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1.
Artigo em Inglês | MEDLINE | ID: mdl-39324380

RESUMO

The inflammatory cytokine resistin, which is encoded by the RETN gene, plays a variety of roles in cancer. This study aimed to assess the relationship between RETN gene expression and cancer stage, survival prognosis, immune infiltration, and drug sensitivity, and whether the rs3219175 G > A polymorphism affected the expression of the RETN gene and cancer risk. The clinical significance of RETN gene expression and the rs3219175 polymorphism in cancer was analyzed by the GSCA platform, GTEx database and STATA software. The results showed that RETN gene expression was associated with the stage of thyroid carcinoma, survival prognosis and immune infiltration of certain cancers, and sensitivity to multiple drugs. The rs3219175 polymorphism could influence the expression of the RETN gene in a wide range of tissues. Furthermore, RETN gene rs3219175 polymorphism was significantly associated with cancer risk [GA vs. GG: OR = 2.27, 95%CI = 1.26-4.09; (GA + AA) vs. GG: OR = 2.23, 95%CI = 1.28-3.88; A vs. G: OR = 1.72, 95%CI = 1.15-2.58]. In conclusion, the current study suggested that resistin might serve as a prognostic marker and therapeutic target for certain cancers, and the rs3219175 polymorphism might be used as a marker for predicting cancer risk.

2.
Acta Biomater ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299624

RESUMO

Root caries is the main cause of oral pain and tooth loss in the elderly. Protecting root lesions from environmental disturbances, resisting pathogens, and facilitating remineralization over time are essential for addressing root caries, but are challenging due to the irregular root surface and the complex oral environment. Hagfish secretes slime when facing danger, which converts into gels upon contact with seawater, suffocating the predators. Inspired by hagfish's defense mechanism, a fluid-hydrogel conversion strategy is proposed to establish a mechanical self-regulating multifunctional platform for root caries treatment. The fluid system (silk fibroin-tannic acid-black phosphorene-urea, ST-BP-U), in which urea disrupts the hydrogen bonds between silk fibroin and tannic acid, can easily spread on the irregular root surface and permeate into dentinal tubules. Upon contact with the surrounding water, urea diffuses, prompting the hydrogel re-formation and creating intimate attachments with micromechanical inlay locks. Meanwhile, BP increases the crosslinking of the re-formed hydrogel network, resulting in reinforced cohesion for robust wet adhesion to the tooth root. This process establishes a structured platform for effective antimicrobial phototherapy and dentin remineralization promotion. This water-responsive fluid-hydrogel conversion system adapts to the irregular root surface in the dynamic wet environment, holding promise for addressing root caries. STATEMENT OF SIGNIFICANCE: Root caries bring a heavy burden to the aging society, but the irregular root surface and dynamic moist oral environment always hinder non-surgical therapeutic effects. Here, we propose a water-responsive fluid-hydrogel conversion strategy aimed at mechanical self-regulation on the irregular and wet root interface to construct a functional structural platform. The liquid system (ST-BP-U) that prebreak intermolecular hydrogen bonds can easily spread on irregular surfaces and dentin tubules. When encountering water, hydrogen bonds re-form, and BP increases the crosslinking of the hydrogel formed in situ. Based on this firm wet-adhesion platform, it provides powerful phototherapy effects and promotes dentin remineralization. This fluid-hydrogel conversion system turns the disadvantages of wet environment into advantages, offering a promising strategy for root caries.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39319421

RESUMO

Photothermal therapy (PTT) encounters challenges of rapid thermal loss and potential tissue damage. In response, we propose a Heat-Boost and Lock implant coating strategy inspired by the thermal adaptation of biological membranes, enabling precise local photothermal utilization. This coating incorporates a poly(tannic acid) (pTA) bridging layer on implants, facilitating stable layer-by-layer integration of a black phosphorus (BP) photothermal layer and a top cell membrane Heat-Boost and Lock layer. The cell membrane layer significantly curtails photothermal loss (extending the heat retention by 17.62%) and stores energy within its phospholipid bilayer, boosting photothermal effects near implants (achieving a temperature increasement of 275%). Theoretical analysis indicates that these local heat preservation properties of the cell membrane arise from its low thermal conductivity and phase-change properties. In a Staphylococcus aureus-infected bone implant model, our coating demonstrates precise antibacterial action around implants (reach an antibacterial ratio of 99.52%). The synergetic locking function of cell membrane and pTA delays BP biodegradation, ensuring favorable photothermal stability and long-term osteo-inductive performance (increasing the bone volume fraction by 53.45%). Beyond providing an endogenic biointerface, this strategy extends the application of cell membrane in local thermal management, offering possibilities for effective and safe PTT modalities.

