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1.
Surg Obes Relat Dis ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39396883

RESUMO

BACKGROUND: Reporting of obesity-associated metabolic disease severity and longitudinal response to bariatric surgery is not standardized. We updated our co-morbidity scoring tool to the Assessment of Obesity-related Metabolic Conditions (AOMC) to combine pharmacotherapy and biochemical data to score diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DYS) severity. OBJECTIVES: The aim of this study is to determine whether the AOMC system more accurately stages metabolic disease severity than a clinically based Assessment of Obesity-Related Comorbidities (AORC) system. SETTING: University hospital, United States. METHODS: A retrospective cohort study of prospectively collected demographic, clinical, and biochemical data was performed on adults evaluated for bariatric surgery over 6years. AORC versus AOMC scores and disease severity were compared using McNemar's and Wilcoxon's tests. RESULTS: Of 1442 patients, AOMC newly diagnosed metabolic disease in more patients than did AORC: DM (73.4% versus 44.5%), HTN (91.7% versus 67.9%), and DYS (63.8% versus 53.4%). Of those on pharmacotherapy, AOMC found fewer patients with adequately controlled disease: DM (39.9% versus 97.7%), HTN (64.7% versus 99.3%), and DYS (51.8% versus 99.0%). For those in whom both scores could be calculated, disease severity was upstaged in most patients: DM (65.9%), HTN (42.9%), and DYS (30.9%). There were also significant shifts toward higher scores for all conditions and severity classifications, with more patients diagnosed with pre-metabolic and severe disease (untreated/uncontrolled). CONCLUSIONS: Our study demonstrated that the severity of DM, HTN, and DYS is vastly under-represented by clinical history alone and lacks standardized assessments. Our AOMC tool more accurately describes longitudinal metabolic response to bariatric surgery.

2.
Front Immunol ; 15: 1411392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351218

RESUMO

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.


Assuntos
Galectina 1 , Transplante de Células-Tronco Hematopoéticas , Linfócitos T Reguladores , Animais , Camundongos , Galectina 1/imunologia , Galectina 1/metabolismo , Linfócitos T Reguladores/imunologia , Camundongos Endogâmicos C57BL , Rejeição de Enxerto/imunologia , Transplante Homólogo , Complexo Principal de Histocompatibilidade/imunologia , Sobrevivência de Enxerto/imunologia , Camundongos Endogâmicos BALB C , Tolerância Imunológica
3.
Biomed Pharmacother ; 180: 117582, 2024 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-39467472

RESUMO

Retinal hypoxia causes severe visual impairment and dysfunction in retinal pigment epithelial (RPE) cells, triggering a cascade of events leading to cellular apoptosis. Oxidative stress induced by hypoxia plays a significant role in the development of retinal diseases; however, the precise pathogenesis remains unclear. Oleocanthal, a phenolic compound in extra virgin olive oil, is known for its diverse biological properties. This study aims to investigate the potential anti-oxidative effects of oleocanthal against CoCl2-induced hypoxia in ARPE-19 cells. The cell culture model enabled the evaluation of apoptosis, DNA damage, and ROS levels using MTT assay, Western blot, Annexin V/PI staining, JC-1 staining, MitoSOX, H2DCFDA, immunocytochemistry, and comet assays. Our results showed that oleocanthal effectively protected RPE cells against CoCl2-induced damage by enhancing cell viability, reducing DNA damage, and decreasing ROS levels. Moreover, oleocanthal attenuated CoCl2-induced MMP loss by elevating the JC-1 aggregate/monomer ratio. Furthermore, CoCl2-induced cell apoptosis via up-regulating MAPK signaling, while oleocanthal mitigated this effect. These findings shed light on the molecular mechanisms underlying oleocanthal's protection against oxidative stress induced by hypoxia, offering potential insights for the development of novel therapeutic agents for retinal hypoxia.

