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1.
Int J Biol Macromol ; 281(Pt 3): 136461, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39393743

RESUMO

Novel strategy is urgently needed to overcome the bacterial infection all over the world due to unreasonable use of biotics. In recent years, nanozymes have attracted great interests of researchers for their high catalytic efficiency and biocompatibility. In this study, a novel multiple enzyme-mimic polypeptide-based carbon nanoparticle was synthesized by N-carboxyanhydride mediated ring opening polymerization (ROP) and Fe coordination for actualizing ROS regulation and photo-thermal therapy. The multiple enzyme-mimic activities of the nanozyme, such as peroxidase, oxidase, catalase, and glutathione peroxidase, were detailly explored in ROS regulation for potential utilization in bacterial inhibition. The photo-thermal effect of the nanozyme was investigated under 808 nm NIR irradiation. Enhanced inhibition rate of the as prepared nanozyme was observed against Gram-negative Escherichia coli (99.03 %) and Gram positive Staphylococcus aureus (99.78 %) planktonic bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) was chosen as the drug resistant bacteria model to evaluate the efficiency in bacterial biofilm disruption. Improved healing efficacy of 99.05 % against MRSA wound infection and excellent biosafety were observed in mice model experiments for the as prepared nanozyme. In conclusion, the as synthesized nanozyme with ROS regulation, enhanced bacteria inhibition, and excellent biocompatibility could be potentially applied in clinic against bacterial infection.

2.
Cureus ; 16(9): e69194, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39398664

RESUMO

Actinomycosis is a rare chronic infectious disease, most commonly affecting the cervicofacial, pulmonary, or genitourinary areas. It is caused by the Actinomyces spp. bacteria, which are facultative anaerobes and gram-positive, nonsporing rods. The disease is characterized by the formation of cold abscesses or fistulas, as well as granulomatous tissue, reactive fibrosis, and necrosis, which can resemble local malignancy. Cutaneous actinomycosis in the trunk or extremities is extremely rare and is usually related to previous surgical procedures or trauma. However, we report one such rare case of cutaneous actinomycosis of the forearm without previous precipitating factors, which was successfully treated with prolonged antibiotherapy.

3.
Int J Biol Macromol ; : 136604, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39419145

RESUMO

In this paper, we designed a novel "Freeze-thaw" type hydrogel microneedle (PP-CDLut-AMY MN). The "Freeze-thaw" cycle endows the MN excellent water absorption, with a dissolution rate of up to 486 %. The addition of polydopamine@polypyrrole (PP) enabled the MN to have a stable temperature increase to approximately 50 °C under near-infrared light irradiation, which exhibited killing rates of 99 % and 98 % against free S. aureus and E. coli, respectively. Natural macromolecule α-Amylase (AMY) was used as a bacterial biofilm disintegrator, and the destruction rate of S. aureus biofilm reached 83.2 %. Meanwhile, the incorporation of Hydroxypropyl-ß-cyclodextrin @Luteolin (CDLut) provided the MN with good antioxidant properties, which could scavenge 73.35 % of DPPH free radicals. In vivo experiments have shown that the MN can effectively promote the healing of wounds infected by S. aureus biofilm and that the stable and gentle photothermal effect did not cause unnecessary damage to the surrounding tissues. We believe that this novel hydrogel MN has great potential to combat bacterial biofilms associated with wound infections.

4.
Cureus ; 16(9): e69460, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39411639

RESUMO

Cutibacterium acnes, previously known as Propionibacterium acnes, is a gram-positive rod in the pilosebaceous glands and commonly implicated in acne vulgaris. Its role in prosthetic joint infections, particularly in shoulder surgeries, has recently gained attention due to its prevalence around the shoulder girdle. This review collates evidence on the pathogenic role of C. acnes in shoulder surgeries, discussing preventive measures, risk factors, clinical presentation, investigation, and treatment strategies. C. acnes infections are complex, often presenting with non-specific symptoms and delayed diagnoses. Risk factors include male sex, presence of hair, shoulder steroid injections, and previous shoulder surgeries. Investigations such as inflammatory markers, synovial fluid analysis, diagnostic arthroscopy, tissue cultures, and advanced molecular techniques like next-generation sequencing and multiplex polymerase chain reaction are explored for their effectiveness in detecting C. acnes. Treatment strategies range from prolonged antibiotics and antibiotic spacers to single-stage and two-stage revision surgeries. Studies indicate that single-stage revision may provide better outcomes compared to two-stage revision. Effective management of C. acnes infections requires careful assessment, relevant investigations, and tailored treatment approaches. This review emphasizes the need for further research to address intraoperative contamination and to develop more efficient diagnostic and treatment methods.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39332598

