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1.
Proc Natl Acad Sci U S A ; 121(28): e2400737121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38968127

RESUMEN

In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. While animals exhibit a characteristic genome topology defined by topologically associating domains (TADs), plants display similar features with a more diverse conformation across species. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.


Asunto(s)
Epigenoma , Histonas , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Histonas/metabolismo , Histonas/genética , Epigénesis Genética , Genoma de Planta , Cromatina/metabolismo , Cromatina/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Heterocromatina/metabolismo , Heterocromatina/genética , Código de Histonas/genética
2.
Nucleic Acids Res ; 52(6): 3469-3482, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38421613

RESUMEN

Gene-editing technologies have revolutionized biotechnology, but current gene editors suffer from several limitations. Here, we harnessed the power of gamma-modified peptide nucleic acids (γPNAs) to facilitate targeted, specific DNA invasion and used T7 endonuclease I (T7EI) to recognize and cleave the γPNA-invaded DNA. Our data show that T7EI can specifically target PNA-invaded linear and circular DNA to introduce double-strand breaks (DSBs). Our PNA-Guided T7EI (PG-T7EI) technology demonstrates that T7EI can be used as a programmable nuclease capable of generating single or multiple specific DSBs in vitro under a broad range of conditions and could be potentially applied for large-scale genomic manipulation. With no protospacer adjacent motif (PAM) constraints and featuring a compact protein size, our PG-T7EI system will facilitate and expand DNA manipulations both in vitro and in vivo, including cloning, large-fragment DNA assembly, and gene editing, with exciting applications in biotechnology, medicine, agriculture, and synthetic biology.


Asunto(s)
Roturas del ADN de Doble Cadena , Desoxirribonucleasa I , Ácidos Nucleicos de Péptidos , Desoxirribonucleasa I/metabolismo , ADN/genética , ADN/metabolismo , ADN Circular , Edición Génica
3.
Nucleic Acids Res ; 52(17): 10220-10234, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39149894

RESUMEN

The 3D chromatin organization plays a major role in the control of gene expression. However, our comprehension of the governing principles behind nuclear organization remains incomplete. Particularly, the spatial segregation of loci with similar repressive transcriptional states in plants poses a significant yet poorly understood puzzle. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome.


Asunto(s)
Arabidopsis , Elementos Transponibles de ADN , Epigénesis Genética , Genoma de Planta , Heterocromatina , Elementos Transponibles de ADN/genética , Heterocromatina/metabolismo , Heterocromatina/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Cromatina/metabolismo , Cromatina/genética , Histonas/metabolismo , Histonas/genética , Genómica/métodos
4.
Nucleic Acids Res ; 51(17): 9491-9506, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37560931

RESUMEN

Programmable site-specific nucleases promise to unlock myriad applications in basic biology research, biotechnology and gene therapy. Gene-editing systems have revolutionized our ability to engineer genomes across diverse eukaryotic species. However, key challenges, including delivery, specificity and targeting organellar genomes, pose barriers to translational applications. Here, we use peptide nucleic acids (PNAs) to facilitate precise DNA strand invasion and unwinding, enabling prokaryotic Argonaute (pAgo) proteins to specifically bind displaced single-stranded DNA and introduce site-specific double-strand breaks (DSBs) independent of the target sequence. We named this technology PNA-assisted pAgo editing (PNP editing) and determined key parameters for designing PNP editors to efficiently generate programable site-specific DSBs. Our design allows the simultaneous use of multiple PNP editors to generate multiple site-specific DSBs, thereby informing design considerations for potential in vitro and in vivo applications, including genome editing.


Asunto(s)
Roturas del ADN de Doble Cadena , Edición Génica , Ácidos Nucleicos de Péptidos , Sistemas CRISPR-Cas , ADN/genética , Edición Génica/métodos , Genoma , Ácidos Nucleicos de Péptidos/metabolismo , Proteínas Argonautas/metabolismo
5.
Genome Res ; 31(7): 1230-1244, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34083408

