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1.
Hemasphere ; 8(7): e86, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38948924

RESUMO

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

3.
Clin Transl Oncol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914756

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38904883

RESUMO

Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia are considered emerging pathogens classified as a public health problem due to extensive antimicrobial resistance. Therefore, the discovery of new therapeutic strategies has become crucial. This study aimed to evaluate the antimicrobial activity of gallic acid and methyl gallate against non-fermenting bacteria. The study included five clinical isolates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia. The minimum inhibitory concentrations of gallic acid and methyl gallate were determined by the broth microdilution method. Growth curves, metabolic activity, and biofilm formation of each bacterial strain in the presence or absence of phenolic compounds were performed. Finally, the therapeutic efficacy of the compounds was evaluated using an in vivo model. Gallic acid and methyl gallate showed antibacterial activity against bacterial strains in a concentration range of 64 to 256 µg/mL, both compounds reduced bacterial growth and metabolic activity of the strains, even at subinhibitory concentrations. Only, methyl gallate exhibited activity to inhibit the formation of bacterial biofilms. Moreover, gallic acid and methyl gallate increased larval survival by up to 60% compared to 30% survival of untreated larvae in a bacterial infection model in Galleria mellonella. Our results highlight the potential of gallic acid and methyl gallate as therapeutic alternatives for infections by emerging non-fermentative bacteria.

5.
Clin Transl Oncol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909323

RESUMO

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

6.
Reg Anesth Pain Med ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925712

RESUMO

BACKGROUND: Current understanding of the mechanism of action of the pericapsular nerve group (PENG) block is primarily based on cadaver studies. We performed an imaging study in patients undergoing hip surgery to enhance the understanding of the analgesic mechanisms following a PENG block. MATERIALS AND METHODS: 10 patients scheduled for hip surgery received an ultrasound-guided PENG block with 18 mL of 0.5% ropivacaine mixed with 2 mL of a contrast agent. After completion of the block, a high-resolution CT scan was performed to obtain a three-dimensional reconstruction of the injectate's dispersion. RESULTS: The CT imaging revealed that injectate was mainly confined to the epimysium of the iliacus and the psoas muscle, with a minor spread to the hip capsule. Contrast dye was detected within the iliacus and/or the psoas muscle in all patients. No observed spread to either the subpectineal plane or the obturator foramen was detected. CONCLUSION: Our study suggests that the analgesic effect of the PENG block may be related to the block of the branches of the femoral nerve traveling within the iliopsoas muscle without a spread pattern commensurate with the block of the obturator nerve. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06062134).

7.
J Clin Med ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38930078

RESUMO

Background: Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These issues can lead to functional impairments, including difficulties in chewing, swallowing, and speech. The fibula flap is widely used for mandibular reconstruction due to its long bone segment and robust vascular supply, though it may not always provide adequate bone height for optimal dental rehabilitation. This systematic review aims to determine if the double-barreled fibula flap (DBFF) configuration is a viable alternative for mandibular reconstruction and to evaluate the outcomes of dental implants placed in this type of flap. Materials and Methods: This study adhered to the Cochrane Collaboration criteria and PRISMA guidelines and was registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols Database (INPLASY2023120026). We included clinical studies published in English, Spanish, or French that focused on adult patients undergoing segmental mandibulectomy followed by DBFF reconstruction and dental rehabilitation. Data sources included Medline/PubMed, the Cochrane Library, EMBASE, Scopus, and manual searches. Two reviewers independently screened and selected studies, with discrepancies resolved by a third reviewer. Data extraction captured variables such as publication year, patient demographics, number of implants, follow-up duration, flap survival, implant failure, and aesthetic outcomes. The risk of bias was assessed using the JBI appraisal tool, and the certainty of evidence was evaluated using the GRADE approach. Results: A total of 17 clinical studies were included, evaluating 245 patients and 402 dental implants. The average patient age was 43.7 years, with a mean follow-up period of 34.3 months. Flap survival was high, with a 98.3% success rate and only four flap losses. The implant failure rate was low at 1.74%. Esthetic outcomes were varied, with only three studies using standardized protocols for evaluation. The overall certainty of evidence for flap survival was moderate, low for implant failure, and very low for aesthetics due to the subjective nature of assessments and variability in reporting. Conclusions: The primary limitations of the evidence included in this review are the observational design of the studies, leading to an inherent risk of bias, inconsistency in reporting methods, and imprecision in outcome measures. Additionally, the subjective nature of aesthetic evaluations and the variability in assessment tools further limit the reliability of the findings. The DBFF technique demonstrates excellent outcomes for mandibular reconstruction, with high flap survival and low implant failure rates, making it a viable option for dental rehabilitation. However, the evidence for aesthetic outcomes is less certain, highlighting the need for more rigorous and standardized research. This review supports the DBFF as a good alternative for mandibular reconstruction with successful dental implant integration, although further studies are needed to enhance the reliability of aesthetic evaluations.

