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1.
Front Immunol ; 15: 1450135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355236

RESUMO

Background: Cellular senescence (CS) is believed to be a major factor in the evolution of cancer. However, CS-related lncRNAs (CSRLs) involved in colon cancer regulation are not fully understood. Our goal was to create a novel CSRLs prognostic model for predicting prognosis and immunotherapy and exploring its potential molecular function in colon cancer. Methods: The mRNA sequencing data and relevant clinical information of GDC TCGA Colon Cancer (TCGA-COAD) were obtained from UCSC Xena platform, and CS-associated genes was acquired from the CellAge website. Pearson correlation analysis was used to identify CSRLs. Then we used Kaplan-Meier survival curve analysis and univariate Cox analysis to acquire prognostic CSRL. Next, we created a CSRLs prognostic model using LASSO and multivariate Cox analysis, and evaluated its prognostic power by Kaplan-Meier and ROC curve analysis. Besides, we explored the difference in tumor microenvironment, somatic mutation, immunotherapy, and drug sensitivity between high-risk and low-risk groups. Finally, we verified the functions of MYOSLID in cell experiments. Results: Three CSRLs (AC025165.1, LINC02257 and MYOSLID) were identified as prognostic CSRLs. The prognostic model exhibited a powerful predictive ability for overall survival and clinicopathological features in colon cancer. Moreover, there was a significant difference in the proportion of immune cells and the expression of immunosuppressive point biomarkers between the different groups. The high-risk group benefited from the chemotherapy drugs, such as Teniposide and Mitoxantrone. Finally, cell proliferation and CS were suppressed after MYOSLID knockdown. Conclusion: CSRLs are promising biomarkers to forecast survival and therapeutic responses in colon cancer patients. Furthermore, MYOSLID, one of 3-CSRLs in the prognostic model, could dramatically regulate the proliferation and CS of colon cancer.


Assuntos
Biomarcadores Tumorais , Senescência Celular , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Microambiente Tumoral , RNA Longo não Codificante/genética , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Humanos , Prognóstico , Senescência Celular/genética , Senescência Celular/imunologia , Biomarcadores Tumorais/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Feminino , Masculino , Pessoa de Meia-Idade , Linhagem Celular Tumoral
2.
Org Lett ; 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39446038

RESUMO

Here we report the modular synthesis of 1,5-disubstituted tetrazoles using two highly chemoselective reactions, ligations of N-fluorosulfurylamidines with amines and diazotransfer reactions between FSO2N3 and N-monosubstituted amidines, respectively. Enabled by sulfur(VI) fluoride exchange (SuFEx) click chemistry, we have successfully synthesized a series of N-fluorosulfurylamidines and identified them as stable and scalable organic synthons. We then discover that N-fluorosulfurylamidines react selectively toward a series of aliphatic amines, resulting in the formation of N-monosubstituted amidines that can react further with FSO2N3 to deliver 1,5-disubstituted tetrazoles. Our work provides a new platform for generating a library of 1,5-disubstituted tetrazoles with diverse structures, which is unprecedented.

3.
ACS Nano ; 18(42): 29261-29272, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39390635

RESUMO

Although quasi-two-dimensional (quasi-2D) perovskites are ideal material platforms for highly efficient linearly polarized electroluminescence owing to their anisotropic crystal structures, so far, there has been no practical implementation of these materials for the demonstration of linearly polarized perovskite light-emitting diodes (LP-PeLEDs). This scarcity is due to difficulty in orientation and phase distribution control of the quasi-2D perovskites while minimizing the defects, all of which are required to manifest aligned transition dipole moments (TDMs). To achieve this multifaceted goal, herein, we introduce a synergistic strategy to quasi-2D perovskites by incorporating both a trimethylolpropane triacrylate anchoring layer and 18-Crown-6 molecular passivator into the film fabrication process. It is found that the interfacial anchoring layer guides the oriented growth of perovskites along the (110) plane, whereas the molecular passivator reduces the number of defects and homogenizes the crystal phase. As a result, a quasi-2D perovskite film with macroscopically aligned TDM that renders high radiative recombination and the degree of linear polarization (DoLP) is constructed. This "coherence-programmed emission layer" demonstrates highly efficient LP-PeLEDs, not only achieving a maximum external quantum efficiency of ∼23.7%, a brightness of ∼36,142 cd/m2, and a DoLP of ∼38%, but also significantly improving the signal-to-interference-and-noise ratio in a multi-cell visible light communication system.

