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1.
Mol Genet Genomics ; 299(1): 56, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787424

RESUMO

Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.


Assuntos
Proteína Beclina-1 , Neoplasias da Mama , Gradação de Tumores , RNA Mensageiro , Humanos , Feminino , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Intervalo Livre de Doença , Biomarcadores Tumorais/genética , Idoso , Egito
2.
Chembiochem ; : e202400417, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923227

RESUMO

MicroRNAs (miRNAs) regulate gene expression through RNA interference. Consequently, miRNA inhibitors, such as anti-miRNA oligonucleotides (AMOs), have attracted attention for treating miRNA overexpression. To achieve efficient inhibition, we developed 2-amino-6-vinylpurine (AVP) nucleosides that form covalent bonds with uridine counterparts in RNA. We demonstrated that mRNA cross-linked with AVP-conjugated antisense oligonucleotides with AVP were protected from gene silencing by exogenous miRNA. However, endogenous miRNA function could not be inhibited in cells, probably because of slow cross-linking kinetics. We recently developed ADpVP, an AVP derivative bearing a 7-propynyl group-which boasts faster reaction rate than the original AVP. Here, we synthesized dADpVP-a deoxy analog of ADpVP-through a simplified synthesis protocol. Evaluation of the cross-linking reaction revealed that the reaction kinetics of dADpVP were comparable to those of ADpVP. In addition, structural analysis of the cross-linked adduct discovered N3 linkage against uridine. Incorporating dADpVP into two types of miRNA inhibitors revealed a marginal impact on AMO efficacy yet improved the performance of target site blockers. These results indicate the potential of cross-linking nucleosides for indirect miRNA function inhibition.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38850492

RESUMO

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

4.
Int J Mol Sci ; 25(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38473901

RESUMO

One of the most significant environmental challenges to crop growth and yield worldwide is soil salinization. Salinity lowers soil solution water potential, causes ionic disequilibrium and specific ion effects, and increases reactive oxygen species (ROS) buildup, causing several physiological and biochemical issues in plants. Plants have developed biological and molecular methods to combat salt stress. Salt-signaling mechanisms regulated by phytohormones may provide additional defense in salty conditions. That discovery helped identify the molecular pathways that underlie zinc-oxide nanoparticle (ZnO-NP)-based salt tolerance in certain plants. It emphasized the need to study processes like transcriptional regulation that govern plants' many physiological responses to such harsh conditions. ZnO-NPs have shown the capability to reduce salinity stress by working with transcription factors (TFs) like AP2/EREBP, WRKYs, NACs, and bZIPs that are released or triggered to stimulate plant cell osmotic pressure-regulating hormones and chemicals. In addition, ZnO-NPs have been shown to reduce the expression of stress markers such as malondialdehyde (MDA) and hydrogen peroxide (H2O2) while also affecting transcriptional factors. Those systems helped maintain protein integrity, selective permeability, photosynthesis, and other physiological processes in salt-stressed plants. This review examined how salt stress affects crop yield and suggested that ZnO-NPs could reduce plant salinity stress instead of osmolytes and plant hormones.


Assuntos
Nanopartículas , Óxido de Zinco , Antioxidantes/farmacologia , Salinidade , Peróxido de Hidrogênio/metabolismo , Óxido de Zinco/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Solo , Estresse Fisiológico
5.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892391

RESUMO

Plants endure the repercussions of environmental stress. As the advancement of global climate change continues, it is increasingly crucial to protect against abiotic and biotic stress effects. Some naturally occurring plant compounds can be used effectively to protect the plants. By externally applying priming compounds, plants can be prompted to trigger their defensive mechanisms, resulting in improved immune system effectiveness. This review article examines the possibilities of utilizing exogenous alpha-, beta-, and gamma-aminobutyric acid (AABA, BABA, and GABA), which are non-protein amino acids (NPAAs) that are produced naturally in plants during instances of stress. The article additionally presents a concise overview of the studies' discoveries on this topic, assesses the particular fields in which they might be implemented, and proposes new avenues for future investigation.


