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1.
J Am Chem Soc ; 146(18): 12645-12655, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651821

RESUMO

The increased production of plastics is leading to the accumulation of plastic waste and depletion of limited fossil fuel resources. In this context, we report a strategy to create polymers that can undergo controlled depolymerization by linking renewable feedstocks with siloxane bonds. α,ω-Diesters and α,ω-diols containing siloxane bonds were synthesized from an alkenoic ester derived from castor oil and then polymerized with varied monomers, including related biobased monomers. In addition, cyclic monomers derived from this alkenoic ester and hydrosiloxanes were prepared and cyclized to form a 26-membered macrolactone containing a siloxane unit. Sequential ring-opening polymerization of this macrolactone and lactide afforded an ABA triblock copolymer. This set of polymers containing siloxanes underwent programmed depolymerization into monomers in protic solvents or with hexamethyldisiloxane and an acid catalyst. Monomers afforded by the depolymerization of polyesters containing siloxane linkages were repolymerized to demonstrate circularity in select polymers. Evaluation of the environmental stability of these polymers toward enzymatic degradation showed that they undergo enzymatic hydrolysis by a fungal cutinase from Fusarium solani. Evaluation of soil microbial metabolism of monomers selectively labeled with 13C revealed differential metabolism of the main chain and side chain organic groups by soil microbes.


Assuntos
Fusarium , Polimerização , Siloxanas , Siloxanas/química , Óleos de Plantas/química , Polímeros/química , Estrutura Molecular , Hidrolases de Éster Carboxílico
2.
Breast Cancer Res ; 26(1): 14, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254240

RESUMO

BACKGROUND: This study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients. METHODS: We conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service's eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCA mutation group, the BRCAx group, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients. RESULTS: Among 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11-13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76-4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted. CONCLUSION: Breast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.


Assuntos
Proteína BRCA1 , Neoplasias da Mama , Humanos , Feminino , Proteína BRCA1/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Estudos Retrospectivos , Proteína BRCA2/genética , República da Coreia/epidemiologia
3.
Ann Surg Oncol ; 31(5): 3168-3176, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368292

RESUMO

OBJECTIVE: This study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive. METHODS: This study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group. RESULTS: Mean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70-2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69-5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02). CONCLUSION: Collectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.


Assuntos
Neoplasias da Mama , Linfadenopatia , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/patologia , Mastectomia Simples , Mastectomia , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Linfadenopatia/cirurgia , Axila/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia
4.
Ann Surg Oncol ; 31(8): 5189-5196, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38695982

RESUMO

BACKGROUND: Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. METHODS: This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). RESULTS: The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). CONCLUSION: The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent.


Assuntos
Axila , Neoplasias da Mama , Metástase Linfática , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Idoso , Adulto , Recidiva Local de Neoplasia/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Mastectomia
5.
FASEB J ; 34(7): 9141-9155, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32421247

RESUMO

Human-induced pluripotent stem cells (hiPSCs) are invaluable sources for drug screening and toxicity tests because of their differentiation potential and proliferative capacity. Recently, the CRISPR-Cas9-mediated homologous recombination system has enabled reporter knock-ins at desired loci in hiPSCs, and here, we generated a hiPSC reporter line expressing mCherry-tagged cytochrome P450 1A1 (CYP1A1), which can be utilized to screen for the modulators of aryl hydrocarbon receptor (AHR) in live cells. CYP1A1-mCherry hiPSCs exhibited typical characteristics of pluripotent stem cells such as marker expression, differentiation potential, and normal karyotype. After differentiation into hepatocyte-like cells (HLCs), CYP1A1-mCherry fusion protein was expressed and localized at the endoplasmic reticulum, and induced by AHR agonists. We obtained 23 hits modulating CYP1A1 expression from high-content screening with 241 hepatotoxicity chemicals and nuclear receptor ligands, and identified three upregulating chemicals and two downregulating compounds. Responses of hiPSC-HLCs against an AHR agonist were more similar to human primary hepatocytes than of HepG2 hepatocellular carcinoma cells. This platform has the advantages of live-cell screening without sacrificing cells (unlike previously available CYP1A1 reporter cell lines), as well as an indefinite supply of cells, and can be utilized in a wide range of screening related to AHR- and CYP1A1-associated diseases in desired cell types.