4.
Therap Adv Gastroenterol ; 17: 17562848241290685, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39421001

RESUMO

The prevalence of anxiety, depression, and other psychological comorbidities among patients with inflammatory bowel disease (IBD) significantly exceeds that of the general population. Moreover, a bidirectional relationship exists between psychological comorbidities and IBD. This intricate interplay has substantial clinical implications, impacting treatment adherence, therapeutic efficacy, and disease recurrence rates. In this review, we explore the multifaceted mechanisms through which psychological factors influence IBD progression, treatment response, and prognosis. Specifically, we delve into the involvement of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, enteric nervous system, microbiota-gut-brain axis, systemic inflammatory cytokines, and immune cell function. Additionally, we discuss the potential benefits of antidepressant therapy in mitigating IBD risk and the role of psychotropic drugs in reducing peripheral inflammation. Recognizing and addressing psychological comorbidity is pivotal in comprehensive IBD management. We advocate for the integration of biopsychosocial approaches into IBD treatment strategies, emphasizing the need for innovative psychological interventions as adjuncts to conventional therapies. Rigorous research investigating the impact of antidepressants and behavioral interventions on IBD-specific outcomes may herald a paradigm shift in IBD management.

5.
Nanomaterials (Basel) ; 14(19)2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39404318

RESUMO

Femtosecond-laser-fabricated black silicon has been widely used in the fields of solar cells, photodetectors, semiconductor devices, optical coatings, and quantum computing. However, the responsive spectral range limits its application in the near- to mid-infrared wavelengths. To further increase the optical responsivity in longer wavelengths, in this work, silicon (Si) was co-hyperdoped with nitrogen (N) and selenium (Se) through the deposition of Se films on Si followed by femtosecond (fs)-laser irradiation in an atmosphere of NF3. The optical and crystalline properties of the Si:N/Se were found to be influenced by the precursor Se film and laser fluence. The resulting photodetector, a product of this innovative approach, exhibited an impressive responsivity of 24.8 A/W at 840 nm and 19.8 A/W at 1060 nm, surpassing photodetectors made from Si:N, Si:S, and Si:S/Se (the latter two fabricated in SF6). These findings underscore the co-hyperdoping method's potential in significantly improving optoelectronic device performance.

6.
Biomed Pharmacother ; 180: 117486, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39321506

RESUMO

Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/ß-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs.

7.
Eur J Cardiothorac Surg ; 66(3)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39298445

RESUMO

OBJECTIVES: Despite excellent 5-year survival, there are limited data on the long-term prognostic characteristics of clinical stage IA part-solid lung adenocarcinoma. The objective was to elucidate the dynamics of prognostic characteristics through conditional survival analysis. METHODS: Consecutive patients who underwent complete resection for clinical stage IA part-solid lung adenocarcinoma between 2011 and 2015 were retrospectively reviewed. Conditional survival is defined as the probability of surviving further y years, conditional on the patient has already survived x years. The conditional recurrence-free survival (CRFS) and conditional overall survival (COS) were analysed to evaluate prognosis over time, with conditional Cox regression analysis performed to identify time-dependent prognostic factors. RESULTS: A total of 1539 patients were included with a median follow-up duration of 98.4 months, and 80 (5.2%) patients experienced recurrence. Among them, 20 (1.3%) recurrence cases occurred after 5 years of follow-up with 100% intrathoracic recurrence. The 5-year CRFS increased from 95.8% to 97.4%, while the 5-year COS maintained stable. Multivariable Cox analysis revealed that histologic subtype was always an independent prognostic factor for CRFS even after 5 years of follow-up, while the independent prognostic value of consolidation-to-tumour ratio, visceral pleural invasion and lymph node metastasis was observed only within 5 years. Besides, age, pathologic size and lymph node metastasis maintained independent predictive value for COS during long-term follow-up, while consolidation-to-tumour ratio was predictive for COS only within 5 years of follow-up. CONCLUSIONS: The independent prognostic factors for clinical stage IA part-solid lung adenocarcinoma changed over time, along with gradually increasing 5-year CRFS and stable 5-year COS.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Análise de Sobrevida , Recidiva Local de Neoplasia/epidemiologia , Adulto , Pneumonectomia , Seguimentos
8.
Appl Microbiol Biotechnol ; 108(1): 474, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320489

