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1.
Avicenna J Phytomed ; 14(4): 455-469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952773

RESUMO

Objective: This study assessed the cardioprotective properties of Persicaria maculosa (PME) and Citrus sinensis (CME) hydro-methanolic extracts, besides Citrus sinensis aqueous extract (CWE) against doxorubicin (DOX)-induced cardiotoxicity. Materials and Methods: The extracts were characterized. Mice were divided into eight groups: control (saline), DOX, protected (injected with 200 mg/kg of PME, CWE or CME for 21 days, orally, and DOX), and extracts (PME, CWE or CME administration, orally, for 21 days). DOX was injected (5 mg/kg, ip) on days 8, 13 and 18 of the experiment. Cardiac tumor necrosis factor-alpha (TNF-α), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and carbonyl reductase 1 (CBR1) expression levels, besides superoxide dismutase, catalase, malondialdehyde, nitric oxide and total protein levels were evaluated. Serum lactate dehydrogenase, creatine phosphokinase cardiac isoenzyme, aspartate transaminase, cholesterol, triglycerides and creatinine levels, as well as the cardiac tissues were examined. Results: Comparing with the control, DOX considerably (p<0.01) up-regulated TNF-α expression, malondialdehyde, nitric oxide, cardiac enzymes, lipids and creatinine levels, while it significantly (p<0.01) down-regulated Nrf2 and CBR1. Additionally, DOX interfered with antioxidant enzymes' activities (p<0.01). Conversely, protected groups showed a significant (p<0.01) amelioration of DOX-induced cardiotoxic effects. Conclusion: The current study provides a new understanding of P. maculosa and C. sinensis cardioprotective mechanisms. The extracts' cardioprotective effects may be due to their antioxidant activities, ability to maintain the redox homeostasis through regulation of important antioxidant genes and primary antioxidant enzymes, and capability to recover inflammatory cytokines and lipids levels. Noteworthy, the tested extracts showed no toxic changes on the normal mice.

2.
Asian Pac J Cancer Prev ; 25(6): 2033-2042, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918665

RESUMO

OBJECTIVE: This study evaluated a specialized rehabilitation program's impact on senior cancer patients' quality of life. METHODS: one hundred and thirty patients aged ≥65 years with various cancer types undergoing/recovering from treatment were enrolled in oncology clinics in Al-Ahsa, Saudi Arabia. The intervention arm (n=65) participated in a tailored geriatric cancer rehabilitation program. The control group (n=65) received standard oncology care. The Functional Assessment of Cancer Therapy-General (FACT-G) tool assessed the quality of life across physical, social, emotional, and functional domains. T-tests and multivariate regression analyses compared outcomes. RESULT: Total FACT-G scores showed a significantly higher quality of life for the geriatric cancer rehabilitation group versus standard care. Rehabilitation patients also demonstrated meaningful improvements across physical, social, and functional subscales. Rehabilitation involvement was the most predictive factor for optimized outcomes. CONCLUSION: Specialized geriatric cancer rehabilitation meaningfully improved several quality of life domains in older patients over standard care. Despite persistent barriers, rehabilitation programming optimized older cancer patients' physical and psychosocial health. Oncology and geriatrics must collaborate to ensure evidence-based rehabilitation access meets older cohorts' unique needs.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Idoso , Neoplasias/reabilitação , Neoplasias/psicologia , Masculino , Feminino , Avaliação Geriátrica , Idoso de 80 Anos ou mais , Arábia Saudita , Prognóstico , Seguimentos , Estudos de Casos e Controles
3.
bioRxiv ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38853996

RESUMO

Background: Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics. Methods: A Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on Fusobacterium nucleatum ( Fn ), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice ( CPC-APC Min+/- ) and patients (FAP, Lynch Syndrome, PJS, and JPS). Results: The MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon Fn infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon Fn infection was higher in CPC-APC Min+/- organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs. Conclusions: Computational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.

