Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 199
Filtrar
1.
Perfusion ; : 2676591241259140, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830625

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. OBJECTIVES: The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. METHODS: A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). RESULTS: The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. CONCLUSION: Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

2.
Heliyon ; 10(9): e29554, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694027

RESUMO

Incised marine valleys (IVS) are hot topics in exploring the stratigraphic oil and gas-bearing plays. Multiple channelized sandstone lenses at varying depths [m], thicknesses [m], and porosities [%] constrain seismic impedance. The presence of hydrocarbon-bearing resources affects the seismic impedance (density (g/cc) and velocity (m/s)). Therefore, a quantitative prediction has been carried out for determining the thickness [m], porosity [%], and depths [m] of laterally distributed channelized sandstone lenses (SLS) for IVS, Indus offshore Basin (IOB), Pakistan, using 2-D instantaneous spectral porosity quantitative modelling (2DSSM), continuous wavelet transforms-based (CWT) 2-D instantaneous spectral density modelling (2DSSDM), and spectral decomposition tools. The 2DSSM remained limited in predicting the number of channelized sandstone lenses and their quantitative stratigraphic attributes. The 45-Hz-based processing of conventional 2DSSM has resolved the two channelized sandstone lenses of the stratigraphic trap. The deepest channelized sandstone lens has attained 1-6 m thickness with a lateral extent of 3 km, within the porosity range of 18-33 %. The highest confidence level for predicted petrophysical attributes such as 13 m-thick pay zones, -0.08, -0.067, and -0.07 acoustic impedances [g/c.c.*m/s], and 28 % porosities with R2 > 0.85 have validated interpretations. The response of 45-Hz CWT waveform-based inverted density and thickness simulations has predicted the highest thicknesses and lowest densities of reservoir sandstones within the meandering channel belt of the deepwater depositional system. The predicted densities and thicknesses for the coarse-grained sandstone lenses of point bars were 1.8-1.9 g/cc and 15 m, respectively. In the same way, the quantitative estimates of predicted density and simulated thickness have shown a strong coefficient correlation (R2 > 0.80), which confirms the presence of gas-bearing prospects within the IVS. The facies-controlled migration is thought to be the movement of the reservoir facies of the point bars and channelled sandstone-filled lenses to the side.

3.
Heliyon ; 10(10): e30660, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38774334

RESUMO

Understanding the precursors leading to rock fracture is crucial for ensuring safety in mining and geotechnical engineering projects. To effectively discern these precursors, a collaborative monitoring approach that integrates multiple sources of information is imperative. This paper considered a rock multi-parameter monitoring loading system, incorporating infrared radiation and acoustic emission monitoring technologies to simultaneously track the rock fracture process. The study delves into the spatiotemporal evolution patterns of infrared radiation and acoustic emission in rock under loading. Utilizing stress, cumulative acoustic emission count, and average infrared radiation temperature (AIRT), the paper establishes a comprehensive evaluation model termed "acoustic-thermal-stress" fusion information, employing principal component analysis (PCA). The research reveals that the sensitivity to rock sample damage response follows the sequence of cumulative acoustic emission count, AIRT, and stress. Furthermore, a novel method for identifying rock fracture precursors is proposed, based on the first derivative of the comprehensive evaluation model. This method addresses the limitations of single physical field information, enhancing the robustness of monitoring data. It determines the average stress level of fracture precursors to be 0.77σmax. Subsequently, the study defines the probability function of rock damage during loading and fracture, enabling the realization of probability-based warnings for rock fracture. This approach introduces a new perspective on rock fracture prediction, significantly contributing to safety monitoring and warning systems in mine safety and geotechnical engineering. The findings of this research hold paramount engineering significance, offering valuable insights for enhancing safety measures in such projects.

4.
Clin Neurol Neurosurg ; 240: 108271, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38569247

RESUMO

Vacuolar protein sorting 13 homolog D (VPS13D) gene encodes a protein involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. This study reports a novel homozygous mutation (c.12494T>C p.Ile4165Thr) in the VPS13D gene in a Saudi female diagnosed with autosomal recessive spinocerebellar ataxia type 4 (SCAR4). The patient's clinical presentation, including progressive weakness, ataxia, and numbness, aligns with SCAR4 characteristics. The comprehensive evaluation, comprising neurological examination, brain MRI, and genetic testing, revealed distinctive features consistent with autosomal recessive inheritance. The genetic mutation spectrum enrichment emphasizes the intricate interplay of genetic factors in SCAR4. Although no specific treatment exists, rehabilitation and supportive therapy remain central. The identified mutation contributes valuable insights for clinical management and genetic counseling, urging the ongoing collection of VPS13D gene mutation data to explore genotype-phenotype correlations in spinocerebellar ataxias. This study underscores the importance of multidisciplinary care and lays the foundation for future research directions in understanding and treating SCAR4.