RESUMO

BACKGROUND: There has been an unprecedented increase of immunocompromised (IC) patients in clinical practice due to various reasons. Bacterial infections are a major cause of morbidity and mortality in this population. Emerging antibacterial resistance poses a significant challenge for prophylaxis and treatment. OBJECTIVES: We aim to provide an update on antibacterial prophylaxis and management, particularly in high-risk IC patients, including those with acute leukaemia and haematopoietic stem cell transplantation. SOURCES: We reviewed original articles, systematic reviews, metanalyses and guidelines using PubMed, Scopus and Web of Science. CONTENT: We discussed the pros and cons of fluoroquinolone (FQ) prophylaxis in neutropenic patients in the context of personalized medicine. We also attempted to give an outline of empirical treatment of presumed bacterial infections and targeted therapy options for documented bacterial infections considering the recent surge of multiresistant bacteria in haematological cancer patients and local epidemiology. The shortcomings of the current strategies and future needs are discussed in detail. IMPLICATIONS: Antibacterial prophylaxis with FQs may still have a role in preventing bacterial infections in carefully selected high-risk haematology patients. Empirical treatment algorithms still need to be adjusted according to host and local factors. Use of rapid diagnostic methods may lessen the need of broad spectrum empirical antibiotic usage. However, these tests may not be easily available due to budget constraints in countries with limited resources but high rate of the bacterial resistance. Although new antimicrobials provide opportunities for effective and less toxic treatment of highly resistant bacterial infections, large-scale data from IC patients are very limited. Using data-driven approaches with AI tools may guide the selection of appropriate patients who would benefit most from such prophylactic and treatment regimens.

6.
Cells ; 13(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39272979

RESUMO

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5' or 3' ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses.


Assuntos
Pulmão , Ativação de Macrófagos , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Ativação de Macrófagos/genética , Animais , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , Macrófagos/metabolismo , Macrófagos/imunologia , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Inflamação/genética , Inflamação/patologia
7.
Pharmacotherapy ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39239762

RESUMO

BACKGROUND: Kidney transplant recipients are at higher risk of infections due to immunosuppression, especially in the perioperative period after receiving induction therapy. Administration of iron has been linked to bacterial infections. This study investigated if receipt of intravenous iron at the time of kidney transplant increased bacterial infections post-transplant. METHODS: This single-center, retrospective study compared patients who received intravenous iron at the time of kidney transplant to those who did not. Patients were followed for 12 weeks after transplant. The primary outcome was incidence of bacterial infections following transplant; hemoglobin and transfusion needs were also examined. RESULTS: A total of 416 patients who received intravenous iron were compared to 416 patients who did not. Bacterial infections were similar between groups (14.4% iron group vs. 15.9% non-iron group). Intravenous iron did not influence bacterial infections on univariable or multivariable analyses when other infection confounders were accounted for. Patients who did not receive intravenous iron required more packed red blood cell transfusions in the 3 months following transplantation, but this was driven by factors other than intravenous iron as demonstrated by a post-hoc analysis. CONCLUSIONS: Intravenous iron did not increase the risk of bacterial infections in the immediate post-kidney transplant setting. Bacterial infections after transplant were associated with female sex, increasing age at transplant, receipt of transfusions, and increased duration of urinary catheters.

8.
J Infect ; 89(5): 106273, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278277

RESUMO

OBJECTIVE: To explore the risk factors for pulmonary bacterial infection (PBI) after lung transplantation (LTX) and to evaluate the impact of PBI on short-term postoperative mortality. METHODS: We retrospectively analyzed data on 549 recipients who underwent LTX at the Affiliated Wuxi People's Hospital of Nanjing Medical University, China, between January 2018 and December 2021. The risk factors for PBI after LTX were explored by univariate analysis and multivariate logistic regression. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of one-, two-, and three-year mortality. Subgroup analysis was performed by the time of postoperative PBI (≤7 days or 8-30 day after surgery). RESULTS: The incidence of postoperative PBI in 549 recipients was 82.70% (454/549). Preoperative history of infections with multidrug-resistant bacteria (OR 12.34, 95% CI 1.69-1572.39), Acinetobacter baumannii infection in donor (OR 3.08, 95% CI 1.26-9.66), and longer cold ischemia time (OR 1.16, 95% CI 1.03-1.32) were risk factors for postoperative PBI. Postoperative PBI was associated with one-year (HR 1.80, 95% CI 1.09-2.96), two-year (HR 1.91, 95% CI 1.20-3.04), and three-year mortality (HR 2.03, 95% CI 1.29-3.19). Subgroup analysis showed that PBI within 7 days after surgery was associated with one-year (HR 1.86, 95% CI 1.12-3.08), two-year (HR 1.99, 95% CI 1.25-3.17), and three-year mortality (HR 2.13, 95% CI 1.35-3.36), while PBI at 8-30 days after surgery was not associated with short-term mortality (one-year: HR 1.36, 95% CI 0.69-2.69; two-year: HR 1.48, 95% CI 0.80-2.76; three-year: HR 1.51, 95% CI 0.82-2.77). CONCLUSIONS: Donor-recipient and surgical factors are risk factors for PBI after LTX. Active prevention and treatment of PBI within the first 7 days after surgery may improve short-term survival.