RESUMO

(R)-3-Isobutylglutarate monoamide (R-IBM) is a key intermediate in the synthesis of the analgesic drug pregabalin. Recently, the imidase BpIH derived from Burkholderia phytofirmans was identified as a promising catalyst for the industrial production of R-IBM. Notably, this catalyst has the distinct advantage of achieving a 100% theoretical yield from 3-isobutyl glutarimide (IBI). In this study, homology modeling and structure alignment techniques were used to determine the substrate binding pocket of BpIH. Semi-rational design was used to analyze the amino acid residue conservation in the binding pocket region of BpIH. Interestingly, mutations of several low-conserved amino acid located 6-9 Å from the substrate significantly enhanced the catalytic activity of BpIH. Among them, the triple mutant Y37FH133NS226I (YHS-I) showed approximately a fivefold increase in enzyme activity and a significantly improved catalytic efficiency (kcat/Km). Under the same reaction time and conditions, YHS-I successfully converted IBI into R-IBM with a conversion rate of 88.87%, with an enantiomeric excess (ee) of the product exceeding 99.9%. In comparison, wild-type BpIH had a conversion rate of only 38.15%. Molecular dynamics and docking results indicated that YHS-I had higher rigidity around the mutation sites. The synergistic substitutions of Y37F, H133N, and S226I altered the interaction network within the mutation site, enhancing the protein's affinity for the substrate and improving catalytic efficiency. KEY POINTS: • 100% theoretical yield of R-IBM by BpIH compared with 50% by resolution • Semi-rational design of BpIH based on conservativity with homologous enzymes • Mutant with enzyme activity of sixfold and product ee value of 99.9.


Assuntos
Burkholderia , Burkholderia/enzimologia , Burkholderia/genética , Cinética , Sítios de Ligação , Especificidade por Substrato , Modelos Moleculares , Glutaratos/metabolismo , Amidoidrolases
9.
Cell Mol Gastroenterol Hepatol ; : 101413, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39349246

RESUMO

Previously, eosinophils were primarily regarded as effector toxic cells involved in allergic diseases and parasitic infections. Nevertheless, new research has shown that eosinophils are diverse and essential for immune regulation and tissue homeostasis. Their functional plasticity has been observed in patients with inflammatory diseases, cancer, infections, and other disorders. Although eosinophils are infrequently observed within the liver during periods of homeostasis, they are recruited to the liver in various liver diseases, including liver parasitosis, acute liver injury, autoimmune liver disease, and hepatocellular carcinoma. Furthermore, eosinophils have demonstrated the capacity to promote liver regeneration. This article explores the multifaceted roles of eosinophils in liver diseases, aiming to provide insights that could lead to more effective clinical therapies for these conditions.

10.
Molecules ; 29(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39202828

RESUMO

The interfacial dilational rheology of silica nanoparticles (NPs) directly reflects the relationship between surface structure and interfacial behaviors in NPs, which has attracted significant attention in various industrial fields. In this work, modified silica nanoparticles (MNPs) with various alkyl chain lengths were synthesized and systematically characterized using Fourier transform infrared spectra, Zeta potential, and water contact angle measurements. It was found that the MNPs were successfully fabricated with similar degrees of modification. Subsequently, the interfacial behaviors of the MNPs in an n-octane/water system were investigated through interfacial dilational rheological experiments. The length of the modified alkyl chain dominated the hydrophilic-lipophile balance and the interfacial activity of the MNPs, evaluated by the equilibrium interfacial tension (IFT) variation and dilational elasticity modulus. In the large amplitude compression experiment, the balance between the electrostatic repulsion and interfacial activity in the MNPs was responsible for their ordered interfacial arrangement. The MNPs with the hexyl alkyl chain (M6C) presented the optimal amphipathy and could partly overcome the repulsion, causing a dramatic change in surface pressure. This was further confirmed by the variations in IFT and dilational elasticity during the compression path. The study provides novel insights into the interfacial rheology and interactions of functionally modified NPs.

