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An ideal antibacterial wound dressing with strong antibacterial behavior versus highly drug-resistant bacteria and great wound-healing capacity is still being developed. There is a clinical requirement to progress the current clinical cares that fail to fully restore the skin structure due to post-wound infections. Here, we aim to introduce a novel two-layer wound dressing using decellularized bovine skin (DBS) tissue and antibacterial nanofibers to design a bioactive scaffold with bio-mimicking the native extracellular matrix of both dermis and epidermis. For this purpose, polyvinyl alcohol (PVA)/chitosan (CS) solution was loaded with antibiotics (colistin and meropenem) and electrospun on the surface of the DBS scaffold to fabricate a two-layer antibacterial wound dressing (DBS-PVA/CS/Abs). In detail, the characterization of the fabricated scaffold was conducted using biomechanical, biological, and antibacterial assays. Based on the results, the fabricated scaffold revealed a homogenous three-dimensional microstructure with a connected pore network, a high porosity and swelling ratio, and favorable mechanical properties. In addition, according to the cell culture result, our fabricated two-layer scaffold surface had a good interaction with fibroblast cells and provided an excellent substrate for cell proliferation and attachment. The antibacterial assay revealed a strong antibacterial activity of DBS-PVA/CS/Abs against both standard strain and multidrug-resistant clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Our bilayer antibacterial wound dressing is strongly suggested as an admirable wound dressing for the management of infectious skin injuries and now promises to advance with preclinical and clinical research.
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Quitosana , Nanofibras , Infecção dos Ferimentos , Animais , Bovinos , Antibacterianos/farmacologia , Antibacterianos/química , Pele , Cicatrização , Quitosana/química , Álcool de Polivinil/química , Infecção dos Ferimentos/tratamento farmacológico , Nanofibras/químicaRESUMO
This study aimed to evaluate the effects of ursolic acid (UA) on Angiotensin II (Ang II)-treated neonatal rat cardiac fibroblasts (rCFs) as an in vitro model of cardiac fibrosis. The rCFs were isolated from two-day-old neonatal rats. An in vitro model of cardiac fibrosis was established using 500â¯nm Ang II treatment for 48â¯h. The cells were then treated with 5 and 10⯵M of UA for 24 and 48â¯h. Masson's trichrome staining, hydroxyproline content assay, scratch assay, apoptosis assay, measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) levels, real-time PCR, immunocytology and western blotting, were employed to assess the impact of UA. Ang II induced fibrosis in rCFs, as evidenced by the examination of various fibrotic markers. Upon treatment with 5 and 10⯵M of UA, the amount of fibrosis in Ang II-treated rCFs was significantly decreased, so that the hydroxyproline concentration was reduced to 0.3 and 0.7 times, respectively. The RNA expression of the Col1a1, Col3a1, Tgfb1, Acta2 and Mmp2 genes had a decrease as well as Nrf2 and HO-1 had an increase after UA treatment. UA could lessen the harmful effects of cardiac fibrosis in a dose- and time-dependent manner, due to its antiapoptotic, antioxidant and cardioprotective properties. This suggests the potential of UA for treatment of cardiac fibrosis.
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Background and Aims: Acute kidney injury (AKI) is a common complication in pediatric cardiac intensive care unit (CICU). This study aims to identify the prevalence, risk factors, and outcomes of AKI in pediatrics admitted to a CICU unit of a tertiary hospital. Methods: We retrospectively gathered the data of 253 randomly selected patients admitted to the CICU unit from March 2018 to March 2022. Data were collected from EHRs. We used the Kidney Disease Improving Global Outcomes (KDIGO) criteria for identifying AKI in patients. Results: Overall, AKI prevalence was 22.9% in our population. In the multivariable analysis, vancomycin intake (odds ratio [OR]: 2.109, 95% confidence interval [CI]: 1.15-3.84), angiography (OR: 4.38, 95% CI: 1.28-14.93), and mechanical ventilation (OR: 2.08, 95% CI: 1.02-4.23) were independent risk factors of AKI development and patients with AKI had a higher in-hospital mortality rate (OR: 5.81, 95% CI: 2.55-13.19), higher need for cardiopulmonary resuscitation (OR: 3.08, 95% CI: 1.17-8.09), and longer ICU length of stay (OR: 6.49, 95% CI: 3.31-9.67). Furthermore, furosemide administration was associated with lower risk of developing AKI (OR: 0.52, 95% CI: 0.27-0.97). Conclusion: AKI is common and is associated with worse outcomes in patients with congenital heart disease. Our results emphasize the importance of early identification and monitoring of AKI in the pediatric CICU setting.
