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BACKGROUND/OBJECTIVE: To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies comparing BF versus FS in the treatment of COPD from inception to July 17, 2023. Outcomes, including exacerbations, hospitalizations, pneumonia, emergency department (ED) visits for COPD, length of hospitalization, and number of exacerbations, were compared using risk ratio (RR) with corresponding 95% confidence interval (CI) or weighted mean difference (WMD) with 95% CI. All statistical analyses were performed using Stata version 12.0. RESULTS: Ten studies comprising a total of 136,369 participants were included. Compared with those treated with FS, patients with COPD treated with BF experienced a reduced number of exacerbations (RR 0.91 [95% CI 0.83-1.00]; p = 0.040), hospitalizations (RR 0.77 [95% CI 0.67-0.88]; p < 0.001), and frequency of pneumonia (RR 0.77 [95% CI 0.64-0.92]; p = 0.05). However, no significant difference was observed between BF and FS in terms of ED visits for COPD (RR 0.87 [95% CI 0.69-1.10]; p = 0.243), length of hospitalization (WMD -0.18 [95% CI -0.62-0.27]; p = 0.437), and number of exacerbations (WMD -0.06 [95% CI -0.28-0.16]; p = 0.602). Notably, no significant heterogeneity was noted in length of hospitalization between the two groups, whereas clear heterogeneity was observed in other outcomes (I2 > 50%, p < 0.05). CONCLUSION: Compared with FS, BF therapy appears to be a more promising treatment strategy for patients with moderate-to-severe COPD; however, this should be verified in further high-quality studies.
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Broncodilatadores , Combinación Budesonida y Fumarato de Formoterol , Combinación Fluticasona-Salmeterol , Hospitalización , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Humanos , Combinación Fluticasona-Salmeterol/uso terapéutico , Broncodilatadores/uso terapéutico , Hospitalización/estadística & datos numéricos , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Neumonía , Índice de Severidad de la Enfermedad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Progresión de la Enfermedad , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricosRESUMEN
Class IIa bacteriocins produced in lactic acid bacteria are short cationic peptides with antimicrobial activity. In the search for new biopreservation agents, class IIa bacteriocins are considered to be the best potential candidates, not only due to their large abundance but also because of their high biological activity and excellent thermal stability. However, regulated by the biosynthetic regulatory system, the natural class IIa bacteriocin yield is low, and the extraction process is complicated. The biotechnological production of class IIa bacteriocins in various cell factories has been attempted to improve this situation. In this review, we focus on the application of biotechnological routes for class IIa bacteriocin production. The drawbacks and improvements in the production of class IIa bacteriocins in various cell factories are discussed. Furthermore, we present the main challenge of class IIa bacteriocins, focusing on increasing their production by constructing suitable cell factories. Recombinant bacteriocins have made considerable progress from inclusion body formation, dissolved form and low antibacterial activity to yield recovery. The development of prospective cell factories for the biotechnological production of bacteriocins is still required, which may facilitate the application of bacteriocins in the food industry.
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Bacteriocinas , Biotecnología , Bacteriocinas/biosíntesis , Biotecnología/métodos , Antibacterianos/biosíntesis , Antibacterianos/farmacología , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/biosíntesis , Lactobacillales/metabolismoRESUMEN
In recent years, the emerging concern regarding safety issues associated with live bacterial cells is enhancing the interest in using cell components and metabolites derived from microbiota. Therefore, the term "postbiotics" is increasingly found in food microbiology, food scientific and commercial products. Postbiotics is defined as non-viable microorganisms or their components that provide benefits to the host. Many in vivo and in vitro experiments have shown that beneficial microbiota-generated extracellular nanoparticles (NPs) confer unique health promoting functions to the intestinal local and systemic effects, which can be considered as a novel postbiotics. Meanwhile, the postbiotics-NPs is a protective complex, delivering bioactive components to reach distant tissues and organs at high concentrations. These properties demonstrate that postbiotics-NPs may contribute to the improvement of host health by regulating specific gut microbiota and physiological functions, while the exact mechanisms are not fully elucidated. This review highlights the current understanding of postbiotics-NPs functional properties and mechanisms of health benefits, especially focusing on the interactions in gut microbiota and host, functions in human health and potential applications in future functional food and biomedical fields.