4.
Geriatr Nurs ; 58: 274-281, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38843756

RESUMO

BACKGROUND: This study examines the experiences of geriatric nurses in palliative care. It aims to understand how these experiences influence their well-being and the quality of care. METHODS: Conducted in the Alahsa region of Saudi Arabia, the study employs qualitative methods, utilizing in-depth interviews with 12 geriatric nurses. The analysis employs a thematic approach, enriched by iterative reflections within a multidisciplinary research team. RESULTS: The analysis reveals main themes: 1) the deep emotional connections between nurses and their patients; 2) the challenges faced, including compassion fatigue, high patient mortality, and communication hurdles; 3) the impact of these challenges on the quality of care, highlighting issues like diminished empathy; 4) the coping strategies used by nurses, such as self-care practices and continuous education. CONCLUSIONS: The study concludes that coping strategies, including self-care and ongoing professional development, are vital for sustaining the nurses' well-being and ensuring the continued provision of high-quality care to Older Adults patients.

5.
Biol Proced Online ; 26(1): 16, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831428

RESUMO

BACKGROUND: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1ß), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

6.
Geriatr Nurs ; 57: 199-207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696877

RESUMO

BACKGROUND: Chronic pain diminishes the quality of life for many Older Adults individuals. Identifying effective coping methods to enhance pain resilience is imperative as populations age. Older Adults commonly use religious faith and spiritual practices to endure pain, yet little research has explored their impact on pain tolerance. METHODS: This cross-sectional study examined relationships between positive/negative religious coping styles and pain endurance in 200 Arab elders with chronic pain. Participants completed the Brief Arab Religious Coping Scale, Numeric Pain Rating Scale, WHOQOL-BREF, and demographic/medical history questionnaires. RESULTS: Quantitative analysis demonstrated significant positive associations between positive religious reappraisal and active spiritual coping with higher self-reported pain endurance (p<.05). Negative religious coping styles lacked meaningful relationships with pain tolerance. Multiple regression confirmed the unique effects of reappraisal and spiritual practice on improving pain resilience, controlling for covariates. CONCLUSIONS: Outcomes align with perspectives highlighting multidimensional neurocognitive, emotional, and psychosocial pain relief from religious coping. Findings underscore integrating positive faith-based resources in biopsychosocial paradigms for Older Adult's pain management. Additional research should investigate causal pathways and contextual factors influencing religious coping effects on diverse Older Adult subgroups.


Assuntos
Adaptação Psicológica , Árabes , Dor Crônica , Humanos , Masculino , Feminino , Estudos Transversais , Idoso , Dor Crônica/psicologia , Árabes/psicologia , Inquéritos e Questionários , Resiliência Psicológica , Qualidade de Vida/psicologia , Espiritualidade , Manejo da Dor/psicologia , Medição da Dor
7.
bioRxiv ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38746404