11.
ACS Appl Mater Interfaces ; 16(35): 46090-46101, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39174346

RESUMO

Epigallocatechin gallate (EGCG)-based nanosystems have garnered significant attention for their ability to alleviate inflammation due to their excellent anti-inflammatory properties and enhanced drug delivery capabilities. However, the degradation of EGCG in strongly acidic environments poses a challenge for potential administration, particularly in oral formulations, where gastric resistance is essential. In this study, we develop a "disintegration and reorganization" strategy to create acid-resistant antioxidant nanoparticles (EGA NPs) based on EGCG and 5-aminosalicylic acid (5-ASA) for mitigating inflammation in colitis and acute kidney injury. At acidic pH, the ester bond in EGCG breaks down, producing two building blocks. These, together with 5-ASA and formaldehyde, form oligomers through a combination of phenol-aldehyde condensation and the Mannich reaction. The resulting oligomers self-assemble into EGA NPs, which exhibit significant stability under both acidic and neutral pH conditions. This stability makes them suitable for oral administration, allowing them to withstand harsh gastric conditions, as well as for intravenous injection. Importantly, these oligomers retain the antioxidant and anti-inflammatory properties of EGCG, effectively scavenging reactive oxygen species and reducing intracellular oxidative stress. Additionally, EGA shows potential as a drug carrier, efficiently loading the anti-inflammatory agent curcumin (Cur) to form Cur@EGA NPs. In vivo studies demonstrate the efficacy of Cur@EGA and EGA in alleviating acute colitis and kidney injury following oral and intravenous administration, respectively. These nanoparticulate formulations exhibit superior inflammation reduction compared to free Cur in vivo. Overall, our findings introduce a novel acid-resistant nanoplatform based on EGCG for the treatment of acute inflammation.


Assuntos
Injúria Renal Aguda , Antioxidantes , Catequina , Nanopartículas , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Camundongos , Nanopartículas/química , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Colite/tratamento farmacológico , Colite/patologia , Inflamação/tratamento farmacológico , Concentração de Íons de Hidrogênio , Mesalamina/química , Mesalamina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Masculino , Portadores de Fármacos/química , Humanos
12.
J Biochem Mol Toxicol ; 38(9): e23809, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39148263

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is an alarming ailment that leads to severe liver damage and increases the risk of serious health conditions. The prevalence of NAFLD due to oxidative stress could be mitigated by plant-derived antioxidants. This study aims to investigate the effects of syringic acid (SA) on NAFLD in a high-fat diet (HFD) rat model. Twenty-four rats were randomly divided into four groups (n = 6): normal control, HFD, SA-administered HFD, and positive control SA on a normal diet. Rats in the normal control and positive control groups received a normal diet, and the remaining groups received an HFD for 8 weeks. SA (20 mg/kg b.w.) was orally (gavage) administered for 8 weeks. Lipid profiles were controlled by SA against HFD-fed rats (p < 0.05). SA reduced the serum aspartate aminotransferase and alanine aminotransferase levels by 70%-190%. SA also suppressed pro-inflammatory cytokines and attenuated histopathological and immunohistochemical changes against HFD-fed rats. SA reversed oxidative stress by suppressing the malondialdehyde formation by 82% and replenished the nonenzymatic and enzymatic antioxidant activities (p < 0.05). Gene expressions of nuclear factor-erythroid 2-related factor/heme oxygenase 1 (Nrf2/HO-1) were elevated in SA-treated rats. Ameliorative effects of SA on NAFLD induced by an HFD in rats were prominent through the reversal of oxidative stress and inflammation, regulated by an intrinsic mechanism of defense against oxidative stress, the Nrf2/HO-1 pathway.


Assuntos
Ácido Gálico , Heme Oxigenase (Desciclizante) , Fator 2 Relacionado a NF-E2 , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ratos , Masculino , Transdução de Sinais/efeitos dos fármacos , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia
13.
Hepatol Commun ; 8(8)2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39101776

RESUMO

BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.


Assuntos
Armadilhas Extracelulares , Fígado , Trombose , Armadilhas Extracelulares/metabolismo , Animais , Camundongos , Fígado/patologia , Fígado/metabolismo , Trombose/etiologia , Trombose/patologia , Colestase/patologia , Colestase/complicações , Modelos Animais de Doenças , Masculino , Tromboplastina/metabolismo , Trombofilia/etiologia , Trombofilia/sangue , Fibrina/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Humanos , Infiltração de Neutrófilos , Fator Xa/metabolismo , Trombina/metabolismo
14.
J Sports Sci ; 42(14): 1313-1322, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39133765

RESUMO

This review aims to investigate the dose-response relationship between walking speed and all-cause mortality. PubMed, Web of Science, Embase and Cochrane Library were searched to September, 2023 for cohort studies. A meta-analysis estimated the overall hazard ratio (HR) of mortality incidence and 95% Confidence Interval (CI) for individuals with the fastest walking speed compared to those with the slowest walking speed. Subgroup analyses were conducted based on sex, age and speed-measuring methods. Dose-response meta-analyses were examined by using "mvmeta" packages available in STATA. A total of 13 studies involving 530,841 participants were included. Of these, 11 studies provided data for dose-response meta-analyses. Individuals in the fastest walking-speed category had a 43% lower risk of all-cause mortality compared to those in the slowest walking-speed category (HR = 0.57, 95% CI 0.48-0.66). There was an inverse linear dose-response relationship between walking speed and all-cause mortality; for every 0.1 m/s increment in walking speed, the risk of mortality decreased by 6% (HR = 0.94; 0.92-0.96). There was an inverse nonlinear dose-response relationship between them when participants' age was larger than 65 years, but linear dose-response relationships were detected in both the timed walking speed test and self-reported walking speed measurements.


