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1.
Int J Biol Macromol ; 272(Pt 1): 132893, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38838883

RESUMEN

Foodborne pathogens result in a great harm to human, which is an urgent problem to be addressed. Herein, a novel cellulose-based packaging films with excellent anti-bacterial properties under visible light were prepared. A porphyrin-based covalent organic polymer (Por-COPs) was constructed, then covalently grafted onto dialdehyde cellulose (DAC). The addition of Por-COPs enhanced the mechanical, hydrophobicity, and water resistance of the DAC-based composite films. DAC/Por-COP-2.5 film exhibited outstanding properties for the photodynamic inactivation of bacteria under visible light irradiation, delivering inactivation efficiencies of 99.90 % and 99.45 % towards Staphylococcus aureus and Escherichia coli within 20 min. The DAC/Por-COPs films efficiently generated •O2- and 1O2 under visible light, thereby causing oxidative stress to cell membranes for bacterial inactivation. The prepared composite film forms a protective barrier against bacterial contamination. Results guide the development of high performance and more sustainable packaging films for the food sector.


Asunto(s)
Celulosa , Escherichia coli , Porfirinas , Staphylococcus aureus , Celulosa/química , Celulosa/análogos & derivados , Celulosa/farmacología , Porfirinas/química , Porfirinas/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Luz , Embalaje de Alimentos/métodos , Polímeros/química , Polímeros/farmacología , Esterilización/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología
2.
J Nanobiotechnology ; 22(1): 324, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858692

RESUMEN

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.


Asunto(s)
Neoplasias de la Mama , Glutatión , Nanopartículas , Especies Reactivas de Oxígeno , Dióxido de Silicio , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Nanopartículas/química , Animales , Glutatión/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Ratones , Dióxido de Silicio/química , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Xantonas/química , Xantonas/farmacología , Taninos/química , Taninos/farmacología , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Liberación de Fármacos , Antineoplásicos/farmacología , Antineoplásicos/química
3.
Medicine (Baltimore) ; 103(24): e38506, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875383

RESUMEN

Blood cell ratios are a standard clinical index for the assessment of inflammation. Although a large number of epidemiological investigations have shown that inflammation is a potential risk factor for the development of coronary heart disease (CHD), there is not sufficient and direct evidence to confirm the relationship between blood cell ratios and CHD. Therefore, this study aimed to elucidate the effect of blood cell ratios on the incidence of coronary heart disease. This 10-year national study included data from 24,924 participants. The independent variable was blood cell ratios, and the dependent variable was coronary heart diseases (yes or no). The relationship between blood cell ratios and coronary heart disease was verified using baseline characteristic analysis, multivariate logistic regression analysis, smoothed fitted curves, and subgroup analysis. This study found that in multiple logistic regression analysis showed significant positive correlation between monocyte counts × meutrophil counts/lymphocyte counts (SIRI) (OR = 1.495; 95% CI = 1.154-1.938), monocyte-lymphocyte ratio (MLR) (OR = 3.081; 95% CI = 1.476-6.433) and the incidence of CHD; lymphocyte-monocyte ratio (LMR) (OR = 0.928;95% CI = 0.873-0.987), monocyte-lymphocyte ratio (PLR) (OR = 0.997;95% CI = 0.994-1.000) showed negative correlation with CHD. The smoothed curve fitting shows a nonlinear relationship between SIRI, LMR, PLR, and CHD, with an inverted U-shaped curve between SIRI and CHD, an L-shaped angle between LMR and CHD, and a U-shaped curve between PLR and CHD, respectively. Their inflection points are 1.462, 3.75, and 185.714, respectively. SIRI has an inverted U-shaped curve with coronary heart disease, suggesting that low levels of SIRI increase the risk of CHD; LMR with an L-shaped curve with CHD, and PLR with a U-shaped curve with CHD, suggesting that the risk of CHD can be prevented when LMR and PLR are reduced to a certain level. This has positive implications for the prevention and treatment of CHD.


Asunto(s)
Enfermedad Coronaria , Humanos , Masculino , Femenino , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/sangre , Persona de Mediana Edad , Incidencia , Adulto , Anciano , Monocitos , Factores de Riesgo , Recuento de Linfocitos , Recuento de Leucocitos
4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2689-2698, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812169

RESUMEN

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.