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Background: The arterial stiffness measured by pulsed wave velocity (PWV) is associated with heart failure (HF). However, the effectiveness of arterial stiffness and PWV as prognostic indicators in patients with HFpEF and HFrEF is still unclear. In this systematic review and meta-analysis, we synthesized the prognostic value of PWV and arterial stiffness in HF patients. Methods: Four databases, including Embase, PubMed, Scopus, and Web of Science, were systematically searched for published studies assessing the relationship between PWV and HF from inception up to August 31, 2023. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. The standardized mean difference (SMD) and their corresponding 95% confidence intervals (CI) were used to compare PWV in HF (HFrEF and HFpEF) and controls. Meta-regressions based on age, year of publication, sample size, and gender (male percentage) were also conducted. Results: The systematic search yielded 5,977 results, of which 58 met our inclusion criteria and 24 were analyzed quantitatively. Studies included 64,687 patients with a mean age of 53.7 years, and 41,803 (67.3%) were male. Meta-analysis of 19 studies showed that PWV was significantly higher in HF patients compared to the controls (SMD 1.04, 95% CI 0.43-1.66, P < 0.001, I 2 = 93%). Moreover, nine studies have measured PWV among HFrEF and HFpEF patients and found no significant difference (SMD -0.51, 95% CI -1.03 to 0.02, P = 0.057, I2 = 95%). Moreover, increased PWV was linked to an increased chance of developing new-onset HF in individuals with cardiovascular risk factors. Conclusions: Patients with HF exhibit significantly higher arterial stiffness, as indicated by PWV, compared to the normal population. However, this association was not significant between HFrEF and HFpEF patients. Future research is warranted to establish the potential prognostic role of PWV in HF. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023479683, PROSPERO (CRD42023479683).
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PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy. METHODS: We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study. RESULTS: The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade ≥ 2 (RR 2.36, 95% CI 1.86-2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%-3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated. CONCLUSIONS: CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy.
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Chronic non-healing wounds negatively impact quality of life and are a significant financial drain on health systems. The risk of infection that exacerbates comorbidities in patients necessitates regular application of wound care. Understanding the mechanisms underlying impaired wound healing are therefore a key priority to inform effective new-generation treatments. In this study, we demonstrate that 14-3-3-mediated suppression of signaling through ROCK is a critical mechanism that inhibits the healing of diabetic wounds. Accordingly, pharmacological inhibition of 14-3-3 by topical application of the sphingo-mimetic drug RB-11 to diabetic wounds on a mouse model of type II diabetes accelerated wound closure more than 2-fold than vehicle control, phenocopying our previous observations in 14-3-3ζ-knockout mice. We also demonstrate that accelerated closure of the wounded epidermis by 14-3-3 inhibition causes enhanced signaling through the Rho-ROCK pathway and that the underlying cellular mechanism involves the efficient recruitment of dermal fibroblasts into the wound and the rapid production of extracellular matrix proteins to re-establish the injured dermis. Our observations that the 14-3-3/ROCK inhibitory axis characterizes impaired wound healing and that its suppression facilitates fibroblast recruitment and accelerated re-epithelialization suggest new possibilities for treating diabetic wounds by pharmacologically targeting this axis.
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BACKGROUND: Unlike diabetes, the effect of prediabetes on outcomes in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) is not much investigated. We investigated the association between fasting glycemic status and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS undergoing PCI and had mid to long-term follow-up after coronary stenting. METHODS: Registry-based retrospective cohort study included ACS patients who underwent PCI at the Tehran Heart Center from 2015 to 2021 with a median follow-up of 378 days. Patients were allocated into normoglycemic, prediabetic, and diabetic groups. The primary and secondary outcomes were MACCE and its components, respectively. Unadjusted and adjusted Cox models were used to evaluate the association between glycemic status and outcomes. RESULTS: Among 13 682 patients, 3151 (23%) were prediabetic, and 5834 (42.6%) were diabetic. MACCE risk was significantly higher for diabetic versus normoglycemic (adjusted hazard ratio [aHR]: 1.22, 95% confidence interval [CI]: 1.06-1.41), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 0.95, 95% CI: 0.78-1.10). All-cause mortality risk was significantly higher in diabetic versus normoglycemic (aHR: 1.42, 95% CI: 1.08-1.86), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 1.15, 95% CI: 0.84-1.59). Among other components of MACCE, only coronary artery bypass grafting was significantly higher in diabetic patients, and not prediabetic, compared with normoglycemic. CONCLUSIONS: Prediabetic ACS patients undergoing PCI, unlike diabetics, are not at increased risk of MACCE and all-cause mortality. While prediabetic patients could be regarded as having the same risk as nondiabetics, careful consideration to provide more intensive pre- and post-PCI care in diabetic patients is mandatory.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Irã (Geográfico)/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de RiscoRESUMO
The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental and clinical evidence has now accumulated to demonstrate essential roles of numerous ECM components in all cancer types. Latest findings also suggest that multiple tumor types express, and use to their advantage, atypical ECM components that are not found in the cancer tissue of origin. However, the understanding of cancer-specific expression patterns of these ECM proteins and their exact roles in selected tumor types is still sketchy. In this review, we summarize the latest data on the aberrant expression of bone and cartilage ECM proteins in epithelial cancers and their specific functions in the pathogenesis of carcinomas and discuss future directions in exploring the utility of this selective group of ECM components as future drug targets.