8.
Blood Adv ; 8(13): 3478-3487, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38717869

RESUMO

ABSTRACT: The efficacies of chimeric antigen receptor T cells (CAR-Ts) and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-Ts and 37 received BiAbs. CAR-Ts produced a higher overall response rate (ORR) than BiAbs (97.1% vs 56.8%, P = .002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs 10.8 months; P = .090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs 22.6 months; P = .021). BiAbs after CAR-Ts yielded a higher ORR and longer PFS2 than did nonredirecting T-cell therapies after CAR-Ts (ORR: 87.5% vs 50.0%; PFS2: 22.9 vs 12.4 months). By contrast, BiAbs after BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the nonredirecting T-cell therapies (ORR: 28.6%; PFS2: 8.1 months). Although this is a pooled analysis of different trials with different products and the patient profile is different for CAR-Ts and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, although the PFS was similar with the 2 approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/imunologia , Imunoterapia Adotiva/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Linfócitos T/imunologia , Anticorpos Biespecíficos/uso terapêutico , Adulto , Resultado do Tratamento
9.
Enferm Clin (Engl Ed) ; 34(3): 224-231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38821226

RESUMO

Cancer impacts the person's physical health, psychosocial and spiritual wellbeing. The humanization of care is an essential element to achieve integral wellbeing of the individual. The aim of this article is to present a clinical case, using the nursing process with the NANDA, NOC and NIC taxonomies, and based on the principles of Watson's theory of humanized care. The participant is a 45-year-old woman with gastric cancer in palliative stage. The assessment was performed using Gordon's functional patterns and the Watson Caritas Patient Score scale to evaluate the care received previously in the health system. Eight nursing diagnoses were identified, prioritizing 3 diagnoses using the clinical reasoning web (decisional conflict, anxiety, and ineffective self-management of health). Expected outcomes and nursing interventions were planned and implemented through moments of care using health education through tele-nursing and the intentional use of Caritas processes of care in the transpersonal relationship. The results were evaluated with the scales of the indicators and anxiety was also evaluated with the Beck Anxiety Inventory. Health education in oncology nursing contributed to improve informed decision making, reducing anxiety and providing emotional support to facilitate self-management of health. The participant perceived as humanized care throughout the sessions, reflected in the final evaluation with the Watson Caritas Patient Score scale.


Assuntos
Enfermagem Oncológica , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/enfermagem , Neoplasias Gástricas/psicologia , Pessoa de Meia-Idade
10.
Biol Proced Online ; 26(1): 13, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750435

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38763988

RESUMO

DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case-control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38794880

RESUMO

BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.

