strains, BA1 to BA3, were used for the assay. Bacterial colonies were scraped from NA plates and suspended in 10 mM MgCl2 added with 0.02% Silwet L-77. The concentrations of the suspensions were adjusted to 4.4-5.8 x 108 cfu/ml. The suspensions were sprayed onto three-month-old, cutting-propagated bougainvillea plants (to runoff). Controls were treated with bacteria-free solutions. Three plants were used for each treatment group (and the controls). The plants were placed in a growth chamber (27/25°C, day/night; 14-hour photoperiod) and bagged for three days. Within 20 days post inoculation, brown, necrotic lesions resembling those observed in the sampling site were observed on all inoculated plants, but not on the controls. One strain was re-isolated for each treatment group and the re-isolated strains all shared the same colony morphology and 16S rDNA sequence with BA1 to BA5. Additional PCR testing of these re-isolated strains using Pf and Pr also produced the expected amplicon. This is the first formal report of R. andropogonis affecting bougainvilleas in Taiwan. The pathogen has been reported causing diseases of betel palm (Areca catechu), corn and sorghum in Taiwan (Hseu et al. 2007; Hsu et al. 1991), some of which are economically important (Lisowicz 2000; Navi et al. 2002). As such, infected bougainvilleas could potentially serve as an inoculum source for these diseases.

16.
Molecules ; 28(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37049761

RESUMO

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm-2, 97.22 ± 1.39% at 720 g a.i.·hm-2, 100.00% at 900.00 g a.i.·hm-2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm-2), and pomelo peel oil (100.00% at 900 g a.i.·hm-2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.


Assuntos
Citrus , Inseticidas , Óleos Voláteis , Rutaceae , Tisanópteros , Zanthoxylum , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Inseticidas/farmacologia , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Citrus/química , Zanthoxylum/química
17.
Health Soc Work ; 48(3): 179-187, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37279367

RESUMO

This article aims to investigate the impact of psychological distress and hopelessness as mediators in the relationship between alcohol use disorder (AUD) and suicidal ideation among young adults. The study employed data from the 2019 National Survey on Drug Use and Health, focusing on participants aged 18 to 25. The PROCESS macro was used to conduct a moderated mediation analysis. The findings revealed that AUD, psychological distress, and hopelessness were all significant risk factors for suicidal ideation among young adults. Furthermore, psychological distress and hopelessness served as significant mediators in the relationship between AUD and suicidal ideation. The study highlights the need for interventions and treatments that address co-occurring alcohol use and psychological distress/hopelessness in both sexes, for young adults at risk of suicide. In summary, the study underscores the importance of recognizing the underlying factors that contribute to suicidal ideation among young adults, especially those with AUD, psychological distress, and hopelessness.


Assuntos
Alcoolismo , Suicídio , Adulto Jovem , Humanos , Masculino , Feminino , Ideação Suicida , Caracteres Sexuais , Fatores de Risco
18.
BMC Oral Health ; 23(1): 1003, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098000

RESUMO

BACKGROUND: With advances in pulp preservation procedures (PPP), indications for PPP extend to exposed pulp with symptoms in teeth with carious lesions. Scenario/text-based questionnaire studies report a high preference for PPP for exposed pulp with no pulpal symptoms. However, negative perceptions towards PPP for exposed pulp in carious teeth are prevalent among dentists. Identifying the differences in PPP preference rates in questionnaire studies and actual clinical situations is necessary to determine the current status of PPP. In this study, a clinical case/photo-based design was devised to overcome the limitations of scenario/text-based questionnaires. This study aimed to evaluate the reasons dentists prefer root canal treatment (RCT) in cases where PPP is potentially indicated. METHODS: A questionnaire containing three cases of PPP with successful results was administered to dentists. The cases were selected to elicit comprehensive responses from the dentists. Clinical photos of the pulp exposure sites were presented to dentists without describing the tooth conditions, including the extent of pulp exposure and tooth decay, pulpal surface conditions, or restorability. The questions were focused on the reasons for selecting RCT in cases where was practiced. Questionnaire data were collected using Google e-forms. Chi-squared and Fisher's exact test (P < 0.05) were used for statistical analyses. RESULTS: Pulpal diagnosis was not a dominant factor in treatment decision-making for pulp exposure during caries removal. Reasons for selecting RCT where PPP was potentially indicated included the event of pulp exposure itself and the dentists' desire to prevent post-PPP symptoms. Apart from symptomatic pulp, the tooth conditions influenced the establishment of pulpal diagnosis and selection of treatment modality. Moreover, the tooth condition and dentists' desire for good patient prognosis influenced the negative perceptions towards PPP. CONCLUSIONS: Unfavourable tooth conditions, in association with a desire for preventing post-PPP symptoms, prevent dentists from attempting PPP for pulp exposed during caries removal with no/slight symptoms. Improving negative perceptions towards PPP through accumulation of data on the high success rates of PPP is a prerequisite for achieving widespread application of PPP.


