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1.
J Hosp Infect ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964506

RESUMO

INTRODUCTION: Surgical site infections are significant postoperative risks, antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class Ⅲ wounds, as there is currently a lack of evidence in the existing literature. METHODS: A multicenter randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China. 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. RESULTS: A total of 440 participants (median [IQR] age, 63.0 [54.0, 70.0] years; 282 males [64.09%]; 437 patients were of Han race [99.32%]) were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 [14.49%] vs 52 [23.01%]; risk difference, 1.76%, 95%CI, 1.08% to 2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 [5.61%] vs 31 [13.37%]; risk difference,2.68%; 95%CI,1.34%to5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). CONCLUSION: The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole as a valuable prophylactic antibiotic. Our findings provided valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.

2.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167299, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878833

RESUMO

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

3.
Biomater Res ; 28: 0031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38845842

RESUMO

The abdominal wall plays a crucial role in safeguarding the internal organs of the body, serving as an essential protective barrier. Defects in the abdominal wall are common due to surgery, infection, or trauma. Complex defects have limited self-healing capacity and require external intervention. Traditional treatments have drawbacks, and biomaterials have not fully achieved the desired outcomes. Hydrogel has emerged as a promising strategy that is extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to its unique properties. This review summarizes the five prominent properties and advances in using hydrogels to enhance the healing and repair of abdominal wall defects: (a) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (b) tunable mechanical properties matching those of the abdominal wall that adapt to normal movement deformations while reducing tissue stress, thereby influencing regulating cell behavior tissue regeneration; (c) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (d) promotion of cell interactions by simulating hydrated extracellular matrix environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation; (e) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advances of hydrogels for repairing defects in the abdominal wall are also mentioned. Finally, an overview is provided on the current obstacles and constraints faced by hydrogels, along with potential prospects in the repair of abdominal wall defects.

4.
ACS Appl Mater Interfaces ; 16(23): 30430-30442, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38814614

RESUMO

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.


Assuntos
Traumatismos Abdominais , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Quitosana/química , Quitosana/farmacologia , Camundongos , Polímeros/química , Polímeros/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Cicatrização/efeitos dos fármacos , Pressão , Masculino , Ratos
5.
Infect Drug Resist ; 17: 1685-1697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711471

RESUMO

Purpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains. Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently. Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%). Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next "superbug" highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.

6.
J Hazard Mater ; 467: 133756, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38350322

RESUMO

An efficient cathode for a Fenton-like reaction based on hydrogen peroxide (H2O2) has significant implications for the potential application of the advanced oxidation process. However, the low H2O2 selectivity and efficient activation remain challenging in wastewater treatment. In the present study, a single Fe atom doped, nitrogen-coordinated molybdenum disulfide (Fe1/N/MoS2) cathode that exhibited asymmetric wettability and self-absorption molecular oxygen was successfully prepared for pollutant degradation. The X-ray absorption near-edge structure and extended X-ray absorption fine structure of Fe1N3 in the Fe1/N/MoS2 catalyst were determined. The electronic structure demonstrated favorable H2O2 selectivity (75%) in a neutral solution and the cumulative hydroxyl radical concentration was 14 times higher than the pure carbon felt. After 10 consecutive reaction experiments, the removal ratio of paracetamol still reached 97%, and the catalytic performance did not decrease significantly. This work deeply understands the catalytic mechanism of Fenton-like reaction between single Fe atom and MoS2 double reaction sites, and proves that the regulation of the electronic structure of Fe single atom is an effective strategy to improve the activity of Fenton-like reaction.