4.
Adv Mater ; : e2405953, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101293

RESUMO

Implant-associated infections (IAIs) are the main cause of prosthetic implant failure. Bacterial biofilms prevent antibiotic penetration, and the unique metabolic conditions in hypoxic biofilm microenvironment may limit the efficacy of conventional antibiotic treatment. Escaping survival bacteria may not be continually eradicated, resulting in the recurrence of IAIs. Herein, a sonosensitive metal-organic framework of Cu-TCPP (tetrakis(4-carboxyphenyl) porphyrin) nanosheets and tinidazole doped probiotic-derived membrane vesicles (OMVs) with high-penetration sonodynamic therapy (SDT), bacterial metabolic state interference, and bacterial cuproptosis-like death to eradicate IAIs is proposed. The Cu-TCPP can convert O2 to toxic 1O2 through SDT in the normoxic conditions, enhancing the hypoxic microenvironment and activating the antibacterial activity of tinidazole. The released Cu(II) under ultrasound can be converted to Cu(I) by exogenous poly(tannic acid) (pTA) and endogenous glutathione. The disruption of the bacterial membrane by SDT can enhance the Cu(I) transporter activity. Transcriptomics indicate that the SDT-enhanced Cu(I) overload and hypoxia-activated therapy hinder the tricarboxylic acid cycle (TCA), leading to bacterial cuproptosis-like death. Moreover, the OMVs-activated therapy can polarize macrophages to a M2-like phenotype and facilitate bone repair. The sonodynamic biofilm microenvironment modulation strategy, whereby the hypoxia-enhanced microenvironment is potentiated to synergize SDT with OMVs-activated therapy, provides an effective strategy for antibacterial and osteogenesis performance.

5.
Adv Sci (Weinh) ; : e2405764, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166390

RESUMO

In treating infectious diseases, achieving selective bacterial inhibition is crucial for preserving the microecological equilibrium. The current approaches predominantly rely on synthetic materials tailored to specific bacteria, considering their cell walls or oxygen requirements. Herein, inspired by intricate bacterial communication, a natural implant is proposed coating utilizing bacterial outer membrane vesicles (OMVs), essential components in bacterial signaling, integrated onto diverse implant surfaces through a universal poly (tannic acid) bridging layer. This coating is homogenous and stable, unexpectedly promoting the proliferation of parental bacteria while inhibiting heterologous bacteria both in vitro and in vivo. Through high-throughput sequencing and bioinformatics analysis, the selective bacteriostatic ability arises from OMVs, upregulating anti-oxidative stress genes in heterologous bacteria and activating biofilm-related genes in parental bacteria. This study positions OMVs as an appealing biomaterial for selective bacterial inhibition through a biological approach, showcasing their potential in regulating the microecological balance through a natural interface modification strategy.

6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 488-493, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38952087

RESUMO

Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis. Methods Gene expression datasets from GEO (GSE30528, GSE30529) and RNA sequencing (RNA-seq) data from the Karolinska Kidney Research Center were used. Gene set enrichment analysis (GSEA) was conducted to examine differences in immune-related gene expression in the glomeruli and tubules (DKD) patients. To identify immune-related genes (IRGs) and TFs, differential expression analysis was carried out using the Limma and DESeq2 software packages. Key immune-related TFs were pinpointed through co-expression analysis. The interaction network between TFs and IRGs was constructed using the STRING database and Cytoscape software. Furthermore, the Nephroseq database was employed to investigate the correlation between the identified TFs and clinical-pathological features. Results When compared to normal control tissues, significant differences in the expression of immune genes were observed in both the glomeruli and tubules of individuals with Diabetic Kidney Disease (DKD). Through differential and co-expression analysis, 50 immune genes and 9 immune-related transcription factors (TFs) were identified in the glomeruli. In contrast, 131 immune response genes (IRGs) and 41 immune-related TFs were discovered in the renal tubules. The protein-protein interaction (PPI) network highlighted four key immune-related TFs for the glomeruli: Interferon regulatory factor 8 (IRF8), lactotransferrin (LTF), CCAAT/enhancer binding protein alpha (CEBPA), and Runt-related transcription factor 3 (RUNX3). For the renal tubules, the key immune-related TFs were FBJ murine osteosarcoma viral oncogene homolog B (FOSB), nuclear receptor subfamily 4 group A member 1 (NR4A1), IRF8, and signal transducer and activator of transcription 1 (STAT1). These identified TFs demonstrated a significant correlation with the glomerular filtration rate (GFR), highlighting their potential importance in the pathology of DKD. Conclusion Bioinformatics analysis identifies potential genes associated with DKD pathogenesis and immune dysregulation. Further validation of the expression and function of these genes may contribute to immune-based therapeutic research for DKD.