4.
Heliyon ; 10(19): e39018, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39430494

RESUMO

Inherited heat enhancement capabilities and their significance in the field of medical sciences and industry make nanofluids the focus of research nowadays. Furthermore, due to the remarkable advancements in bionanotechnology and its significance in biomedical fields such as drug delivery systems, cancer tumor therapy, bioimaging, and many others, it has emerged as a key research area. Contribution of cilia for the flow in ductus efferentes of human male reproductive tract is elaborated. A novel mathematical scheme is presented for the heat and mass transfer of MHD micropolar nanofluid transport in an asymmetric channel lined with cilia. The pertinent equations of nanofluid transport are exposed to lubrication approximation theory and solution for the physical problem is examined with efficient bvp4c technique in MATLAB. Fluid rheology is explored with the variations of different transport parameters like Hartmann number, Grashof number, Brownian motion, buoyancy, thermophoresis and Darcy number. It is reported that nanofluid transport is affected with rise in the Lorentz force and show reverse behavior with rising permeability. The temperature of the nanofluid in ciliated microchannel is raised with enhanced value of Hartmann number, Grashof number, Prandtl number, and Darcy number while diffusion phenomenon of nanofluid is slowed down with these parameters. Spinning motion of the nanofluid is enhanced with Grashof number and slow down with nanoparticle Grashof number and different behavior is recorded for Darcy and viscosity parameters in different flow regime. Reported investigation presents crucial findings for ciliary transport of micropolar nanofluid and tackled with appropriate selection of micropolar parameter, Brownian motion parameter, thermophoresis and Grashof number. Moreover, this investigation will be handful for cilia-based actuators which work as micro-mixers in controlling the flow in minute bio-sensors and may prove their worth in micro-pumps employed in various drug-delivery systems.

5.
Surg Endosc ; 38(11): 6446-6455, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39266760

RESUMO

BACKGROUND: We previously showed worse outcomes among lower socioeconomic status (SES) groups following metabolic/bariatric surgery (MBS). In light of healthcare changes in response to COVID-19, this study aims to evaluate post-pandemic MBS outcomes and determine if prior socioeconomic disparities persisted in the post-COVID era. METHODS: A retrospective chart review of patients undergoing primary Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between 2015 and 2022 was performed. Patients were stratified into pre- and post-COVID groups. Post-COVID cohort was further stratified into high (HT) and low (LT) tier status based on Distressed Communities Index, a geocoded composite measure of SES. Preoperative characteristics and postoperative outcomes were compared between pre- and post-COVID cohorts, as well as between post-COVID HT and LT groups. RESULTS: Of 709 patients, 82.9% were pre-COVID and 17.1% were post-COVID. Post-COVID cohort had greater rate of public insurance (46% vs. 37%, p < 0.001), longer wait time to surgery (mean 358 ± 609.8 days vs 241.9 ± 368.5 days, p = 0.045), and were more likely to undergo RYGB (69% vs. 56%, p = 0.010). Post-COVID patients also had lower risk of any complications on multivariable analysis (OR 0.599, 95% CI 0.372-0.963), had higher follow-up rates at post-discharge (95.8% vs 79.7%, p < 0.005), 6-month (93% vs. 82%, p < 0.001) and 12-month visits (75% vs. 63%, p = 0.005), and lost more weight at 12 months (67% excess weight loss (%EWL) vs. 58%EWL, p = 0.002). Among post-COVID HT and LT cohorts, previously seen disparities in complications were no longer seen. Finally, there were no differences in weight or follow-up rates between post-COVID HT and LT. CONCLUSIONS: Post-COVID changes to MBS care have resulted in improved short-term outcomes and reduced disparities for patients of lower SES. Further studies are needed to identify these positive factors to perpetuate practice patterns that optimize care for patients of all socioeconomic status.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Cirurgia Bariátrica , Disparidades em Assistência à Saúde/estatística & dados numéricos , Gastrectomia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Derivação Gástrica , Complicações Pós-Operatórias/epidemiologia , Fatores Socioeconômicos , Classe Social , Resultado do Tratamento , SARS-CoV-2 , Disparidades Socioeconômicas em Saúde
6.
Front Pharmacol ; 15: 1414790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246660

RESUMO

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-kß signaling pathway, Wnt-B catenin signaling pathway, JAK-STAT pathway, TNF-α-mediated pathway, MAPK/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules like NF-kß, SOCS, ß-catenin, BAX, BAK, VEGF, STAT, Bcl2, p53, caspases, and CDKs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondary metabolites obtained from natural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This work is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted.