RESUMO

The host EnguLfment and cell MOtility protein 1 (ELMO1) is a cytosolic microbial sensor that facilitates bacterial sensing, internalization, clearance, and inflammatory responses. We have shown previously that ELMO1 binds bacterial effector proteins, including pathogenic effectors from Salmonella and controls host innate immune signaling. To understand the ELMO1-regulated host pathways, we have performed liquid chromatography Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the global quantification of proteins regulated by ELMO1 in macrophages during Salmonella infection. Comparative proteome analysis of control and ELMO1-depleted murine J774 macrophages after Salmonella infection quantified more than 7000 proteins with a notable enrichment in mitochondrial-related proteins. Gene ontology enrichment analysis revealed 19 upregulated and 11 downregulated proteins exclusive to ELMO1-depleted cells during infection, belonging to mitochondrial functions, metabolism, vesicle transport, and the immune system. By assessing the cellular energetics via Seahorse analysis, we found that Salmonella infection alters mitochondrial metabolism, shifting it from oxidative phosphorylation to glycolysis. Importantly, these metabolic changes are significantly influenced by the depletion of ELMO1. Furthermore, ELMO1 depletion resulted in a decreased ATP rate index following Salmonella infection, indicating its importance in counteracting the effects of Salmonella on immunometabolism. Among the proteins involved in mitochondrial pathways, mitochondrial fission protein DRP1 was significantly upregulated in ELMO1-depleted cells and in ELMO1-KO mice intestine following Salmonella infection. Pharmacological Inhibition of DRP1 revealed the link of the ELMO1-DRP1 pathway in regulating the pro-inflammatory cytokine TNF-α following infection. The role of ELMO1 has been further characterized by a proteome profile of ELMO1-depleted macrophage infected with SifA mutant and showed the involvement of ELMO1-SifA on mitochondrial function, metabolism and host immune/defense responses. Collectively, these findings unveil a novel role for ELMO1 in modulating mitochondrial functions, potentially pivotal in modulating inflammatory responses. Significance Statement: Host microbial sensing is critical in infection and inflammation. Among these sensors, ELMO1 has emerged as a key regulator, finely tuning innate immune signaling and discriminating between pathogenic and non-pathogenic bacteria through interactions with microbial effectors like SifA of Salmonella . In this study, we employed Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the proteome alterations mediated by ELMO1 in macrophages following WT and SifA mutant Salmonella infection. Our findings highlight a substantial enrichment of host proteins associated with metabolic pathways and mitochondrial functions. Notably, we validated the mitochondrial fission protein DRP1 that is upregulated in ELMO1-depleted macrophages and in ELMO1 knockout mice intestine after infection. Furthermore, we demonstrated that Salmonella -induced changes in cellular energetics are influenced by the presence of ELMO1. This work shed light on a possible novel link between mitochondrial dynamics and microbial sensing in modulating immune responses.

8.
Sci Rep ; 14(1): 11395, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762558

RESUMO

In order to protect the copper against corrosion, a novel corrosion inhibitor known as diphenyl ((2-aminoethyl) amino) (4-methoxyphenyl) methyl) phosphonate (DAMP) was developed. Acid solutions of HCl and H2SO4 were the aggressive solutions employed in this study. Analysis using the FT-IR, 1H-NMR, 31P-NMR, 13C-NMR and BET confirmed that the DAMP was successfully synthesized. The anti-corrosion capabilities of DAMP are evaluated using a combination of chemical, electrochemical and quantum studies. The DAMP has been found to be crucial in preventing the corrosion of copper in both HCl and H2SO4 acid. This was obviously implied by the observation that the corrosion rate of copper in acid solutions decreased when DAMP was added. It is significant to note that 180 ppm produced the highest levels of inhibiting efficiency (96.6% for HCl and 95.2% for H2SO4). The tendency of DAMP to adsorb on the surface of copper through its hetero-atoms (O, N, and P) is the main factor for the anti-corrosion capabilities of DAMP. Results from SEM/EDX tests supported this. The actual adsorption takes place via various active centers, physical and chemical mechanisms that are coordinated with the estimated quantum parameters. Additionally, the adsorption of DAMP adheres to the Langmuir isotherm.

9.
Chemosphere ; 359: 142362, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38768786

RESUMO

Quantitative Structure Activity Relation (QSAR) models are mathematical techniques used to link structural characteristics with biological activities, thus considered a useful tool in drug discovery, hazard evaluation, and identifying potentially lethal molecules. The QSAR regulations are determined by the Organization for Economic Cooperation and Development (OECD). QSAR models are helpful in discovering new drugs and chemicals to treat severe diseases. In order to improve the QSAR model's predictive power for biological activities of naturally occurring indoloquinoline derivatives against different cancer cell lines, a modified machine learning (ML) technique is presented in this paper. The Arithmetic Optimization Algorithm (AOA) operators are used in the suggested model to enhance the performance of the Sinh Cosh Optimizer (SCHO). Moreover, this improvement functions as a feature selection method that eliminates superfluous descriptors. An actual dataset gathered from previously published research is utilized to evaluate the performance of the suggested model. Moreover, a comparison is made between the outcomes of the suggested model and other established methodologies. In terms of pIC50 values for different indoloquinoline derivatives against human MV4-11 (leukemia), human HCT116 (colon cancer), and human A549 (lung cancer) cell lines, the suggested model achieves root mean square error (RMSE) of 0.6822, 0.6787, 0.4411, and 0.4477, respectively. The biological application of indoloquinoline derivatives as possible anticancer medicines is predicted with a high degree of accuracy by the suggested model, as evidenced by these findings.