Assuntos
Aminoácidos , Estresse Fisiológico , Aminoácidos/metabolismo , Plantas/metabolismo , Mudança Climática , Ácido gama-Aminobutírico/metabolismo
6.
BMC Oral Health ; 24(1): 760, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965507

RESUMO

BACKGROUND: Preservation of the remaining structures while maintaining an esthetic appearance is a major objective in removable partial prosthodontics. So, the aim of the current study was to compare the stresses induced on the supporting structures by two digitally produced esthetic core materials; Zirconia and Polyetheretherketone when used as an extracoronal attachment in distal extension removable partial dentures using strain gauge analysis. METHODS: A mandibular Kennedy class II stone cast with the necessary abutments' preparations was scanned. The mandibular left canine and first premolar teeth were virtually removed. An acrylic mandibular left canine and first premolar teeth were prepared with heavy chamfer finish line and scanned. Virtual superimposition of the acrylic teeth in their corresponding positions was done. Two strain gauge slots were designed: distal to the terminal abutment and in the residual ridge. Two models and two sets of scanned teeth were digitally printed. The printed teeth were then placed in their corresponding sockets in each model and scanned. The attachment design was selected from the software library and milled out of Zirconia in the model ZR and Polyetheretherketone in the model PE. Five removable partial dentures were constructed for each model. The strain gauges were installed in their grooves. A Universal testing machine was used for unilateral load application of 100 N (N). For each removable partial denture, five measurements were made. The data followed normal distribution and were statistically analyzed by using unpaired t test. P value < 0.05 was considered to be statistically significant. RESULTS: During unilateral loading unpaired t test showed statistically significant difference (p = 0.0001) in the microstrain values recorded distal to the abutment between the models ZR (-1001.6 µÎµ ± 24.56) and PE (-682.6 µÎµ ± 22.18). However, non statistically significant difference (p = 0.3122) was observed in the residual ridge between them; ZR (16.2 µÎµ ± 4.53) and PE (15 µÎµ ± 3.74). CONCLUSIONS: In removable partial dentures, Polyetheretherketone extracoronal attachment induces less stress on the supporting abutments compared to the zirconia one with no difference in the stresses induced by them on the residual ridge.


Assuntos
Benzofenonas , Planejamento de Dentadura , Prótese Parcial Removível , Cetonas , Polímeros , Zircônio , Cetonas/química , Humanos , Zircônio/química , Polietilenoglicóis , Análise do Estresse Dentário , Materiais Dentários/química , Desenho Assistido por Computador , Dente Suporte , Estresse Mecânico , Estética Dentária , Teste de Materiais
7.
BMC Oral Health ; 24(1): 410, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566034

RESUMO

BACKGROUND: To clinically compare the effect of the conventional and the digital workflows on the passive fit of a screw retained bar splinting two inter-foraminal implants. METHODS: The current study was designed to be a parallel triple blinded randomised clinical trial. Thirty six completely edentulous patients were selected and simply randomized into two groups; conventional group (CG) and digital group (DG). The participants, investigator and outcome assessor were blinded. In the group (CG), the bar was constructed following a conventional workflow in which an open top splinted impression and a lost wax casting technology were used. However, in group (DG), a digital workflow including a digital impression and a digital bar milling technology was adopted. Passive fit of each bar was then evaluated clinically by applying the screw resistance test using the "flag" technique in the passive and non passive situations. The screw resistance test parameter was also calculated. Unpaired t-test was used for intergroup comparison. P-value < 0.05 was the statistical significance level. The study protocol was reviewed by the Research Ethics Committee in the author's university (Rec IM051811). Registration of the clinical trial was made on clinical trials.gov ID NCT05770011. An informed consent was obtained from all participants. RESULTS: Non statistically significant difference was denoted between both groups in all situations. In the passive situation, the mean ± standard deviation values were 1789.8° ± 20.7 and1786.1° ± 30.7 for the groups (CG) and (DG) respectively. In the non passive situation, they were 1572.8° ± 54.2 and 1609.2° ± 96.9. Regarding the screw resistance test parameter, they were 217° ± 55.3 and 176° ± 98.8. CONCLUSION: Conventional and digital fabrication workflows had clinically comparable effect on the passive fit of screw retained bar attachments supported by two dental implants.