Assuntos
Citocromo P-450 CYP1A1/química , Fluorescência , Hepatócitos/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Preparações Farmacêuticas/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Diferenciação Celular , Citocromo P-450 CYP1A1/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/enzimologia , Transdução de Sinais
6.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641624

RESUMO

(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal-if not scientific or clinical-evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.


Assuntos
Canabidiol/farmacologia , Células-Tronco Neurais/citologia , Neuroglia/citologia , Neurônios/citologia , Animais , Canabidiol/química , Células Cultivadas , Humanos , Estrutura Molecular , Células-Tronco Neurais/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Cultura Primária de Células
7.
Phys Chem Chem Phys ; 22(32): 17867-17879, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32766621

RESUMO

Steady-state and transient absorption spectra with <50 fs time resolution were obtained for two conjugated polymers, both with ≈200 conjugated double bonds (N), constrained in planar, stable, polyene frameworks. Solutions of the polymers exhibit the same S2 → S1 → S* → S0 decay pathway observed for the N = 11-19 polyene oligomers and for zeaxanthin homologues with N = 11-23. Comparisons with the excited state dynamics of polydiactylene and a much longer, more disordered polyene polymer (poly(DEDPM)) show that the S2, S1, and S* lifetimes of the four polymers are almost identical. The S* signals in the polymers are assigned to absorption from vibrationally excited ground states. In spite of significant heterogeneities and variations in conjugation lengths in these long polyenes, their S0 → S2 absorptions are vibronically-resolved in room temperature solutions with electronic origins at ≈600 nm. The limiting wavelength for the S0 → S2 transitions is consistent with the persistence of bond length alternation in the electronic ground states and a HOMO-LUMO band gap in polyenes with N ≈ 200. The coincidence of the well-resolved S0 → S2 electronic origins and the convergence of the excited state lifetimes in the four polymers point to a common, "nearly infinite" polyene limit.

9.
J Am Chem Soc ; 138(7): 2244-51, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26878670

RESUMO

Tandem ring-opening/ring-closing metathesis (RO/RCM) results in extremely fast living polymerization; however, according to previous reports, only monomers containing certain combinations of cycloalkenes, terminal alkynes, and nitrogen linkers successfully underwent tandem polymerization. After examining the polymerization pathways, we proposed that the relatively slow intramolecular cyclization might lead to competing side reactions such as intermolecular cross metathesis reactions to form inactive propagating species. Thus, we developed two strategies to enhance tandem polymerization efficiency. First, we modified monomer structures to accelerate tandem RO/RCM cyclization by enhancing the Thorpe-Ingold effect. This strategy increased the polymerization rate and suppressed the chain transfer reaction to achieve controlled polymerization, even for challenging syntheses of dendronized polymers. Alternatively, reducing the reaction concentration facilitated tandem polymerization, suggesting that the slow tandem RO/RCM cyclization step was the main reason for the previous failure. To broaden the monomer scope, we used monomers containing internal alkynes and observed that two different polymer units with different ring sizes were produced as a result of nonselective α-addition and ß-addition on the internal alkynes. Thorough experiments with various monomers with internal alkynes suggested that steric and electronic effects of the alkyne substituents influenced alkyne addition selectivity and the polymerization reactivity. Further polymerization kinetics studies revealed that the rate-determining step of monomers containing certain internal alkynes was the six-membered cyclization step via ß-addition, whereas that for other monomers was the conventional intermolecular propagation step, as observed in other chain-growth polymerizations. This conclusion agrees well with all those polymerization results and thus validates our strategies.