Assuntos
Algoritmos , Relação Quantitativa Estrutura-Atividade , Quinolinas , Humanos , Quinolinas/química , Quinolinas/farmacologia , Linhagem Celular Tumoral , Aprendizado de Máquina , Antineoplásicos/farmacologia , Antineoplásicos/química , Indóis/química , Indóis/farmacologia
10.
Int J Nanomedicine ; 19: 3537-3554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638365

RESUMO

Introduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology. Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut. Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 µg; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis. Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results. Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non-invasive IBD therapy.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Dióxido de Silício , Humanos , Camundongos , Animais , Células CACO-2 , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Peptídeos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico
11.
Cureus ; 16(3): e55974, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601400

RESUMO

Atrial myxoma, though the most common primary cardiac tumor, often presents with nonspecific symptoms that can obscure its diagnosis. This case report details an unusual presentation of dyspnea on exertion (DOE) in a patient initially considered to have chronic obstructive pulmonary disease (COPD), a common pulmonary etiology of DOE. The diagnostic journey underscores the critical importance of considering atrial myxoma in patients with DOE, especially when symptoms are not fully explained by apparent pulmonary conditions. Our findings highlight the necessity of a comprehensive diagnostic approach, including the early use of resting transthoracic echocardiogram, to unveil less common causes like atrial myxoma. This case reinforces the pivotal role of considering alternative diagnoses in complex presentations of DOE, thereby guiding more accurate and tailored patient management.

12.
Stem Cell Rev Rep ; 20(5): 1299-1310, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38498294

RESUMO

OBJECTIVE AND DESIGN: Annexin A1 (ANXA1) plays a role in maintaining intestinal hemostasis, especially following mucosal inflammation. The published data about ANXA1 was derived from experimental animal models where there is an overlapping between epithelial and immune cells. There is no in vitro gut epithelial model that can assess the direct effect of ANXA1 on the gut epithelium. METHODS: We developed high-throughput stem-cell-based murine epithelial cells and bacterial lipopolysaccharides (LPS) were used to induce inflammation. The impact of ANXA1 and its functional part (Ac2-26) was evaluated in the inflamed model. Intestinal integrity was assessed by the transepithelial electrical resistance (TEER), and FITC-Dextran permeability. Epithelial junction proteins were assessed using confocal microscopy and RT-qPCR. Inflammatory cytokines were evaluated by RT-qPCR and ELISA. RESULTS: LPS challenge mediated a damage in the epithelial cells as shown by a drop in the TEER and an increase in FITC-dextran permeability; reduced the expression of epithelial junctional proteins (Occludin, ZO-1, and Cadherin) and increased the expression of the gut leaky protein, Claudin - 2. ANXA1 and Ac2-26 treatment reduced the previous damaging effects. In addition, ANXA1 and Ac2-26 inhibited the inflammatory responses mediated by the LPS and increased the transcription of the anti-inflammatory cytokine, IL-10. CONCLUSION: ANXA1 and Ac2-26 directly protect the epithelial integrity by affecting the expression of epithelial junction and inflammatory markers. The inflamed gut model is a reliable tool to study intestinal inflammatory diseases, and to evaluate the efficacy of potential anti-inflammatory drugs and the screening of new drugs that could be candidates for inflammatory bowel disease.