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Background: Pulmonary thromboembolism (PE) is the third leading cause of cardiovascular events. The conventional modeling methods and severity risk scores lack multiple laboratories, paraclinical and imaging data. Data science and machine learning (ML) based prediction models may help better predict outcomes. Materials and methods: In this retrospective registry-based design, all consecutive hospitalized patients diagnosed with pulmonary thromboembolism (based on pulmonary CT angiography) from 2011 to 2019 were recruited. ML based algorithms [Gradient Boosting (GB) and Deep Learning (DL)] were applied and compared with logistic regression (LR) to predict hemodynamic instability and/or all-cause mortality. Results: A total number of 1,017 patients were finally enrolled in the study, including 465 women and 552 men. Overall incidence of study main endpoint was 9.6%, (7.2% in men and 12.4% in women; p-value = 0.05). The overall performance of the GB model is better than the other two models (AUC: 0.94 for GB vs. 0.88 and 0.90 for DL and LR models respectively). Based on GB model, lower O2 saturation and right ventricle dilation and dysfunction were among the strongest adverse event predictors. Conclusion: ML-based models have notable prediction ability in PE patients. These algorithms may help physicians to detect high-risk patients earlier and take appropriate preventive measures.
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Millions of people die annually due to uncured wound infections. Healthcare systems incur high costs to treat wound infections. Tt is predicted to become more challenging due to the rise of multidrug-resistant conditions. During the last decades, smart antibacterial hydrogels could attract attention as a promising solution, especially for skin wound infections. These antibacterial hydrogels are termed 'smart' due to their response to specific physical and chemical environmental stimuli. To deliver different drugs to particular sites in a controlled manner, various types of crosslinking strategies are used in the manufacturing process. Smart hydrogels are designed to provide antimicrobial agents to the infected sites or are built from polymers with inherent disinfectant properties. This paper aims to critically review recent pre-clinical and clinical advances in using smart hydrogels against skin wound infections and propose the next best thing for future trends. For this purpose, an introduction to skin wound healing and disease is presented and intelligent hydrogels responding to different stimuli are introduced. Finally, the most promising investigations are discussed in their related sections. These studies can pave the way for producing new biomaterials with clinical applications.
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AIM: Glycyrrhiza glabra (G. glabra) or licorice with isoflavonoid, flavonoids, and triterpenoid glycosides (saponins) components are highly regarded in the cosmetic industry. This study has been planned as the first project for formulating a new herbal shampoo by utilizing the aqueous extracts of G. glabra. MATERIALS AND METHODS: The dried powdered root of G. glabra was extracted with boiled water through percolation method, and the pH was set by ammonia; then it was used with other constituents to formulate the herbal shampoo. The desirability of licorice shampoo was evaluated by physicochemical tests including visual inspection, detergency evaluation, pH assessment, percentage of solid contents, viscosity, foaming volume, and wetting time and compared with a commercial shampoo. Also, the product was checked for microbial control and consumers were asked about the quality of the licorice shampoo. RESULTS: The licorice shampoo has excellent cleansing ability, acceptable clarity, and viscosity. The volume of created foam and the wetting time were similar to the commercial shampoo. No microbial contamination was observed during the microbial control assessment tests. The licorice shampoo scored well on consumer's poll and was free from complication and also able to obviate hair and scalp problems. DISCUSSION AND CONCLUSION: The results indicated that the consumers were satisfied with using the formulated licorice shampoo. Licorice shampoo seems to be helpful in obviation of hair problems, but specific investigations are required to prove this claim. The shampoo was safe from microbial contamination and showed acceptable results in physicochemical evaluations. Licorice shampoo could be useful in the treatment of many hair diseases, so further research is needed for discovering the potential of licorice shampoo.