9.
ACS Nano ; 18(37): 25446-25464, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39240217

RESUMO

The alarming rise in global antimicrobial resistance underscores the urgent need for effective antibacterial drugs. Drawing inspiration from the bacterial-entrapment mechanism of human defensin 6, we have fabricated biomimetic peptide nanonets composed of multiple functional fragments for bacterial eradication. These biomimetic peptide nanonets are designed to address antimicrobial resistance challenges through a dual-approach strategy. First, the resulting nanofibrous networks trap bacteria and subsequently kill them by loosening the membrane structure, dissipating proton motive force, and causing multiple metabolic perturbations. Second, these trapped bacterial clusters reactivate macrophages to scavenge bacteria through enhanced chemotaxis and phagocytosis via the PI3K-AKT signaling pathway and ECM-receptor interaction. In vivo results have proven that treatment with biomimetic peptide nanonets can alleviate systemic bacterial infections without causing noticeable systemic toxicity. As anticipated, the proposed strategy can address stubborn infections by entrapping bacteria and awakening antibacterial immune responses. This approach might serve as a guide for the design of bioinspired materials for future clinical applications.


Assuntos
Antibacterianos , Materiais Biomiméticos , Macrófagos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Macrófagos/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Animais , Camundongos , Peptídeos/química , Peptídeos/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Células RAW 264.7 , Fagocitose/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos
10.
Bioact Mater ; 42: 68-84, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39280579

RESUMO

Biofilm-related biomaterial infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation. To date, a large body of research can be reviewed for coatings which potentially prevent bacterial infection while promoting implant integration. Yet only a very small number has been translated from bench to bedside. This study provides an in-depth analysis of the stability, antibacterial mechanism, and biocompatibility of medical grade polycaprolactone (mPCL), coated with human serum albumin (HSA), the most abundant protein in blood plasma, and tannic acid (TA), a natural polyphenol with antibacterial properties. Molecular docking studies demonstrated that HSA and TA interact mainly through hydrogen-bonding, ionic and hydrophobic interactions, leading to smooth and regular assemblies. In vitro bacteria adhesion testing showed that coated scaffolds maintained their antimicrobial properties over 3 days by significantly reducing S. aureus colonization and biofilm formation. Notably, amplitude modulation-frequency modulation (AMFM) based viscoelasticity mapping and transmission electron microscopy (TEM) data suggested that HSA/TA-coatings cause morphological and mechanical changes on the outer cell membrane of S. aureus leading to membrane disruption and cell death while proving non-toxic to human primary cells. These results support this antibiotic-free approach as an effective and biocompatible strategy to prevent biofilm-related biomaterial infections.

11.
Cureus ; 16(8): e67425, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310591

RESUMO

Burn patients are generally prone to infection, which causes the patient's condition to be even worse. However, there is no study regarding the difference between the mortality rate of infected and non-infected patients. Therefore, the aim was to identify and compare the global mortality rate between infected and non-infected patients who were admitted to plastic surgery units. We searched PubMed, ScienceDirect, and Google Scholar and finally included five articles for this meta-analysis. We determined the odds ratio (OR) value by forest plot and assessed the study bias by a funnel plot. We also analyzed the quality and heterogeneity. The OR was determined as 0.43 (95%CI: 0.07-2.60), indicating a higher mortality rate in infected burn patients as compared to non-infected patients. The funnel plot showed no significant study bias. The quality of the studies was assessed high as well, and the heterogeneity was determined significant (I2>75%). The sensitivity analysis with the fixed effect model reconfirmed our main outcome. However, as a study limitation, we could not specifically determine the impact of strain-specific infection on the mortality rate and could not find more relevant research regarding this issue. We conclude that the overall non-infected burn patient mortality rate is lower as compared to the infected burn patients; however, non-infected patients can be prone to death if the burn degree is higher, the respiratory organ is injured, or the treatment is poor or delayed.