7.
Biomater Sci ; 12(4): 837-862, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38196386

RESUMO

Inflammatory bowel disease (IBD) is a chronic disorder that affects millions of individuals worldwide. However, current drug therapies for IBD are plagued by significant side effects, low efficacy, and poor patient compliance. Consequently, there is an urgent need for novel therapeutic approaches to alleviate IBD. Hydrogels, three-dimensional networks of hydrophilic polymers with the ability to swell and retain water, have emerged as promising materials for drug delivery in the treatment of IBD due to their biocompatibility, tunability, and responsiveness to various stimuli. In this review, we summarize recent advancements in hydrogel-based drug delivery systems for the treatment of IBD. We first identify three pathophysiological alterations that need to be addressed in the current treatment of IBD: damage to the intestinal mucosal barrier, dysbiosis of intestinal flora, and activation of inflammatory signaling pathways leading to disequilibrium within the intestines. Subsequently, we discuss in depth the processes required to prepare hydrogel drug delivery systems, from the selection of hydrogel materials, types of drugs to be loaded, methods of drug loading and drug release mechanisms to key points in the preparation of hydrogel drug delivery systems. Additionally, we highlight the progress and impact of the hydrogel-based drug delivery system in IBD treatment through regulation of physical barrier immune responses, promotion of mucosal repair, and improvement of gut microbiota. In conclusion, we analyze the challenges of hydrogel-based drug delivery systems in clinical applications for IBD treatment, and propose potential solutions from our perspective.


Assuntos
Hidrogéis , Doenças Inflamatórias Intestinais , Humanos , Hidrogéis/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Intestinos , Mucosa Intestinal/metabolismo , Sistemas de Liberação de Medicamentos/métodos
8.
Water Res ; 249: 120978, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38071905

RESUMO

Monitoring urinary markers of dietary, disease, and stress by wastewater-based epidemiology (WBE) is a promising tool to better understand population health and wellbeing. However, common urinary biomarkers are subject to degradation in sewer systems and their fates have to be assessed before they can be used in WBE. This study investigated the stability of 31 urinary biomarkers (12 food biomarkers, 8 vitamins, 9 oxidative stress biomarkers, and 1 histamine biomarker) in a laboratory sewer sediment reactor and evaluated their suitability for WBE, considering their detectability in real wastewater and in-sewer stability. These biomarkers showed various transformation patterns, among which 16 compounds had half-lives <2 h while other 15 compounds presented moderate to high stability (2 to >500 h). Thirteen biomarkers showed potential for WBE because of their consistently measurable concentrations in untreated wastewater and sufficient in-sewer stability. Eighteen biomarkers were unsuitable due to their rapid in-sewer degradation and/or undetectable concentration levels in untreated wastewater using previous methods. Transformation rates of these biomarkers showed generally weak relationships with molecular properties but relatively higher correlations with biological activities in sewers. Overall, this study determined in-sewer stability of 31 health-related biomarkers through laboratory experiments, providing new findings to WBE for population health assessment.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Humanos , Vigilância Epidemiológica Baseada em Águas Residuárias , Poluentes Químicos da Água/análise , Biomarcadores , Alimentos , Esgotos
9.
Int J Surg ; 110(1): 119-129, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37800568

RESUMO

OBJECTIVE: This study aimed to construct and validate a clinical prediction model for surgical site infection (SSI) risk 30 days after gastrointestinal surgery. MATERIALS AND METHODS: This multicentre study involving 57 units conducted a 30-day postoperative follow-up of 17 353 patients who underwent gastrointestinal surgery at the unit from 1 March 2021 to 28 February 2022. The authors collected a series of hospitalisation data, including demographic data, preoperative preparation, intraoperative procedures and postoperative care. The main outcome variable was SSI, defined according to the Centres for Disease Control and Prevention guidelines. This study used the least absolute shrinkage and selection operator (LASSO) algorithm to screen predictive variables and construct a prediction model. The receiver operating characteristic curve, calibration and clinical decision curves were used to evaluate the prediction performance of the prediction model. RESULTS: Overall, 17 353 patients were included in this study, and the incidence of SSI was 1.6%. The univariate analysis combined with LASSO analysis showed that 20 variables, namely, chronic liver disease, chronic kidney disease, steroid use, smoking history, C-reactive protein, blood urea nitrogen, creatinine, albumin, blood glucose, bowel preparation, surgical antibiotic prophylaxis, appendix surgery, colon surgery, approach, incision type, colostomy/ileostomy at the start of the surgery, colostomy/ileostomy at the end of the surgery, length of incision, surgical duration and blood loss were identified as predictors of SSI occurrence ( P <0.05). The area under the curve values of the model in the train and test groups were 0.7778 and 0.7868, respectively. The calibration curve and Hosmer-Lemeshow test results demonstrated that the model-predicted and actual risks were in good agreement, and the model forecast accuracy was high. CONCLUSIONS: The risk assessment system constructed in this study has good differentiation, calibration and clinical benefits and can be used as a reference tool for predicting SSI risk in patients.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fatores de Risco , Modelos Estatísticos , Estudos Prospectivos , Prognóstico , Estudos Retrospectivos
10.
Carbohydr Polym ; 326: 121508, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142061