Assuntos
Anexina A1 , Inflamação , Mucosa Intestinal , Lipopolissacarídeos , Anexina A1/metabolismo , Anexina A1/genética , Animais , Lipopolissacarídeos/farmacologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Citocinas/metabolismo , Permeabilidade , Peptídeos
13.
J Orthod Sci ; 13: 7, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516108

RESUMO

BACKGROUND: Demineralization of the enamel surface, which appears as white spot lesions during and after removal of the fixed orthodontic appliance, is the most common disadvantage of the orthodontic treatment course. Using the remineralizing agents during and after orthodontic treatment helps to avoid those enamel defects. OBJECTIVE: The present study aims to assess the remineralizing effect of the chicken eggshell powder on the demineralized enamel surfaces after debonding the orthodontic bracket system. MATERIALS AND METHODS: The current study was performed on 80 prepared premolar crowns embedded into acrylic molds. The samples were prepared to receive routine steps of the bonding process for the bracket system. The paste of the chicken eggshell powder was added to the samples after the debonding process. Scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) were used to evaluate the remineralization effect of the chicken eggshell powder. Also, the Vickers microhardness tester was used to assess the enamel surface microhardness. RESULTS: It was found that the mean value of the Ca/P ratio for the samples before bonding of the orthodontic bracket system was (4.17 ± 2.2). This value significantly decreased to (2 ± 1.3) after debonding of the orthodontic bracket system and then showed a significant increase to (4.79 ± 2.65) after remineralization. These results were assured by the values of the Vickers microhardness tester. CONCLUSION: The chicken eggshell powder has an excellent remineralization effect for the demineralized enamel surface after debonding the orthodontic enamel surface.

14.
Int J Gen Med ; 17: 669-683, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435115

RESUMO

Introduction: Gastroesophageal reflux disease (GERD) and functional constipation (FC) are two common gastrointestinal disorders that affect many age groups in the community. A few studies were conducted to find the association between GERD and FC, but no study had been conducted in Saudi Arabia. Therefore, this study aims to find the overlap between GERD and FC and associated risk factors among the general population in the Eastern Province, Saudi Arabia. Methods: A cross-sectional study was conducted in the eastern province of Saudi Arabia between August and September 2022. GERDQ and Rome IV criteria were used to collect the data with participants' characteristics through an online questionnaire. Results: Out of 2007 respondents, 1481 filled the required criteria, among them 320 (21.6%) had GERD, and 1292 (87.2%) respondents had FC based on the listed criteria. Eighty percent of respondents with GERD had overlapping FC. Men were more likely than women to experience this significant relationship (53.1% versus 46.9%). Conclusion: There is a significant relationship between GERD and FC among the general population of the eastern province of Saudi Arabia. Consequently, this study could be used to improve the understanding of the overlapping between these gastrointestinal disorders and further new guidelines could be carried out to find the best treatment for these patients.

15.
Anticancer Agents Med Chem ; 24(6): 436-442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305388

RESUMO

BACKGROUND: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. OBJECTIVE: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. METHODS: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. RESULTS: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. CONCLUSION: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.


Assuntos
Antineoplásicos , Carcinoma de Ehrlich , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Estresse Oxidativo , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Quinolinas , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , PTEN Fosfo-Hidrolase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinolinas/farmacologia , Quinolinas/química , Quinolinas/síntese química , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Alcaloides Indólicos
16.
Int J Biol Macromol ; 255: 128125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984571