RESUMEN

In animals, distant H3K27me3-marked Polycomb targets can establish physical interactions forming repressive chromatin hubs. In plants, growing evidence suggests that H3K27me3 acts directly or indirectly to regulate chromatin interactions, although how this histone modification modulates 3D chromatin architecture remains elusive. To decipher the impact of the dynamic deposition of H3K27me3 on the Arabidopsis thaliana nuclear interactome, we combined genetics, transcriptomics, and several 3D epigenomic approaches. By analyzing mutants defective for histone H3K27 methylation or demethylation, we uncovered the crucial role of this chromatin mark in short- and previously unnoticed long-range chromatin loop formation. We found that a reduction in H3K27me3 levels led to a decrease in the interactions within Polycomb-associated repressive domains. Regions with lower H3K27me3 levels in the H3K27 methyltransferase clf mutant established new interactions with regions marked with H3K9ac, a histone modification associated with active transcription, indicating that a reduction in H3K27me3 levels induces a global reconfiguration of chromatin architecture. Altogether, our results reveal that the 3D genome organization is tightly linked to reversible histone modifications that govern chromatin interactions. Consequently, nuclear organization dynamics shapes the transcriptional reprogramming during plant development and places H3K27me3 as a key feature in the coregulation of distant genes.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39075799

RESUMEN

INTRODUCTION: Transvenous lead extraction (TLE) is generally considered a safe procedure, albeit not without risks. While gender-based disparities have been noted in short-term outcomes following TLE, a notable gap exists in understanding the long-term consequences of this procedure. The objective of this analysis was to investigate sex differences in both acute and long-term outcomes among patients who underwent TLE at a tertiary referral center. METHODS: In this retrospective cohort study, consecutive patients who underwent TLE between January 2014 and January 2016 were enrolled. The primary outcome comprised a composite of all-cause mortality and need for repeated TLE procedures. Secondary outcomes included fluoroscopy time, lead extraction techniques, success rates, and major and minor complications. Results were compared between female and male cohorts. RESULTS: The study population comprised 191 patients (median age, 70 years), 29 (15.2%) being women and 162 men (84.8%). Study groups had similar baseline characteristics. Complete procedural success was achieved in 189 out of 191 patients (99.0%), with no significant difference observed between the two groups (p = .17). No major complications were reported in the total cohort. However, there was a significantly higher incidence of minor complications in women compared to men (17.2% vs. 2.5%, p < .01). Following a median follow-up of 6.5 years, the incidence of the primary composite outcome occurred similarly between the study groups (log-rank p = .68). CONCLUSION: Women who underwent TLE exhibited a significantly higher incidence of minor acute intra- and peri-procedural complications than men. However, no differences in long-term outcomes between genders were observed.

7.
J Exp Bot ; 75(3): 802-818, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37924151

RESUMEN

Plants employ sophisticated molecular machinery to fine-tune their responses to growth, developmental, and stress cues. Gene expression influences plant cellular responses through regulatory processes such as transcription and splicing. Pre-mRNA is alternatively spliced to increase the genome coding potential and further regulate expression. Serine/arginine-rich (SR) proteins, a family of pre-mRNA splicing factors, recognize splicing cis-elements and regulate both constitutive and alternative splicing. Several studies have reported SR protein genes in the rice genome, subdivided into six subfamilies based on their domain structures. Here, we identified a new splicing factor in rice with an RNA recognition motif (RRM) and SR-dipeptides, which is related to the SR proteins, subfamily SC. OsSCR106 regulates pre-mRNA splicing under abiotic stress conditions. It localizes to the nuclear speckles, a major site for pre-mRNA splicing in the cell. The loss-of-function scr106 mutant is hypersensitive to salt, abscisic acid, and low-temperature stress, and harbors a developmental abnormality indicated by the shorter length of the shoot and root. The hypersensitivity to stress phenotype was rescued by complementation using OsSCR106 fused behind its endogenous promoter. Global gene expression and genome-wide splicing analysis in wild-type and scr106 seedlings revealed that OsSCR106 regulates its targets, presumably through regulating the alternative 3'-splice site. Under salt stress conditions, we identified multiple splice isoforms regulated by OsSCR106. Collectively, our results suggest that OsSCR106 is an important splicing factor that plays a crucial role in accurate pre-mRNA splicing and regulates abiotic stress responses in plants.