Asunto(s)
Neoplasias de la Mama , Proliferación Celular , Emulsiones , Verde de Indocianina , Humanos , Verde de Indocianina/química , Células MCF-7 , Emulsiones/química , Proliferación Celular/efectos de los fármacos , Femenino , Tamaño de la Partícula , Geles/química , Nanopartículas/química , Composición de Medicamentos/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Portadores de Fármacos/química
6.
Front Immunol ; 15: 1358036, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690262

RESUMEN

Background: It remains unclear whether BPIV3 infection leads to stress granules formation and whether G3BP1 plays a role in this process and in viral replication. This study aims to clarify the association between BPIV3 and stress granules, explore the effect of G3BP1 on BPIV3 replication, and provide significant insights into the mechanisms by which BPIV3 evades the host's antiviral immunity to support its own survival. Methods: Here, we use Immunofluorescence staining to observe the effect of BPIV3 infection on the assembly of stress granules. Meanwhile, the expression changes of eIF2α and G3BP1 were determined. Overexpression or siRNA silencing of intracellular G3BP1 levels was examined for its regulatory control of BPIV3 replication. Results: We identify that the BPIV3 infection elicited phosphorylation of the eIF2α protein. However, it did not induce the assembly of stress granules; rather, it inhibited the formation of stress granules and downregulated the expression of G3BP1. G3BP1 overexpression facilitated the formation of stress granules within cells and hindered viral replication, while G3BP1 knockdown enhanced BPIV3 expression. Conclusion: This study suggest that G3BP1 plays a crucial role in BPIV3 suppressing stress granule formation and viral replication.


Asunto(s)
ADN Helicasas , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , Gránulos de Estrés , Replicación Viral , Animales , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , ADN Helicasas/metabolismo , ADN Helicasas/genética , ARN Helicasas/metabolismo , ARN Helicasas/genética , Gránulos de Estrés/metabolismo , Bovinos , Factor 2 Eucariótico de Iniciación/metabolismo , Infecciones por Respirovirus/inmunología , Infecciones por Respirovirus/metabolismo , Interacciones Huésped-Patógeno/inmunología , Fosforilación , Línea Celular , Gránulos Citoplasmáticos/metabolismo
7.
J Agric Food Chem ; 72(15): 8859-8870, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38564481

RESUMEN

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.


Asunto(s)
Ácidos Grasos Monoinsaturados , Aceites de Pescado , Agua , Triglicéridos/química , Aceites de Pescado/química , Digestión
9.
J Med Virol ; 96(3): e29487, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38482901

RESUMEN

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.


Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Rotavirus , Sapovirus , Humanos , Norovirus/genética , Microesferas , Rotavirus/genética , Sapovirus/genética , Heces , Infecciones por Caliciviridae/diagnóstico
10.
Nutrition ; 122: 112387, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38430844

RESUMEN

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.


Asunto(s)
COVID-19 , Enfermedades Gastrointestinales , Infecciones por VIH , Humanos , Nutrición Enteral/métodos , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Pandemias , COVID-19/terapia , COVID-19/complicaciones , Unidades de Cuidados Intensivos , Enfermedades Gastrointestinales/etiología , Biomarcadores , Enfermedad Crítica/terapia
11.
Appl Microbiol Biotechnol ; 108(1): 248, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38430229

RESUMEN

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks. However, traditional LAB oral vaccines use plasmids for exogenous protein expression and antibiotic genes as selection markers. Antibiotic genes can be diffused through transposition, transfer, or homologous recombination, resulting in the generation of drug-resistant strains. To overcome these issues, genome-editing technology has been developed to achieve gene expression in LAB genomes. In this study, we used the CRISPR-NCas9 system to integrate the PEDV S1 gene into the genome of alanine racemase-deficient Lactobacillus paracasei △Alr HLJ-27 (L. paracasei △Alr HLJ-27) at the thymidylate synthase (thyA) site, generating a strain, S1/△Alr HLJ-27. We conducted immunization assays in mice and piglets to evaluate the level of immune response and evaluated its protective effect against PEDV through challenge tests in piglets. Oral administration of the strain S1/△Alr HLJ-27 in mice and piglets elicited mucosal, humoral, and cellular immune responses. The strain also exhibited a certain level of resistance against PEDV infection in piglets. These results demonstrate the potential of S1/△Alr HLJ-27 as an oral vaccine candidate for PEDV control. KEY POINTS: • A strain S1/△Alr HLJ-27 was constructed as the candidate for an oral vaccine. • Immunogenicity response and challenge test was carried out to analyze the ability of the strain. • The strain S1/△Alr HLJ-27 could provide protection for piglets to a certain extent.