14.
Drugs Context ; 132024.
Artigo em Inglês | MEDLINE | ID: mdl-38817803

RESUMO

Background: For a medication dispensing service to function with quality, continuous evaluation is required, which is why it is necessary to have reliable measurement tools that make it possible. Quality indicators can serve as tools for managing quality, as they are variables that directly or indirectly measure changes in a situation and help evaluate the progress made in addressing it. This article aims to determine the feasibility and reliability of a quality indicator system for a drug dispensing service for paediatric outpatients in two Mexican hospitals. Methods: A study of the development type of health systems and services at a microlevel was conducted from October 2020 to October 2021 in the pharmaceutical service of two Mexican hospitals. To determine the feasibility of the quality indicators, a retrospective evaluation was performed, which considered the indicators that could be calculated with the available information to be feasible. To determine reliability, an inter-observer agreement study (Kappa (κ)) was performed. Results: The feasibility analysis revealed that all five reference indicators related to the structure were feasible in both hospitals. In the Infantil of the Californias hospital, all six process indicators evaluated were feasible, whilst only one was found feasible in H+ Querétaro. As for outcome indicators, only one was feasible in the Infantil of the Californias hospital. The causes of non-feasibility in both hospitals were the non-documentation of the primary data related to the stages of the process and the lack of instruments to measure patient satisfaction. The reliability of the indicators showed little variability. Conclusion: Although not all indicators were feasible, solutions were proposed so that the 15 reference indicators could be used if an organization decided to do so. The reliability of the indicators was demonstrated, evidencing the importance of the data sheet as a tool to generate valid reliable measures.This article is part of the Hospital pharmacy, rational use of medicines and patient safety in Latin America Special Issue: https://www.drugsincontext.com/special_issues/hospital-pharmacy-rational-use-of-medicines-and-patient-safety-in-latin-america/.

15.
Hemasphere ; 8(5): e62, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38774657

RESUMO

Over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5.3 months, with significant differences according to the interval between infusion and progression (<2 months [1.9 months], 2-6 months [5.2 months], and >6 months [not reached]). After progression, 237 (61%) patients received treatment. Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab-bendamustine-rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT). In terms of survival, 12-month progression-free survival and OS was 36.2% and 51.0% for POLA, 32.0% and 50.1% for BsAb, 30.8% and 37.5% for RT, 29.9% and 27.8% for ICI, 7.3% and 20.8% for LENA, and 6.1% and 18.3% for CT. Thirty-two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow-up of 15.1 months. In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T-cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T-cell therapy failure.

16.
Farm Hosp ; 48(3): T133-T140, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38705829

RESUMO

OBJECTIVE: The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs. METHOD: A systematic review was performed following the PRISMA 2020 guidelines by searching PubMed with the descriptors: (silicone) AND (syringes) AND ((intraocular) OR (intravitreal)) and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences. RESULTS: Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone; the administration technique; the physicochemical aspects of silicone release; and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialised syringes, the existing syringes for this use have been collected, finding 2 that will probably be commercialised in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic. CONCLUSIONS: From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.


Assuntos
Injeções Intravítreas , Óleos de Silicone , Seringas , Humanos , Uso Off-Label , Espanha
17.
Can J Occup Ther ; : 84174241255467, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38803166

RESUMO

Background: In Canada, internationally educated physiotherapists (IEPTs) and occupational therapists (IEOTs) may work as occupational/physical therapy assistants (OTAs/PTAs) while pursuing Canadian licensure. This experience presents personal and professional opportunities and challenges. Purpose: We explored a) the barriers and facilitators experienced by IEPTs and IEOTs working as OTAs/PTAs while pursuing licensure in Canada and b) how might their professional identity changes during this period. Methods: In this cross-sectional qualitative study, we sampled IEPTs and IEOTs working as assistants using online focus groups. Reflexive thematic analysis of data was used to generate themes. Findings: Fourteen IEPTs or IEOTs participated reporting barriers including financial impacts while working as an OTA/PTA, discrimination, and challenges completing licensing exams. Facilitators while working as OTA/PTAs included social support, acculturation with Canadian systems, and career opportunities. Changes to professional identity encompassed accepting a new identity, reclaiming their old identity, or having a strong sense of identity within a healthcare profession. Participants advocated for bridging programs and modifications for examination processes for IEPTs and IEOTs to improve their experiences while pursuing licensure in Canada. Conclusion: Increased advocacy is needed to address the current experiences of IEPTs and IEOTs working as OTA/PTAs after migration.