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Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Microbiota/fisiología , Intestinos/microbiología , Alimentos Funcionales , Promoción de la SaludRESUMEN
The theory of the brain-gut axis has confirmed that gut microbiota and metabolites are involved in the progression of neurodegenerative diseases through multiple pathways. However, few studies have highlighted the role of gut microbiota in cognitive impairment induced by aluminum (Al) exposure and its correlations with the homeostasis of essential metal content in the brain. To explore the relationship between alterations in the content of essential metals in the brain and relative abundance changes in gut microbiota induced by Al exposure, the Al, zinc (Zn), copper (Cu), iron (Fe), chromium (Cr), manganese (Mn), and cobalt (Co) content level in the hippocampus, olfactory bulb, and midbrain tissue were measured by inductively coupled plasma mass spectrometry (ICP-MS) methods after Al maltolate was intraperitoneally injected every other day for exposed groups. Then the unsupervised principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe) were used to analyze the relative abundance of the gut microbiota community and the structure of the gut microbiome. Finally, the correlations between gut microbiota composition and essential metal content in the different exposure groups were explored by using the Pearson correlation coefficient method. Based on the results, we indicated that the content of Al in the hippocampus, olfactory bulb, and midbrain tissue was increased and then decreased with the increasing exposure duration, with peaks occurring between 14 and 30 days. Concomitantly, Al-exposure decreased the Zn, Fe, and Mn levels in these tissues. 16 S rRNA gene sequencing results indicated that significant differences in the intestinal microbial community structure at the phylum, family, and genus levels were found in the Day 90 exposed group compared with the Day 7 exposed group. Ten enriched species in the exposed group were identified as markers at the three levels. Furthermore, ten bacteria at the genus level were identified to have a significantly strong correlation (r = 0.70-0.90) with Fe, Zn, Mn, and Co.
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Aluminio , Microbioma Gastrointestinal , Ratas , Animales , Aluminio/toxicidad , Aluminio/metabolismo , Metales/metabolismo , Zinc/metabolismo , Manganeso/metabolismo , Cobalto/metabolismo , Encéfalo , HomeostasisRESUMEN
With the constant increase in protein demand globally, it is expedient to develop a strategy to effectively utilize protein, particularly those extracted from plant origin, which has been associated with low digestibility, poor techno-functional properties, and inherent allergenicity. Several thermal modification approaches have been developed to overcome these limitations and showed excellent results. Nevertheless, the excessive unfolding of the protein, aggregation of unfolded proteins, and irregular protein crosslinking have limited its application. Additionally, the increased consumer demand for natural products with no chemical additives has created a bottleneck for chemical-induced protein modification. Therefore, researchers are now directed toward other nonthermal technologies, including high-voltage cold plasma, ultrasound, high-pressure protein, etc., for protein modification. The techno-functional properties, allergenicity, and protein digestibility are greatly influenced by the applied treatment and its process parameters. Nevertheless, the application of these technologies, particularly high-voltage cold plasma, is still in its primary stage. Furthermore, the protein modification mechanism induced by high-voltage cold plasma has not been fully explained. Thus, this review meets the necessity to assemble the recent information on the process parameters and conditions for modifying proteins by high-voltage cold plasma and its impact on protein techno-functional properties, digestibility, and allergenicity.
