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1.
Cell ; 174(1): 172-186.e21, 2018 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-29958106

RESUMEN

The fusion oncoprotein CBFß-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1. Here, we demonstrate that CBFß-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. Upon pharmacologic inhibition of the CBFß-SMMHC/RUNX1 interaction, RUNX1 shows increased binding at three MYC distal enhancers, where it represses MYC expression by mediating the replacement of the SWI/SNF complex component BRG1 with the polycomb-repressive complex component RING1B, leading to apoptosis. Combining the CBFß-SMMHC inhibitor with the BET inhibitor JQ1 eliminates inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis indicated that the three enhancers are physically connected with the MYC promoter, and genome-editing analysis demonstrated that they are functionally implicated in deregulation of MYC expression. This study reveals a mechanism whereby CBFß-SMMHC drives leukemia maintenance and suggests that inhibitors targeting chromatin activity may prove effective in inv(16) leukemia therapy.


Asunto(s)
Apoptosis , Cromatina/metabolismo , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/metabolismo , Animales , Apoptosis/efectos de los fármacos , Azepinas/farmacología , Azepinas/uso terapéutico , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Línea Celular Tumoral , Proteínas Cromosómicas no Histona/química , Proteínas Cromosómicas no Histona/metabolismo , Inversión Cromosómica/efectos de los fármacos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/química , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , ADN/química , ADN/metabolismo , ADN Helicasas/metabolismo , Modelos Animales de Enfermedad , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Nucleares/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Proto-Oncogénicas c-myc/genética , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Triazoles/farmacología , Triazoles/uso terapéutico
3.
Int J Mol Sci ; 24(12)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37373146

RESUMEN

The rising prevalence of antibiotic-resistance is currently a grave issue; hence, novel antimicrobial agents are being explored and developed to address infections resulting from multiple drug-resistant pathogens. Biogenic CuO, ZnO, and WO3 nanoparticles can be considered as such agents. Clinical isolates of E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans from oral and vaginal samples were treated with single and combination metal nanoparticles incubated under dark and light conditions to understand the synergistic effect of the nanoparticles and their photocatalytic antimicrobial activity. Biogenic CuO and ZnO nanoparticles exhibited significant antimicrobial effects under dark incubation which did not alter on photoactivation. However, photoactivated WO3 nanoparticles significantly reduced the number of viable cells by 75% for all the test organisms, thus proving to be a promising antimicrobial agent. Combinations of CuO, ZnO, and WO3 nanoparticles demonstrated synergistic action as a significant increase in their antimicrobial property (>90%) was observed compared to the action of single elemental nanoparticles. The mechanism of the antimicrobial action of metal nanoparticles both in combination and in isolation was assessed with respect to lipid peroxidation due to ROS (reactive oxygen species) generation by measuring malondialdehyde (MDA) production, and the damage to cell integrity using live/dead staining and quantitating with the use of flow cytometry and fluorescence microscopy.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Óxidos , Óxidos/farmacología , Cobre/farmacología , Óxido de Zinc/farmacología , Tungsteno/farmacología , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Candida albicans/efectos de los fármacos
4.
J Environ Manage ; 346: 118971, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37729832

RESUMEN

Microplastic pollution is a serious environmental problem that affects both aquatic and terrestrial ecosystems. Small particles with size of less than 5 mm, known as microplastics (MPs), persist in the environment and pose serious threats to various species from micro-organisms to humans. However, terrestrial environment has received less attention than the aquatic environment, despite being a major source of MPs that eventually reaches water body. To reflect its novelty, this work aims at providing a comprehensive overview of the current state of MPs pollution in the global environment and various solutions to address MP pollution by integrating applied technology, policy instruments, and legislation. This review critically evaluates and compares the existing technologies for MPs detection, removal, and degradation, and a variety of policy instruments and legislation that can support the prevention and management of MPs pollution scientifically. Furthermore, this review identifies the gaps and challenges in addressing the complex and diverse nature of MPs and calls for joint actions and collaboration from stakeholders to contain MPs. As water pollution by MPs is complex, managing it effectively requires their responses through the utilization of technology, policy instruments, and legislation. It is evident from a literature survey of 228 published articles (1961-2023) that existing water technologies are promising to remove MPs pollution. Membrane bioreactors and ultrafiltration achieved 90% of MPs removal, while magnetic separation was effective at extracting 88% of target MPs from wastewater. In biological process, one kg of wax worms could consume about 80 g of plastic/day. This means that 100 kg of wax worms can eat about 8 kg of plastic daily, or about 2.9 tons of plastic annually. Overall, the integration of technology, policy instrument, and legislation is crucial to deal with the MPs issues.