Assuntos
Mutação , Proteínas , Ataxias Espinocerebelares , Humanos , Feminino , Arábia Saudita , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/diagnóstico por imagem , Mutação/genética , Proteínas de Transporte Vesicular/genética , Homozigoto , Adulto , Linhagem
5.
RSC Adv ; 14(20): 14051-14067, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38686286

RESUMO

Thiosemicarbazones of isatin have been found to exhibit versatile bioactivities. In this study, two distinct types of isatin-triazole hybrids 3a and 3b were accessed via copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), together with their mono and bis-thiosemicarbazone derivatives 4a-h and 5a-h. In addition to the characterization by physical, spectral and analytical data, a DFT study was carried out to obtain the optimized geometries of all thiosemicarbazones. The global reactivity values showed that among the synthesized derivatives, 4c, 4g and 5c having nitro substituents are the most soft compounds, with compound 5c having the highest electronegativity and electrophilicity index values among the synthesized series, thus possessing strong binding ability with biomolecules. Molecular docking studies were performed to explore the inhibitory ability of the selected compounds against the active sites of the anticancer protein of phosphoinositide 3-kinase (PI3K). Among the synthesized derivatives, 4-nitro substituted bisthiosemicarbazone 5c showed the highest binding energy of -10.3 kcal mol-1. These findings demonstrated that compound 5c could be used as a favored anticancer scaffold via the mechanism of inhibition against the PI3K signaling pathways.

7.
Pak J Med Sci ; 40(4): 782-784, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545008

RESUMO

We identified the PACS2 gene responsible for the multifunctional sorting protein that play a role in nuclear gene expression as well as pathway traffic regulation. Diseases associated with PACS2 include early infantile epileptic encephalopathy (EIEE66), alacrima, achalasia, and mental retardation syndrome. Whole exome sequencing (WES) technique was used for the identification of variants that may lead to the disease. We identified a consanguineous Saudi family segregating developmental delay, mental retardation and epilepsy. Our results showed a heterozygous missense variant PACS2 gene leading to intellectual disability, epilepsy and cause epileptic encephalopathies (EIEE66) disorder. WES data was analyzed and identified variants were further confirmed by Sanger sequencing validation technique. We identified a heterozygous missense c.625G>A p.Glu209Lys in exon-6 of PACS2. The detected heterozygous mutation in the exon-6 region of PACS2 gene change the protein features and may cause disease. Further, explain the possibility that PACS2 gene play important role to cause intellectual disability, epilepsy and epileptic encephalopathies in this Saudi family.

8.
Biomed Rep ; 20(4): 67, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476606

RESUMO

Partner and localiser of BRCA2 (PALB2), also known as FANCN, is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of PALB2 are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.3: c.3296C>G (p.Thr1099Arg) in PALB2 gene (OMIM: 610355) that caused FA with mild pulmonary valve stenosis and dysmorphic and atypical features, including lymphangiectasia, non-immune hydrops fetalis and right-sided pleural effusion in a preterm female baby. WES results were further validated by Sanger sequencing. WES improves the screening and detection of novel and causative genetic variants to improve management of disease. To the best of our knowledge, the present study is the first reported FA case in a Saudi family with phenotypic atypical FA features. The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity.