Asunto(s)
Oryza , Oryza/genética , Oryza/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Empalme del ARN , Empalme Alternativo , Plantas/metabolismo , Estrés Fisiológico/genética
8.
Virol J ; 21(1): 75, 2024 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539202

RESUMEN

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Proteínas Virales/genética , Filogenia , Genómica , Brotes de Enfermedades
9.
Mol Biol Rep ; 51(1): 815, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39009695

RESUMEN

BACKGROUND: Urinary bladder cancer (UBC)is a common tumor of the urinary tract. OBJECTIVES: To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. DESIGN AND METHODS: One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. RESULTS: The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. CONCLUSION: It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.


Asunto(s)
Predisposición Genética a la Enfermedad , Genotipo , Interleucina-6 , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria , Humanos , Interleucina-6/genética , Interleucina-6/sangre , Egipto/epidemiología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/sangre , Femenino , Polimorfismo de Nucleótido Simple/genética , Masculino , Persona de Mediana Edad , Alelos , Estudios de Casos y Controles , Anciano , Adulto , Frecuencia de los Genes/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Estudios de Asociación Genética
10.
J Biochem Mol Toxicol ; 38(4): e23690, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38493304

RESUMEN

The cytotoxic activity, EGFR/VEGFR2 target inhibition, apoptotic activity, RT-PCR gene expression, in vivo employing a solid-Ehrlich carcinoma model, and in silico investigations for highlighting the binding affinity of eight quinoxaline derivatives were tested for anticancer activities. The results showed that compound 8 (N-allyl quinoxaline) had potent cytotoxicity against A594 and MCF-7 cancer cells with IC50 values of 0.86 and 1.06 µM, respectively, with noncytotoxic activity against WISH and MCF-10A cells having IC50 values more than 100 µM. Furthermore, it strongly induced apoptotic cell death in A549 and MCF-7 cells by 43.13% and 34.07%, respectively, stopping the cell cycle at S and G1-phases. For the molecular target, the results showed that compound 8 had a promising EGFR inhibition activity with an IC50 value of 0.088 µM compared to Sorafenib (IC50 = 0.056 µM), and it had a promising VEGFR2 inhibition activity with an IC50 value of 0.108 µM compared to Sorafenib (IC50 = 0.049 µM). Treatment with compound 8 ameliorated biochemical and histochemical parameters near normal in the in vivo investigation, with a tumor inhibition ratio of 68.19% compared to 64.8% for 5-FU treatment. Finally, the molecular docking study demonstrated the binding affinity through binding energy and interactive binding mode inside the EGFR/VEGFR2 proteins. Potent EGFR and VEGFR2 inhibition of compound 8 suggests its potential for development as a selective anticancer drug.


Asunto(s)
Antineoplásicos , Quinoxalinas , Humanos , Relación Estructura-Actividad , Sorafenib/farmacología , Simulación del Acoplamiento Molecular , Quinoxalinas/farmacología , Apoptosis , Antineoplásicos/química , Receptores ErbB/metabolismo , Proliferación Celular , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas/farmacología
11.
Bioorg Chem ; 150: 107622, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996545

RESUMEN

Novel thieno[2,3-d]pyrimidine analogues were designed, synthesized and evaluated for anti-proliferative activity against HepG-2, PC-3 and MCF-7 cancer cell lines. In addition, WI-38 normal cell line was used to explore the safety of all the tested compounds. Compounds 2 (IC50 = 4.29 µM HePG-2, 10.84 µM MCF-7), 6 (IC50 = 14.86 µM HePG-2, 8.04 µM PC-3 and 12.90 µM MCF-7) and 17 (IC50 = 9.98 µM HePG-2, 33.66 µM PC-3 and 14.62 µM MCF-7) were the most promising candidates on the tested cancer cells with high selective toxicity-sparing normal cells. A further mechanistic evaluation revealed promising kinase inhibitory activity, where compound 2 inhibited VEGFR-2 and AKT at IC50 = 0.161 and 1.06 µM, respectively, Furthermore, derivative 6 inhibited VEGFR-2 and AKT at IC50 = 0.487 and 0.364 µM, respectively, while compound 17 showed IC50 = 0.164 and 0.452 µM, respectively. Moreover, compounds 2, 6 resulted in G1 phase cell cycle arrest while candidate 17 arrest cell cycle at G2/M phase. Similar to the apoptosis results, compound 17 showed the highest autophagic induction among the evaluated derivatives. Finally, docking studies were conducted to assess the binding patterns of these active derivatives. The results showed that the binding patterns inside the active sites of both the VEGFR-2 and AKT-1 (allosteric pocket) crystal structures were identical to the reference ligands.