7.
Surg Obes Relat Dis ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39343661

RESUMO

BACKGROUND: Severity stratification and longitudinal evaluation of metabolic conditions in response to Roux-en-Y gastric bypass (RYGB) are not standardized. Our Assessment of Obesity-related Metabolic Comorbidities (AOMC) scoring tool combines pharmacotherapy and biochemical data to objectively define type 2 diabetes (T2D), hypertension (HTN), and dyslipidemia (DYS) severity. We previously showed that AOMC more accurately describes disease severity than clinical history alone. OBJECTIVES: We aimed to show that AOMC more precisely and reproducibly measures metabolic disease response to RYGB and preoperative disease severity influences remission rates. SETTING: University hospital, United States. METHODS: AOMC scores for T2D, DYS, and HTN were calculated preoperatively and postoperatively (1-, 2-, and 5-years) for patients who underwent RYGB over 14 years. Generalized linear mixed-effect models were used to evaluate AOMC score trends and remission over time. RESULTS: Of 351 patients, 214, 188, and 303, presented with any T2D, DYS, or HTN respectively. One-year remission rates were: T2D 57.1%, DYS 59.7%, and HTN 29.3%. Over 5 years post-RYGB, remission rates declined for T2D (P < .05) and DYS (P < .05) but remained steady for HTN (P > .05). Remission was associated with preoperative disease severity: those with premetabolic disease had the highest remission rates (i.e., 1-year: pre-T2D 81.4%, pre-DYS 91.4%, pre-HTN 53.5%, all P < .05), while those with most severe scores preoperatively (untreated/uncontrolled) had the lowest remission rates. CONCLUSIONS: AOMC allows precise assessment of comorbidity severity and disease-specific postoperative quantification of comorbidity responses and remission rates. These findings can guide preoperative metabolic disease optimization and postoperative metabolic recovery expectations and standardize communication regarding comorbidity severity.

8.
Molecules ; 29(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39202829

RESUMO

Microalgae-mediated nanoparticle (NP) biosynthesis is a promising green synthesis method that overcomes the challenges of conventional synthesis methods. The novel Desmochloris edaphica strain CCAP 6006/5 was isolated, purified, and characterized morphologically and genetically. GC-MS analysis of the algal biomass (DBio) phytochemicals showed the abundance for elaidic acid (18.36%) and monoolein (17.37%). UV-VIS spectroscopy helped analyze the effects of the AgNO3 concentration, algal/silver nitrate ratio, temperature, reaction time, illumination, and pH on AgNP synthesis. DBio extract or cell-free medium (DSup) of D. edaphica successfully biosynthesized small silver NPs (AgNPs), namely, DBio@AgNPs and DSup@AgNPs, under optimum reaction conditions. TEM and SEM showed a quasi-spherical shape, with average diameters of 15.0 ± 1.0 nm and 12.0 ± 0.8 nm, respectively. EDx and mapping analyses revealed that silver was the main element, the NP hydrodynamic diameters were 77.9 and 62.7 nm, and the potential charges were -24.4 and -25.8 mV, respectively. FTIR spectroscopy revealed that the DBio@AgNPs, and DSup@AgNPs were coated with algal functional groups, probably derived from algal proteins, fatty acids, or polysaccharides, representing reductant and stabilizer molecules from the synthesis process. They showed significant anticancer activity against breast cancer cells (MCF-7), low toxicity against normal kidney cells (Vero), and potent inhibitory activity against Staphylococcus aureus, Bacillus subtilis, and Shigella flexneri. D. edaphica is a novel biomachine for synthesizing small, stable and potent therapeutic AgNPs.