9.
Sci Rep ; 14(1): 5627, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454096

RESUMO

Plant extracts are actively being used worldwide due to the presence of biologically active constituents helping in the preservation of food, and to aid against various diseases owing to their antimicrobial and antioxidant potential. The present research work was carried out to investigate the phytochemical constituents, antimicrobial activity, and antioxidant activity of different extracted samples of Euphorbia parviflora. Anti-microbial studies were carried out by Agar well diffusion while the DPPH method was employed for investigating anti-oxidant activity. Three samples from methanol, chloroform, and ethyl acetate extract were tested against five different bacterial strains comprising two species from Gram-negative bacteria i.e., Staphylococcus aureus and Bacillus subtilis and three species from Gram-positive bacteria i.e. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia along two fungal strains i.e. Candida albicans and Aspergillus niger. The results of the qualitative phytochemical analysis showed that methanolic, chloroformic, and ethylacetate extract of Euphorbia parviflora consist of alkaloids, reducing sugars, flavonoids, terpenoids, tannins, and saponins. The total phenol and flavonoid content of E. parviflora showed that the methanolic extract of E. parviflora had a significantly higher total phenolic content (53.73 ± 0.30 mg of GAE/g) and flavonoid content (44.62 ± 0.38 mg of than other extracts. The content of total phenolic and flavonoids was more in methanolic extract as compared to other extracts of E. prolifera. The HPLC analysis showed that in the chloroform extract of E. parviflora Cinnamic acid (4.32 ± 2.89 mg/g) was dominant, in methanol extract quercetin (3.42 ± 2.89 mg/g) was dominant and in ethyl acetate extract of E. parviflora catechin (4.44 ± 2.89 mg/g) was found dominant. The antimicrobial activity revealed that amongst all the extracts the highest antibacterial activity was shown by methanolic extract against B. subtilis and Staphylococcus aureus as compared to the other extracts. The antioxidant activity revealed that methanolic extract of E. parviflora demonstrated higher antioxidant activity (82.42 ± 0.02) followed by chloroform extract (76.48 ± 0.08) at 150 µg/mL. The aim of this study was primarily to evaluate the potential of this plant as a reliable source of antimicrobials and antioxidants that may be used for the treatment of various infectious diseases in the future. The study provides evidence that this plant can act as a reliable source of antimicrobial and antioxidant agents and might be used against several infectious diseases.


Assuntos
Acetatos , Anti-Infecciosos , Doenças Transmissíveis , Euphorbia , Euphorbiaceae , Antioxidantes/farmacologia , Antioxidantes/química , Metanol/química , Clorofórmio , Cromatografia Líquida de Alta Pressão , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Flavonoides/análise , Fenóis/análise , Testes de Sensibilidade Microbiana
10.
Food Sci Nutr ; 12(2): 661-674, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38370077

RESUMO

The current study focuses on Punica granatum L. (pomegranate) peel and peel extract and their use as functional foods, food additives, or physiologically active constituents in nutraceutical formulations. The pomegranate peel extract is a good source of bioactive substances needed for the biological activity of the fruit, including phenolic acids, minerals, flavonoids (anthocyanins), and hydrolyzable tannins (gallic acid). The macromolecules found in pomegranate peel and peel extract have been recommended as substitutes for synthetic nutraceuticals, food additives, and chemo-preventive agents because of their well-known ethno-medical significance and chemical properties. Moreover, considering the promises for both their health-promoting activities and chemical properties, the dietary and nutraceutical significance of pomegranate peel and pomegranate peel extract appears to be underestimated. The present review article details their nutritional composition, phytochemical profile, food applications, nutraceutical action, and health benefits.

11.
BMC Complement Med Ther ; 24(1): 91, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365652

RESUMO

BACKGROUND: Methanolic and chloroformic extract of Achillea millefolium and Chaerophyllum villosum were evaluated for HPLC analysis, genotoxic and antioxidant potential. MATERIALS AND METHODS: Genotoxic activity was carried out on human blood lymphocytes via comet assay and antioxidant activity was studied through DPPH method. RESULTS: The genotoxic potential of A. millefolium and C. villosum's methanolic and chloroformic extract was analysed using comet assay technique. Comet shaped human lymphocytes cells were observed when treated with different concentrations (50 mg/mL, 75 mg/mL, 100 mg/mL) of methanolic and chloroformic extract of both plants. Reading was taken on the basis of damaged DNA head and tail length. Greater the length of tail as compared to head, greater will be the damage and vice versa. Total comet score was obtained from A. millefolium subjected to different concentrations. After a time interval of 24 h both the extract showed dose dependant genoprotection with maximum genoprotectivity at 98.7 ± 12.7 and 116 ± 5.3 at 50 mg/100 mL for methanolic and chloroformic extract respectively. Similarly Total Comet score was obtained from C. villosum subjected to different concentrations of methanolic and chloroformic extract. After 24 h exhibited dose dependent genoprotection with maximum protectivity at 85.7 ± 22.0 and 101.7 ± 8.6 at 50 mg/100 mL for methanolic and chloroformic extract were determined. The antioxidant activity revealed that methanolic extract of A. millefolium showed highest antioxidant activity (84.21%) at 300 mg/ml after 90 min while the chloroformic extract of C. villosum exhibited highest (68.46%) antioxidant activity (59.69%) at 300 µg/ml after 90 min but less than the standard drug ascorbic acid (88.72%). Quantitative phytochemical screening revealed high percentage of alkaloids (27.4%), Phenols (34.5%), Flavonoids (32.4%) as compared to Tannins (12%) in methanolic extract of A.millefolium. While high percentage of alkaloids (31.4), Phenols (19.3%), Flavonoids (35.5%) as compared to Tannins (16.6%) in chloroformic extract of C. villosum. CONCLUSION: The present results showed that A. millefolium and C. villosum possess a number of important compounds and revealed genoprotective property which may be used to treat several genetic disorders such as alzeimer's disease in future (Grodzicki W, Dziendzikowska K, Antioxidants 9(3):229, 2020).


