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1.
J Hazard Mater ; 476: 135155, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38991637

RESUMEN

The gap between serious soil heavy metals pollution and inefficient soil remediation threatens human health. This study proposed a method to improve the phytoremediation efficiency using bamboo vinegar (BV) solution and the potential mechanism was discussed. The results demonstrated that the application of BV increases the content of cadmium (Cd) in vacuole and cell wall hemicellulose 2 in leaves of Perilla frutescens. Simultaneously, it enhanced enzyme activities of superoxide dismutase and catalase in leaves. Therefore, this process alleviated the damage of Cd to functional tissues of Perilla frutescens, thus improving the tolerance of plants to Cd. Moreover, the BV application reduced the Cd content bound by root cell wall pectin fractions and insoluble phosphate, subsequently improving the ability of oxalic acids to carry Cd to the aerial parts. Consequently, the aerial parts obtained a larger amount of Cd enrichment. Overall, the Transfer Factor of Cd from roots to stems and enrichment of Cd in Perilla frutescens were maximally increased by 57.70 % and 54.03 % with the application of 50-fold and 300-fold diluted BV under 2 mg·L-1 Cd stress, respectively. The results can provide a theoretical basis for the promotion of phytoremediation of Cd-contaminated soil treatment technology.


Asunto(s)
Ácido Acético , Biodegradación Ambiental , Cadmio , Perilla frutescens , Contaminantes del Suelo , Cadmio/metabolismo , Cadmio/toxicidad , Ácido Acético/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Perilla frutescens/metabolismo , Perilla frutescens/química , Lípidos de la Membrana/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Catalasa/metabolismo , Superóxido Dismutasa/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Polisacáridos/metabolismo
2.
Coron Artery Dis ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767051

RESUMEN

BACKGROUND: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. METHODS: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. RESULTS: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. CONCLUSION: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

3.
Heliyon ; 10(7): e28809, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596065

RESUMEN

Background: Sepsis is a life-threatening condition characterized by an aberrant host response to infection, resulting in multi-organ dysfunction. The application of currently available prognostic indicators for sepsis in primary hospitals is challenging. In this retrospective study, we established a novel index, the neutrophil-to-lymphocyte-to-monocyte ratio (NLMR), based on routine blood examination upon admission, and assessed its prognostic value for early mortality risk in adult patients with septic shock. Methods: This study included clinical data from adult patients with septic shock who were admitted to the hospital between January 1, 2018, and December 31, 2022. Training and validation sets were constructed, and patients were categorized into "survival" and "death" groups based on their survival status within the 28-day hospitalization period. Baseline data, including demographic characteristics and comorbidities, and laboratory results, such as complete blood count parameters, were collected for analysis. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were documented.The NLMR was determined through the utilization of multivariate binary logistic regression analysis, leading to the development of a risk model aimed at predicting early mortality in adult patients suffering from septic shock. Results: Overall, 112 adult patients with septic shock were enrolled in this study, with 84 and 28 patients in the training and validation sets, respectively. Multivariate binary logistic analysis revealed that the neutrophil, lymphocyte, and monocyte counts independently contributed to the mortality risk (odds ratios = 1.22, 0.08, and 0.16, respectively). The NLMR demonstrated an area under the receiver operating characteristic curve (ROC-AUC) of 0.83 for internal validation in the training set and 0.97 for external validation in the validation set. Both overall model quality values were significantly high at 0.74 and 0.91, respectively (P < 0.05). NLMR exhibited a higher ROC-AUC value of 0.88 than quick SOFA (ROC-AUC = 0.71), SOFA (ROC-AUC = 0.83), and APACHE II (ROC-AUC = 0.78). Conclusion: NLMR may be a potential marker for predicting the risk of early death in adult patients with septic shock, warranting further exploration and verification.

4.
Heliyon ; 10(7): e28141, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560197

RESUMEN

Background: Weaning patients from mechanical ventilation is a critical clinical challenge post cardiac surgery. The effective liberation of patients from the ventilator significantly improves their recovery and survival rates. This study aimed to develop and validate a clinical prediction model to evaluate the likelihood of successful extubation in post-cardiac surgery patients. Method: A predictive nomogram was constructed for extubation success in individual patients, and receiver operating characteristic (ROC) and calibration curves were generated to assess its predictive capability. The superior performance of the model was confirmed using Delong's test in the ROC analysis. A decision curve analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. Results: Among 270 adults included in our study, 107 (28.84%) experienced delayed extubation. A predictive nomogram system was derived based on five identified risk factors, including the proportion of male patients, EuroSCORE II, operation time, pump time, bleeding during operation, and brain natriuretic peptide (BNP) level. Based on the predictive system, five independent predictors were used to construct a full nomogram. The area under the curve values of the nomogram were 0.880 and 0.753 for the training and validation cohorts, respectively. The DCA and clinical impact curves showed good clinical utility of this model. Conclusion: Delayed extubation and weaning failure, common and potentially hazardous complications following cardiac surgery, vary in timing based on factors such as sex, EuroSCORE II, pump duration, bleeding, and postoperative BNP reduction. The nomogram developed and validated in this study can accurately predict when extubation should occur in these patients. This tool is vital for assessing risks on an individual basis and making well-informed clinical decisions.