Asunto(s)
Virus de la Diarrea Epidémica Porcina , Vacunas Virales , Animales , Porcinos , Ratones , Anticuerpos Antivirales , Virus de la Diarrea Epidémica Porcina/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Antibacterianos
12.
Int J Food Microbiol ; 413: 110603, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38306773

RESUMEN

Human noroviruses (HuNoVs) are the most predominant viral agents of acute gastroenteritis. Vegetables are important vehicles of HuNoVs transmission. This study aimed to assess the HuNoVs prevalence in vegetables. We searched the Web of Science, Excerpta Medica Database, PubMed, and Cochrane databases until June 1, 2023. A total of 27 studies were included for the meta-analysis. Statistical analysis was conducted using Stata 14.0 software. This analysis showed that the pooled HuNoVs prevalence in vegetables was 7 % (95 % confidence interval (CI): 3-13) worldwide. The continent with largest number of studies was Europe, and the highest number of samples was lettuce. As revealed by the results of the subgroup meta-analysis, the prevalence of GI genogroup was the highest (3 %, 95 % CI: 1-7). A higher prevalence was seen in vegetables from farms (18 %, 95 % CI: 5-37), while only 4 % (95 % CI: 1-8) in retail. The HuNoVs prevalence of ready-to-eat vegetables and non-ready-to-eat vegetables was 2 % (95 % CI: 0-8) and 9 % (95 % CI: 3-16), respectively. The prevalence by quantitative real time RT-PCR was 8 % (95 % CI: 3-15) compared to 3 % (95 % CI: 0-13) by conventional RT-PCR. Furthermore, the HuNoVs prevalence in vegetables was 6 % (95 % CI: 1-14) in ISO pretreatment method and 8 % (95 % CI: 1-19) in non-ISO method, respectively. This study is helpful in comprehensively understanding the prevalence of HuNoVs contamination in vegetables worldwide.


Asunto(s)
Gastroenteritis , Norovirus , Humanos , Verduras , Norovirus/genética , Genotipo , Reacción en Cadena en Tiempo Real de la Polimerasa
13.
Medicine (Baltimore) ; 103(8): e37152, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38394523

RESUMEN

Plasma atherogenic index (AIP) reflects a novel intricate biochemical indicator of lipids' metabolism. The involvement of lipid metabolism for pathogenesis concerning nonalcoholic fatty liver disease (NAFLD) has been established. However, the precise association across AIP and hepatic steatosis and fibrosis remains unclear. This present investigation explored the potential correlation across AIP, hepatic steatosis and fibrosis. Data were acquired through National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Hepatic steatosis was detected through the controlled attenuation parameter (CAP), while hepatic fibrosis was examined via liver stiffness measurement (LSM). The study employed multiple linear, Fitted smoothed curves and subgroup analyses were used for investigating relationships between the AIP, CAP, and LSM. The study recruited 6239 participants. In multivariate linear regression analysis, findings indicated a remarkable correlation between AIP and exacerbated NAFLD risk [odds ratio (95% confidence interval), 1.17 (1.12, 1.21)]. Analysis further revealed a positive link across AIP and hepatic steatosis, as indicated through the CAP [ß (95% CI), 4.07 (3.32, 4.82)]. Tests for non-linearity, revealed a non-linear correlation between AIP and CAP (inflection point = 0.22). Subgroup analyses assessed the consistency of the link across AIP and CAP, indicating that the association remained comparable across all subgroups. Following the adjustment for all relevant variables, the linear regression analysis revealed a lack of statistical significance across the AIP and hepatic fibrosis. [LSM, ß (95% CI), -0.39 (-1.06, 0.28), P = .2501]. Smooth-fitting curves examined the link across AIP and LSM and showed a U-shaped pattern, indicating their positive correlation with AIP less than 0.48. However, no significant correlation was observed with AIP more than 0.48. This study highlighted a substantial positive relationship across AIP and hepatic steatosis, as measured through CAP, and suggests that it may be used as an efficient and rapid measure for clinical prediction of hepatic steatosis.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Hígado/patología , Encuestas Nutricionales , Biopsia , Cirrosis Hepática/diagnóstico
14.
J Hazard Mater ; 466: 133627, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301440