Assuntos
Biologia Computacional , Nefropatias Diabéticas , Fatores de Transcrição , Humanos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/metabolismo , Fatores de Transcrição/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Glomérulos Renais/imunologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Redes Reguladoras de Genes , Túbulos Renais/imunologia , Túbulos Renais/metabolismo
7.
Mater Horiz ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990315

RESUMO

Photothermal therapy (PTT) encounters challenges in addressing deep tissue infections, characterized by limited penetration or potential hyperthermal damage to surrounding tissues, initiating undesirable inflammatory cascades. Inspired by polar bear thermal regulation, we present a "bio-based endogenic thermal-adaptive booster" implant coating. This coating integrates a photothermal poly(tannic acid) (pTA) layer, mimicking the "polar bear dark skin", securely linked with anti-inflammatory dexamethasone (Dex), resembling the "secretion", and a red blood cell membrane (RBCM) layer, forming the insulating "transparent fur". The RBCM "fur" demonstrates unexpectedly superior local heat storage, amplifying the photothermal effect of the pTA "skin" by 1.30 times and boosting localized photothermal antibacterial efficiency by 1.30-fold (approximately 99%) compared to those without RBCM. Furthermore, RBCM sustains Dex release and offers additional protection against thermal inflammation, releasing Dex 1.90 times more under NIR irradiation than under non-photothermal conditions. In a rat infectious bone model, the photothermal-boosting implant coating provides a favorable biological interface and achieves a 99.97% photothermal antibacterial ratio, enhancing osseointegration without evident tissue harm, evidenced by a 2.47-fold increase in bone volume fraction and a 2.24-fold reduction in pro-inflammatory cytokines compared to those lacking a RBCM. Insights derived from cell membrane-based thermal-adaptive coatings herald a paradigm shift in efficient and safe PTT.

8.
World J Clin Cases ; 12(21): 4469-4475, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070822

RESUMO

BACKGROUND: Respiratory viruses are increasingly detected in children with community-acquired pneumonia. Further strategies to limit antibiotic use in children with viral pneumonia are warranted. AIM: To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production. METHODS: A total of 60 children with viral pneumonia were recruited: 30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment. Outcome measures included peripheral blood levels of inflammatory cytokines, CD4+, CD8+, Th1, Th2, Th17 and Treg, clinical efficacy, and incidence of adverse reactions. RESULTS: Compared with the control group, the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment. Compared with the control group, the observation group showed a significant increase in CD4+/CD8+ and Th1/Th2 levels, and a decrease in Th17/Treg levels after treatment. The total effective rates in the observation group and the control group were 93.75% and 85.00%, respectively, which was a significant difference (P = 0.003). CONCLUSION: Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children. The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.

9.
Nanoscale ; 16(31): 14734-14747, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39046363

RESUMO

Conventional nanomedicines typically employ a significant amount of excipients as carriers for therapeutic delivery, resulting in generally low drug-loading and compromised anti-cancer efficacy. Here, we propose a small-molecule nanomedicine (CMC NP) directly assembled using a chemotherapeutic drug (chlorambucil, CBL) and a phototherapeutic agent (chlorin e6, Ce6), and stabilized by metal coordination. The CMC NP exhibits exceptionally high drug loading (89.21%), robust stability, and smart disassembly in response to glutathione (GSH). Such a straightforward yet multifunctional delivery strategy could be a better alternative to overcome the above shortcomings of conventional nanomedicines while achieving enhanced efficacy. The CMC NP not only directly induces CBL-induced chemotherapy but also elicits synergistic antitumor responses through Ce6-mediated photodynamic and photothermal therapies. Owing to the multifaceted efforts from photodynamic, photothermal and chemo-therapies, the CMC NP exhibits excellent antitumor efficacy with negligible systemic toxicity which is untenable in traditional CBL-induced chemotherapy. Therefore, this study provides a feasible strategy for overcoming existing challenges and presents a potential opportunity to augment the clinical therapeutic effectiveness associated with conventional nanomedicine.