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Gases em Plasma , Gases em Plasma/farmacología , Alérgenos , Proteínas/químicaRESUMEN
Chondroitin sulfate (CS) is a well-known bioactive substance with multiple biological functions, which can be extracted from animal cartilage or bone. Sturgeon, the largest soft bone animal with ~20% cartilage content, is a great candidate for CS production. Our recent study confirmed the role of sturgeon chondroitin sulfate (SCS) in reducing colorectal cancer cell proliferation and tumor formation. Here, we further studied the effect of SCS on modulating gut microbiome structure in colorectal cancer bearing mice. In this study, the transplanted tumor mice model was constructed to demonstrate that SCS can effectively halt the growth of transplanted colorectal tumor cells. Next, we showed that SCS significantly altered the gut microbiome, such as the abundance of Lactobacillales, Gastranaerophilales, Ruminiclostridiun_5 and Ruminiclostridiun_6. According to linear discriminant analysis (LDA) and abundance map analysis of the microbial metabolic pathways, the changes in microbial abundance led to an increase of certain metabolites (e.g., Phe, Tyr, and Gly). Fecal metabolome results demonstrated that SCS can significantly reduce the amount of certain amino acids such as Phe, Pro, Ala, Tyr and Leu presented in the feces, suggesting that SCS might inhibit colorectal cancer growth by modulating the gut microbiome and altering the production of certain amino acids. Our results revealed the therapeutic potential of SCS to facilitate treatment of colorectal cancer. This study provides insights into the development of novel food-derived therapies for colorectal cancer.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Aminoácidos/metabolismo , Animales , Sulfatos de Condroitina/química , Neoplasias Colorrectales/patología , Heces/química , Peces/metabolismo , Metaboloma , RatonesRESUMEN
Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed that IRW treatment protects osteoblasts against Ang II induced decline in cell proliferation and restores protein levels of collagen type I alpha 2 chain (COL1A2) and alkaline phosphatase (ALP) levels in MC3T3-E1 cells (p < 0.05). Apart from augmentation of these mineralization factors, the angiotensin II (Ang II) induced apoptotic stress in osteoblasts was mitigated by IRW as well. At the molecular level, IRW abolished the cytochrome-c release via modulation of pro-and anti-apoptotic genes in MC3T3-E1 cells (p < 0.05). Interestingly, IRW also increased cellular levels of cytoprotective local RAAS factors such as MasR, Ang (1−7), ACE2, and AT2R, and lowered the levels of Ang II effector receptor (AT1R). Further, our results indicated a lower content of inflammation and osteoclastogenesis biomarkers such as cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-κB), and receptor activator of nuclear factor kappa-B ligand (RANKL) following IRW treatment in MC3T3-E1 cells (p < 0.05). The use of an antagonist-guided cell study indicated that IRW contributed to the process of cytoprotection and proliferation of osteoblasts via Runt-related transcription factor 2 (RUNX2) in face of Ang II stress in an AT2R dependent manner. The key findings of our study showed that IRW could potentially have a therapeutic role in the treatment and/or prevention of bone disorders.
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Angiotensina II , Oligopéptidos , Angiotensina II/metabolismo , Angiotensina II/farmacología , FN-kappa B/metabolismo , Oligopéptidos/metabolismo , Oligopéptidos/farmacología , Osteoblastos/metabolismo , Péptidos/farmacología , Receptores de Angiotensina/metabolismoRESUMEN
BACKGROUND: Previous studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. OBJECTIVE: To explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. METHODS: In this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. RESULTS: One hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. CONCLUSION: Based on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.
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Contaminantes Ocupacionales del Aire/sangre , Disfunción Cognitiva/epidemiología , Metales/sangre , Adulto , China/epidemiología , Cognición , Disfunción Cognitiva/sangre , Estudios Transversales , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metalurgia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
Food microbial contamination not only poses the problems of food insecurity and economic loss, but also contributes to food waste, which is another global environmental problem. Therefore, effective packaging is a compelling obstacle for shielding food items from outside contaminants and maintaining its quality. Traditionally, food is packaged with plastic that is rarely recyclable, negatively impacting the environment. Bio-based materials have attracted widespread attention for food packaging applications since they are biodegradable, renewable, and have a low carbon footprint. They provide a great opportunity to reduce the extensive use of fossil fuels and develop food packaging materials with good properties, addressing environmental problems and contributing significantly to sustainable development. Presently, the developments in food chemistry, technology, and biotechnology have allowed us to fine-tune new methodologies useful for addressing major safety and environmental concerns regarding packaging materials. This review presents a comprehensive overview of the development and potential for application of new bio-based materials from different sources in antimicrobial food packaging, including carbohydrate (polysaccharide)-based materials, protein-based materials, lipid-based materials, antibacterial agents, and bio-based composites, which can solve the issues of both environmental impact and prevent foodborne pathogens and spoilage microorganisms. In addition, future trends are discussed, as well as the antimicrobial compounds incorporated in packaging materials such as nanoparticles (NPs), nanofillers (NFs), and bio-nanocomposites.
