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1.
Neural Regen Res ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39248177

RESUMEN

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

2.
J Org Chem ; 89(17): 12658-12667, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39159404

RESUMEN

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

3.
Microbiome ; 12(1): 137, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044261

RESUMEN

BACKGROUND: Haematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features. RESULTS: A total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections. CONCLUSIONS: Analysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life. Video Abstract.


Asunto(s)
Virus ADN , Enfermedades Hematológicas , Virus ARN , Virosis , Humanos , Masculino , Femenino , Virus ADN/aislamiento & purificación , Virus ADN/genética , Persona de Mediana Edad , Virosis/sangre , Virosis/virología , Adulto , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/sangre , Virus ARN/aislamiento & purificación , Viroma , Anciano , Torque teno virus/aislamiento & purificación , Torque teno virus/genética , Estudios de Cohortes , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Adulto Joven
4.
Water Res ; 259: 121850, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38851109

RESUMEN

Iron (Fe0, Fe (II), and Fe (III)) has been previously documented to upregulate the expression of key genes, enhancing the production of volatile fatty acids (VFAs) to achieve waste/wastewater resource recovery. However, the precise mechanism by why iron influences gene expression remains unclear. This study applied iron-assisted fermentation systems to explore the behind enhancing mechanism by constructing regulon networks among genes, microbes, and transcription factors. In iron-conditioned systems, a significant enhancement in VFAs production and upregulation of genes expression (1.19-3.92 folds) related to organic conversion and the electron transfer chain was observed. Besides, gene co-expression network and Procrustes analysis identified ten hub transcription factors (e.g., arsR, crp, iscR, perR) and their major contributors (genus) (e.g., Paludibacter, Acinetobacter, Tolumonas). Further analysis suggested that most of hub transcription factors were implicated in iron homeostasis regulation, which speculated that the induced iron homeostasis transcription factors probably effectively regulated the expression of genes encoding enzymes involving in VFAs production and electron transfer of functional microbes, in the case of Paludibacter, Acinetobacter, and Tolumonas while regulating the iron homeostasis, resulting in the efficient production of VFAs in iron-conditioned systems. This study might contribute to an enhanced understanding of the underlying genetic mechanisms by why iron influences gene expression regulation of microbes, which also provides a genetic theoretical basis for improving system VFAs production and resource recovery.


Asunto(s)
Ácidos Grasos Volátiles , Fermentación , Hierro , Factores de Transcripción , Hierro/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Ácidos Grasos Volátiles/metabolismo , Homeostasis , Regulación Bacteriana de la Expresión Génica , Bacterias/metabolismo , Bacterias/genética
5.
Clin Nutr ; 43(7): 1816-1831, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38870662

RESUMEN

BACKGROUND: Optical atrophy 1 (OPA1), a protein accountable for mitochondrial fusion, facilitates the restoration of mitochondrial structure and function following cerebral ischemia/reperfusion (I/R) injury. The OPA1-conferred mitochondrial protection involves its expression and activity, which can be improved by SIRT3 in non-cerebral ischemia. Nevertheless, it remains obscure whether SIRT3 enhances the expression and activity of OPA1 after cerebral I/R injury. METHODS: Mature male Sprague Dawley rats were intracranially injected with adeno-associated viral-Sirtuin-3(AAV-SIRT3) and AAV-sh_OPA1, followed by a 90-min temporary blockage of the middle cerebral artery and subsequent restoration of blood flow. Cultured cortical neurons of rats were transfected with LV-SIRT3 or LV-sh_OPA1 before a 2-h oxygen-glucose deprivation and reoxygenation. The rats and neurons were subsequently treated with a selective OPA1 activity inhibitor (MYLS22). The interaction between SIRT3 and OPA1 was assessed by molecular dynamics simulation technology and co-immunoprecipitation. The expression, function, and specific protective mechanism of SIRT3 were examined by various analyses. RESULTS: SIRT3 interacted with OPA1 in the rat cerebral cortex before and after cerebral I/R. After cerebral I/R damage, SIRT3 upregulation increased the OPA1 expression, which enhanced deacetylation and OPA1 activity, thus alleviating cerebral infarct volume, neuronal apoptosis, oxidative pressure, and impairment in mitochondrial energy production; SIRT3 upregulation also improved neuromotor performance, repaired mitochondrial ultrastructure and membrane composition, and promoted the mitochondrial biogenesis. These neuroprotective effects were partly reversed by OPA1 expression interference and OPA1 activity inhibitor MYLS22. CONCLUSION: In rats, SIRT3 enhances the expression and activity of OPA1, facilitating the repair of mitochondrial structure and functional recovery following cerebral I/R injury. These findings highlight that regulating SIRT3 may be a promising therapeutic strategy for ischemic stroke.