Asunto(s)
Antineoplásicos , Apoptosis , Autofagia , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-akt , Pirimidinas , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Pirimidinas/farmacología , Pirimidinas/síntesis química , Pirimidinas/química , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Autofagia/efectos de los fármacos , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Línea Celular Tumoral
12.
Biochem Genet ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028381

RESUMEN

Nephrotic syndrome is one of the most prevalent pediatric kidney illnesses seen in pediatric nephrology clinics. Steroid resistance in children with nephrotic syndrome is a primary cause of renal failure and is characterized by nephrotic range proteinuria that does not respond to conventional steroid therapy. The current work was intended to investigate the possible role of the Phospholipase C epsilon 1 (rs7922612) and collagen4 alpha 3 (rs375290088) single nucleotide polymorphisms as risk factors for developing nephrotic syndrome among Egyptian children. The study was conducted on 100 children with nephrotic syndrome and 100 age- and sex-matched healthy individuals. Geno typing was performed by two methods of polymerase chain reaction for the analysis of PLCE1 (rs7922612) and COL4A3 (rs375290088) variants. We observed a higher percentage of the heterozygous and homozygous variant genotypes of PLCE1 (rs7922612) SNP in NS patients in comparison with the controls (P < 0.001 for both). The frequencies of the PLCE1 (rs7922612) variant showed a statistically significant elevated risk of NS using several genetic models, including the dominant (OR = 9.12), recessive (OR = 2.31), and allelic (OR = 1.62) models (P < 0.001 for each). In addition, the PLCE1 (rs7922612) genotypes and alleles frequencies did not differ significantly between SRNS compared to SSNS cases. Furthermore, there was no significant difference regarding COL4A3 (rs375290088) polymorphism, neither between the NS and control groups nor between SDNS and SRNS. PLCE1 (rs7922612) is considered an independent risk factor for nephrotic syndrome in Egyptian pediatrics.COL4A3 (rs375290088) polymorphism is not correlated to Egyptian NS patients.

13.
Biochem Genet ; 62(2): 1304-1324, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37594641

RESUMEN

The kidney lost a lot of protein in the urine when you have nephrotic syndrome (NS). Clinical manifestations mostly common in NS include massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic nephrotic syndrome is currently classified into steroid-dependent (SDNS) and steroid-resistant (SRNS) based on the initial response to corticosteroid therapy at presentation. Several reports examined the association of the MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs741301 G > A) variant as risk factors for Nephrotic Syndrome. This study aimed to determine the potential effect of the MYH9 gene (rs3752462, C > T) and ELMO1 gene (rs741301) variant on the risk of (NS) among Egyptian Children. This study included two hundred participants involving 100 nephrotic syndrome (NS) cases and 100 healthy controls free from nephrotic syndrome (NS). The MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs G > A741301) variant were analyzed by ARMS-PCR technique. Nephrotic syndrome cases include 74% SRNS and 26% SDNS. Higher frequencies of the heterozygous carrier (CT) and homozygous variant (TT) genotypes of the MYH9 (rs3752462, C > T) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the MYH9 (rs3752462, C > T variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.85, p < 0.001), dominant (OR 3.97, p < 0.001) models, and the recessive model OR 5.94, p < 0.001). Higher frequencies of the heterozygous carrier (GA) and homozygous variant (AA) genotypes of ELMO1gene (rs G > A741301) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the ELMO1 (rs G > A741301) variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.15, p < 0.001), dominant models (OR 2.8, p < 0.001), and the recessive model (OR 4.17, p = 0.001). Both MYH9 and ELMO1 gene variants are significantly different in NS in comparison with the control group (p < 0.001). The MYH9 gene (rs3752462, C > T) and ELMO1gene (rs G > A741301) variants were considered independent risk factors for NS among Egyptian Children.