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Materiales Biocompatibles , Contaminación de Alimentos , Microbiología de Alimentos , Embalaje de Alimentos , Antiinfecciosos/química , Antiinfecciosos/farmacología , Materiales Biocompatibles/química , Biopolímeros/química , Fenómenos Químicos , Contaminación de Alimentos/prevención & control , Embalaje de Alimentos/métodos , Embalaje de Alimentos/tendencias , Conservación de Alimentos , Humanos , Nanocompuestos/químicaRESUMEN
Chondroitin sulfate (CS) is a food-derived bioactive substance with multiple biological functions, which exists in animal cartilage and/or bone. Sturgeon, a type of cartilaginous fish, is rich in CS. Our recent study demonstrated the effect of sturgeon chondroitin sulfate (SCS) on reducing colorectal cancer cell proliferation and tumor formation. However, the molecular mechanisms of its anticancer activity remain unknown. In this study, the cell proliferation assay and flow cytometric analysis were used to examine the cell viability and apoptosis of colon cancer cell HT-29 cells and normal colonic epithelial cell NCM460 cells. Transcriptomic and proteomic studies were used to identify the main targets of SCS. SCS showed little effect on the genes/proteins expression profile of NCM460 cells but more sensitive to HT-29, in which 188 genes and 10 proteins were differentially expressed after SCS treatment. Enrichment analysis of those genes/proteins showed that the majority of them are involved in DNA replication, cell cycle progression and apoptosis. Quantitative RT-PCR and Western blot were used to determine essential genes/proteins and networks targeted by SCS to exert inhibiting the development of colorectal cancer function. This study provided great insights into developing food-derived novel therapeutics for colorectal cancer treatment.
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Biomarcadores de Tumor/metabolismo , Sulfatos de Condroitina/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes , Proteoma/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Animales , Apoptosis , Biomarcadores de Tumor/genética , Ciclo Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Peces/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Natural transformation increases the genetic diversity of bacteria, but is costly and must be strictly controlled. We previously found that deletion of ccpA, a key regulator of carbon catabolite repression (CCR), reduced transformation efficiency of Streptococcus oligofermentans, the current work further investigated the regulatory mechanisms of CcpA. The competence operon comCDE is subjected to basal and autoregulatory transcription. A luciferase reporter detected a transcriptional readthrough (TRT) from the upstream tRNAArg into the comCDE operon, which was induced by L -arginine. Insertion of the Escherichia coli T1T2 terminator downstream of tRNAArg abolished TRT, and reduced the basal comCDE transcription by 77% and also the transformation efficiency. Deletion of ccpA increased tRNAArg TRT and tRNAArg -comCDE polycistronic transcript by twofold. An in vitro transcription assay determined that CcpA promoted the transcription termination of tRNAArg TRT, and RNA EMSA and SPR assays detected equal binding affinity of CcpA to both the RNA and DNA of tRNAArg . These results indicate that CcpA controls the basal comCDE transcription by post-transcriptional actions. Overexpression of comDE or its phospho-mimicking mutant comDED58E reduced transformation efficiency, indicating that excessive ComE impairs competence development. CCR-regulated competence was further confirmed by higher tRNAArg TRT but lower transformation efficiency in galactose than in glucose.
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Proteínas Bacterianas/metabolismo , Represión Catabólica , Regulación Bacteriana de la Expresión Génica , Proteínas Represoras/metabolismo , Streptococcus/crecimiento & desarrollo , Streptococcus/metabolismo , Proteínas Bacterianas/genética , Carbono/metabolismo , Regulación del Desarrollo de la Expresión Génica , Operón , Proteínas Represoras/genética , Streptococcus/genética , Transcripción GenéticaRESUMEN
BACKGROUND: To investigate the relationship between an increase in the pre- and post-operative mean platelet volume (MPV) and superficial femoral artery in-stent restenosis (ISR) rate. METHODS AND RESULTS: We recruited patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to March 2018. All patients gave venous blood three days before and following implantation. Doppler ultrasound, computed tomography angiography or digital subtraction angiography were used for regular follow-up examination. Logistic regression was used to identify predictors of ISR after superficial femoral artery stenting. We enrolled 173 patients, of which 34 (19.6%) were determined as having ISR for a mean of 8.9 ± 2.7 months (3-12 months). Neutrophil count, neutrophil ratio, lymphocyte ratio and platelet count pre-implantation, and platelet count and MPV after stent implantation, and the pre- and post-operative mean platelet volume difference (MPVD) and mean platelet volume difference ratio (MPVDR) were all statistically different when comparing the ISR and non-restenosis groups (p < 0.05). A positive correlation was found for post-operative MPV and presence of ISR (r = 0.58; P < 0.001). A MPVD not less than 1.5 fL was associated with an odds ratio of 9.17 (95% CI [3.76 to 22.35]; P < 0.001) for presence of ISR. A MPVDR of not less than 17.9% was associated with an odds ratio of 7.68 (95% CI [3.19 to 18.49]; P < 0.001) for occurrence of ISR. CONCLUSIONS: An increase in pre- and post-operative MPV was correlated with the occurrence of superficial femoral artery ISR.