Assuntos
Achillea , Alcaloides , Humanos , Antioxidantes/química , Achillea/química , Taninos , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Fenóis/análise , Dano ao DNA
13.
Heliyon ; 10(4): e25907, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390160

RESUMO

Seismic attributes can play an important role in the exploration of hydrocarbon-bearing stratigraphic systems. Incised valley systems are developed during the falling sea, which causes the deposition of coarse-grained sandstone facies inside the low-standing tracts (LST). These regional phenomena constrain the quantitative attributes of ultra-thin-bedded stratigraphic petroleum traps, e.g., vertical and lateral variations in the thickness, accommodation space, lithology, and porosity. This study deals with the application of the continuous wavelet transform (CWT) of a spectral decomposition (SD) tool on a 3D post-stack seismic volume of the Miano gas Field, Lower Indus basin, Pakistan. The results show that the CWT accurately detected the regionally faulted/fractured system and distinguished the frequency-dependent amplitude anomalies. The wedge model resolved a 24-meter-thick gas-bearing resource. Quality control analysis was carried out using CWT-based broadband processing between the designed amplitude spectrum of 17 Hz and 70 Hz. The reservoirs with over 25% porosity that were located within the shale-dominated facies with less than 8% porosity were imaged through the processing of the instantaneous spectral porosity model at the 48-Hz tuning block. Moreover, 190 to 165-m-thick thin-bedded sandstone reservoirs at a 25% porosity zone were resolved using 22-Hz and 28-Hz, which implicates the sea standstill and medium-to-coarse-grained depositional reservoir facies. The ultra-thin-bedded traps inside the laterally continuous stratigraphic lens of 121 m and the prograding clinoform lens of 101-m within the incised valley petroleum system were resolved using 48-Hz, which implicates the falling sea and fine-scaled transgressed erosional facies. These implications suggest that the identified regional stratigraphic traps have development potential for this gas field. The treatment of the inverted model at the highest frequencies can be utilized to investigate the porous stratigraphically trapped facies of LST and can serve as an important analogue for the leading gas field of the Indus Basin and similar basins.

14.
Genes Genomics ; 46(4): 475-487, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38243045

RESUMO

BACKGROUND: ATP1A3 is a gene that encodes the ATPase Na + /K + transporting subunit alpha-3 isoenzyme that is widely expressed in GABAergic neurons. It maintains metabolic balance and neurotransmitter movement. These pathways are essential for the proper functioning of the nervous system. A mutation in the ATP1A3 gene demonstrates remarkable genotype-phenotype heterogeneity. OBJECTIVES: To provide insight into patients with ATP1A3 mutation. MATERIAL AND METHODS: These cases were identified using next generation sequencing. The patients' clinical and genetic data were retrieved. Detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data of all pediatric patients were extracted. RESULTS: The study included 14 females and 12 males in addition to two novel females cases. Their mean current age is 6.3 ± 4.24 years. There were 11.54% preterm pregnancies with 5 cases reporting pregnancy complications. Mean age of seizure onset was 1.07 ± 1.06 years. Seizure semiology included generalized tonic-clonic, staring spells, tonic-clonic, and others. Levetiracetam was the most frequently used Anti-seizure medication. The three most frequently reported classical symptoms included alternating hemiplegia of childhood (50%), cerebellar ataxia (50%), and optic atrophy (23.08%). Non-classical symptoms included dystonia (73.08%), paroxysmal dyskinesias (34.62%), and encephalopathy (26.92%). Developmental delay was reported among 84.62% in cognitive, 92.31% in sensorimotor, 80.77% in speech, and 76.92% in socioemotional. EEG and MRI were non-specific. CONCLUSION: Our study demonstrated high heterogeneity among patients with pathogenic variants in the ATP1A3 gene. Such variation is multifactorial and can be a predisposition of wide genetic and clinical variables. Many patients shared few similarities in their genetic map including repeatedly reported de novo, heterozygous, mutations in the gene. Clinically, higher females prevalence of atypical presentation was noted. These findings are validated with prior evidence and the comprehensive analysis in this study.