14.
Parasitol Res ; 123(1): 86, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38182847

RESUMEN

With the opening of the Suez Canal in 1869, many changes have occurred in the Mediterranean Sea ecosystem so became a home to many invasive Lessepsian marine species that have migrated from the Red Sea. About 500 marine species including pufferfish have immigrated and rapidly established a population in the Mediterranean Sea causing significant impact on its ecosystem and fisheries sector. The parasitic fauna of these pufferfish has scarcely been studied in the Mediterranean Sea and also in their native habitat. During this surveillance study on the invasive pufferfish species from the Egyptian Mediterranean coast, the female cymothoid isopod Elthusa raynaudii was detected from the branchial cavity and also in the buccal cavity of 23.9% of the examined Lagocephalus sceleratus. The isolated isopod species was firstly identified and described through electron microscopy and molecular phylogeny based on the sequences of mitochondrial 16S rRNA gene. Additionally, the description of eggs, embryonic stage, and manca of E. raynaudii was firstly provided. The pathological impact on the infested fish tissues was investigated and revealed curling and loss of secondary gill lamellae in addition to mucous exudates in between the gill filaments and granuloma formation in the gill arch. The study provided the first report of L. sceleratus as a new host for the isopod E. raynaudii collected from the Egyptian Mediterranean coast as a new locality record. The role of the Lessepsian invasive pufferfish in transmitting parasites to the native fish species was discussed.


Asunto(s)
Isópodos , Tetraodontiformes , Femenino , Animales , Filogenia , Plata , Ecosistema , Mar Mediterráneo , ARN Ribosómico 16S/genética , Especies Introducidas
15.
Arch Pharm (Weinheim) ; 357(9): e2400225, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38822393

RESUMEN

The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target-oriented chemotherapeutics.


Asunto(s)
Antineoplásicos , Apoptosis , Neoplasias , Quinoxalinas , Quinoxalinas/farmacología , Quinoxalinas/síntesis química , Quinoxalinas/química , Humanos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Relación Estructura-Actividad , Animales , Estructura Molecular , Terapia Molecular Dirigida , Línea Celular Tumoral
16.
Sensors (Basel) ; 24(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39204840

RESUMEN

This comprehensive review delves into the forefront of biosensor technologies and their critical roles in disease biomarker detection and therapeutic drug monitoring. It provides an in-depth analysis of various biosensor types and applications, including enzymatic sensors, immunosensors, and DNA sensors, elucidating their mechanisms and specific healthcare applications. The review highlights recent innovations such as integrating nanotechnology, developing wearable devices, and trends in miniaturisation, showcasing their transformative potential in healthcare. In addition, it addresses significant sensitivity, specificity, reproducibility, and data security challenges, proposing strategic solutions to overcome these obstacles. It is envisaged that it will inform strategic decision-making, drive technological innovation, and enhance global healthcare outcomes by synthesising multidisciplinary insights.


Asunto(s)
Técnicas Biosensibles , Monitoreo de Drogas , Técnicas Biosensibles/métodos , Humanos , Monitoreo de Drogas/métodos , Nanotecnología/métodos , Dispositivos Electrónicos Vestibles , Biomarcadores/análisis , Atención a la Salud
17.
Crit Care Nurs Q ; 47(4): 378-399, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39265117

RESUMEN

The aim of this study was to develop a bundle to increase safety of intra-hospital transport in critically ill patients. A qualitative design with Delphi approach was conducted for creation of an intra-hospital transport bundle in 3 steps. First, doctors and nurses were questioned about their encounters with intra-hospital transport incidents. Second, several databases were looked through to find published checklists and recommendations for intra-hospital transport. Third, using this strategy, a bundle was created and reviewed with subject matter experts. The content validity index (CVI), which assesses the degree of expert agreement, was utilized to evaluate each item in the generated bundle. Two evaluation cycles were required before a minimal index could be reached. We looked at the content validity and important weighting of the items. The scale-CVI was calculated using the average of all the elements, and it was 1. The created bundle serves as a framework for directing doctors and nurses during intra-hospital transportation and offers continuity of care to improve patient safety. The techniques suggested in this study can be used to adapt this bundle to the needs of other hospitals.