RESUMO

The clinical treatment of enterocutaneous fistula is challenging and causes significant patient discomfort. Fibrin gel can be used to seal tubular enterocutaneous fistulas, but it has low strength and poor digestion resistance. Based on in situ bioprinting and the anti-digestive properties of xanthan gum (XG), we used carboxymethyl chitosan (CMC) and xanthan gum modified by grafted glycidyl methacrylate (GMA) and aldehyde (GCX) as the ink to print a double network hydrogel that exhibited high strength and an excellent anti-digestive performance. In addition, in vitro studies confirmed the biocompatibility, degradability, and self-healing of hydrogels. In our rabbit tubular enterocutaneous fistula model, the in situ printed hydrogel resisted corrosion due to the intestinal fluid and acted as a scaffold for intestinal mucosal cells to proliferate on its surface. To summarize, in situ bioprinting GCX/CMC double network hydrogel can effectively block tubular enterocutaneous fistulas and provide a stable scaffold for intestinal mucosal regeneration.


Assuntos
Bioimpressão , Fístula Intestinal , Animais , Humanos , Coelhos , Hidrogéis , Polissacarídeos Bacterianos/uso terapêutico
11.
World J Emerg Surg ; 18(1): 56, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057900

RESUMO

Surgeons in their daily practice are at the forefront in preventing and managing infections. However, among surgeons, appropriate measures of infection prevention and management are often disregarded. The lack of awareness of infection and prevention measures has marginalized surgeons from this battle. Together, the Global Alliance for Infections in Surgery (GAIS), the World Society of Emergency Surgery (WSES), the Surgical Infection Society (SIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), the American Association for the Surgery of Trauma (AAST), and the Panamerican Trauma Society (PTS) have jointly completed an international declaration, highlighting the threat posed by antimicrobial resistance globally and the need for preventing and managing infections appropriately across the surgical pathway. The authors representing these surgical societies call all surgeons around the world to participate in this global cause by pledging support for this declaration for maintaining the effectiveness of current and future antibiotics.


Assuntos
Antibacterianos , Cirurgiões , Humanos , Estados Unidos , Antibacterianos/uso terapêutico
12.
Animal Model Exp Med ; 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38158631

RESUMO

INTRODUCTION: This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing. RESULTS: The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p < 0.05). Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups. Histopathological examinations revealed fibrous hyperplasia, inflammatory cell infiltration, neovascularization, and collagen deposition in all groups. Group B demonstrated enhanced granulation tissue generation, neovascularization, and collagen deposition compared to the other groups (p < 0.05). CONCLUSIONS: Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA. This model successfully replicated the pathological and physiological changes in postoperative patients with OA, specifically the progress of abdominal skin wound healing. It provides a practical and reliable animal model for OA research.

13.
Nat Commun ; 14(1): 7856, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030636

RESUMO

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.


Assuntos
Diabetes Mellitus , Hidrogéis , Humanos , Ratos , Animais , Hidrogéis/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ácido Poliglutâmico , Química Click , Cicatrização/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Diabetes Mellitus/patologia , Impressão Tridimensional
14.
Cell Mol Life Sci ; 80(11): 337, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37897551

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Disbiose/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Inflamação/tratamento farmacológico , Alquilação , Quinase Syk
15.
Int J Biol Sci ; 19(15): 4931-4947, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781519

RESUMO

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.