Assuntos
Clorambucila , Clorofilídeos , Nanomedicina , Fotoquimioterapia , Humanos , Animais , Camundongos , Clorambucila/química , Clorambucila/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Glutationa/química , Glutationa/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C
10.
Water Res ; 262: 122123, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39067271

RESUMO

Identifying the sources and cycling of phosphorus (P) is particularly important for formulating effective P management strategies in inland water. The oxygen isotopic compositions of phosphate (δ18OP) are recognized as a promising tool to solve this problem. However, the application of δ18OP in freshwater sediment is currently constrained by multiple difficulties. In this study, we presented a novel pretreatment method for δ18OP analysis of sediment inorganic P pools. Our results showed that the new method has advantages of simple operation, less time-consuming, and high P recovery rates. Specifically, we replaced the traditional Mg-induced co-precipitation (MAGIC) method by introducing Zr-Oxides gels with high selective adsorption function for phosphate. This made subsequent processing simpler and reduced the time consumption to ∼10 days, and the range of P recovery rates were from 88 % to 104 %. Furthermore, we emphasized the necessity of vacuum roasting following lyophilized Ag3PO4 to eliminate residual oxygen-containing impurities (e.g., NO3-, Ag2O, and organic matter). Additionally, evidences from microscopy and spectroscopy confirmed that this method ultimately yielded high-purity Ag3PO4 with the Ag:P molar ratios of 3.35:1. Importantly, combining direct synthesis Ag3PO4 between KH2PO4 and AgNO3 with the Ag3PO4 obtained by the method revealed no stark oxygen isotopic fractionation of phosphate during the pretreatment processes. The newly established δ18OP pretreatment methods here can also be extended to broader studies of the biogeochemical cycling of P in aquatic ecosystems, potentially advancing the understanding of the global P cycle.


Assuntos
Água Doce , Sedimentos Geológicos , Isótopos de Oxigênio , Fósforo , Sedimentos Geológicos/química , Água Doce/química , Fosfatos/química
11.
J Infect Dev Ctries ; 18(5): 687-693, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38865397

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) spread rapidly in Shanghai in February 2022. Patients with asymptomatic and mild symptoms were admitted to Fangcang shelter hospitals for centralized quarantine. METHODOLOGY: A total of 5,217 non-severe patients hospitalized in the Longyao Fangcang and Shilong Fangcang hospitals were included in the study. Demographic and clinical characteristics, comorbidity, exposure history, treatment and disease duration were analyzed. Univariate analysis and binomial logistic regression analysis were performed to identify the factors influencing nucleic acid change from positive to negative over 14 days. RESULTS: Consecutive positive nucleic acid test results (days) were significantly associated with advanced age (OR = 1.343, 95% CI 1.143 to 1.578, p < 0.001), smoking (OR = 0.510, 95% CI 0.327 to 0.796, p = 0.003) and vaccination (OR = 0.728, 95% CI 0.641 to 0.827, p < 0.001). However, there was no significant difference between asymptomatic and mild symptomatic patients (p = 0.187). In univariate analysis, comorbidities including diabetes, hypertension, cardiovascular system, malignant tumors, autoimmune diseases and cerebral apoplexy were associated with consecutive positive nucleic acid test results, but there was no significant difference in binomial logistics regression analysis. CONCLUSIONS: Aging and comorbid conditions lead to the prolongation of positive nucleic acid test results for several days. Improving vaccination coverage is beneficial for prevention and control of the epidemic. The management and treatment methods of Shanghai Fangcang shelter hospitals had important referential significance, which can provide valuable guidance for the prevention and control of the COVID-19 epidemic in the future.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , China/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Adulto , Idoso , SARS-CoV-2/genética , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Comorbidade , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Hospitais/estatística & dados numéricos
12.
Reprod Domest Anim ; 59(5): e14583, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747479