RESUMEN

Aqueous film forming foam (AFFF)-impacted asphalt and concrete may serve as potential secondary sources of per- and polyfluoroalkyl substances (PFAS) to the environment through surficial leaching. We aimed to understand the vertical distribution and surficial release of PFAS from AFFF-impacted asphalt and concrete cores collected from various locations (∼10-70 m distance between samples). Among the PFAS analyzed, 6:2 FTS was observed as having the highest concentration in the surface layer (0 - 0.5 cm) of concrete (225 µg kg-1) and in the runoff from the concrete (2600 ng L-1). PFOS was detected at the highest concentration in the surface layer (0 - 0.5 cm) of asphalt (47 µg kg-1) and associated runoff (780 ng L-1). The total mass of PFAS released during three rainfall simulations accounts for a fraction of the total mass in the surface layer (0 - 0.5 cm), ranging from 0.10 - 9.8% and 0.078 - 2.4% for asphalt and concrete cores, respectively. Asphalt exhibited a higher release rate than concrete, demonstrated by the higher total release coefficient of PFAS (4 - 16 m-2) compared to that of concrete cores (1 - 5 m-2). These results suggested that, similar to concrete, AFFF-impacted asphalt may be a secondary source of PFAS to the environment.

15.
Exp Hematol Oncol ; 13(1): 14, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326887

RESUMEN

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

16.
Small ; 20(24): e2307963, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38183362

RESUMEN

pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.


Asunto(s)
Péptidos , Concentración de Iones de Hidrógeno , Péptidos/química , Conformación Proteica en Lámina beta , Ensayos Analíticos de Alto Rendimiento/métodos , Nanofibras/química , Interacciones Hidrofóbicas e Hidrofílicas , Benzotiazoles/química
17.
Clin Cancer Res ; 30(7): 1248-1255, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38190117

RESUMEN

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.


Asunto(s)
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patología , Resultado del Tratamiento , Proteína Potenciadora del Homólogo Zeste 2 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Inhibidores Enzimáticos/uso terapéutico
18.
Virol J ; 21(1): 28, 2024 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-38268010

RESUMEN

BACKGROUND: Porcine epidemic diarrhea (PED) is an infectious disease of the digestive tract caused by the porcine epidemic diarrhea virus (PEDV), characterized by vomiting, severe diarrhea, and high mortality rates in piglets. In recent years, the distribution of this disease in China has remarkably increased, and its pathogenicity has also increased. PEDV has been identified as the main cause of viral diarrhea in piglets. This study aimed to understand the genetic evolution and diversity of PEDV to provide a theoretical basis for the development of new vaccines and the prevention and treatment of PED. METHODS: A PEDV strain was isolated from the small intestine of a diarrheal piglet using Vero cells. The virus was identified using reverse transcription-polymerase chain reaction (RT-PCR), indirect immunofluorescence assay (IFA), and transmission electron microscopy. The whole genome sequence was sequenced, phylogenetic analysis was conducted using MEGA (version 7.0), and recombination analysis was performed using RDP4 and SimPlot. The S protein amino acid sequence was aligned using Cluster X (version 2.0), and the S protein was modeled using SWISS-MODEL to compare differences in structure and antigenicity. Finally, the piglets were inoculated with PEDV to evaluate its pathogenicity in newborn piglets. RESULT: PEDV strain CH/HLJ/18 was isolated. CH/HLJ/18 shared 89.4-99.2% homology with 52 reference strains of PEDV belonging to the GII-a subgroup. It was a recombinant strain of PEDV BJ-2011-1 and PEDV CH_hubei_2016 with a breakpoint located in ORF1b. Unique amino acid deletions and mutations were observed in the CH/HLJ/18 S protein. The piglets then developed severe watery diarrhea and died within 7 d of inoculation with CH/HLJ/18, suggesting that CH/HLJ/18 was highly pathogenic to newborn piglets. CONCLUSION: A highly pathogenic recombinant PEDV GII-a strain, CH/HLJ/18, was identified in China, with unique deletion and mutation of amino acids in the S protein that may lead to changes in protein structure and antigenicity. These results will be crucial for understanding the prevalence and variation of PEDV and for preventing and controlling PED.