Assuntos
Parafusos Ósseos , Implantes Dentários , Boca Edêntula , Humanos , Desenho Assistido por Computador , Técnica de Moldagem Odontológica , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante/métodos , Fluxo de Trabalho
8.
J Prosthodont ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520400

RESUMO

PURPOSE: Evaluation of the strain transmitted to the abutments and residual ridge by polyetherketoneketone material compared to the cobalt-chromium one in distal extension removable partial dentures (RPDs) to fulfill the objective of preservation of the supporting structures. MATERIALS AND METHODS: A virtual model simulating a Kennedy class I partially edentulous mandibular arch was designed. Two models, one for each group, were printed. Five RPDs were made in each group. In group CR, the framework was milled from a cobalt-chromium alloy. While in group PK, it was milled from a polyetherketoneketone blank. Strain gauge rosettes were bonded distal to the last abutment and posteriorly in the distal end of the residual ridge. Unilateral vertical and oblique loadings were applied. Mann-Whitney U test was used for inter-group comparisons while the Friedman test was used for intra-group comparisons and corrected by Wilcoxon Signed-Rank Sum. The significance level was set at p ≤ 0.05. RESULTS: During unilateral vertical load application, a statistically significant difference was found between both groups distal to the abutment in the loaded and unloaded sides as well as the residual ridge on the unloaded side. During oblique load application, a statistically significant difference was found between both groups in all slots. CONCLUSION: Polyetherketoneketone material induces less stress on the abutments and more stress on the residual ridges compared to the cobalt-chromium ones. Therefore, it may be recommended for weak abutments supporting RPDs.

9.
Oncologist ; 28(5): e254-e262, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36648325

RESUMO

BACKGROUND: Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. METHOD: This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). RESULTS: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). CONCLUSION: Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Sunitinibe/uso terapêutico , Carcinoma de Células Renais/patologia , Bevacizumab/efeitos adversos , Neoplasias Renais/patologia , Anticorpos Monoclonais Humanizados , Pirróis/efeitos adversos
10.
Ann Surg Oncol ; 30(1): 426-432, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36042103

RESUMO

BACKGROUND: The peritoneum frequently is the only recurrence site after radical resection of gastric cancer. Data suggest that hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) reduce peritoneal recurrence and possibly improve survival for patients with resected gastric and serosal involvement. This study aimed to evaluate the efficacy of combining prophylactic HIPEC and IORT after radical resection of localized gastric cancer. METHODS: In this retrospective study, the medical records of adult patients with histologically proven gastric/gastroesophageal adenocarcinoma who underwent radical resection with curative intent were evaluated for recurrence and survival according to whether they received prophylactic HIPEC and IORT. RESULTS: The eligibility criteria were met by 58 patients, 33 of whom underwent prophylactic HIPEC and IORT after radical surgery. Overall, 91% the HIPEC/IORT group and 72% of the surgery-only group had ≤pT3 disease. The median follow-up period was 26.6 months for the HIPEC/IORT group and 50.6 months for the surgery group. Locoregional recurrence occurred for six patients (18.1%) in the HIPEC/IORT group and five patients (20%) in the surgery-only group, with peritoneal metastasis (PM) occurring in respectively three (9%) and six (24%) patients. The median recurrence-free survival (RFS) duration was 23.2 months (95% confidence interval [CI] 6.5-39.9 months) for the HIPEC/IORT group versus 24.8 months (95% CI 0.0-51.1 months) for the surgery-only group (p = 0.88), and the corresponding 5-year overall survival (OS) estimates were 69% and 58%. CONCLUSION: Prophylactic HIPEC and IORT after radical surgery for localized gastric or gastroesophageal cancer did not improve RFS or OS for an unselected group of patients at risk for peritoneal recurrence.