5.
Nat Commun ; 15(1): 2654, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38531972

RESUMEN

The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.


Asunto(s)
Anabaena , Myoviridae , Proteínas de la Cápside/química , Cápside
6.
Eur J Pharmacol ; 969: 176425, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38387717

RESUMEN

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.


Asunto(s)
Lesión Renal Aguda , Compuestos de Anilina , Microbioma Gastrointestinal , Tetrahidronaftalenos , Humanos , Lipopolisacáridos , Receptor de Anafilatoxina C5a , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Riñón , Inflamación , Colon
7.
Int Wound J ; 21(1): e14606, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38272797

RESUMEN

Keloid is a fibroproliferative disease of unknown aetiology, which has a significant impact the quality of life of patients. Ferroptosis plays an important role in the occurrence and development of fibrosis, but there is still a lack of research related to keloids. The objective of this work was to identify the hub genes related to ferroptosis in keloid to better understand the keloid process. The microarray data (GSE7890 GSE145725, and GSE44270) (23 keloid and 22 normal fibroblast) were analysed via the gene expression comprehensive database (GEO). Only GSE7890 met the FerrDB database. Cell cycle and pathway analysis were performed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to differentially expressed genes (DEG). The differential genes were confirmed in other GEO datasets (GSE145725 and GSE44270), and multi-fibrosis-gene correlation analysed. To validate these hub genes, quantitative real-time PCR (qRT-PCR) was conducted. A total of 581 DEGs were screened, with 417 genes down-regulated and 164 genes up-regulated, with 11 ferroptosis genes significantly up-regulated in both keloid and normal tissue, and 6 genes are consistent with our findings and are associated with multiple fibrosis genes. The qRT-PCR results and tissues of normal skin and keloid agreed with our predictions. Our findings provide new evidence for the ferroptosis-related molecular pathways and biomarker of keloid.


Asunto(s)
Ferroptosis , Queloide , Humanos , Ferroptosis/genética , Queloide/genética , Calidad de Vida , Biomarcadores , Biología Computacional
8.
Photodiagnosis Photodyn Ther ; 45: 103945, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38135108

RESUMEN

OBJECTIVE: Prompt and effective wound repair is an essential strategy to promote recovery and prevent infection in patients with various types of trauma. Platelets can release a variety of growth factors upon activation to facilitate revascularization and tissue repair, provided that their activation is uncontrollable. The present study is designed to explore the selective activation of platelets by photodynamic and photothermal effects (PDE/PTE) as well as the trauma repair mediated by PDE/PTE. MATERIALS AND METHODS: In the current research, platelets were extracted from the blood of mice. Indocyanine green (ICG) was applied to induce PDE/PTE. The uptake of ICG by platelets was detected by laser confocal microscopy and flow cytometry. The cellular integrity was measured by microscopy. The reactive oxygen species (ROS) generation and temperature of platelets were assayed by 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) and temperature detector. The activation of platelets was measured by western blots (WB), dynamic light scattering (DLS), and scanning electron microscopy (SEM). The release of growth factor was detected by enzyme-linked immuno sorbent assay (Elisa), wherein the in vitro cell proliferation was investigated by 5-Ethynyl-2'-deoxyuridine (EDU) assay. The wound infection rates model and histological examination were constructed to assay the ICG-loaded platelet-mediated wound repair. RESULTS: Platelets could load with ICG, a kind of photodynamic and photothermal agent, as carriers and remain intact. Near-infrared (NIR) laser irradiation of ICG-loaded platelets (ICG@PLT) facilitated higher temperature and ROS generation, which immediately activated ICG@PLT, as characterized by increased membrane p-selectin (CD62p), cyclooxygenase-2 (COX-2), thromboxane A2 receptor (TXA2R) expression, elevated hydrated particle size, and prominent aggregation in platelets. Further investigation revealed that massive insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) were released from the activated ICG@PLT, which also promoted the proliferation of endothelial cells and keratinocytes in co-culture. In consequence, activated platelets and increased neovascularization could be observed in rats with wound infection treated by ICG@PLT in the presence of NIR. More impressively, the hydrogel containing ICG@PLT accelerated wound healing and suppressed inflammation under NIR, exhibiting excellent wound repair properties. CONCLUSION: Taken together, the current work identified that platelets could be activated by PDE/PTE and thereby release growth factor, potentiating wound repair in a controlled manner.