18.
Orphanet J Rare Dis ; 19(1): 148, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582886

RESUMO

BACKGROUND: Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. RESULTS: We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. CONCLUSIONS: With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.


Assuntos
DNA Mitocondrial , Atrofia Óptica Hereditária de Leber , Humanos , DNA Mitocondrial/genética , Atrofia Óptica Hereditária de Leber/genética , Linhagem , Mutação/genética , Fenótipo
19.
Cells ; 13(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38667306

RESUMO

Several studies have reported the successful use of bio-orthogonal catalyst nanoparticles (NPs) for cancer therapy. However, the delivery of the catalysts to the target tissues in vivo remains an unsolved challenge. The combination of catalytic NPs with extracellular vesicles (EVs) has been proposed as a promising approach to improve the delivery of therapeutic nanomaterials to the desired organs. In this study, we have developed a nanoscale bio-hybrid vector using a CO-mediated reduction at low temperature to generate ultrathin catalytic Pd nanosheets (PdNSs) as catalysts directly inside cancer-derived EVs. We have also compared their biodistribution with that of PEGylated PdNSs delivered by the EPR effect. Our results indicate that the accumulation of PdNSs in the tumour tissue was significantly higher when they were administered within the EVs compared to the PEGylated PdNSs. Conversely, the amount of Pd found in non-target organs (i.e., liver) was lowered. Once the Pd-based catalytic EVs were accumulated in the tumours, they enabled the activation of a paclitaxel prodrug demonstrating their ability to carry out bio-orthogonal uncaging chemistries in vivo for cancer therapy.


Assuntos
Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Humanos , Animais , Catálise , Camundongos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Paládio/química , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Linhagem Celular Tumoral , Distribuição Tecidual , Polietilenoglicóis/química , Nanopartículas/química , Pró-Fármacos , Camundongos Nus
20.
Curr Microbiol ; 81(6): 156, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656548

RESUMO

Aspergillus fumigatus and Fusarium solani infections have become severe health threat; both pathogens are considered a priority due to the increasing emergence of antifungal-resistant strains and high mortality rates. Therefore, the discovery of new therapeutic strategies has become crucial. In this study, we evaluated the antifungal and antivirulence effects of vanillin and tannic acid against Aspergillus fumigatus and Fusarium solani. The minimum inhibitory concentrations of the compounds were determined by the microdilution method in RPMI broth in 96-well microplates according to CLSI. Conidial germination, protease production, biofilm formation, and in vivo therapeutic efficacy assays were performed. The results demonstrated that vanillin and tannic acid had antifungal activity against Aspergillus fumigatus, while tannic acid only exhibited antifungal activity against Fusarium solani. We found that vanillin and tannic acid inhibited conidial germination and secreted protease production and biofilm formation of the fungal pathogens using sub-inhibitory concentrations. Besides, vanillin and tannic acid altered the fungal membrane permeability, and both compounds showed therapeutic effect against aspergillosis and fusariosis in an infection model in Galleria mellonella larvae. Our results highlight the antivirulence effect of vanillin and tannic acid against priority pathogenic fungi as a possible therapeutic alternative for human fungal infections.


Assuntos
Antifúngicos , Aspergillus fumigatus , Benzaldeídos , Biofilmes , Fusarium , Testes de Sensibilidade Microbiana , Polifenóis , Taninos , Benzaldeídos/farmacologia , Fusarium/efeitos dos fármacos , Taninos/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Aspergillus fumigatus/efeitos dos fármacos , Animais , Aspergilose/microbiologia , Aspergilose/tratamento farmacológico , Virulência/efeitos dos fármacos , Larva/microbiologia , Larva/efeitos dos fármacos , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Esporos Fúngicos/efeitos dos fármacos , Mariposas/microbiologia , Mariposas/efeitos dos fármacos
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