RESUMO

Transforming lignin into aromatic monomers is critically attractive to develop green and sustainable energy supplies. However, the usage of the additional catalysts like metal or base/acid is commonly limited by the caused repolymerized and environmental issues. The key step is to mediate electron transfer in lignin to trigger lignin C-C/C-O bonds cleavage without the catalysts mentioned above. Here, we report that the ionic liquids [BMim][ClO4] was found to trigger lignin electron transfer to cleave the C-C/C-O bonds for aromatic monomers without any additional catalyst. The proton transfer from [BMim]+ to [ClO4]- could polarize the anion and decrease its structure stability, upon which the active hydroxyl radical generated and induced lignin C-C/C-O bonds fragmentation via free radical-mediated routes with the assistance of photothermal synergism. About 4.4 wt% yields of aromatic monomers, mainly composed of vanillin and acetosyringone, are afforded in [BMim][ClO4] under UV-light irradiation in the air at 80 °C. This work opens the way to produce value-added aromatic monomers from lignin using an eco-friendly, energy-efficient, and simple route that may contribute to the sustainable utilization of renewable natural resources.


Assuntos
Líquidos Iônicos , Líquidos Iônicos/química , Lignina/química , Álcalis , Percloratos , Catálise
17.
J Hazard Mater ; 465: 133203, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38103294

RESUMO

Antibacterial compounds that reduce extracellular polymeric substances (EPS) are needed to avoid bacterial biofilms in water pipelines. Herein, green one-pot synthesis of α-aminophosphonates (α-Amps) [A-G] was achieved by using ionic liquid (IL) as a Lewis acid catalyst. The synthesized α-Amp analogues were tested against different bacteria such as Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The representative [B] analogue showed an efficient antibacterial effect with MIC values of 3.13 µg/mL for E. coli, P. aeruginosa, and 6.25 µg/mL for B. subtilis. Additionally, a strong ability to eliminate the mature bacterial biofilm, with super-MIC values of 12.5 µg/mL for E. coli, P. aeruginosa, and 25 µg/mL for B. subtilis. Moreover, bacterial cell disruption by ROS formation was also tested, and the compound [B] revealed the highest ROS level compared to other compounds and the control, and efficiently destroyed the extracellular polymeric substances (EPS). The docking study confirmed strong interactions between [B] analogue and protein structures with a binding affinity of -6.65 kCal/mol for the lyase protein of gram-positive bacteria and -6.46 kCal/mol for DNA gyrase of gram-negative bacteria. The results showed that α-Amps moiety is a promising candidate for developing novel antibacterial and anti-biofilm agents for clean water supply.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/química , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio , Bactérias , Biofilmes , Testes de Sensibilidade Microbiana
18.
Nat Commun ; 14(1): 8169, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071370

RESUMO

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.


Assuntos
COVID-19 , DNA Glicosilases , Cricetinae , Animais , Humanos , COVID-19/genética , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Genoma , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo
19.
Microorganisms ; 11(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38138042

RESUMO

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are transmitted through the fecal-oral route. HAV outbreaks and one HEV outbreak have been reported in Egypt. However, the impact of HAV-HEV co-infection is not known. In this study, we assessed HEV markers in acute HAV-infected patients (n = 57) enrolled in Assiut University hospitals. We found that 36.8% of HAV-infected patients were also positive for HEV markers (anti-HEV IgM and HEV RNA), while 63.2% of the patients were HAV mono-infected. Demographic and clinical criteria were comparable in both HAV mono-infected patients and HAV-HEV co-infected patients. Although liver enzymes were not significantly different between the two groups, liver transaminases were higher in the co-infected patients. Six patients developed acute liver failure (ALF); five of them were HAV-HEV-co-infected patients. The relative risk of ALF development was 8.5 times higher in HAV-HEV co-infection compared to mono-infection. Three cases of ALF caused by HAV-HEV co-infection were reported in children (below 18 years) and two cases were reported in adults. All patients developed jaundice, coagulopathy, and encephalopathy; all were living in rural communities. In conclusion: HAV-HEV co-infection can be complicated by ALF. The risk of ALF development in HAV-infected patients is higher when coinfection with HEV is present.

20.
Microorganisms ; 11(12)2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38138096

RESUMO

Acute hepatitis is defined as an inflammation or injury in the hepatocytes that continues for a short period of time (less than 6 months) [...].

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