Assuntos
Cárie Dentária , Cavidade Pulpar , Humanos , Tratamento do Canal Radicular , Polpa Dentária , Capeamento da Polpa Dentária , Cárie Dentária/terapia , Inquéritos e Questionários
19.
J Foot Ankle Surg ; 62(5): 779-784, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37031886

RESUMO

The present study was performed to determine the incidence and risk factors of contralateral Achilles tendon rupture after an initial tendon rupture, and to identify the associated patient characteristics. Medical records of 181 adult patients with acute Achilles tendon rupture were reviewed. We investigated the risk factors for contralateral Achilles tendon rupture and calculated the incidence density (per 100 person-years), survival rate, hazard ratios, and 95% confidence intervals. The risk factors were extracted, including blood type, age, body mass index (BMI), occupation, underlying comorbidities, history of alcohol intake or smoking, injury mechanism, and fluoroquinolone antibiotic or steroid use. Military personnel and manual laborers, including farmers and firefighters were considered to have an occupation involving physical activity. Ten patients (5.5%) were identified as having nonsimultaneous, contralateral Achilles tendon rupture a mean of 3.3 years (range 1.0-8.3 years) after the initial tendon rupture. The incidence density of contralateral tendon rupture was 0.89 per 100 person-years. The 8-year survival rate of contralateral tendon rupture was 92.2%. Unadjusted and adjusted hazard ratios (with 95% confidence intervals, p value) of blood type O were 3.71 (1.07-12.82, p = .038) and 2.90 (0.81-10.32, p = .101), respectively, and those of occupations involving physical activity were 5.87 (1.64-20.98, p = .006) and 4.69 (1.27-17.28, p = .02), respectively. Based on the present data, blood type O and occupations involving physical activity are significantly associated with an increased risk of contralateral tendon rupture in adult patients who have sustained Achilles tendon rupture.


Assuntos
Tendão do Calcâneo , Traumatismos dos Tendões , Adulto , Humanos , Tendão do Calcâneo/cirurgia , Ruptura/cirurgia , Fatores de Risco , Incidência , Traumatismos dos Tendões/epidemiologia , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/complicações
20.
Medicina (Kaunas) ; 59(8)2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37629746

RESUMO

Background and Objectives: Surgical treatment for primary hyperparathyroidism (PHPT) has evolved from bilateral exploration through a long transcervical incision to focused parathyroidectomy with a minimal incision above the pathologic gland. Recently, endoscopic or robot-assisted parathyroid surgery without direct neck incision has been introduced. The aim of this study was to investigate the effectiveness of indocyanine green (ICG) fluorescence as a new method for the visual identification of abnormal hyperfunctioning parathyroid glands in robot-assisted parathyroidectomy using FireflyTM technology. We also aimed to conduct a comparative analysis between robot-assisted parathyroidectomy and conventional focused parathyroidectomy in order to identify clinical differences between the two surgical approaches. Materials and Methods: A total of 37 patients with PHPT underwent parathyroidectomy at a single university hospital between September 2018 and December 2022. Thirty-one patients underwent open focused parathyroidectomy (open group), and six patients underwent robot-assisted parathyroidectomy (robot group). Pre-operative localization via parathyroid SPECT-CT and an intraoperative parathyroid hormone (IOPTH) assay were used to successfully remove the pathologic parathyroid in both groups. ICG was administered only in the robot group. Results: Pathologic parathyroid showed a persistent fluorescence pattern under near-infrared vision. After the removal of the fluorescent parathyroid gland, IOPTH was normalized in all six patients in the robot group. However, the open group showed shorter hospital stays (1.8 ± 1.2 vs. 3.0 ± 0.0 days, p < 0.001) and shorter operation times (91.1 ± 69.1 vs. 152.5 ± 23.6 min, p = 0.001) than the robot group. After 6 months of surgery, PTH, calcium, and ionized calcium levels were all normalized without significant differences between the groups. Conclusions: Robot-assisted parathyroidectomy using ICG is helpful for the visual identification of the pathologic parathyroid gland. The advantage of robot parathyroidectomy is a better cosmetic outcome. However, it still does not show better clinical outcomes than conventional open focused parathyroidectomy.


Assuntos
Hiperparatireoidismo Primário , Robótica , Humanos , Paratireoidectomia , Verde de Indocianina , Cálcio , Fluorescência , Hiperparatireoidismo Primário/cirurgia , Hormônio Paratireóideo
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