Assuntos
Antibacterianos , Antineoplásicos , Nanopartículas Metálicas , Prata , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Química Verde , Testes de Sensibilidade Microbiana , Microalgas/química , Linhagem Celular Tumoral , Células MCF-7 , Staphylococcus aureus/efeitos dos fármacos
9.
Cells ; 13(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39120276

RESUMO

Circular RNAs (circRNAs) are cardinal players in numerous physiological and pathological processes. CircRNAs play dual roles as tumor suppressors and oncogenes in different oncological contexts, including hepatocellular carcinoma (HCC). Their roles significantly impact the disease at all stages, including initiation, development, progression, invasion, and metastasis, in addition to the response to treatment. In this review, we discuss the biogenesis and regulatory functional roles of circRNAs, as well as circRNA-protein-mRNA ternary complex formation, elucidating the intricate pathways tuned by circRNAs to modulate gene expression and cellular processes through a comprehensive literature search, in silico search, and bioinformatics analysis. With a particular focus on the interplay between circRNAs, epigenetics, and HCC pathology, the article sets the stage for further exploration of circRNAs as novel investigational theranostic agents in the dynamic realm of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Medicina de Precisão , RNA Circular , RNA não Traduzido , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Medicina de Precisão/métodos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Biologia Computacional/métodos
10.
Nanomaterials (Basel) ; 14(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39120413

RESUMO

As an environmentally friendly material, biochar is increasingly being utilized in the field of heat transfer and thermal conduction. In this study, nano-biochar was prepared from high-pressure homogenization (HPH) using sesame stalks as the raw material. It was incorporated into ethylene glycol (EG) and its dispersion stability, viscosity, and thermal conductivity were investigated. The nano-biochar was stably dispersed in EG for 28 days. When the concentration of the nano-biochar added to EG was less than 1%, the impact on viscosity was negligible. The addition of 5 wt.% nano-biochar to EG improved the thermal conductivity by 6.72%, which could be attributed to the graphitized structure and Brownian motion of the nano-biochar. Overall, nano-biochar has the potential to be applied in automotive thermal management.

11.
Chirurgie (Heidelb) ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150539

RESUMO

BACKGROUND: Supra-sphincteric and high trans-sphincteric fistula are very challenging procedures for both the patient and the surgeon. We aimed to evaluate the outcomes of anal sphincter repair in the management of supra-sphincteric and high trans-sphincteric fistula-in-ano in terms of postoperative wound infection, bleeding, incontinence to flatus or stool, and recurrence within 1 year. PATIENTS AND METHODS: This single-center prospective cohort trial conducted from June 2020 to December 2023 at the Ain Shams University Hospitals included 20 patients who presented with supra-sphincteric or high trans-sphincteric fistula. There were nine (45%) male and 11 (55%) female patients, with a mean age of 41.5 years postoperatively. RESULTS: The mean duration of the procedure was 90.3 min (SD ± 11.9). During the first 2 weeks, ten (50%) patients scored their postoperative pain as mild, eight (40%) as moderate, and two (10%) as severe. Wound infection occurred in two (10%) patients and postoperative bleeding in three (15%) patients in the form of spotting after defecation. There were no cases of incontinence to stool. However, there were three (15%) cases of incontinence to gases. There were two cases (10%) of recurrence at the 1­year follow-up. Postoperative patient satisfaction was assessed on a 5­point Likert scale after 2 weeks: One patient (5%) was very dissatisfied, three (15%) patients were dissatisfied, and two (10%) patients were unsure, while five (25%) patients were satisfied and nine (45%) were very satisfied. CONCLUSION: Immediate sphincter repair in supra-sphincteric and high trans-sphincteric fistula through a lay-open procedure was determined to be safe, easier than classic operations, and associated with a low incidence of recurrence at the 1­year follow-up and a high quality of life.

12.
Expert Opin Ther Targets ; 28(8): 669-687, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39136530

RESUMO

INTRODUCTION: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy. AREAS COVERED: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy. EXPERT OPINION: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.