Asunto(s)
Fotoquimioterapia , Infección de Heridas , Humanos , Ratones , Ratas , Animales , Verde de Indocianina/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Cicatrización de Heridas , Péptidos y Proteínas de Señalización Intercelular , Línea Celular Tumoral
9.
Front Psychiatry ; 14: 1291988, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38130293

RESUMEN

Background: Sexual dysfunction is commonly observed in individuals with Major Depressive Disorder (MDD), along with various psychological symptoms such as anxiety, somatic complaints, interpersonal sensitivity, and obsessive-compulsive tendencies. However, there is a research gap in understanding the impact of these psychological symptoms on sexual functioning in MDD. Furthermore, there is limited data on the incidence of sexual dysfunction among drug-naive MDD patients in West China. This study aims to determine the prevalence of sexual dysfunction in this patient population and explore its association with other psychological indicators. Methods: We conducted a retrospective analysis of patient data from October 2020 to September 2022 using propensity score matching. A focused group of 165 males and 490 females was selected from a total of 1941 MDD patients. This allowed for a comparative analysis of demographic data, as well as scores from the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Symptom Checklist-90 (SCL-90), the Arizona Sexual Experience Scale (ASEX). Results: Our findings reveal that 46.2% of drug-naive MDD patients experienced sexual dysfunction. Notably, there was a higher prevalence of sexual dysfunction among female patients (50.3%) compared to males (37.5%). MDD patients without sexual dysfunction consistently exhibited higher SDS scores than those with sexual dysfunction (p < 0.01), There were no statistically significant differences between male and female MDD patients with or without concomitant sexual dysfunction in terms of Somatic complaints, Obsessive-compulsive, Interpersonal sensitivity, Anxiety, Phobic anxiety, Paranoid ideation, Psychoticism and Diet/sleep difficulties (p > 0.05). In addition, male MDD patients with sexual dysfunction showed a emerging trend towards elevated Hostility scores on the SCL-90 (p = 0.058), male MDD patients with sexual dysfunction showed an increasing trend in hostility scores on the SCL-90, whereas female MDD patients with sexual dysfunction did not show such a trend. Conclusion: The study highlights a significant gender difference in the prevalence of sexual dysfunction among MDD patients, with females being more susceptible than males. There is a positive correlation between the severity of depression and sexual dysfunction in both genders. Interestingly, male MDD patients demonstrated a potential protective effect of hostility against sexual dysfunction, which was not observed in female patients.

10.
Front Aging Neurosci ; 15: 1159711, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37671084

RESUMEN

Aims: Observational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD. Methods: This is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy. Results: Through MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970-0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503-1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05). Conclusion: Sleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.

11.
Front Med (Lausanne) ; 10: 1183326, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37396905

RESUMEN

Background: We aimed to investigate the causal association between TIM-3, an immune checkpoint inhibitor, and anterior uveitis (AU), as well as associated systemic immune diseases. Materials and methods: We performed two-sample Mendelian randomization (MR) analyses to estimate the causal effects of TIM-3 on AU and three associated systemic diseases, namely ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) associated with AU, AS, CD, and UC were selected as the outcomes: AU GWAS with 2,752 patients with acute AU accompanied with AS (cases) and 3,836 AS patients (controls), AS GWAS with 968 cases and 336,191 controls, CD GWAS with 1,032 cases and 336,127 controls, and UC GWAS with 2,439 cases and 460,494 controls. The TIM-3 dataset was used as the exposure (n = 31,684). Four MR methods, namely, inverse-variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode, were used in this study. Comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the potential impact of horizontal pleiotropy. Results: Our studies show that TIM-3 is significantly associated with CD using the IVW method (OR = 1.001, 95% CI = 1.0002-1.0018, P-value = 0.011). We also found that TIM-3 may be a protective factor for AU although these results lacked significance (OR = 0.889, 95% CI = 0.631-1.252, P-value = 0.5). No association was observed between the genetic predisposition to particular TIM-3 and susceptibility to AS or UC in this study. No potential heterogeneities or directional pleiotropies were observed in our analyses. Conclusion: According to our study, a small correlation was observed between TIM-3 expression and CD susceptibility. Additional studies in different ethnic backgrounds will be necessary to further explore the potential roles and mechanisms of TIM-3 in CD.