Asunto(s)
GTP Fosfohidrolasas , Accidente Cerebrovascular Isquémico , Mitocondrias , Sirtuina 3 , Animales , Masculino , Ratas , Modelos Animales de Enfermedad , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Accidente Cerebrovascular Isquémico/metabolismo , Mitocondrias/metabolismo , Neuronas/metabolismo , Ratas Sprague-Dawley , Recuperación de la Función , Daño por Reperfusión/metabolismo , Sirtuina 3/metabolismo , Sirtuina 3/genética , Sirtuinas
6.
Clin Lung Cancer ; 25(6): 509-518, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38879394

RESUMEN

BACKGROUND: The ADAURA trial confirmed adjuvant Osimertinib's efficacy in EGFR-mutated Non-small-cell lung cancer (NSCLC), yet the limited mature overall survival (OS) data at approval poses a challenge. This study explores patient preferences in the absence of complete OS information, hypothesizing that disease-free survival (DFS) benefit alone may influence adjuvant Osimertinib pursuit. METHODS: At Roswell Park Comprehensive Cancer Center (Jan-Dec 2021), patients assessed for adjuvant therapy received a survey probing OS and DFS preferences. Scenarios were (a) minimum OS justifying Osimertinib, (b) minimum DFS improvement justifying 3-years of adjuvant Osimertinib, (c) minimum 5-year DFS percent change, and (d) minimum OS justifying copay changes. Results were analyzed. RESULTS: Of 524 NSCLC patients, 51 participated. Scenario 1 saw 56% requiring a 12-month OS benefit for Osimertinib justification. In scenario 2, 72% deemed a 12-month DFS benefit sufficient. Scenario 3 revealed 31% opting out despite a 10% OS increase. Scenario 4 showed varied willingness to pay, with 33% unwilling to any shoulder copayment even with a 10-year OS benefit. CONCLUSION: This study explores patient preferences without complete OS data, revealing diverse thresholds. Factors include employment, education, and willingness to pay. Findings underscore shared decision-making importance. Limitations include sample size, potential biases, and regional focus; larger cohorts are needed for validation.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Prioridad del Paciente , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Quimioterapia Adyuvante/métodos , Adulto , Antineoplásicos/uso terapéutico , Anciano de 80 o más Años , Indoles , Pirimidinas
7.
Cell Biol Toxicol ; 40(1): 31, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767771