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Arteriosclerosis Obliterante/terapia , Plaquetas , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Arteria Femoral , Volúmen Plaquetario Medio , Stents , Anciano , Anciano de 80 o más Años , Arteriosclerosis Obliterante/sangre , Arteriosclerosis Obliterante/diagnóstico , Constricción Patológica , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Biologically active, artificially synthesized two-peptide bacteriocin PlnEF was used to study its mode of action on sensitive bacteria Lactobacillus plantarum pl2. The data obtained showed that PlnEF induced membrane permeabilization, allowing for the efflux of electrolytes, which was evidenced by the increased extracellular conductivity, the dissipation of transmembrane electrical potential and pH gradient, and rapid intracellular ATP depletion after L. plantarum pl2 cells were treated with PlnEF for minutes. Laser confocal microscopy showed that PlnEF accumulated very quickly in L. plantarum pl2 cells and the accumulation of PlnEF caused damage to cell membrane. Scanning electron microscopy and transmission electron microscopy further showed that PlnEF induced morphological changes and structure disruption to L. plantarum pl2 cells, such as the formation of blebs, microspheres, membrane deformation and cell lysis. In summary, the data obtained show that PlnEF caused cell membrane damage to L. plantarum pl2 cells. Our study reveals the antimicrobial mechanism of two-peptide bacteriocin PlnEF against L. plantarum.
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Bacteriocinas/farmacología , Membrana Celular/metabolismo , Lactobacillus plantarum/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Fuerza Protón-Motriz/efectos de los fármacos , Bacteriocinas/química , Membrana Celular/químicaRESUMEN
OBJECTIVE: To investigate the off-label use of oral glucocorticoids in outpatients. METHODS: The information of outpatient glucocorticoids prescriptions from January 1st to June 30th in 2012 were collected from the information system in our hospital, then the software of Excel was employed to statistically analyze the data including the amount of drugs used in different departments,as well as the age, sex, and diagnosis of the patients. The diagnoses were compared with those included in the labels approved by China Food and Drug Administration and US Food and Drug Administration and domestic and foreign guidelines. RESULTS: It was found that 16.53% of the cases were off-label use,and dexamethasone had the highest proportion (60.50%) of off-label use. Most of the off-label use had evidence support, such as multiple myeloma and myasthenia gravis, while some cases did not, such as epilepsy and sudden deafness. CONCLUSION: The management of off-label use should be further strengthened to promote the safe and rational use of glucocorticoids.