Assuntos
Gasderminas , Processamento de Proteína Pós-Traducional , Proteólise , Endopeptidases , Imunidade Inata , Peptídeo Hidrolases
16.
Bioact Mater ; 30: 1-14, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37534235

RESUMO

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

17.
Clin Transl Med ; 13(7): e1334, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37475188

RESUMO

BACKGROUNDS: The stimulator of interferon genes (STING) is an important driver in various inflammatory diseases. METHODS AND RESULTS: Here, we have demonstrated that inhibition of RIPK3 and MLKL dampens STING signaling, indicating that necroptosis may be involved in sustaining STING signaling. Furthermore, RIPK3 knockout in HT-29 cells significantly suppressed STING signaling. Mechanistically, RIPK3 inhibits autophagic flux during STING activation. RIPK3 knockout inhibits STING signaling by intensifying STING autophagy. In contrast, MLKL regulates the STING pathway bidirectionally. MLKL deficiency enhances STING signaling, whereas suppression of MLKL-mediated pore formation restricts STING signaling. Mechanistically, upon abrogating the pro-necroptotic activity of MLKL, MLKL bound to activated STING is secreted to the extracellular space, where it restricts TBK1 and IRF3 recruitment. Targeting necroptotic signaling ameliorates STING activation during DMXAA-induced intestinal injury and sepsis. CONCLUSIONS: These findings elucidate molecular mechanisms linking necroptosis to the STING pathway, and suggest a potential benefit of therapeutic targeting of necroptosis in STING-driven inflammatory diseases.


Assuntos
Proteínas Quinases , Sepse , Humanos , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Autofagia , Sepse/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
18.
Int J Bioprint ; 9(5): 764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457930

RESUMO

Biomedical implants have recently shown excellent application potential in tissue repair and replacement. Applying three-dimensional (3D) printing to implant scaffold fabrication can help to address individual needs more precisely. Fourdimensional (4D) printing emerges rapidly based on the development of shape-responsive materials and design methods, which makes the production of dynamic functional implants possible. Smart implants can be pre-designed to respond to endogenous or exogenous stimuli and perform seamless integration with regular/ irregular tissue defects, defect-luminal organs, or curved structures via programmed shape morphing. At the same time, they offer great advantages in minimally invasive surgery due to the small-to-large volume transition. In addition, 4D-printed cellular scaffolds can generate extracellular matrix (ECM)-mimetic structures that interact with the contacting cells, expanding the possible sources of tissue/organ grafts and substitutes. This review summarizes the typical technologies and materials of 4D-printed scaffolds, and the programming designs and applications of these scaffolds are further highlighted. Finally, we propose the prospects and outlook of 4D-printed shape-morphing implants.

19.
Ann Surg ; 278(5): e988-e994, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37309899

RESUMO

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.


Assuntos
Laparoscopia , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Prospectivos , Estudos de Coortes , Laparoscopia/efeitos adversos , Fatores de Risco , Incidência
20.
Int J Bioprint ; 9(3): 682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273990

RESUMO

Peritoneal adhesion is a critical issue after abdominal surgery. Cell-based methods for preventing peritoneal adhesion have not yet been fully investigated. Here, we constructed a highly biomimetic peritoneal scaffold by seeding mesothelial cells, the natural physiological barrier of the peritoneum, onto a melt electrowriting-printed scaffold. The scaffolds with the microfibers crossed at different angles (30°, 60°, and 90°) were screened based on mesothelial cell proliferation and orientation. Thirty degrees were more suitable for improving proliferation of mesothelial cells and cell growth in a single direction; therefore, the 30° peritoneal scaffold could better mimic the physiological structure of native peritoneum. Mechanistically, such a peritoneal scaffold was able to act as a barrier to prevent peritoneal resident macrophages from migrating to the site of the peritoneal lesion. In vivo mesothelial cell tracking using lentivirus technology confirmed that the peritoneal scaffold, compared to the scaffold without mesothelial cells, could prevent peritoneal adhesion and was directly involved in the repair of injured peritoneum. This study suggests that the peritoneal scaffolds can potentially prevent peritoneal adhesion, offering a new approach for clinical treatment.

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