RESUMEN

Mitochondrial dysfunction contributes to cerebral ischemia-reperfusion (CI/R) injury, which can be ameliorated by Sirtuin-3 (SIRT3). Under stress conditions, the SIRT3-promoted mitochondrial functional recovery depends on both its activity and expression. However, the approach to enhance SIRT3 activity after CI/R injury remains unelucidated. In this study, Sprague-Dawley (SD) rats were intracranially injected with either adeno-associated viral Sirtuin-1 (AAV-SIRT1) or AAV-sh_SIRT1 before undergoing transient middle cerebral artery occlusion (tMCAO). Primary cortical neurons were cultured and transfected with lentiviral SIRT1 (LV-SIRT1) and LV-sh_SIRT1 respectively before oxygen-glucose deprivation/reoxygenation (OGD/R). Afterwards, rats and neurons were respectively treated with a selective SIRT3 inhibitor, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). The expression, function, and related mechanism of SIRT1 were investigated by Western Blot, flow cytometry, immunofluorescence staining, etc. After CI/R injury, SIRT1 expression decreased in vivo and in vitro. The simulation and immune-analyses reported strong interaction between SIRT1 and SIRT3 in the cerebral mitochondria before and after CI/R. SIRT1 overexpression enhanced SIRT3 activity by increasing the deacetylation of SIRT3, which ameliorated CI/R-induced cerebral infarction, neuronal apoptosis, oxidative stress, neurological and motor dysfunction, and mitochondrial respiratory chain dysfunction, promoted mitochondrial biogenesis, and retained mitochondrial integrity and mitochondrial morphology. Meanwhile, SIRT1 overexpression alleviated OGD/R-induced neuronal death and mitochondrial bioenergetic deficits. These effects were reversed by AAV-sh_SIRT1 and the neuroprotective effects of SIRT1 were partially offset by 3-TYP. These results suggest that SIRT1 restores the structure and function of mitochondria by activating SIRT3, offering neuroprotection against CI/R injury, which signifies a potential approach for the clinical management of cerebral ischemia.


Asunto(s)
Isquemia Encefálica , Mitocondrias , Neuronas , Daño por Reperfusión , Sirtuina 1 , Sirtuina 3 , Animales , Masculino , Ratas , Apoptosis , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Mitocondrias/metabolismo , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Sirtuina 1/metabolismo , Sirtuina 1/genética , Sirtuina 3/metabolismo , Sirtuina 3/genética , Sirtuinas
8.
Foods ; 13(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38790856

RESUMEN

Harvested wampee fruit is susceptible to disease, resulting in postharvest losses. Acidic electrolyzed water (AEW), a safe and innovative sterilization technology, plays a role in enhancing disease resistance in harvested produce. In this study, the efficacy of AEW in delaying wampee disease development was assessed, along with its association with disease resistance metabolism. Wampee fruit was treated with AEW (pH 2.5) at different available chlorine concentrations (ACCs) (20, 40, 60, and 80 mg/L) and subsequently stored at 25 °C for 8 days. Results revealed that 40 mg/L ACC in AEW (pH 2.5) was most effective in improving the postharvest quality of wampee fruit. Compared with control wampee fruit, those treated with 40 mg/L ACC in AEW exhibited lower incidence of fruit disease, higher pericarp lignin content, and higher activities of pericarp disease resistance enzymes (DREs), such as cinnamate-4-hydroxylase, phenylalanine ammonia-lyase, chitinase, ß-1,3-glucanase, polyphenol oxidase, 4-coumarate CoA ligase, and cinnamyl alcohol dehydrogenase. These results suggested that AEW elevated DRE activities, promoted lignin accumulation, and ultimately enhanced disease resistance, suppressed disease development, and improved storage quality in harvested wampee fruit. Consequently, AEW emerged as a safe technology to mitigate the disease development and enhance the storage quality of harvested wampee fruit.

9.
Food Chem ; 447: 138873, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38452536

RESUMEN

Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure-activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC50: 48.73 ± 7.59 µM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.


Asunto(s)
Hidrolisados de Proteína , Relación Estructura-Actividad Cuantitativa , Simulación del Acoplamiento Molecular , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Péptidos/farmacología , Péptidos/química , Músculos/metabolismo , Iones , Angiotensinas , Peptidil-Dipeptidasa A/metabolismo
10.
Molecules ; 29(5)2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38474646

RESUMEN

Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Peptidil-Dipeptidasa A , Inhibidores de la Enzima Convertidora de Angiotensina/química , Simulación del Acoplamiento Molecular , Peptidil-Dipeptidasa A/metabolismo , Cromatografía Liquida , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem , Péptidos/química , Angiotensinas
11.
Sci Total Environ ; 922: 171339, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38428595