Assuntos
Convulsões , ATPase Trocadora de Sódio-Potássio , Masculino , Feminino , Recém-Nascido , Humanos , Criança , Lactente , Pré-Escolar , Fenótipo , Mutação , Genótipo , ATPase Trocadora de Sódio-Potássio/genética
15.
Gene ; 894: 147986, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37956964

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport. OBJECTIVES: A molecular diagnostics study of families presenting oculocutaneous albinism. METHODS: In this study, 17 consanguineous OCA families consisting of 93 patients were investigated. Whole Exome Sequencing (WES) of the index patient in each family were performed. Short listed variants of WES were Sanger validated for Mendelian segregation in obligate carriers and other available family members. Variant prioritization and pathogenicity were classified as per the criteria of American College Medical Genetics and Genomics (ACMG). Comparative computational modelling was performed to predict the potential damaging effect of the altered proteins. RESULTS: 15 pathogenic variations: c.132 T > A, c.346C > T, c.488C > G, c.1037G > A in TYR, c.1211C > T, c.1441G > A, c.1706_1707insT, c.2020C > G, c.2402G > C, c.2430del, in OCA2, c.1067G > A in TYRP1 and c.451C > T, c.515G > T, c.766C > T, c.917G > A in MC1R genes were identified. Three variants in OCA2 gene were characterized: c.1706_1707insT, c.2430del, and c.2402G > C, all of which were not reported before in OCA families. CONCLUSION: A few studies focusing on mutation screening of OCA patients have been reported before; however, this study has uniquely presents the Pakhtun ethnic population residing on the North-Western boarder. It explains that TYR, OCA2, TYRP1, and MC1R variations lead to non-syndromic OCA phenotype The overlapping phenotypes of OCA can precisely be diagnosed for its molecular pathogenicity using WES. This study recommends WES as a first-line molecular diagnostic tool, and provides a basis for developing customized genetic tests i.e. pre-marital screening to reduce the disease burden in the future generations.


Assuntos
Albinismo Oculocutâneo , Humanos , Sequenciamento do Exoma , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/diagnóstico , Testes Genéticos , Mutação , Proteínas de Membrana Transportadoras/genética , Glicoproteínas de Membrana/genética , Oxirredutases/genética
16.
Pharmacol Ther ; 254: 108579, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160914

RESUMO

Cancer, a noncommunicable disease, is the leading cause of mortality worldwide and is anticipated to rise by 75% in the next two decades, reaching approximately 25 million cases. Traditional cancer treatments, such as radiotherapy and surgery, have shown limited success in reducing cancer incidence. As a result, the focus of cancer chemotherapy has switched to the development of novel small molecule antitumor agents as an alternate strategy for combating and managing cancer rates. Heterocyclic compounds are such agents that bind to specific residues in target proteins, inhibiting their function and potentially providing cancer treatment. This review focuses on privileged heterocyclic pharmacophores with potent activity against carbonic anhydrases and kinases, which are important anticancer targets. Evaluation of ongoing pre-clinical and clinical research of heterocyclic compounds with potential therapeutic value against a variety of malignancies as well as the provision of a concise summary of the role of heterocyclic scaffolds in various chemotherapy protocols have also been discussed. The main objective of the article is to highlight key heterocyclic scaffolds involved in recent anticancer drug design that demands further attention from the drug development community to find more effective and safer targeted small-molecule anticancer agents.