10.
J Am Chem Soc ; 138(35): 11227-33, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27557057

RESUMO

It is well-known that Ru-based Grubbs catalysts undergo a highly selective α-addition to alkynes to promote exo-cyclization during ring-closing enyne metathesis (RCEYM) or to produce conjugated polyenes containing five-membered rings during the cyclopolymerization (CP) of 1,6-heptadiynes. There are a few reports of ß-selective addition to alkynes using Schrock catalysts based on Mo but none for readily accessible and easy-to-use Ru-based catalysts. We report the first example of ß-selective addition to alkynes using Grubbs Z-selective catalyst, which produces only endo products during the RCEYM reaction of terminal enynes and promotes the CP of 1,6-heptadiyne derivatives to give conjugated polyenes containing a six-membered ring as a major repeat unit. This unique preference for ß-selectivity originated from the side-bound approach of alkynes to the catalyst, where the steric hindrance between the chelating N-heterocyclic carbene ligand of the catalyst and the alkynes disfavored α-addition. To enhance the ß-selectivity for CP further, one could increase the size of the substrates on the monomers and lower the reaction temperature to obtain conjugated polyenes containing up to 95% six-membered rings. Moreover, the physical properties of the resulting polymer were analyzed in detail and compared with those of the conjugated polyenes containing only five-membered rings prepared from the same monomer but with a conventional Grubbs catalyst.

12.
J Am Chem Soc ; 136(29): 10508-14, 2014 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-24980051

RESUMO

Cyclopolymerization (CP) of 1,6-heptadiyne derivatives using the Grubbs catalysts has been known to afford conjugated polyenes in low yields in dichloromethane (DCM), the most common solvent for olefin metathesis polymerization and a good solvent for typical conjugated polymers. Based on our previous work that showed highly efficient CP using the Grubbs catalysts in tetrahydrofuran (THF), we developed a new polymerization system using weakly coordinating additives with the third-generation Grubbs catalyst in DCM. The polymerization efficiency of various monomers and their controls dramatically increased by adding 3,5-dichloropyridine, yielding polymers with narrow polydispersity indices (PDIs) at low temperatures. These new reaction conditions not only expand the monomer scope by resolving the solubility concerns of conjugated polymers but also more effectively reduced the chain transfer. Consequently, fully conjugated diblock copolymer was successfully prepared. Additionally, kinetic analysis has revealed that low CP efficiency in DCM resulted from the rapid decomposition of the propagating carbene. This decomposition was effectively suppressed by both pyridine additives and THF, suggesting that weakly coordinating additives stabilize the living chain end. Furthermore, we observed that the turnover number of CP was higher at lower temperatures (0-10 °C) than at ambient temperatures, consistent with the understanding that the lifetime of a propagating carbene is greater at lower temperatures. Steric protection was also shown to increase the stability of the propagating carbene, as shown by a higher turnover number for the 3,3-dimethyl-substituted 1,6-heptadiyne compared to the nonfunctionalized monomer.