RESUMEN

Inappropriate sterilization strategies inhibit microalgal growth when culturing microalgae with anaerobic digestate. This study aimed to scientifically select a low-cost disinfection pretreatment of anaerobic digestate for large-scale microalgae cultivations. In this work, three different methods, including autoclaving, ultraviolet or NaClO treatments, were employed to sterilize the municipal anaerobic digestate. Scenedesmus quadricauda was then cultured in diluted liquid digestate for the simultaneous lipid production and nutrient removal. The results indicated that the growth of S. quadricauda was inhibited after NaClO treatment due to the residual free chlorine. The 15-min ultraviolet effectively mitigated microbial contamination and increasing nutrient availability, enhancing the electron transport of microalgal photosynthesis. After 6-days cultivation, the microalgal biomass concentration of the ultraviolet group was 1.09 g/L, comparable to that of the autoclaving group (1.15 g/L). High nutrient removal efficiency was observed: COD (93.30 %), NH4+-N (92.56 %), TN (85.82 %) and TP (95.12 %). Moreover, S. quadricauda outcompeted the indigenous microorganisms, contributing to its dominance in the culture system of ultraviolet group. The facultative anaerobe Comamonadaceae and aerobes Moraxellaceae, rather than strict anaerobe Paludibacteraceae and Bacteroidetes_vadinHA17, played vital roles in synergistic removal of contaminants by bacteria and algae. The potential competition for nitrogen and phosphorus by bacteria contributed to the ultraviolet group having the greatest lipid content (48.19 %). Therefore, this work suggested using 15-min ultraviolet treatment for anaerobic digestate in large-scale microalgae cultivation.


Asunto(s)
Microalgas , Scenedesmus , Rayos Ultravioleta , Anaerobiosis , Bacterias , Biomasa , Nitrógeno , Bacteroidetes , Lípidos
12.
Org Lett ; 25(49): 8824-8828, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38032230

RESUMEN

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

13.
Dig Dis ; 41(6): 835-844, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37607491

RESUMEN

INTRODUCTION: The pathogenesis of epigastric pain in functional dyspepsia (FD) is complex. The study aims to explore the effect of sleep improvement on this symptom. METHODS: In total, 120 patients with FD-associated epigastric pain and insomnia were randomly divided into experimental and control groups using the envelope method. After applying the exclusion criteria, 107 patients were enrolled in the experimental (56 patients) and control (51 patients) groups. Insomnia was graded according to the Pittsburgh Sleep Quality Index (PSQI). In the experimental group, eszopiclone 3 mg, eszopiclone 3 mg + estazolam 1 mg, and eszopiclone 3 mg + estazolam 2 mg were given to patients with mild, moderate, and severe insomnia, respectively. In the control group, patients were given 1, 2, or 3 tablets of vitamin B complex. Patient sleep quality was monitored with Sleepthing. Epigastric pain was evaluated with a Numeric Rating Scale. The serum levels of IL-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Pain scores, sleep parameters, and serum levels of inflammatory mediators were compared before and after treatment. RESULTS: After treatment, the pain scores, sleep parameters, and TNF-α and IL-6 levels in the experimental group were significantly lower than those in the control group (p < 0.05). PSQI insomnia scores were significantly associated with pain scores, IL-6, and TNF-α (p < 0.05) but not in IL-8 and IL-1ß levels (p > 0.05) among the three groups. CONCLUSIONS: Improving sleep with eszopiclone and/or estazolam alleviates FD-associated epigastric pain, possibly by inhibiting related downstream transmission pathways and reducing the release of inflammatory mediators.