Assuntos
Mortalidade , Velocidade de Caminhada , Humanos , Velocidade de Caminhada/fisiologia , Fatores Etários , Causas de Morte , Modelos de Riscos Proporcionais , Fatores de Risco , Caminhada/fisiologia
15.
NPJ Vaccines ; 9(1): 130, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033177

RESUMO

Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus's glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I-VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.

16.
Int J Surg ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963751

RESUMO

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

17.
Sci Rep ; 14(1): 15389, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965256

RESUMO

The objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children's Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.


Assuntos
Hérnia Inguinal , Herniorrafia , Laparoscopia , Humanos , Hérnia Inguinal/cirurgia , Masculino , Laparoscopia/métodos , Feminino , Estudos Retrospectivos , Pré-Escolar , Criança , Herniorrafia/métodos , Herniorrafia/instrumentação , Agulhas , Lactente , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
18.
J Cardiothorac Surg ; 19(1): 458, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026210

RESUMO

Mediastinal myelolipoma is a rare condition and has no obvious symptoms. In the past 20 years, some clinical cases have been documented. However, the literature has not systematically summarized its imaging features. The aim of this paper is to present a case of right posterior mediastinal myelolipoma and to review and summarize its imaging features. Twenty-six articles were included in our study, which included a total of 26 patients and 33 lesions; 90.9% of the lesions were located in the mediastinum at the level from the 8th thoracic vertebral body to the thoracic 12th vertebral body. Among the cases with unilateral mediastinum, 68.4% of the cases were located in the right posterior mediastinum. Bilateral lesions accounted for almost one-fourth of all lesions. After contrast medium was injected, 93.9% of the lesions had mild to moderate enhancement; 84.8% of the lesions contained fat density; and 75.8%, 69.7%, 87.9%, and 75.8% of the lesions showed clear boundary, regular shape, heterogeneity and were encapsulated, respectively. Only 12.1% of the lesions contained calcification. An inhomogeneous mass in the right posterior mediastinum near the spine, including fat density, is the predominant imaging marker of most mediastinal myelolipomas.


Assuntos
Neoplasias do Mediastino , Mielolipoma , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias do Mediastino/diagnóstico por imagem , Mielolipoma/diagnóstico por imagem , Mielolipoma/cirurgia , Mielolipoma/patologia , Tomografia Computadorizada por Raios X
19.
Cell Host Microbe ; 32(8): 1331-1346.e6, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-38959900

RESUMO

The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15). FGF15 promotes hepatocyte expression of ornithine aminotransferase (OAT), which facilitates the metabolism of accumulated ornithine in the liver into glutamate, thereby providing sufficient glutamate for ammonia detoxification via the glutamine synthesis pathway. Collectively, these findings uncover a potential therapeutic strategy for ALD involving dietary fiber supplementation and B. acidifaciens.


Assuntos
Amônia , Bacteroides , Fibras na Dieta , Fatores de Crescimento de Fibroblastos , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Animais , Bacteroides/metabolismo , Camundongos , Fibras na Dieta/metabolismo , Amônia/metabolismo , Microbioma Gastrointestinal/fisiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/microbiologia , Masculino , Fígado/metabolismo , Hepatócitos/metabolismo , Ácidos e Sais Biliares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Humanos , Inativação Metabólica , Amidoidrolases
20.
Clin Res Hepatol Gastroenterol ; 48(7): 102410, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38950678

RESUMO

BACKGROUND: Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis. OBJECTIVE: The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation. METHODS: The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed. RESULTS: Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota. CONCLUSION: These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission.


Assuntos
Constipação Intestinal , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Loperamida , Ratos Sprague-Dawley , Constipação Intestinal/tratamento farmacológico , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Eixo Encéfalo-Intestino/efeitos dos fármacos , Neurotransmissores/metabolismo , Trânsito Gastrointestinal/efeitos dos fármacos , Antidiarreicos/farmacologia , Modelos Animais de Doenças , Serotonina/metabolismo , Serotonina/sangue , Disbiose/tratamento farmacológico
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