12.
World J Psychiatry ; 14(9): 1319-1325, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39319226

RESUMO

BACKGROUND: Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment. In surgical treatment, accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects. AIM: To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy. METHODS: A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped. The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing, and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing; the control group only sent bacterial culture and drug sensitivity testing during the operation. RESULTS: White blood cell count, C-reactive protein, procalcitonin, 3 days after surgery, showed better postoperative index than the control group (P < 0.05). The hospital stay in the observation group was significantly shorter than that in the control group. The hospitalization cost in the observation group was significantly lower than that in the control group, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION: Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics, improving treatment outcomes and reducing medical costs to some extent.

13.
Int J Biol Macromol ; 279(Pt 3): 135302, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233148

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.


Assuntos
Alginatos , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Probióticos , Cicatrização , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Alginatos/química , Alginatos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Probióticos/farmacologia , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Nanopartículas/química
14.
Indian J Nephrol ; 34(3): 265-267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114390

RESUMO

Renal vein thrombosis (RVT) is not an uncommon condition in patients occurring nephrotic syndrome. Renal cyst by bacterial infection is also rare. Only one case for RVT complicated with infected renal cyst is reported in the English literature. A 78-year-old female was admitted for fever and drowsy mentality for 4 days. Contrast-enhanced computed tomography (CECT) of the abdomen showed 3.7 cm sized irregular shaped exophytic cyst well enhanced in left kidney upper pole and the left RVT. The culture of cystic fluid revealed Klebsiella pneumoniae. Our patient was effectively treated with antibiotics for 8 weeks and anticoagulant for 12 weeks. At 12-week follow-up, CECT of the kidney showed decreased cyst and nearly disappeared RVT. The possibility of RVT in patients with renal cyst infection by bacteria warrants consideration.

15.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125890

RESUMO

Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.


Assuntos
Infecções Bacterianas , Fibrose Cística , Farmacorresistência Bacteriana Múltipla , Terapia por Fagos , Fibrose Cística/terapia , Fibrose Cística/microbiologia , Humanos , Terapia por Fagos/métodos , Infecções Bacterianas/terapia , Antibacterianos/uso terapêutico , Bacteriófagos/fisiologia
16.
Cell ; 187(18): 4946-4963.e17, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39089253

RESUMO

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier. Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.


Assuntos
Barreira Hematoencefálica , Plexo Corióideo , Lipopolissacarídeos , Macrófagos , Doenças Neuroinflamatórias , Neutrófilos , Plexo Corióideo/metabolismo , Animais , Camundongos , Doenças Neuroinflamatórias/metabolismo , Barreira Hematoencefálica/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Neutrófilos/metabolismo , Neutrófilos/imunologia , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Masculino , Junções Íntimas/metabolismo , Células Epiteliais/metabolismo , Feminino
17.
Mol Cell Proteomics ; 23(9): 100829, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147027

RESUMO

Listeria monocytogenes is a foodborne intracellular bacterial model pathogen. Protective immunity against Listeria depends on an effective CD8+ T cell response, but very few T cell epitopes are known in mice as a common animal infection model for listeriosis. To identify epitopes, we screened for Listeria immunopeptides presented in the spleen of infected mice by mass spectrometry-based immunopeptidomics. We mapped more than 6000 mouse self-peptides presented on MHC class I molecules, including 12 high confident Listeria peptides from 12 different bacterial proteins. Bacterial immunopeptides with confirmed fragmentation spectra were further tested for their potential to activate CD8+ T cells, revealing VTYNYINI from the putative cell wall surface anchor family protein LMON_0576 as a novel bona fide peptide epitope. The epitope showed high biological potency in a prime boost model and can be used as a research tool to probe CD8+ T cell responses in the mouse models of Listeria infection. Together, our results demonstrate the power of immunopeptidomics for bacterial antigen identification.