Asunto(s)
Dispepsia , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Dispepsia/complicaciones , Dispepsia/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Eszopiclona , Estazolam , Factor de Necrosis Tumoral alfa , Interleucina-6 , Mediadores de Inflamación , Interleucina-8 , Sueño , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Resultado del Tratamiento
14.
Sci Total Environ ; 899: 165696, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37482355

RESUMEN

Hydrolysis acidification (HA) is a promising method for wastewater treatment and resource recovery. However, the extended time required for bacterial reactivation after starvation or a change in living conditions often poses a challenge to the efficient operation of the system. Although the addition of zero-valent iron (ZVI) could enhance HA performance, its effects on sludge reactivation in the HA process are not fully understood. In this study, ZVI was employed to accelerate sludge reactivation and its involved genetic mechanisms were unveiled. The results demonstrated that ZVI addition activated the sludge within 35 days with stable HA performance. Sludge characteristics revealed that ZVI improved active biomass, enzyme activity (by 11.4 % âˆ¼ 26.7 %), ETS activity (by 566 %), and cell viability, with a higher concentration of MLVSS, live cells, more microbial byproducts in EPS, and relative abundance of HA bacteria (63.41 %). Moreover, metatranscriptome analysis showed that ZVI upregulated the expression of genes related to key enzymes in carbohydrate degradation metabolism, biosynthesis of electron transfer media such as heme and ubiquinone, and biosynthesis of vital cofactors like vitamin B12 and folate during microbial growth and metabolism. These findings suggest that ZVI enhanced electron transfer, bacterial growth, and metabolism, resulting in effective starch conversion and VFAs generation. Overall, these results deepen our understanding of the mechanism by which ZVI enhanced HA sludge reactivation, providing valuable information for addressing sludge starvation issues in HA systems.


Asunto(s)
Hierro , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Hidrólisis , Anaerobiosis , Bacterias , Concentración de Iones de Hidrógeno , Expresión Génica
15.
World J Oncol ; 14(3): 178-187, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37350807

RESUMEN

Background: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein-1 (PD-1) inhibitors or PD-1 ligand-1 (PD-L1) inhibitors have led to remarkable improvement in outcomes of non-small cell lung cancer (NSCLC). Unfortunately, the significant benefits of ICI therapy are frequently limited by resistance to treatment and adverse effects, and the predictive value of pre-treatment tumor tissue PD-L1 expression is limited. Development of less invasive biomarkers that could identify responders and non-responders in early on-treatment could markedly improve the treatment regimen. Accumulating evidence suggests that baseline gut microbiota profile is associated with response to PD-1/PD-L1 blockade therapy. However, change in the gut microbiome composition during PD-1/PD-L1 blockade therapy and its relation to response remain unclear. Methods: Here, we analyzed pre- and on-treatment fecal samples from five NSCLC patients receiving anti-PD-1 immunotherapy, alone or in tandem with chemotherapy, and performed 16S rRNA sequencing. Results: The overall alpha diversity of the baseline gut microbiome was similar between three responders and two non-responders. While the gut microbiome composition remained stable overall during treatment (R2 = 0.145), responders showed significant changes in microbiome diversity between pre- and on-treatment samples during anti-PD-1 therapy compared to non-responders (P = 0.0274). Within the diverse microbiota, responders showed decreases in the abundance of genera Odoribacter, Gordonibacter, Candidatus Stoquefichus, Escherichia-Shigella, and Collinsella, and increase in abundance of Clostridium sensu stricto 1. In contrast, non-responders demonstrated on-treatment increases in genera Prevotella, Porphyromonas, Streptococcus, and Escherichia-Shigella, and decrease in abundance of Akkermansia. Conclusions: This pilot study identified a substantial change in gut microbiome diversity between pre- and on-treatment samples in NSCLC patients responding to anti-PD-1 therapy compared to non-responders. Our findings highlight the potential utility of gut microbiota dynamics as a noninvasive biomarker to predict response to PD-1/PD-L1 blockade therapy for a wide variety of malignancies, which sets a path for future investigation in larger prospective studies.