Assuntos
Antineoplásicos , Compostos Heterocíclicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Desenvolvimento de Medicamentos
17.
Front Pediatr ; 11: 1288542, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38046674

RESUMO

Background: The mitochondria are a cellular power house. Tissues are involved in frequent energy consumption, and any failure or irregularity in the continuous energy production could lead to abnormalities. The leucine-rich pentatricopeptide repeat (LRPPRC) gene is one of the mitochondrial-related functions genes; variations in these genes are responsible for complex phenotypes that affect many organs such as the brain, liver, and muscles. Materials and methods: This study enrolled a family with Leigh syndrome-like phenotype. The molecular diagnosis was conducted by first performing whole exome sequencing (WES), followed by Sanger sequencing. Results: A novel splice-site variant (c.469 + 2T > A) at the exon-intron boundary in the LRPPRC gene was identified using the WES data analysis. Sanger validation confirmed the autosomal recessive inheritance of the identified variant. Based on the ACMG criteria for variant classification, PVS1 and PM2 suggest that the identified variant in the LRPPRC gene is likely to be pathogenic. Conclusion: To the best of our knowledge, there have been no previous reports of this variant in the LRPPRC gene. Our research not only identifies a novel variant in the LRPPRC gene, but also confirms the unresolved molecular diagnosis of the family. WES can be used as a first-line diagnostic tool in familial cases, particularly in those cases when detailed clinical phenotyping is not possible. Once the molecular diagnosis is confirmed in a family, it is necessary to conduct a thorough re-evaluation of the patients' specific clinical phenotypes in order to establish a clear genotype-phenotype correlation.

18.
Bioinformation ; 19(4): 369-374, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822833

RESUMO

Marine sponges are a host of different symbiotic groups of bacteria playing crucial roles in the protection and survival of marine sponges. Marine symbiotic bacteria from sponges are promising sources of bioactive chemicals and are increasingly being investigated. Therefore, the present study was undertaken to analyze total compounds from active symbiotic bacterial strain from sponge, Pione vastifical. Potential bacterial strain EA276 previously isolated from P. vastifical and was identified as Spongiobacter sp. Among 57 isolates, only 42% exhibited antagonistic activity. Four major classes of bacteria were reported previously where γ-Proteobacteria, was the dominant class. From these active antagonistic bacterial isolates, a potential bacterial strain Spongiobacter sp. EA276 was selected, and total metabolites were identified using GC and LC-MS analyses. Using LC-MS analysis bioactive compounds Dichlorphenamide, Amifloxacin and Carbenicillin are identified in both positive and negative mode. Plant growth hormones, Indole-3-acetic acid and Methyl jasmonate were identified using GC-MS analysis from culture extract of strain Spongiobacter sp. EA276. Our results highlighted the significance of marine flora inhabiting sponges from the Red Sea as potential source of bioactive compounds and plant growth hormones of biological and agricultural significance.

19.
RSC Adv ; 13(43): 30462-30490, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37854486

RESUMO

s-Triazine possesses an auspicious status in the field of drug discovery and development owing to its presence in many naturally occurring compounds as well as commercially available drugs like enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. Easy, cost-effective, and efficient access to its derivatives in addition to their splendid biological activities such as anticancer, anti-inflammatory, antiviral, anticonvulsant, anti-tubercular, antidiabetic, antimicrobial, makes it an attractive heterocyclic nucleus in the field of medicinal chemistry. Other than the direct access of its derivatives from simple commercially available starting materials like amidine, the s-triazine derivatives have also been obtained starting from an inexpensive commercially available 2,4,6-trichloro-1,3,5-triazine (TCT) commonly known as cyanuric chloride. Owing to the high reactivity and the possibility of sequential substitution of TCT, a variety of biologically active heterocyclic scaffolds have been installed on this nucleus in order to have more potent compounds. These s-triazine-based heterocyclic hybrids have been reported to show enhanced biological activities in recent years. Therefore, it is important to summarize and highlight recent examples of these hybrids which is imperative to attract the attention of the drug development community.

20.
Bioinformation ; 19(3): 226-229, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808372

RESUMO

Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disorder that typically affects young male adults in their second and third decades of life. It usually manifests as painless, subacute, progressive, bilateral vision loss, with more than 90% of affected individuals losing their vision before age 50. Compared with other diseases that cause optic neuritis (multiple sclerosis or neuromyelitis optica spectrum disorders), LHON has worsening visual function in the first 6-12 months of disease progression, is predominantly male, the optic nerve is affected bilaterally from onset, there is no gadolinium enhancement on MRI, no response to disease-modifying therapy, and there is a family history of mutation in mitochondrial DNA. In this article, we describe an interesting and challenging case of LHON due to a homoplasmic variant in the MT -CO3 gene that was initially misdiagnosed as a monophasic demyelinating disorder (clinically isolated syndrome vs acute disseminated encephalomyelitis vs neuromyelitis optica spectrum disorders).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...