Assuntos
Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Junção Esofagogástrica
11.
Heart Fail Rev ; 28(2): 407-417, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36289131

RESUMO

This study hypothesized that imaging provides information indicating the right ventricular (RV) involvement after anterior or inferior ST-elevation myocardial infarction (STEMI), beyond standard electrocardiogram (ECG) due to the increasing interest in RV function and assessment techniques. This study aimed to compare RV function between anterior and inferior MI without RV involvement using different echocardiographic modalities. This study included 100 patients with anterior (50 patients) and inferior (50 patients) STEMI, who underwent primary percutaneous coronary intervention (PPCI) and two-dimensional echocardiographic imaging within 24 h after PPCI with RV function analysis by left ventricular (LV) infarct size, LV filling pressure, and RV strain rate. Our primary endpoint was the subclinical RV dysfunction in anterior or inferior MI using tissue Doppler and speckle tracking (STE). The study population included 80 (80%) males and 20 (20%) females. Patients with the anterior STEMI had higher mean creatine kinase-MB (CKMB) and troponin than those with inferior STEMI. This study revealed worse RV dysfunction in patients with anterior than those with inferior STEMI, as reflected by significantly lower RV systolic function, tricuspid annular plane systolic excursion (p ≤ 0.0001), tissue Doppler-derived velocity (p ≤ 0.0001), and STE-derived strain magnitude and rate (p ≤ 0.0001). RV dysfunction occurs in patients without ECG evidence of RV STEMI. RV dysfunction is worse in anterior than inferior MI. Moreover, RV systolic functions were affected by declined LV ejection fraction irrespective of the infarction site, which clinically implies prognostic, treatment, survival rate, and outcome improvement between both conditions. (Trial registration ZU-IRB#:4142/26-12-2017 Registered 26 December 2017, email: IRB_123@medicine.zu.edu.eg).


Assuntos
Infarto Miocárdico de Parede Inferior , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Disfunção Ventricular Direita , Masculino , Feminino , Humanos , Ecocardiografia/métodos
12.
Bioorg Med Chem Lett ; 95: 129485, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714498

RESUMO

The ubiquitin-proteasome system serves as the major proteolytic degradation pathway in eukaryotic cells. Many inhibitors that covalently bind to the proteasome's active sites have been developed for hematological cancers, but resistance can arise in patients. To overcome limitations of active-site proteasome inhibitors, we and others have focused on developing ligands that target subunits on the 19S regulatory particle (19S RP). One such 19S RP subunit, Rpn-13, is a ubiquitin receptor required for hematological cancers to rapidly degrade proteins to avoid apoptosis. Reported Rpn-13 inhibitors covalently bind to the Rpn-13's Pru domain and have been effective anti-hematological cancer agents. Here, we describe the discovery of TCL-1, a non-covalent binder to the Pru domain. Optimization of TCL-1's carboxylate group to an ester increases its cytotoxicity in hematological cancer cell lines. Altogether, our data provides a new scaffold for future medicinal chemistry optimization to target Rpn-13 therapeutically.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/química , Ubiquitina/metabolismo , Neoplasias Hematológicas/tratamento farmacológico
13.
Rev Med Virol ; 32(5): e2339, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35213764

RESUMO

In dengue-endemic regions, the co-infection with SARS-CoV-2 and dengue is a significant health concern. Therefore, we performed a literature search for relevant papers in seven databases on 26 Spetember 2021. Out of 24 articles, the mortality rate and intensive care unit (ICU) admission were 19.1% and 7.8%, respectively. The mean hospital stay was 11.4 days. In addition, we identified two pregnancies with dengue and COVID-19 co-infection; one ended with premature rupture of membrane and intrauterine growth restriction fetus, while the other one ended with maternal mortality and intrauterine fetal death. COVID-19 and dengue co-infection had worse outcomes regarding mortality rates, ICU admission, and prolonged hospital stay. Thus, wise-decision management approaches should be adequately offered to these patients to enhance their outcomes. Establishing an early diagnosis might be the answer to reducing the estimated significant burden of these conditions.