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Uso Fuera de lo Indicado , Administración Oral , China , Epilepsia , Glucocorticoides , Humanos , Pacientes AmbulatoriosRESUMEN
SCOPE: This study aims to investigate the antihypertensive effect of four chicken muscle-derived angiotensin (Ang)-converting enzymes (ACE)-regulating peptides: Val-Arg-Pro (VRP, ACE inhibition), Leu-Lys-Tyr and Val-Arg-Tyr (LKY and VRY, ACE inhibition and ACE2 upregulation), and Val-Val-His-Pro-Lys-Glu-Ser-Phe (VVHPKESF [V-F], ACE2 upregulation) in spontaneously hypertensive rats. METHODS AND RESULTS: Rats (12-14 weeks old) are grouped: 1) untreated, 2) VRP, 3) LKY, 4) VRY, and 5) V-F. Blood pressure (BP) is monitored using implantable telemetry technology. Over 18-day oral administration of 15 mg kg-1 body weight (BW) per day, only peptide V-F significantly (p < 0.05) reduces BP, decreases circulating Ang II, and increases ACE2 and Ang (1-7) levels, and enhances aortic expressions of ACE2 and Mas receptor (MasR). Peptide V-F also attenuates vascular inflammation (TNFα, MCP-1, IL-1α, IL-15, and cyclooxygenase 2 [COX2]) and vascular oxidative stress (nitrotyrosine). The gastrointestinal (GI)-degraded fragment of peptide V-F, Val-Val-His-Pro-Lys (VVHPK), is also an ACE2-upregulating peptide. Peptides VRP, LKY, and VRY do not reduce BP, possibly due to low bioavailability or other unknown reasons. CONCLUSIONS: Peptide V-F is the first ACE2-upregulating peptide, purified and fractionated from food proteins based on in vitro ACE2 upregulation, that reduces BP associated with the activation of ACE2/Ang (1-7)/MasR axis; the N-terminal moiety VVHPK may be responsible for the antihypertensive effect of V-F.
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Enzima Convertidora de Angiotensina 2 , Pollos , Ratas , Animales , Ratas Endogámicas SHR , Presión Sanguínea , Enzima Convertidora de Angiotensina 2/farmacología , Pollos/metabolismo , Antihipertensivos/farmacología , Péptidos/farmacología , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Angiotensina II/farmacología , Músculos/metabolismoRESUMEN
Introduction: Numerous studies have explored the treatment outcomes of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19. However, direct comparisons between these two drugs are still relatively limited. This study aims to compare the safety and effectiveness of these two drugs in Chinese older patients with early infection to provide strategies for clinical treatment. Methods: Older COVID-19 patients (age ≥65) hospitalized during the winter 2022 epidemic in China were included and divided into Nirmatrelvir-Ritonavir and Azvudine. Demographics, medication information, laboratory parameters, and treatment outcomes were collected. All-cause 28-day mortality, delta cycle threshold (ΔCt), nucleic acid negative conversion time, and incidence of adverse events were defined as outcomes. Propensity score matching (PSM), Kaplan-Meier, Cox proportional hazards model, subgroup analysis, and nomograms were selected to evaluate the outcomes. Results: A total of 1,508 older COVID-19 patients were screened. Based on the inclusion and exclusion criteria, 1,075 patients were eligible for the study. After PSM, the final number of older COVID-19 patients included in the study was 375, and there were no significant differences in demographic characteristics between the two groups (p > 0.05). Compared to the Azvudine group, the Nirmatrelvir-Ritonavir group showed a higher incidence of multiple adverse events (12.8% vs 5.2%, p = 0.009). The incidence of adverse events related to abnormal renal function was higher in the Nirmatrelvir-Ritonavir group compared to the Azvudine group (13.6% vs 7.2%, p = 0.045). There were no significant differences between the two groups in terms of all-cause 28-day mortality (HR = 1.020, 95% CI: 0.542 - 1.921, p = 0.951), whereas there were significant differences in nucleic acid negative conversion time (HR = 1.659, 95% CI: 1.166 - 2.360, p = 0.005) and ΔCt values (HR = 1.442, 95% CI: 1.084 - 1.918, p = 0.012). Conclusion: Azvudine and Nirmatrelvir-Ritonavir have comparable effectiveness in reducing mortality risk. Azvudine may perform better in nucleic acid negative conversion time and virus clearance and shows slightly better safety in older patients. Further studies with a larger sample size were needed to validate the result.
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Sterilization of Northern shrimp (Pandalus borealis) is a key tool to ensure their freshness for post-production transportation. However, in the face of the specific problem of quality deterioration caused by the increase of storage environment temperature due to unexpected circumstances or the prolongation of temporary storage time, it is still a technical challenge to realize intelligent decision-making and higher sterilization efficiency. In this paper, we propose an intelligent UV-Ozone sterilization system suitable for cold chain transportation of Northern shrimp (Pandalus borealis). Using hierarchical analysis, equipartition method and the prediction method of generalized linear model, combined with the technology of intelligent control and remote control, we realized the automatic control of the system's UV irradiance from 324 â¼ 1620 J/m2, and ozone concentration from21.4 â¼ 107 mg/cm3 in a graded manner. The accuracy of the predicted structure was verified using a combination of direct measurement and simulation. In addition, the key model of the system, the intensity level decision model, was tested, and the test results showed that the decision model was able to accurately make decisions during the sterilization of Northern shrimp (Pandalus borealis), and the system was able to achieve a sterilization effect of 1-3 orders of magnitude. This reduces quality loss due to unexpected conditions, facilitates real-time monitoring of transported samples by staff, extends the shelf life of the samples, and improves the accuracy of sterilization, increasing the economic value of Northern shrimp (Pandalus borealis).