5.
Molecules ; 28(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36838866

RESUMEN

One of the foremost causes of wellbore instability during drilling operations is shale swelling and hydration induced by the interaction of clay with water-based mud (WBM). Recently, the use of surfactants has received great interest for preventing shale swelling, bit-balling problems, and providing lubricity. Herein, a novel synthesized magnetic surfactant was investigated for its performance as a shale swelling inhibitor in drilling mud. The conventional WBM and magnetic surfactant mixed WBM (MS-WBM) were formulated and characterized using Fourier Transform Infrared (FTIR) and Thermogravimetric analyzer (TGA). Subsequently, the performance of 0.4 wt% magnetic surfactant as shale swelling and clay hydration inhibitor in drilling mud was investigated by conducting linear swelling and capillary suction timer (CST) tests. Afterward, the rheological and filtration properties of the MS-WBM were measured and compared to conventional WBM. Lastly, the swelling mechanism was investigated by conducting a scanning electron microscope (SEM), zeta potential measurement, and particle size distribution analysis of bentonite-based drilling mud. Experimental results revealed that the addition of 0.4 wt% magnetic surfactant to WBM caused a significant reduction (~30%) in linear swelling. SEM analysis, contact angle measurements, and XRD analysis confirmed that the presence of magnetic surfactant provides long-term swelling inhibition via hydrophobic interaction with the bentonite particles and intercalation into bentonite clay layers. Furthermore, the inhibition effect showed an increase in fluid loss and a decrease in rheological parameters of bentonite mixed mud. Overall, the use of magnetic surfactant exhibits sterling clay swelling inhibition potential and is hereby proffered for use as a drilling fluid additive.


Asunto(s)
Surfactantes Pulmonares , Tensoactivos , Bentonita/química , Arcilla , Minerales , Interacciones Hidrofóbicas e Hidrofílicas , Fenómenos Magnéticos
6.
Molecules ; 28(18)2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37764399

RESUMEN

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 µM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

7.
Curr Issues Mol Biol ; 44(8): 3695-3710, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36005149

RESUMEN

Phytohormones play an essential role in plant growth and development in response to environmental stresses. However, plant hormones require a complex signaling network combined with other signaling pathways to perform their proper functions. Thus, multiple phytohormonal signaling pathways are a prerequisite for understanding plant defense mechanism against stressful conditions. MicroRNAs (miRNAs) are master regulators of eukaryotic gene expression and are also influenced by a wide range of plant development events by suppressing their target genes. In recent decades, the mechanisms of phytohormone biosynthesis, signaling, pathways of miRNA biosynthesis and regulation were profoundly characterized. Recent findings have shown that miRNAs and plant hormones are integrated with the regulation of environmental stress. miRNAs target several components of phytohormone pathways, and plant hormones also regulate the expression of miRNAs or their target genes inversely. In this article, recent developments related to molecular linkages between miRNAs and phytohormones were reviewed, focusing on drought stress.

8.
Genet Res (Camb) ; 2022: 9452234, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35356752

RESUMEN

Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene's promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.


Asunto(s)
Genómica , Polimorfismo de Nucleótido Simple , Animales , Bovinos/genética , Genes Reguladores , Masculino , Mamíferos/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Análisis de Secuencia
9.
Arch Microbiol ; 204(5): 288, 2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35482163

RESUMEN

The imprudent use of agrochemicals to control agriculture and household pests is unsafe for the environment. Hence, to protect the environment and diversity of living organisms, the degradation of pesticides has received widespread attention. There are different physical, chemical, and biological methods used to remediate pesticides in contaminated sites. Compared to other methods, biological approaches and their associated techniques are more effective, less expensive and eco-friendly. Microbes secrete several enzymes that can attach pesticides, break down organic compounds, and then convert toxic substances into carbon and water. Thus, there is a lack of knowledge regarding the functional genes and genomic potential of microbial species for the removal of emerging pollutants. Here we address the knowledge gaps by highlighting systematic biology and their role in adaptation of microbial species from agricultural soils with a history of pesticide usage and profiling shifts in functional genes and microbial taxa abundance. Moreover, by co-metabolism, the microbial species fulfill their nutritional requirements and perform more efficiently than single microbial-free cells. But in an open environment, free cells of microbes are not much prominent in the degradation process due to environmental conditions, incompatibilities with mechanical equipment and difficulties associated with evenly distributing inoculum through the agroecosystem. This review highlights emerging techniques involving the removal of pesticides in a field-scale environment like immobilization, biobed, biocomposites, biochar, biofilms, and bioreactors. In these techniques, different microbial cells, enzymes, natural fibers, and strains are used for the effective biodegradation of xenobiotic pesticides.