Asunto(s)
Enfermedad Crítica , Técnica Delphi , Seguridad del Paciente , Investigación Cualitativa , Humanos , Enfermedad Crítica/terapia , Seguridad del Paciente/normas , Transporte de Pacientes/normas , Transferencia de Pacientes/normas , Lista de Verificación
18.
Inflammopharmacology ; 32(1): 629-642, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37848698

RESUMEN

OBJECTIVE: Sesamol (SES) is a phenolic compound found in sesame seed oil. Several studies have revealed its anti-inflammatory and antioxidant properties. However, its complete underlying mechanistic perspective about cerebral ischemia/reperfusion (I/R) lesions has not yet been disclosed. Consequently, we aimed to scrutinize its neuroprotective mechanism against cerebral injury during a global cerebral I/R in a rat model, considering its impact on autophagy and Notch1/NLRP3 inflammasome signaling regulation. METHODS: To affirm our purpose, adult Wistar rats were allotted into five groups: sham and the other four groups in which transient global cerebral ischemia was induced by bilateral common ligation (2VO) for 1 h, then reperfusion for either 24 h or 5 days: I/R (1/24), I/R (1/5), SES + I/R (1/24), and SES + I/R (1/5). In treated groups, SES (100 mg/kg, p.o., for 21 days) was administered before cerebral I/R induction. The assessment of histopathological changes in brain tissues, immunohistochemistry, biochemical assays, ELISA, and qRT-PCR were utilized to investigate our hypothesis. RESULTS: Advantageously, SES halted the structural neuronal damage with lessened demyelination induced by cerebral I/R injury. Restoring oxidant/antioxidant balance was evident by boosting the total antioxidant capacity and waning lipid peroxidation. Furthermore, SES reduced inflammatory and apoptosis markers. Additionally, SES recovered GFAP, Cx43, and autophagy signaling, which in turn switched off the Notch-1/NLRP3 inflammasome trajectory. CONCLUSIONS: Our results revealed the neuroprotective effect of SES against cerebral I/R injury through alleviating injurious events and boosting autophagy, consequently abolishing Notch1/NLRP3 inflammasome signaling.


Asunto(s)
Benzodioxoles , Isquemia Encefálica , Fenoles , Daño por Reperfusión , Animales , Ratas , Ratas Wistar , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Antioxidantes/farmacología , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Autofagia , Isquemia Encefálica/tratamiento farmacológico , Receptor Notch1
19.
Arch Virol ; 168(2): 62, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36633687

RESUMEN

Foot-and-mouth disease (FMD) is a serious highly contagious viral disease affecting all cloven-hoofed animals, and outbreaks can have a severe economic impact. An inactivated heptavalent oil-adjuvanted FMD vaccine (Aphtovac-7, MEVAC) was prepared from the foot-and-mouth disease virus (FMDV) strains A-Iran05, A-Africa-IV, O-PanAsia2, O-Manisa, O-EA3, SAT-2 Gharbia, and SAT-2 LIB-12. The vaccine potency and effectiveness were evaluated in three groups of 6- to 8-month-old calves and 200 adult dairy cattle under field conditions. All animals were vaccinated with the vaccine preparation, and the three groups of calves were challenged after 28 days by intradermolingual inoculation with 104 50% tissue culture infective dose (TCID50) of FMDV serotype A, O, or SAT-2. Mock-vaccinated calves (two per group) served as unvaccinated controls during the challenge test. Adult dairy cattle were tested for seroconversion using a virus neutralization test at 30, 60, and 120 days post-vaccination. All calves displayed complete protection against challenge with the different serotypes of FMDV when compared to the control groups. Serum samples collected after the primary and booster immunizations at 30 days post-vaccination contained high titers of protective antibodies (≥ 1/32; i.e. 1.5 log10). Antibodies persisted until the end of the study period (120 days), with a peak value around 60 days post-vaccination. The heptavalent FMD vaccine preparation was found to be potent and capable of providing a protective immune response under both experimental and field conditions.