13.
J Breast Cancer ; 27(1): 1-13, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38433090

RESUMO

PURPOSE: In total mastectomy (TM), sentinel lymph node biopsy (SLNB) is recommended but can be omitted for breast-conserving surgery (BCS) in patients with ductal carcinoma in situ (DCIS). However, concerns regarding SLNB-related complications and their impact on quality of life exist. Consequently, further research is required to evaluate the role of axillary surgeries, including SLNB, in the treatment of TM. We aimed to explore the clinicopathological factors and outcomes associated with axillary surgery in patients with a final diagnosis of pure DCIS who underwent BCS or TM. METHODS: We retrospectively analyzed large-scale data from the Korean Breast Cancer Society registration database, highlighting on patients diagnosed with pure DCIS who underwent surgery and were categorized into two groups: BCS and TM. Patients were further categorized into surgery and non-surgery groups according to their axillary surgery status. The analysis compared clinicopathological factors and outcomes according to axillary surgery status between the BCS and TM groups. RESULTS: Among 18,196 patients who underwent surgery for DCIS between 1981 and 2022, 11,872 underwent BCS and 6,324 underwent TM. Both groups leaned towards axillary surgery more frequently for large tumors. In the BCS group, clinical lymph node status was associated with axillary surgery (odds ratio, 11.101; p = 0.003). However, in the TM group, no significant differences in these factors were observed. Survival rates did not vary between groups according to axillary surgery performance. CONCLUSION: The decision to perform axillary surgery in patients with a final diagnosis of pure DCIS does not affect the prognosis, regardless of the breast surgical method. Furthermore, regardless of the breast surgical method, axillary surgery, including SLNB, should be considered for high-risk patients, such as those with large tumors. This may reduce unnecessary axillary surgery and enhance the patients' quality of life.

14.
Stem Cell Res ; 66: 102986, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36493708

RESUMO

CRISPR/Cas9-based transcriptional regulation systems can induce the site-specific activation or repression of endogenous genes. p300 is a transcriptional co-activator that functions as a histone acetyltransferase that regulates gene transcription via chromatin remodeling. Here, we generated a human embryonic stem cell line stably expressing catalytically dead Cas9 (dCas9) fused to the catalytic core domain of human p300 via lentiviral transduction. This cell line can be used for locus-specific histone acetylation in combination with guide RNAs, and is a valuable tool for gene regulation in stem cell research.


Assuntos
Proteína 9 Associada à CRISPR , Células-Tronco Embrionárias Humanas , Humanos , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Regulação da Expressão Gênica , Fatores de Transcrição/genética , Linhagem Celular , Ativação Transcricional
15.
Cancer Res Treat ; 55(2): 562-569, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36164944

RESUMO

PURPOSE: In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer. Materials and Methods: This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group). RESULTS: The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node-positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node-positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups. CONCLUSION: Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Estudos Retrospectivos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Estudos de Coortes , Pontuação de Propensão , Biópsia de Linfonodo Sentinela/métodos , Radioisótopos
16.
Polymers (Basel) ; 15(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36904345

RESUMO

One-step fabrication method for thin films and shells is developed with nature-derived eggshell membrane hydrolysates (ESMHs) and coffee melanoidins (CMs) that have been discarded as food waste. The nature-derived polymeric materials, ESMHs and CMs, prove highly biocompatible with living cells, and the one-step method enables cytocompatible construction of cell-in-shell nanobiohybrid structures. Nanometric ESMH-CM shells are formed on individual probiotic Lactobacillus acidophilus, without any noticeable decrease in viability, and the ESMH-CM shells effectively protected L. acidophilus in the simulated gastric fluid (SGF). The cytoprotection power is further enhanced by Fe3+-mediated shell augmentation. For example, after 2 h of incubation in SGF, the viability of native L. acidophilus is 30%, whereas nanoencapsulated L. acidophilus, armed with the Fe3+-fortified ESMH-CM shells, show 79% in viability. The simple, time-efficient, and easy-to-process method developed in this work would contribute to many technological developments, including microbial biotherapeutics, as well as waste upcycling.

17.
ACS Appl Bio Mater ; 6(5): 1981-1991, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37083357

RESUMO

Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).