Assuntos
Leiomioma , Neoplasias Uterinas , Humanos , Leiomioma/tratamento farmacológico , Feminino , Animais , Neoplasias Uterinas/tratamento farmacológico , Terapia de Alvo Molecular , Microbiota/efeitos dos fármacos , Probióticos/farmacologia , Probióticos/administração & dosagem , Desenvolvimento de Medicamentos , Catequina/farmacologia , Catequina/análogos & derivados , Catequina/administração & dosagem , Vitamina D/farmacologia
13.
Metabolites ; 14(7)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39057691

RESUMO

There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification, as well as predictions of their anticancer, pharmacokinetic, and toxic properties; oral bioavailability; and endocrine disruption using SwissADMET, PASS, ProTox-II, and Endocrine Disruptome web servers. A total of 12 metabolites, with a majority of flavonoids, were identified. Rutin, quercetin, and luteolin flavonoids demonstrated the highest ranked docking scores of -12.39, -11.15, and -10.43, respectively, while the half-maximal inhibitory concentration (IC50) values of these metabolites against XO activity were 11.35 µM, 11.1 µM, and 21.58 µM, respectively. In addition, SwissADMET generated data related to the physicochemical properties and drug-likeness of the metabolites. Similarly, the PASS, ProTox-II, and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of the prominent and promising therapeutic use of A. hierochuntica methanolic-leaf-extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies.

14.
Int J Nanomedicine ; 19: 7323-7352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055376

RESUMO

Background: Prior studies on magnetite (Fe3O4) NPs and carbon nanotubes (CNTs) cytotoxic effects against acute myeloid leukemia (AML) are inconclusive rather than definitive. Purpose: Investigation of the effects of Gum Arabic (GA)-stabilized/destabilized Fe3O4 NPs and CNTs, alone or in combination, on AML cell proliferation. Methods: Hybrid NPs were synthesized, characterized, and assessed for their cytotoxicity against Kasumi-1, HL-60, and THP-1 in comparison to normal primary bone marrow CD34+ cells. The molecular pathways of nanostructures' cytotoxicity were also investigated. Results: The Fe3O4 NPs were effectively synthesized and attached to the surface of the CNTs, resulting in the formation of a novel hybrid through their interaction with the GA colloidal solution in an aqueous media. Although the evaluated nanostructured nanoparticles had significant growth suppression ability against the leukemia cell lines, with IC50 values ranging from 42.437 to 189.842 µg/mL, they exhibited comparatively modest toxicity towards normal hematopoietic cells (IC50: 113.529‒162.656 µg/mL). The incorporation of Fe3O4 NPs with CNTs in a hybrid nanocomposite significantly improved their effectiveness against leukemia cells, with the extent of improvement varying depending on the specific cell type. The nanostructured particles were stabilized by GA, which enhances their ability to inhibit cell proliferation in a manner that depends on the specific cell type. Also, nanoparticles exhibit cytotoxicity due to their capacity to stimulate the production of intracellular ROS, halt the cell cycle at the G1 phase, and induce apoptosis. This is supported by the activation of p53, BAX, cytochrome C, and caspase-3, which are triggered by ROS. The nanostructures lead to an increase in the expression of genes encoding proteins related to oxidative stress (SIRT1, FOXO3, NFE2L2, and MAP3K5) and cyclin-dependent kinase inhibitors (CDKN1A and CDKN1B) in response to ROS. Conclusion: We provide an effective Fe3O4 NPs/CNTs nano-hybrid composite that induces apoptosis and has strong anti-leukemic capabilities. This hybrid nanocomposite is promising for in vivo testing and validation.


Assuntos
Proliferação de Células , Goma Arábica , Leucemia Mieloide Aguda , Nanopartículas de Magnetita , Nanocompostos , Nanotubos de Carbono , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Goma Arábica/química , Goma Arábica/farmacologia , Proliferação de Células/efeitos dos fármacos , Nanopartículas de Magnetita/química , Linhagem Celular Tumoral , Nanocompostos/química , Nanotubos de Carbono/química , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células HL-60 , Antineoplásicos/farmacologia , Antineoplásicos/química , Células THP-1
15.
Obes Surg ; 34(9): 3420-3433, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39042309

RESUMO

INTRODUCTION: Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis. METHODS: This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes. RESULTS: Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity. CONCLUSIONS: Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.