16.
J Transl Med ; 21(1): 297, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-37138283

RESUMEN

OBJECTIVES: Available literature documents that ischemic stroke can disrupt the morphology and function of mitochondria and that the latter in other disease models can be preserved by neuropilin-1 (NRP-1) via oxidative stress suppression. However, whether NRP-1 can repair mitochondrial structure and promote functional recovery after cerebral ischemia is still unknown. This study tackled this very issue and explored the underlying mechanism. METHODS: Adeno-associated viral (AAV)-NRP-1 was stereotaxically inoculated into the cortex and ipsilateral striatum posterior of adult male Sprague-Dawley (SD) rats before a 90-min transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion. Lentivirus (LV)-NRP-1 was transfected into rat primary cortical neuronal cultures before a 2-h oxygen-glucose deprivation and reoxygenation (OGD/R) injury to neurons. The expression and function of NRP-1 and its specific protective mechanism were investigated by Western Blot, immunofluorescence staining, flow cytometry, magnetic resonance imaging, transmission electron microscopy, etc. The binding was detected by molecular docking and molecular dynamics simulation. RESULTS: Both in vitro and in vivo models of cerebral ischemia/reperfusion (I/R) injury presented a sharp increase in NRP-1 expression. The expression of AAV-NRP-1 markedly ameliorated the cerebral I/R-induced damage to the motor function and restored the mitochondrial morphology. The expression of LV-NRP-1 alleviated mitochondrial oxidative stress and bioenergetic deficits. AAV-NRP-1 and LV-NRP-1 treatments increased the wingless integration (Wnt)-associated signals and ß-catenin nuclear localization. The protective effects of NRP-1 were reversed by the administration of XAV-939. CONCLUSIONS: NRP-1 can produce neuroprotective effects against I/R injury to the brain by activating the Wnt/ß-catenin signaling pathway and promoting mitochondrial structural repair and functional recovery, which may serve as a promising candidate target in treating ischemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Animales , Masculino , Ratas Sprague-Dawley , Neuropilina-1 , Simulación del Acoplamiento Molecular , Daño por Reperfusión/patología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Mitocondrias/metabolismo , Apoptosis
17.
Microbiol Spectr ; 11(3): e0090923, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37052483

RESUMEN

Staphylococcus aureus is subdivided into lineages termed sequence types (STs), infections of which necessitate the expression of virulence factors and metabolic adaptation to the host niche. Given that mechanisms underlying the dynamic replacement of sequence types in S. aureus populations have yet to be sufficiently determined, we investigated the role of metabolic determinants in epidemic clones. mleS, encoding the NAD+-dependent malolactic enzyme, was found to be carried by the epidemic clones ST59 and ST398, although not by ST239 and ST5. The genomic location of mleS in the metabolism-associated region flanked by the thiol-specific redox system and glycolysis operon implies that it plays significant roles in metabolism and pathogenesis. Mouse skin abscess caused by the BS19-mleS mutant strain (isogenic mleS mutant in an ST59 isolate) was significantly attenuated and associated with reductions in interleukin-6 (IL-6) and lactic acid production. mleS deletion also impaired S. aureus biofilm formation and survival in RAW264.7 cells. The BS19-mleS-mutant was also characterized by reduced ATP and lactic acid production under microaerobic conditions; however, NAD+/NADH levels remained unaffected. mleS is thus identified as an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones. IMPORTANCE Given the importance of metabolic adaptation during infection, new insights are required regarding the pathogenesis of S. aureus, particularly for epidemic clones. We accordingly investigated the role of metabolic determinants that are unique to the epidemic clones ST59 and ST398. Our results provide evidence that the NAD+-dependent malolactic enzyme-coding gene mleS is an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Ratones , Staphylococcus aureus/genética , Absceso , NAD , Infecciones Estafilocócicas/epidemiología , Macrófagos
18.
Cancer Res Commun ; 3(3): 510-520, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37009132

RESUMEN

Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti-PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non-small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan-Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires. Significance: Current approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológico , Antígeno B7-H1/análisis , Linfocitos T CD8-positivos/química , Inmunoterapia/métodos , Receptores de Antígenos de Linfocitos T/genética , Receptor 1 de Quimiocinas CX3C/genética
19.
J Environ Manage ; 335: 117571, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36871358