RESUMO

Testosterone, an important sex hormone, regulates sexual maturation, testicular development, spermatogenesis and the maintenance of secondary sexual characteristics in males. Testicular Leydig cells are the primary source of testosterone production in the body. Hezuo pigs, native to the southern part of Gansu, China, are characterized by early sexual maturity, strong disease resistance and roughage tolerance. This study employed type IV collagenase digestion combined with cell sieve filtration to isolate and purify Leydig cells from the testicular tissue of 1-month-old Hezuo pigs. We also preliminarily investigated the functions of these cells. The results indicated that the purity of the isolated and purified Leydig cells was as high as 95%. Immunofluorescence analysis demonstrated that the isolated cells specifically expressed the 3ß-hydroxysteroid dehydrogenase antibody. Enzyme-linked immunosorbent assay results showed that the testosterone secretion of the Leydig cells cultured in vitro (generations 5-9) ranged between 1.29-1.67 ng/mL. Additionally, the content of the cellular autophagy signature protein microtubule-associated protein 1 light chain 3 was measured at 230-280 pg/mL. Through this study, we established an in vitro system for the isolation, purification and characterization of testicular Leydig cells from 1-month-old Hezuo pigs, providing a reference for exploring the molecular mechanism behind precocious puberty in Hezuo pigs.


Assuntos
Células Intersticiais do Testículo , Testosterona , Animais , Masculino , Células Intersticiais do Testículo/metabolismo , Testosterona/metabolismo , Suínos , Testículo/citologia , Células Cultivadas , Técnicas de Cultura de Células/veterinária , Separação Celular/métodos , Separação Celular/veterinária
13.
Small ; : e2311967, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712482

RESUMO

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

14.
Front Microbiol ; 15: 1360505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725683

RESUMO

Introduction: Utilizing roughage resources is an effective approach to alleviate the shortage of corn-soybean feed and reducing the costs in the swine industry. Hezuo pig is one group of plateau type local Tibetan pig with strong tolerance to crude feeding. Nevertheless, current research on the roughage tolerance in Hezuo pigs and the microbiological mechanisms behind it is still minimally.This study explored the impact of various ratios of whole-plant silage (WPS) maize on the pH, cellulase activity, short-chain fatty acids (SCFAs), and intestinal microbiota in Hezuo pigs. Methods: Thirty-two Hezuo pigs were randomly divided into four groups (n = 8). The control group received a basal diet, while experimental groups I, II, and III were given diets with incremental additions of 5%, 10%, and 15% air-dried WPS maize, respectively, for 120 days. Results: The findings revealed that compared with the control group, in Group II, the pH of cecum and colon were notably decreased (p < 0.05), while acid detergent fiberdigestibility, the concentration of propionic and isobutyric acid in the cecum, and the concentration of isobutyric acid in the colon were significantly increased (p < 0.05). Also, carboxymethyl cellulase activity in the cecum in group II of Hezuo pigs was significantly higher than that in the other three groups (p < 0.05). Furthermore, the cecum microbiota showed a higher diversity in the group II of Hezuo pigs than that in the control group, as shown by the Simpson and Shannon indices. Specifically, 15 and 24 bacterial species showed a significant difference in relative abundance at the family and genus levels, respectively. Correlation analyses revealed significant associations between bacterial genera and SCFAs concentrations in the cecum. The abundance of Bacteroides and NK4A214_group was positively correlated with amounts of valeric and isovaleric acid but negatively with propionic acid (p < 0.05). The abundance of UCG-010 was positively linked with acetic acid and negatively correlated with butyric acid (p < 0.05). Actinobacillus abundance was positively associated with butyric acid levels (p < 0.05). Discussion: In conclusion, a 10% WPS maize diet improved crude fiber digestibility by lowering cecal and colonic chyme pH, enhancing intestinal cellulase activity, improving SCFA production, and increasing intestinal microbiota diversity.

15.
Front Bioeng Biotechnol ; 12: 1357686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38600946

RESUMO

Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/- mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/- mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/- female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/- murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/- mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/- mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/- mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.

16.
Small ; 20(24): e2307628, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38191883

RESUMO

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.


Assuntos
Ligação de Hidrogênio , Úlcera Gástrica , Animais , Úlcera Gástrica/tratamento farmacológico , Injeções , Adesivos Teciduais/química , Adesivos/química , Fibroínas/química , Taninos/química , Ratos Sprague-Dawley
17.
Am Surg ; 90(6): 1240-1249, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38214585

RESUMO

PURPOSE: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. CONCLUSION: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Valor Preditivo dos Testes , Imuno-Histoquímica
18.
J Mater Chem B ; 12(4): 842-871, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38173410

RESUMO

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.