Assuntos
COVID-19 , Coinfecção , Dengue , Nascimento Prematuro , Coinfecção/epidemiologia , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Feminino , Humanos , Gravidez , SARS-CoV-2
14.
Rev Med Virol ; 32(2): e2278, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34260773

RESUMO

Parkinson's disease (PD) patients who contracted Coronavirus disease 2019 (Covid-19) had a decline in motor functions; nevertheless, there is limited evidence on whether PD patients have a higher risk for contracting Covid-19 or have worse outcomes. This is the first systematic review and meta-analysis to review the impact of PD on the prognosis of Covid-19 patients. We performed a systematic search through seven electronic databases under the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analyses statement (PRISMA) guidelines. The R software version 4.0.2 was used to calculate pooled sample sizes and their associated confidence intervals (95%CI). Finally, we included 13 papers in this study. The pooled prevalence rate of Covid-19 was 2.12% (95%CI: 0.75-5.98). Fever, cough, fatigue and anorexia were the most common symptoms with a rate of 72.72% (95% CI: 57.3 - 92.29), 66.99% (95% CI: 49.08-91.42), 61.58% (95% CI: 46.69-81.21) and 52.55% (95% CI: 35.09-78.68), respectively. The pooled rates were 39.89% (95% CI: 27.09-58.73) for hospitalisation, 4.7% (95% CI: 1.56-14.16) for ICU admission and 25.1% (95%CI: 16.37-38.49) for mortality. On further comparison of hospitalisation and mortality rates among Covid-19 patients with and without PD, there were no significant differences. In conclusion, the prevalence and prognosis of Covid-19 patients seem comparable in patients with PD and those without it. The increased hospitalisation and mortality may be attributed to old age and co-morbidities.


Assuntos
COVID-19 , Doença de Parkinson , COVID-19/epidemiologia , Hospitalização , Humanos , Doença de Parkinson/epidemiologia , Prevalência , SARS-CoV-2
15.
Cell Mol Life Sci ; 79(12): 603, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434396

RESUMO

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM-PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear-cytoplasmic shuttling mediated by the nuclear export receptor CRM1.


Assuntos
Ataxia Telangiectasia , Animais , Camundongos , Ataxia Telangiectasia/genética , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas de Ligação a DNA/metabolismo , Fibroblastos/metabolismo , Proteínas Nucleares/metabolismo , Dano ao DNA
16.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1083-1090, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36435917

RESUMO

INTRODUCTION: To compare sutureless deep sclerectomy to conventional deep sclerectomy regarding their lowering effect on intraocular pressure (IOP) in cases with open-angle glaucoma. METHODS: This is a prospective interventional randomized comparative study that included 60 eyes of 50 patients with open-angle glaucoma (OAG) who were indicated for surgical intervention. Patients were recruited from the glaucoma subspecialty clinic of the Cairo University teaching hospital and were divided into two groups: group A (underwent sutureless deep sclerectomy) and group B (underwent conventional deep sclerectomy). RESULTS: Both surgeries showed significant reduction of IOP all through the study period: in group A, mean reduction was 71.37%, 53.35%, 50.3%, and 44.33% at 1st day, 1 month, 3 months, and 6 months respectively, and in group B, mean reduction was 57.62%, 40.63%, 37.41%, and 31.68% at 1st day, 1 month, 3 months, and 6 months, respectively. Comparison between percentage of reduction in both groups showed no statistically significant difference. Also, use of anti-glaucoma medications dropped significantly at 6 months postoperatively in both groups with no significant difference between the 2 groups. Regarding reported complications, 12.9% in group A and 10.3% in group B presented with non-serious complications. One month postoperatively, UBM detected non-functioning blebs in 6.4% of group A and 3.4% in group B. Other cases with non-functioning blebs were detected at 3 and 6 months postoperatively, and all cases were managed. CONCLUSION: Sutureless deep sclerectomy seems to be a safe and effective modification, with significant IOP reduction in POAG.