Assuntos
Linfócitos T CD8-Positivos , Epitopos de Linfócito T , Listeria monocytogenes , Listeriose , Animais , Listeria monocytogenes/imunologia , Epitopos de Linfócito T/imunologia , Linfócitos T CD8-Positivos/imunologia , Listeriose/imunologia , Listeriose/microbiologia , Camundongos , Proteômica/métodos , Antígenos de Bactérias/imunologia , Camundongos Endogâmicos C57BL , Peptídeos/imunologia , Mapeamento de Epitopos/métodos , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Feminino , Baço/imunologia , Baço/metabolismo
18.
Int J Biol Macromol ; 278(Pt 1): 134637, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128734

RESUMO

Wounds are prone to infection which may be fatal to the life of the patient. The use of antibiotics is essential for managing bacterial infections in wounds, but the long-term use of high doses of antibiotics may lead to bacterial drug resistance and even to creation of superbacteria. Therefore, the development of targeted antimicrobial treatment strategies and the reduction in antibiotic usage are of utmost urgency. In this study, a multifunctional nanodrug delivery system (Cef-rhEGF@ZIF-8@ConA) for the treatment of bacteriostatic infection was synthesized through self-assembly of Zn2+, cefradine (Cef) and recombinant human epidermal growth factor (rhEGF), then conjugated with concanavalin (ConA), which undergoes pH-responsive degradation to release the drugs. First, ConA can specifically combine with bacteria and inhibit the rapid release of Zn2+ ions, thus achieving a long-acting antibacterial effect. Cef exerts its antibacterial effect by inhibiting the synthesis of bacterial membrane proteins. Finally, Zn2+ ions released from the Zn-metal-organic framework (MOF) demonstrate bacteriostatic properties by enhancing the permeability of the bacterial cell membrane. Furthermore, rhEGF upregulates angiogenesis-associated genes, thereby promoting angiogenesis, re-epithelialization and wound healing processes. The results showed that Cef-rhEGF@ZIF-8@ConA has good biocompatibility, with antibacterial efficacy against Staphylococcus aureus and Escherichia coli of 99.61 % and 99.75 %, respectively. These nanomaterials can inhibit the release of inflammatory cytokines and promote the release of anti-inflammatory cytokines, while also stimulating the proliferation of fibroblasts to facilitate wound healing. Taken together, the Cef-rhEGF@ZIF-8@ConA nanosystem is an excellent candidate in clinical therapeutics for bacteriostatic infection and wound healing.


Assuntos
Antibacterianos , Concanavalina A , Estruturas Metalorgânicas , Infecção dos Ferimentos , Zinco , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Concentração de Íons de Hidrogênio , Zinco/química , Zinco/farmacologia , Concanavalina A/química , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Humanos , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Fator de Crescimento Epidérmico/química , Fator de Crescimento Epidérmico/farmacologia , Cicatrização/efeitos dos fármacos
19.
Oncol Lett ; 28(4): 452, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39101001

RESUMO

Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67-year-old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein-1 (PD-1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL-6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune-related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin-related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD-1 inhibitor was administered. In addition, this apparent severe oxaliplatin-related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

20.
IJID Reg ; 12: 100399, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39157419

RESUMO

Objectives: This study aimed to delineate the characteristics and outcomes of gram-negative bacteremia (GNB) in oncology patients; analyze the risk factors for multi-drug-resistant (MDR) GNB; and assess its impact on the recurrence of bloodstream infection (BSI), hospital stay, and 30-day mortality. Methods: Data, including demographics, clinical features, common cancers, and microbiologic findings, were collected retrospectively from electronic medical records of patients admitted with solid tumors and BSI episodes between January and December 2022. Fisher's exact tests were used to determine the effect of MDR-GNB on 30-day mortality and BSI recurrence. The Wilcoxon rank-sum test assessed the differences in the length of hospital stay. Logistic regression models identified the risk factors for MDR-GNB. Results: Among 1074 patients, 77 episodes of GNB bacteremia occurred in 59 individuals (47% male, median age 57.4 years). Of these, 37 (48%) were MDR-GNB. Carbapenem resistance was noted in 9.1% of GNB episodes. Previous antibiotic use was significantly associated with MDR-GNB (odds ratio 7.82; 95% confidence interval 2.52-24). MDR-GNB was linked to longer hospital stays (median 23 vs 10.5 days, P = 0.003) and higher recurrence rates than non-MDR-GNB (35.13% vs 5.0%, P <0.001). However, 30-day mortality did not significantly differ between the groups (35.14% vs 32.5%, P = 0.81). Conclusion: Previous antibiotic use predicted MDR-GNB in patients with solid tumor. MDR-GNB bacteremia increased the length of hospital stay and risk of recurrence compared with non-MDR-GNB bacteremia.

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