Asunto(s)
Contaminantes Ambientales , Plaguicidas , Aclimatación , Biodegradación Ambiental , Suelo
10.
J Appl Microbiol ; 132(3): 1636-1651, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34796583

RESUMEN

Current literature related to the impact of probiotics on the incidence of gastrointestinal tract infections (GITIs) has shown mixed results and no systematic review available with pooled analysis exists. Thus, the aim of this systematic review was to provide contemporary evidence regarding the overall and strain-specific influence of probiotics in preventing GITIs among infants and children attending childcare centres. The review shortlisted 18 RCTs after screening through the initial search results of 779 articles. However, only 15 trials were deemed eligible, addressing at least one outcome in the pooled analysis. It is concluded that the supplementation of probiotics (overall effect) may reduce the risk of GITI episode by 26%, with Lacticaseibacillus paracasei, Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG being specifically potent probiotic strains in reducing GITI episode, duration of infection and absence from childcare respectively. There is insufficient evidence to determine the effect of Bifidobacterium animalis subsp. lactis BB-12 based on the findings of the trials included in this review.


Asunto(s)
Bifidobacterium animalis , Lacticaseibacillus rhamnosus , Probióticos , Niño , Cuidado del Niño , Tracto Gastrointestinal , Humanos , Lactante
11.
Biol Res ; 55(1): 18, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35488278

RESUMEN

BACKGROUND: Glutamate and voltage-gated sodium channels, both have been the target of intense investigation for its involvement in carcinogenesis and progression of malignant disease. Breast cancer with increased level of glutamate often metastasize to other organs (especially bone), whilst re-expression of 'neonatal' Nav1.5, nNav1.5 in breast cancer is known to promote cell invasion in vitro, metastasis in vivo and positive lymph node metastasis in patients. METHODS: In this study, the role of nNav1.5 in regulating glutamate level in human breast cancer cells was examined using pharmacological approach (VGSCs specific blocker, TTX, glutamate release inhibitor, riluzole and siRNA-nNav1.5). Effect of these agents were evaluated based on endogenous and exogenous glutamate concentration using glutamate fluorometric assay, mRNA expression of nNav1.5 using qPCR and finally, invasion using 3D culture assay. RESULTS: Endogenous and exogenous glutamate levels were significantly higher in aggressive human breast cancer cells, MDA-MB-231 cells compared to less aggressive human breast cancer cells, MCF-7 and non-cancerous human breast epithelial cells, MCF-10A. Treatment with TTX to MDA-MB-231 cells resulted in significant reduction of endogenous and exogenous glutamate levels corresponded with significant suppression of cell invasion. Subsequently, downregulation of nNav1.5 gene was observed in TTX-treated cells. CONCLUSIONS: An interesting link between nNav1.5 expression and glutamate level in aggressive breast cancer cells was detected and requires further investigation.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/genética , Línea Celular Tumoral , Femenino , Ácido Glutámico , Humanos , Recién Nacido , Canal de Sodio Activado por Voltaje NAV1.5/genética , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , ARN Interferente Pequeño
12.
Molecules ; 27(20)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36296403

RESUMEN

Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, 1H-NMR and 13C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC50 values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.


Asunto(s)
Diabetes Mellitus , Insulinas , Niño , Humanos , Inhibidores de Glicósido Hidrolasas/química , alfa-Glucosidasas/metabolismo , Simulación del Acoplamiento Molecular , Acarbosa , Sulfonamidas/uso terapéutico , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Diabetes Mellitus/tratamiento farmacológico , Sulfanilamida , Insulinas/uso terapéutico , Estructura Molecular
13.
J Pak Med Assoc ; 72(5): 843-849, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35713042

RESUMEN

OBJECTIVE: To study multinodular goitre patients' surgery by direct observation of surgical technique, and to compare complications with surgeons' skills and experience, for improved training of future thyroid surgeons. METHODS: Based on positivist epistemology and analytical observational design, this prospective double-blind study of a cohort of multinodular goitre patients operated upon by variedly experienced surgeons, was conducted at Bahawal Victoria Hospital Bahawalpur and Nishtar Medical University Hospital Multan, Pakistan, from December 2016 to April 2019. Patients were admitted through outpatient department and operated upon in routine operation lists. The surgeons were specialists/senior registrars, assistant professors, associate professors and professors. The patients were divided into two virtual groups: the one operated upon by surgeons with >3 years of post-fellowship experience and the other operated upon by surgeons with <3 years of post-fellowship experience. Surgeries were directly observed and differences in surgical technique and complications were recorded for respective groups. Data was analysed using SPSS 20. RESULTS: Of the 134 patients, there were 73(54.5%) in group 1 and 61(45.5%) in group 2. Overall, there were 119(88.8%) females and 15(11.2%) males. The overall mean age was 37.17±13.41 years (range: 14-80 years). Of the 25 surgeons, 13(52%) were in group 1 and 12(48%) in group 2. Group 1 had fewer complications compared to group 2, which on certain parameters was statistically significant (p<0.05). CONCLUSIONS: Surgeons' experience and technique were found to have significant relationship with the rate of complications. Direct observation of surgeries is significant for real life evaluation and training of junior surgeons.