Assuntos
Materiais Biocompatíveis , Osteogênese , Materiais Biocompatíveis/uso terapêutico , Regeneração Óssea , Osso e Ossos
19.
BMC Anesthesiol ; 24(1): 20, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200438

RESUMO

BACKGROUND: Postpartum depression (PPD) is a common mental disease in postpartum women, which has received more and more attention in society. Ketamine has been confirmed for its rapid antidepressant effect in women with PPD. We speculate that esketamine, an enantiomer of ketamine, pretreatment during cesarean can also reduce the incidence of PPD. METHODS: All the parturients enrolled in the study were randomly assigned to two groups: the esktamine group (0.2 mg/kg esketamine) and the control group (a same volume of saline). All the drugs were pumped for 40 min started from the beginning of the surgery. The Amsterdam Anxiety and Information Scale (APAIS) scores before the surgery, the Edinburgh postnatal depression scale (EPDS) scores at 4 d and 42 d after surgery, the Pain Numerical Rating Scale (NRS) scores at 6 h, 12 h, 24 h and 48 h post-operation were evaluated, as well as the adverse reactions were recorded. RESULTS: A total of 319 parturients were analyzed in the study. The incidence of PPD (EPDS score > 9) in the esketamine group was lower than the control group at 4 days after surgery (13.8% vs 23.1%, P = 0.0430) but not 42 days after surgery (P = 0.0987). Esketamine 0.2 mg/kg could reduce the NRS score at 6 h,12 h and 24 h after surgery, as well as the use of vasoactive drugs during surgery (P < 0.05). The incidences of maternal dizziness (17.0%), blurred vision (5%), illusion (3.8%) and drowsiness (3.8%) in the esketamine group were higher than those of control group (P < 0.05). CONCLUSIONS: Intraoperative injection of esketamine (0.2 mg/kg) prevented the occurrence of depression (EPDS score > 9) at 4 days after delivery but not 42 days. Esketamine reduced the NRS scores at 6 h, 12 h and 24 h after surgery, but the occurrence of maternal side effects such as dizziness, blurred vision, drowsiness and hallucination were increased. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2100053422) on 20/11/2021.


Assuntos
Depressão Pós-Parto , Ketamina , Gravidez , Humanos , Feminino , Ketamina/uso terapêutico , Cesárea , Incidência , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Tontura
20.
Chemosphere ; 351: 141207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266877

RESUMO

In this study, a vitamin C-regulated CoAl-layered double hydroxide with abundant oxygen vacancies was synthesized via a simple hydrothermal process. The resulting CoAl-layered double hydroxide was employed to activate peroxydisulfate for removal of sulfamethoxazole. The effect of the experimental parameters such as pH, catalyst dose and peroxydisulfate concentration on sulfamethoxazole removal was investigated. The current system exhibited excellent catalytic performance for sulfamethoxazole removal in a broad pH range (i.e., pH 3.0-11.0). Under the optimized condition, 94.2% of sulfamethoxazole was degraded within 15 min, accompanied by a 67.6% reduction in chemical oxygen demand. The effective sulfamethoxazole degradation could be attributed to four pathways. Firstly, the ≡ Co2+ in catalyst reacted with peroxydisulfate to generate reactive species, including SO4•-, •OH, O2•- and 1O2, which could degrade sulfamethoxazole. Secondly, the oxygen vacancies could modulate intrinsic electrons, resulted in the surface activation of catalyst and accelerated charge transfer, which was favorable for the degradation of sulfamethoxazole. Thirdly, the presence of vitamin C not only promoted the formation of oxygen vacancies but also expanded the interlayer spacing of layered double hydroxide. A large interlayer spacing facilitated the diffusion of peroxydisulfate and pollutants in the interlayer and improved the utilization efficiency of the active site. Lastly, the high-valent cobalt species exhibited excellent oxidation ability and enhanced the catalyst performance through continuously being employed as an electron acceptor. This study provided a valuable insight for the design and application of Co-based catalysts in peroxydisulfate-based advanced oxidation processes.


Assuntos
Oxigênio , Sulfametoxazol , Sulfametoxazol/química , Oxigênio/química , Cobalto/química , Ácido Ascórbico , Carvão Mineral , Hidróxidos/química , Vitaminas
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