12.
Hum Vaccin Immunother ; 19(1): 2209001, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-37249310

RESUMEN

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Adulto , Niño , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Método Doble Ciego , Pueblos del Este de Asia , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Inmunogenicidad Vacunal , Infecciones por Papillomavirus/prevención & control , Vacunas Combinadas
13.
Vaccine ; 41(19): 3141-3149, 2023 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-37061370

RESUMEN

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Vacunas de Partículas Similares a Virus , Femenino , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , China , Método Doble Ciego , Pueblos del Este de Asia , Virus del Papiloma Humano , Inmunogenicidad Vacunal , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , Vacunas de Partículas Similares a Virus/efectos adversos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad
14.
Cancer Med ; 12(9): 10899-10907, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36934429

RESUMEN

Salivary gland malignancies are rare and are often acompanied by poor prognoses. So, identifying the populations with risk factors and timely intervention to avoid disease progression is significant. This study provides an effective prediction model to screen the target patients and is helpful to construct a cost-effective follow-up strategy. We enrolled 249 patients diagnosed with salivary gland tumors and analyzed prognostic risk factors using Cox proportional hazard univariable and multivariable regression models. The patients' data were split into training and validation sets on a 7:3 ratio, and the random survival forest (RSF) model was established using the training sets and validated using the validation sets. The maximally selected rank statistics method was used to determine a cut point value corresponding to the most significant relation with survival. Univariable Cox regression suggested age, smoking, alcohol consumption, untreated, neural invasion, capsular invasion, skin invasion, tumors larger than 4 cm, advanced T and N stage, distant metastasis, and non-mucous cell carcinoma were risk factors for poor prognosis, and multivariable analysis suggested that female, aging, smoking, untreated, and non-mucous cell carcinoma were risk factors. The time-dependent ROC curve showed the AUC of the RSF prediction model on 1-, 2-, and 3-year survival were 0.696, 0.779, and 0.765 respectively in the validation sets. Log-rank tests suggested that the cut point 7.42 risk score calculated from the RSF was most effective in dividing patients with significantly different prognoses. The prediction model based on the RSF could effectively screen patients with poor prognoses.


Asunto(s)
Carcinoma , Neoplasias de las Glándulas Salivales , Humanos , Femenino , Pronóstico , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/terapia , Factores de Riesgo , Glándulas Salivales
15.
Pediatr Res ; 94(2): 683-690, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36759750

RESUMEN

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.


Asunto(s)
Cardiomiopatías , Catarata , Humanos , Cardiomiopatías/genética , Pruebas Genéticas , Mutación , Catarata/genética , Catarata/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética
16.
Platelets ; 34(1): 2166677, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36719251

RESUMEN

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals.


What is the context?1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro.2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets.3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm).4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells.What is new?1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug.2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets.3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo.4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions.What is impact?The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.


Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Sistemas de Liberación de Medicamentos/métodos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Neoplasias/tratamiento farmacológico , Rayos Láser
17.
Proc Natl Acad Sci U S A ; 120(4): e2213727120, 2023 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-36656854

RESUMEN

The myophage possesses a contractile tail that penetrates its host cell envelope. Except for investigations on the bacteriophage T4 with a rather complicated structure, the assembly pattern and tail contraction mechanism of myophage remain largely unknown. Here, we present the fine structure of a freshwater Myoviridae cyanophage Pam3, which has an icosahedral capsid of ~680 Å in diameter, connected via a three-section neck to an 840-Å-long contractile tail, ending with a three-module baseplate composed of only six protein components. This simplified baseplate consists of a central hub-spike surrounded by six wedge heterotriplexes, to which twelve tail fibers are covalently attached via disulfide bonds in alternating upward and downward configurations. In vitro reduction assays revealed a putative redox-dependent mechanism of baseplate assembly and tail sheath contraction. These findings establish a minimal myophage that might become a user-friendly chassis phage in synthetic biology.


Asunto(s)
Myoviridae , Ensamble de Virus , Bacteriófago T4/química , Cápside , Proteínas de la Cápside/química , Microscopía por Crioelectrón , Myoviridae/química
18.
Chinese Journal of Oncology ; (12): 666-672, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1045804

RESUMEN

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 μmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

19.
Chinese Journal of Oncology ; (12): 666-672, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1046127

RESUMEN

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 μmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

20.
Front Neurol ; 14: 1308036, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38178887

RESUMEN

Background: Few studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h. Methods: This is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization. Results: In total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p = 0.007) were independent predictors of futile recanalization. Conclusion: Futile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO.

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