Asunto(s)
Enfermedades de los Bovinos , Virus de la Fiebre Aftosa , Fiebre Aftosa , Vacunas Virales , Animales , Bovinos , Egipto , Anticuerpos Antivirales , Adyuvantes Inmunológicos , Vacunación/veterinaria
20.
Conserv Biol ; : e14169, 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37650432

RESUMEN

Protected and conserved areas (PCAs) are key ecosystem management tools for conserving biodiversity and sustaining ecosystem services and social cobenefits. As countries adopt a 30% target for protection of land and sea under the Global Biodiversity Framework of the United Nations Convention on Biological Diversity, a critical question emerging is, which 30%? A risk-based answer to this question is that the 30% that returns the greatest reductions in risks of species extinction and ecosystem collapse should be protected. The International Union for Conservation of Nature (IUCN) Red List protocols provide practical methods for assessing these risks. All species, including humans, depend on the integrity of ecosystems for their well-being and survival. Africa is strategically important for ecosystem management due to convergence of high ecosystem diversity, intense pressures, and high levels of human dependency on nature. We reviewed the outcomes (e.g., applications of ecosystem red-list assessments to protected-area design, conservation planning, and management) of a symposium at the inaugural African Protected Areas Congress convened to discuss roles of the IUCN Red List of Ecosystems in the design and management of PCAs. Recent progress was made in ecosystem assessment, with 920 ecosystem types assessed against the IUCN Red List criteria across 21 countries. Although these ecosystems spanned a diversity of environments across the continent, the greatest thematic gaps were for freshwater, marine, and subterranean realms, and large geographic gaps existed in North Africa and parts of West and East Africa. Assessment projects were implemented by a diverse community of government agencies, nongovernmental organizations, and researchers. The assessments have influenced policy and management by informing extensions to and management of formal protected area networks supporting decision-making for sustainable development, and informing ecosystem conservation and threat abatement within boundaries of PCAs and in surrounding landscapes and seascapes. We recommend further integration of risk assessments in environmental policy and enhanced investment in ecosystem red-list assessment to fill current gaps.


Contribuciones de la Lista Roja de Ecosistemas de la UICN al diseño y manejo basados en riesgos de las áreas conservadas y protegidas en África Resumen Las áreas protegidas y conservadas (APC) son herramientas clave del manejo de ecosistemas para conservar la biodiversidad y mantener los servicios ambientales y los cobeneficios sociales. Conforme los países adoptan un objetivo de 30% para la protección del suelo y el mar bajo el Marco Mundial de Biodiversidad de la Convención sobre la Diversidad Biológica de las Naciones Unidas, surge una pregunta crítica: ¿cuál 30%? Una respuesta basada en riesgos a esta pregunta es que se debe proteger el 30% que rinda la mayor reducción del riesgo de extinción de especies y del colapso del ecosistema. Los protocolos de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza (UICN) proporcionan métodos prácticos para evaluar estos riesgos. Todas las especies, incluidos los humanos, dependen de la integridad de los ecosistemas para su bienestar y supervivencia. África tiene una importancia estratégica para el manejo de ecosistemas debido a la convergencia de una gran diversidad de ecosistemas, presiones intensas y un nivel elevado de dependencia del humano hacia la naturaleza. Revisamos los resultados (p. ej.: aplicaciones de las valoraciones de las listas rojas de ecosistemas al diseño de áreas protegidas, planeación de la conservación y manejo) de un simposio en el primer Congreso de Áreas Protegidas Africanas convocado para discutir el papel de la Lista Roja de Ecosistemas de la UICN en el diseño y manejo de las APC. Existen avances recientes en la evaluación de los ecosistemas, con 920 tipos de ecosistemas evaluados bajo los criterios de la Lista Roja de la UICN en 21 países. Mientras estos ecosistemas comprenden una diversidad de ambientes en todo el continente, los principales vacíos temáticos los encontramos para los dominios subterráneos, de agua dulce y marina, además de que existe un gran vacío geográfico en el norte de África y en partes del este y oeste africano. Los proyectos de evaluación fueron implementados por una comunidad diversa de agencias gubernamentales, organizaciones no gubernamentales e investigadores. La influencia de las evaluaciones sobre las políticas y el manejo se da con la información que proveen a las extensiones y el manejo de las redes de áreas protegidas formales, el apoyo para la toma de decisiones de desarrollo sustentable y la guía para la conservación de ecosistemas y el abatimiento de amenazas dentro de los límites de las APC y en los paisajes terrestres y marinos adyacentes. Recomendamos una mayor integración de las evaluaciones de riesgo dentro de las políticas ambientales y más inversión para las evaluaciones de lista roja de los ecosistemas cubrir los vacíos existentes.

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