Assuntos
Anti-Infecciosos , COVID-19 , Vírus , Humanos , Polifenóis/farmacologia , SARS-CoV-2 , COVID-19/prevenção & controle , Anti-Infecciosos/farmacologia , Desinfecção/métodos , Bactérias , Escherichia coli , Fungos
18.
Biomaterials ; 286: 121575, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35598335

RESUMO

Human in vitro hepatic models that faithfully recapitulate liver function are essential for successful basic and translational research. A limitation of current in vitro models, which are extensively used for drug discovery and toxicity testing, is the loss of drug metabolic function due to the low expression and activity of cytochrome P450 (CYP450) enzymes. Here, we aimed to generate human pluripotent stem cell-derived hepatic organoids (hHOs) with a high drug metabolic ability. We established a two-step protocol to produce hHOs from human pluripotent stem cells for long-term expansion and drug testing. Fully differentiated hHOs had multicellular composition and exhibited cellular polarity and hepatobiliary structures. They also displayed remarkable CYP450 activity and recapitulated the metabolic clearance, CYP450-mediated drug toxicity, and metabolism. Furthermore, hHOs successfully modeled Wilson's disease in terms of Cu metabolism, drug responses, and diagnostic marker expression and secretion. In conclusion, hHOs exhibit high capacity for drug testing and disease modeling. Hence, this hepatic model system provides an advanced tool for studying hepatic drug metabolism and diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Fígado/metabolismo , Modelos Biológicos , Organoides/metabolismo
19.
J Am Chem Soc ; 133(31): 11904-7, 2011 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-21718068

RESUMO

We discovered that ultrafast cyclopolymerization of 1,6-heptadiyne derivatives reached completion in 1 min using a third-generation Grubbs catalyst. After optimization, this superior catalyst selectively produced conjugated polymers having a five-membered-ring structure with excellent molecular weight control and narrow polydispersity index (PDI). This living polymerization allowed us to prepare fully conjugated diblock copolymers with narrow PDIs. Lastly, this catalyst was active enough to polymerize macromonomers with G-3 dendrons in a living manner as well. This dendronized polymer with a highly regioregular polymer backbone and bulky dendrons was visualized by atomic force microscopy, which revealed the structure of a single molecular wire surrounded by insulating dendrons.

20.
Surg Infect (Larchmt) ; 22(7): 741-751, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33533687

RESUMO

Background: Treatment of biliary infection in liver transplant (LT) recipients is a challenge, especially because of ineffectiveness of the antibiotic agents otherwise recommended for non-transplant populations. We aimed to understand the factors underlying the choice of antibiotic therapy. Patients and Methods: A total of 373 bile cultures from LT recipients with biliary complications (n = 127; LT group) and from a non-transplant population that underwent cholecystectomy for acute cholecystitis (n = 246; non-transplant group) between January 2009 and December 2018, were investigated. Results: Polymicrobial cultures (13.4% vs. 1.6%; p < 0.001), Enterococcus faecium (26.0% vs. 8.5%; p < 0.001), and Pseudomonas (13.4% vs. 4.1%; p = 0.001) in the LT group, and non-faecium enterococci (3.9% vs. 18.3%; p < 0.001) and Enterobacteriales (40.2% vs. 54.9%; p = 0.007), especially Escherichia (11.0% vs. 29.7%; p < 0.001), in the non-transplant group, showed higher abundance. Most of the antibiotic agents recommended as initial antibiotic therapy for the non-transplant population as per previous guidelines were not effective in LT recipients. The incidences of Enterococcus faecium (14.9% vs. 32.5%; p = 0.029) in the LT recipients with model for end-stage liver disease (MELD) score >12 and non-faecium enterococci (8.5% vs. 1.3%; p = 0.042) in those with MELD score ≤12 were higher than those in the other group. The incidence of Enterobacteriales increased over time after LT (p = 0.048) and was similar to that in the non-transplant group after one year of LT. Bile micro-organisms in LT recipients, resistant to most antibiotic agents, especially soon after LT changed over time and became similar to those in the non-transplant group after one year of LT. Conclusions: Antibiotic therapy for biliary infection in LT recipients should be different from that in non-transplant populations, considering clinical factors such as the time interval after LT and MELD score.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Antibacterianos/uso terapêutico , Bile , Doença Hepática Terminal/tratamento farmacológico , Humanos , Índice de Gravidade de Doença
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