Assuntos
Glaucoma de Ângulo Aberto , Esclerostomia , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular , Estudos Prospectivos , Esclera/cirurgia , Resultado do Tratamento
17.
Sensors (Basel) ; 23(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36772411

RESUMO

In recent years, harvesting energy from ubiquitous ultralow-frequency vibration sources, such as biomechanical motions using piezoelectric materials to power wearable devices and wireless sensors (e.g., personalized assistive tools for monitoring human locomotion and physiological signals), has drawn considerable interest from the renewable energy research community. Conventional linear piezoelectric energy harvesters (PEHs) generally consist of a cantilever beam with a piezoelectric patch and a proof mass, and they are often inefficient in such practical applications due to their narrow operating bandwidth and low voltage generation. Multimodal harvesters with multiple resonances appear to be a viable solution, but most of the previously proposed designs are unsuitable for ultralow-frequency vibration. This study investigated a novel multimode design, which included a bent branched beam harvester (BBBH) to enhance PEHs' bandwidth output voltage and output power for ultralow-frequency applications. The study was conducted using finite element method (FEM) analysis to optimize the geometrical design of the BBBH on the basis of the targeted frequency spectrum of human motion. The selected design was then experimentally studied using a mechanical shaker and human motion as excitation sources. The performance was also compared to the previously proposed V-shaped bent beam harvester (VBH) and conventional cantilever beam harvester (CBH) designs. The results prove that the proposed BBBH could harness considerably higher output voltages and power with lower idle time. Its operating bandwidth was also remarkably widened as it achieved three close resonances in the ultralow-frequency range. It was concluded that the proposed BBBH outperformed the conventional counterparts when used to harvest energy from ultralow-frequency sources, such as human motion.

18.
Sensors (Basel) ; 23(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37299984

RESUMO

Piezoelectric energy harvesting systems have been drawing the attention of the research community over recent years due to their potential for recharging/replacing batteries embedded in low-power-consuming smart electronic devices and wireless sensor networks. However, conventional linear piezoelectric energy harvesters (PEH) are often not a viable solution in such advanced practices, as they suffer from a narrow operating bandwidth, having a single resonance peak present in the frequency spectrum and very low voltage generation, which limits their ability to function as a standalone energy harvester. Generally, the most common PEH is the conventional cantilever beam harvester (CBH) attached with a piezoelectric patch and a proof mass. This study investigated a novel multimode harvester design named the arc-shaped branch beam harvester (ASBBH), which combined the concepts of the curved beam and branch beam to improve the energy-harvesting capability of PEH in ultra-low-frequency applications, in particular, human motion. The key objectives of the study were to broaden the operating bandwidth and enhance the harvester's effectiveness in terms of voltage and power generation. The ASBBH was first studied using the finite element method (FEM) to understand the operating bandwidth of the harvester. Then, the ASBBH was experimentally assessed using a mechanical shaker and real-life human motion as excitation sources. It was found that ASBBH achieved six natural frequencies within the ultra-low frequency range (<10 Hz), in comparison with only one natural frequency achieved by CBH within the same frequency range. The proposed design significantly broadened the operating bandwidth, favouring ultra-low-frequency-based human motion applications. In addition, the proposed harvester achieved an average output power of 427 µW at its first resonance frequency under 0.5 g acceleration. The overall results of the study demonstrated that the ASBBH design can achieve a broader operating bandwidth and significantly higher effectiveness, in comparison with CBH.