Asunto(s)
Virus de la Diarrea Epidémica Porcina , Chlorocebus aethiops , Animales , Porcinos , Filogenia , Virus de la Diarrea Epidémica Porcina/genética , Células Vero , China/epidemiología , Aminoácidos , Diarrea/veterinaria
19.
Mil Med ; 189(1-2): e148-e156, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-37256764

RESUMEN

BACKGROUND: Taiwan has a substantial number of veterans, but knowledge regarding their emergency department (ED) visits during the coronavirus disease 2019 (COVID-19) pandemic remains limited. This study examined the characteristics of veterans' ED visits during Taiwan's COVID-19 epidemic. METHODS: This was a cross-sectional study conducted at the ED of a large veteran medical center located in Taipei, Taiwan, from May 2018 to October 2021. We analyzed the numbers and features of visits in summer and autumn according to the first wave of the COVID-19 epidemic in Taiwan in 2021. RESULTS: Medical institutions were positively associated with veteran status. Emergency department complaints of trauma (adjusted odds ratio [AOR] = 1.15, 95% CI: 1.06-1.25; summer P < .01) and chest pain/tightness (AOR = 1.65, 95% CI: 1.45-1.87; summer P < .01; AOR = 1.4, 95% CI: 1.26-1.55; P < .01) were associated with increased odds of being a veteran. Triage levels above 2 were positively associated with veteran status in the autumn model (AOR = 1.14, 95% CI: 1.07-1.22; P < .01). Patients hospitalized after ED visits were associated with reduced odds of veteran status (P < .01). Those who spent a long time in the ED were more likely to be veterans than those who spent a shorter time in the ED (P < .01). Veterans were less likely to visit the ED regardless of the time frame of the study period (P < .01), except during the COVID-19 outbreak in the autumn (2019-2020). CONCLUSIONS: The distinctions in ED visits highlighted the individuality of veterans' medical needs. Our findings suggest that the veteran medical system can add to the focus on improving senior-friendly care, fall prevention, quality of life of institutionalized veterans, access for homeless veterans, and care for ambulatory care-sensitive conditions.


Asunto(s)
COVID-19 , Veteranos , Humanos , Taiwán/epidemiología , Pandemias , Calidad de Vida , Estudios Transversales , COVID-19/epidemiología , Servicio de Urgencia en Hospital
20.
Mar Pollut Bull ; 198: 115848, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029673

RESUMEN

In this study, a microalga, Chlorella vulgaris LH-1, with heterotrophic ability to degrade BaP was explored. The effect of BaP concentration on microalga growth was investigated, and the possible biodegradation mechanism of BaP was proposed. Results showed that low BaP concentration (<5 mg/L) had less negative influence on the growth of this microalga under mixotrophic condition, but high BaP concentration (>5 mg/L) had a significant inhibitory effect on its growth. During heterotrophic cultivation, low BaP concentration (<20 mg/L) promoted the growth of C. vulgaris LH-1, whereas high BaP concentration (>20 mg/L) inhibited its growth significantly. The degradation rates of mixotrophic and heterotrophic C. vulgaris LH-1 were 62.56 %-74.13 % and 52.07 %-71.67 %, respectively, when the BaP concentration ranged from 0.5 mg/L to 2 mg/L. The expression of functional enzyme genes of C. vulgaris LH-1 such as phenol 2-monooxygenase activity, protocatechuate 3,4-dioxygenase activity, catechol 1,2-dioxygenase activity, styrene degradation, and benzoate degradation were upregulated in the process of BaP degradation. C. vulgaris LH-1 may degrade BaP by monooxygenase and dioxygenase simultaneously. The degradation of BaP by this microalga under mixotrophic condition goes through the degradation pathway of phthalic acid, whereas it goes through the degradation pathway of benzoic acid under heterotrophic condition.


Asunto(s)
Chlorella vulgaris , Dioxigenasas , Chlorella vulgaris/metabolismo , Benzo(a)pireno , Biodegradación Ambiental , Dioxigenasas/metabolismo
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