Assuntos
Cirurgia Bariátrica , Ácidos e Sais Biliares , Fezes , Obesidade Mórbida , Humanos , Fezes/microbiologia , Projetos Piloto , Masculino , Feminino , Estudos Transversais , Estudos de Casos e Controles , Pessoa de Meia-Idade , Ácidos e Sais Biliares/metabolismo , Adulto , Obesidade Mórbida/cirurgia , Obesidade Mórbida/microbiologia , Microbioma Gastrointestinal/fisiologia , Redução de Peso , Ácido Litocólico/metabolismo
16.
Surg Infect (Larchmt) ; 25(7): 513-520, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38957977

RESUMO

Background: Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Materials and Methods: Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Results: Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m2 showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m2. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Conclusions: Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Cefazolina , Cesárea , Infecção da Ferida Cirúrgica , Humanos , Cefazolina/uso terapêutico , Cefazolina/administração & dosagem , Estudos Retrospectivos , Antibioticoprofilaxia/métodos , Feminino , Cesárea/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Adulto , Infecção da Ferida Cirúrgica/prevenção & controle , Gravidez , Cuidados Pré-Operatórios/métodos
17.
Sci Rep ; 14(1): 17426, 2024 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075176

RESUMO

Rhinoviruses (RVs) cause upper respiratory tract infections and pneumonia in children and adults. These non-enveloped viruses contain viral coats of four capsid proteins: VP1, VP2, VP3, and VP4. The canyon on VP1 used cell surface receptor ICAM-1 as the site of attachment and for the internalization of viruses. To date, there has been no drug or vaccine available against RVs. In this study, bioactive natural compounds of rosemary (Salvia rosmarinus L.), which are known for their pharmacological potential, were considered to target the VP1 protein. A total of 30 bioactive natural compounds of rosemary were taken as ligands to target viral proteins. The PkCSM tool was used to detect their adherence to Lipinski's rule of five and the ADMET properties of the selected ligands. Further, the CB-Dock tool was used for molecular docking studies between the VP1 protein and ligands. Based on the molecular docking and ADMET profiling results, phenethyl amine (4 methoxy benzyl) was selected as the lead compound. A comparative study was performed between the lead compound and two antiviral drugs, Placonaril and Nitazoxanide, to investigate the higher potential of natural compounds over synthetic drugs. Placonaril also targets VP1 but failed in clinical trials while Nitazoxanide was examined in clinical trials against rhinoviruses. It was discovered from this study that the (4 methoxy benzyl) phenethyl amine exhibited less toxicity in comparison to other tested drugs against RVs. More research is needed to determine its potential and make it a good medication against RVs.


Assuntos
Antivirais , Simulação de Acoplamento Molecular , Óleos Voláteis , Extratos Vegetais , Rhinovirus , Antivirais/farmacologia , Antivirais/química , Rhinovirus/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Rosmarinus/química , Simulação por Computador , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/química , Ligantes
18.
Cureus ; 16(6): e63237, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070494