Assuntos
Aceleração , Vibração , Humanos , Fenômenos Físicos , Movimento (Física) , Contagem de Células Sanguíneas
19.
Int J Mol Sci ; 24(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36834941

RESUMO

Research on the use of different parts of the Moringa oleifera plant as a nutritional and pharmaceutical resource for human and animals has increased in recent years. This study aimed to investigate the chemical composition and the TPCs and TFCs of Moringa leaves, the antimicrobial activities of Moringa successive ethanolic, aqueous, crude aqueous extracts, and green-chemically synthesized characterized Ag-NPs. The results indicated that the ethanolic extract recorded the highest activity against E. coli. On the other side, the aqueous extract showed higher activity, and its effects ranged from 0.03 to 0.33 mg/mL against different strains. The MIC values of Moringa Ag-NPs against different pathogenic bacteria ranged from 0.05 mg/mL to 0.13 mg/mL, and the activity of the crude aqueous extract ranged from 0.15 to 0.83 mg/mL. For the antifungal activity, the ethanolic extract recorded the highest activity at 0.04 mg/mL, and the lowest activity was recorded at 0.42 mg/mL. However, the aqueous extract showed effects ranging from 0.42 to 1.17 mg/mL. Moringa Ag-NPs showed higher activity against the different fungal strains than the crude aqueous extract, and they ranged from 0.25 to 0.83 mg/mL. The MIC values of the Moringa crude aqueous extract ranged from 0.74 to 3.33 mg/mL. Moringa Ag-NPs and their crude aqueous extract may be utilized to boost antimicrobial attributes.


Assuntos
Anti-Infecciosos , Moringa oleifera , Humanos , Animais , Moringa oleifera/química , Escherichia coli , Anti-Infecciosos/análise , Etanol/análise , Água/análise , Folhas de Planta/química , Extratos Vegetais/química
20.
J Pak Med Assoc ; 73(Suppl 4)(4): S287-S289, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37482874

RESUMO

Objectives: To identify coronary plaque morphology using grey scale and virtual histology intravascular ultrasound in patients with and without elevated glycated haemoglobin. Method: The cross-sectional study was conducted at the Cardiology Department of Kafrelsheikh University, Egypt, from November 2019 to January 2022, and comprised adult patients of either gender suffering from acute coronary syndrome admitted for catheterisation. The patients were divided into three groups.Diabetic patients were in group A, prediabetic patients with elevated glycated haemoglobin in group B, and patients with normal glycated haemoglobin in group C. All patients were subjected to clinical examination, 12-lead electrocardiogram, coronary angiography and multimodality intravascular ultrasonography scan of proximal segments 3-6cmof non-culprit coronary arteries intra group differences were compared using the analysis of variance (ANOVA) test. RESULTS: Of the 52 patients, 18(34.7%) were females and 34(65.3%) were males. Group A had 18(34.6%)patients; 13(72%) males and 5(28%) females with mean age 57.9±6.9 years. Group B had 17(32.7%) patients;11(64.7%) males and 6(35.3%) females with mean age 56.5±5.5 years. Group C had 17(32.7%) patients; 10(59%) males and 7(41%) females with mean age 59.5±5.1 years(p>0.05). Thin-cap fibroatheroma wassignificantly higher in groups A and B compared to group C (p=0.045). CONCLUSIONS: Patients with raised glycated haemoglobin presenting with acute coronary syndrome were found to have more vulnerable plaque types than those with normal levels.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Placa Aterosclerótica , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Doença da Artéria Coronariana/diagnóstico por imagem , Hemoglobinas Glicadas , Síndrome Coronariana Aguda/diagnóstico por imagem , Estudos Transversais , Angiografia Coronária , Ultrassonografia de Intervenção , Vasos Coronários/diagnóstico por imagem , Valor Preditivo dos Testes
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