RESUMEN

Aerobic activated sludge is widely used to degrade edible oil wastewater in wastewater treatment plants. During this process, the observed poor organics removal performance might be caused by poor sludge settling performance, which might be influenced by extracellular polymeric substances (EPS) and the structure of the microbial community. However, this hypothesis was not confirmed. Thus, this study investigated the response of activated sludge to 50% and 100% edible oil exposure in comparison to glucose, focusing on organics removal performance, characteristics of sludge, EPS, and microbial community structure. Results showed that both concentrations of edible oil influenced the systems' performance, although 100% edible oil showed more significant negative effects than 50% edible oil. The mechanisms behind the influence of edible oil on the aerobic activated sludge system and the differences between the different concentrations of edible oil were revealed. The worse system performance in the edible oil exposure system was due to the worse sludge settling performance, which was significantly affected by edible oil (p < 0.05). The sludge settling performance was mainly inhibited by promoting the formation of floating particles and the enrichment of filamentous bacteria in the 50% edible oil exposure system; biosurfactant secretion was also speculated as the reason, in addition to the above factors, in the 100% edible oil exposure system. The macroscopic largest floating particles, highest total relative abundance of foaming bacteria and biosurfactant production genera (34.32%), lowest surface tension (43.7 mN/m), and highest emulsifying activity (E24 = 25%) of EPS in 100% edible oil exposure systems provide strong evidence.


Asunto(s)
Microbiota , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Matriz Extracelular de Sustancias Poliméricas , Eliminación de Residuos Líquidos/métodos , Aguas Residuales , Bacterias/metabolismo
20.
Biochem Pharmacol ; 210: 115490, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36893816

RESUMEN

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental and reproductive disorders in pups due to the attenuated luteinizing hormone (LH) production during the perinatal stage; however, the administration of α-lipoic acid (LA) to TCDD-exposed pregnant rats reversed the attenuated LH production. Therefore, reproductive disorders in pups are expected to be ameliorated with LA supplementation. To address this issue, pregnant rats orally received low dose TCDD at gestational day 15 (GD15) and proceeded to parturition. The control received a corn oil vehicle. To examine the preventive effects of LA, supplementation with LA was provided until postnatal day 21. In this study, we demonstrated that maternal administration of LA restored the sexually dimorphic behavior of male and female offspring. TCDD-induced LA insufficiency is likely a direct cause of TCDD reproductive toxicity. In the analysis to clarify the mechanism of the decrease in LA, we found evidence suggesting that TCDD inhibits the synthesis and increases the utilization of S-adenosylmethionine (SAM), a cofactor for LA synthesis, resulting in a decrease in the SAM level. Furthermore, folate metabolism, which is involved in SAM synthesis, is disrupted by TCDD, which may adversely affect infant growth. Maternal supplementation of LA restored SAM to its original level in the fetal hypothalamus; in turn, SAM ameliorated abnormal folate consumption and suppressed aryl hydrocarbon receptor activation induced by TCDD. The study demonstrates that the application of LA could prevent and recover next-generation dioxin reproductive toxicity, which provides the potential to establish effective protective measures against dioxin toxicity.


Asunto(s)
Ácido Fólico , Exposición Materna , Dibenzodioxinas Policloradas , Efectos Tardíos de la Exposición Prenatal , Caracteres Sexuales , Desarrollo Sexual , Ácido Tióctico , Animales , Femenino , Masculino , Embarazo , Ratas , Feto/efectos de los fármacos , Feto/metabolismo , Ácido Fólico/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Exposición Materna/efectos adversos , Dibenzodioxinas Policloradas/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/prevención & control , S-Adenosilmetionina/metabolismo , Desarrollo Sexual/efectos de los fármacos , Ácido Tióctico/administración & dosificación , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Reproducción/efectos de los fármacos
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