RESUMO

Introduction While surgical indications for symptomatic cholelithiasis and biliary hypokinesia are clear, hyperkinetic biliary dyskinesia (HBD) is an underrecognized condition with poorly defined symptomology and management guidelines. HBD is typically defined as a gallbladder ejection fraction (EF) ≥ 80% on a hepatobiliary iminodiacetic acid (HIDA) scan. We aimed to identify the prevalence and radiographic reporting of HBD, physician referral patterns, and clinical outcomes following cholecystectomy. Methods  A retrospective cohort study of patients with HIDA scans completed over 21 years at our tertiary care hospital was performed. Demographics, symptomatology, referral patterns, and operative data were collected. HBD was defined as HIDA EF ≥80%. Patients with HBD who underwent cholecystectomy were analyzed. ANOVA and chi-square tests were used to compare variables among patients with or without symptom improvement using Statistical Product and Service Solutions (SPSS; IBM SPSS Statistics for Windows, Armonk, NY). Results Of 1,997 patients (73% female, mean age 51.7 years) who had HIDA scans with reported EF, 730 (36.6%) had an EF≥80%. Only 13.7% of HIDA scans with EF≥80% were reported as hyperkinetic, and the rest are "normal". Cholecystectomy was performed in 57 (7.8%) patients with EF≥80%, most being elective (89.5%) and all minimally invasive. Primary care physicians (PCPs) referred most elective cases to surgery (61.4%). The median time from HIDA to cholecystectomy was 146 days. Chronic cholecystitis was common in pathology (82.5%), while 38.6% had cholelithiasis. Overall, 53 patients (93.0%) reported symptom improvement at a median follow-up of 17.0 days. Patients without improvement had a higher prevalence of chronic gastrointestinal conditions (p<0.05), but not significantly more cholelithiasis, cholecystitis, time to surgery, or elective surgery status. Conclusions HBD is common but often underdiagnosed and thus likely underrecognized by treating physicians. Most HBD patients benefit from cholecystectomy, regardless of cholelithiasis. Patients with persistent symptoms after cholecystectomy may have confounding gastrointestinal diagnoses. Increased awareness among radiologists, referring PCPs, gastroenterologists, and surgeons about HBD and postoperative outcomes is needed to ensure that HBD is adequately treated.

19.
Biomedicines ; 12(7)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39062143

RESUMO

Phormidesmis communis strain AB_11_10 was isolated and identified using microscopy and 16s rRNA sequencing, and its phytochemical constituents were determined using liquid chromatography-quadrupole time-of-flight mass spectrometry. The isolate had a segmented filamentous shape with a blue-green color. Many biomolecules, including organic compounds, amino acids, and fatty acids, were detected. P. communis strain AB_11_10 was used to synthesize gold nanoparticles (Ph-AuNPs) by adjusting the optimum reaction conditions. The concentration, algal/precursor ratio, temperature, reaction time, and pH significantly influenced the synthesis of the Ph-AuNPs. Mixing 1 mL of 0.5 mM of HAuCl4 with 1 mL of algal extract and exposing the mixture to 100 °C for 30 min at pH 5.6 were the optimum conditions for the biosynthesis of Ph-AuNPs at a wavelength of 524.5 nm. The Ph-AuNPs were characterized using TEM, SEM, EDX, and mapping Zeta sizer and FTIR. The Ph-AuNPs had quasi-spherical to triangular shapes with an average diameter of 9.6 ± 4.3 nm. Ph-AuNPs composed of 76.10 ± 3.14% of Au and trace amounts of carbon and oxygen were detected, indicating that the P. communis strain AB_11_10 successfully synthesized Ph-AuNPs. The hydrodynamic diameter of the Ph-AuNPs was 28.5 nm, and their potential charge was -17.7 mV. O-H, N-H, C=C, N-O, C-H, and C-O were coated onto the surfaces of the Ph-AuNPs. These groups correspond to algal phytochemicals, which may have been the main reducing and stabilizing substances during the Ph-AuNP synthesis. The therapeutic activity of the Ph-AuNPs against osteosarcoma cancers was examined in MG-63 and SAOS-2 cell lines, while their biocompatibility was tested against Vero cell lines using a sulforhodamine B assay. The Ph-AuNPs had potent antitumor activity against the MG-63 and SAOS-2 cells, with a low toxicity toward Vero cells. Flow cytometry and cell cycle arrest analyses revealed that the Ph-AuNPs enhanced the apoptotic pathway and arrested the cell cycle in the MG-63 and SAOS-2 cells. P. communis strain AB_11_10 provides a new source to synthesize small, stable, and biocompatible AuNPs that act as apoptotic enhancers in osteosarcoma.

20.
Front Pharmacol ; 15: 1406653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835668

RESUMO

Background: P. aeruginosa, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Aim: We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (» minimum inhibitory concentration, MIC), on virulence and QS in P. aeruginosa. Materials and methods: The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored in vitro and in vivo. A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified. Results: Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of P. aeruginosa infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression. Conclusion: Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.

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