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Almacenamiento de Alimentos , Ozono , Pandalidae , Esterilización , Rayos Ultravioleta , Animales , Esterilización/métodos , Almacenamiento de Alimentos/métodos , Conservación de Alimentos/métodos , Mariscos , RefrigeraciónRESUMEN
Metallothionein is a cysteine-rich protein with a high metal content that is widely found in nature. In addition to heavy metal detoxification, metallothionein is well known as a potent antioxidant. The high sulfhydryl content of metallothionein confers excellent antioxidant activity, enabling it to effectively scavenge free radicals and mitigate oxidative stress damage. In addition, metallothionein can play a neuroprotective role by alleviating oxidative damage in nerve cells, have an anticancer effect by enhancing the ability of normal cells to resist unfavorable conditions through its antioxidant function, and reduce inflammation by scavenging reactive oxygen species. Due to its diverse biological functions, metallothionein has a broad potential for application in alleviating environmental heavy metal pollution, predicting and diagnosing diseases, and developing skin care products and health foods. This review summarizes the recent advances in the classification, structure, biological functions, and applications of metallothionein, focusing on its powerful antioxidant effects and related functions.
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OBJECTIVE: Our objective was to develop a machine learning model capable of predicting irrational medical prescriptions precisely within orthopedic perioperative patients. METHODS: A dataset comprising 3047 instances of suspected irrational medication prescriptions was collected from a sample of 1318 orthopedic perioperative patients from April 2019 to March 2022. Four machine learning models were employed to forecast irrational prescriptions, following which, the performance of each model was meticulously assessed. Subsequently, a thorough variable importance analysis was conducted on the model that performed the best predictive capabilities. Thereafter, the efficacy of integrating this optimal model into the existing audit prescription process was rigorously evaluated. RESULTS: Of the models utilized in this study, the RF model yielded the highest AUC of 92%, whereas the NB model presented the lowest AUC of 68%. Also, the RF model boasted the most robust performance in terms of PPV, reaching 82.4%, and NPV, reaching 86.6%. The ANN and the XGBoost model were neck and neck, with the ANN slightly edging out with a higher PPV of 95.9%, while the XGBoost model boasted an impressive NPV of 98.2%. The RF model singled out the following five factors as the most influential in predicting irrational prescriptions: the type of drug, the type of surgery, the number of comorbidities, the date of surgery after hospitalization, as well as the associated hospital and drug costs. CONCLUSION: The RF model showcased significantly high level of proficiency in predicting irrational prescriptions among orthopedic perioperative patients, outperforming other models by a considerable margin. It effectively enhanced the efficiency of pharmacist interventions, displaying outstanding performance in assisting pharmacists to intervene with irrational prescriptions.
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BACKGROUND: This study analyzed the bleeding adverse events (AEs) resulting from the treatment of B-cell lymphoma with Bruton tyrosine kinase (BTK) inhibitors, according to reports in the US Food and Drug Administration's Adverse Event Reporting System (FAERS). METHODS: Bleeding AEs associated with BTK inhibitors (including ibrutinib, zanubrutinib, and acalabrutinib) from the first quarter of 2013 to the third quarter of 2023 were extracted. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were reported. Preferred Terms (PTs) of Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to System Organ Class terms (SOC) terms and analyzed bleeding AEs associated with three BTK inhibitors. RESULTS: A total of 463 cases of bleeding AEs were included. Contusion, subcutaneous hemorrhage, hematuria, and cerebral hemorrhage were included in PTs. Blood urine was present and subdural hematoma were also reported. The incidence of bleeding AEs was higher with ibrutinib (Case number = 10,696) than with zanubrutinib (Case number = 213) and acalabrutinib (Case number = 314). CONCLUSION: Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.