Asunto(s)
Bocio , Cirujanos , Adulto , Método Doble Ciego , Becas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tiroidectomía/métodos , Adulto Joven
14.
J Pak Med Assoc ; 72(12): 2538-2541, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37246686

RESUMEN

Neonatal severe hyperparathyroidism (NSHPT) is a rare genetic disorder that presents within the first six months of life. We present the case report of a male child who presented to us in the first month of his life with symptoms of lethargy, constipation, and reluctance to feed. One sibling of the child had died earlier with similar symptoms in the first six months of life. Upon physical examination, the child was lethargic, dehydrated, had bradycardia with hyperreflexia. Serum electrolyte analysis showed hypercalcaemia and hypophosphataemia. Further workup revealed elevated serum parathyroid hormone levels and Calcium sensing receptor (CaSR) gene mutation in autosomal recessive patterns. The father was discovered to be heterozygous for the same mutation but is asymptomatic. Diagnosis of neonatal severe hyperparathyroidism was made and the child was managed medically with intravenous fluids, Furosemide, Pamidronate, and Cinacalcet. On inconsistent response to medical therapy, he underwent total parathyroidectomy with auto transplantation of half of the left lower parathyroid gland. Postoperatively, the child is being managed on oral calcium and Alpha Calcidiol supplementation and is doing well.


Asunto(s)
Hipercalcemia , Hiperparatiroidismo Primario , Recién Nacido , Niño , Humanos , Masculino , Hiperparatiroidismo Primario/diagnóstico , Cinacalcet/uso terapéutico , Mutación , Heterocigoto , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Calcio/uso terapéutico
15.
Trop Anim Health Prod ; 54(2): 107, 2022 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-35187616

RESUMEN

BACKGROUND: Haemonchosis is a fatal disease of small ruminants caused by the parasite Haemonchus contortus (H. contortus). The most common drugs used in the treatment of H. contortus include albendazole, oxfendazole, and ivermectin. However, as previously reported in the treatment of haemonchosis, these medicines have acquired drug resistance problems over time. Interestingly, natural plant compounds have demonstrated promising effects in the treatment of H. contortus. Therefore, the current study evaluated the effects of plant extract, Ferula asafetida, against common drugs such as albendazole, oxfendazole, ivermectin, and closantel for the treatment of haemonchosis in small ruminants. METHODOLOGY: The current study was conducted on different small ruminant farms in Kasur District, Punjab, Pakistan. The positive animals (n = 720) after coprological examination were selected in this study and divided into two major groups (n = 360 goats and n = 360 sheep). Further, animals were divided into five treatment groups (A-E) and one control group with no treatment (F). Albendazole, oxfendazole, ivermectin, closantel, and Ferula asafetida were administered orally to groups A-E, respectively. The eggs per gram feces (EPG) were determined through the McMaster technique on days 0, 7th, and 14th of treatment. RESULTS: The results showed a significantly higher efficacy of closantel and Ferula asafetida against H. contortus in both goats (100% and 70%; p < 0.05) and sheep (99% and 87%; p < 0.05), respectively. No correlation was observed between EPG reduction with age and gender in both goats and sheep. CONCLUSION: Allopathic drug closantel and herbal drug, Ferula asafetida, have been proved an effective dewormer against H. contortus in small ruminants.


Asunto(s)
Antihelmínticos , Ferula , Enfermedades de las Cabras , Hemoncosis , Haemonchus , Enfermedades de las Ovejas , Albendazol/farmacología , Albendazol/uso terapéutico , Animales , Antihelmínticos/uso terapéutico , Bencimidazoles , Resistencia a Medicamentos , Enfermedades de las Cabras/tratamiento farmacológico , Cabras , Hemoncosis/tratamiento farmacológico , Hemoncosis/parasitología , Hemoncosis/veterinaria , Ivermectina/farmacología , Ivermectina/uso terapéutico , Óvulo , Recuento de Huevos de Parásitos/veterinaria , Salicilanilidas , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológico , Enfermedades de las Ovejas/parasitología
16.
Pak J Med Sci ; 38(8): 2202-2207, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36415281

RESUMEN

Objectives: To compare the levels of glycated albumin and angiopoietin-2 in Type-Two diabetics with and without diabetic retinopathy. Methods: It was a cross-sectional comparative study done at University of Health Sciences, Lahore after collecting data from recruited patients from the outpatient department of Layton Rahmatulla Benevolent Trust Eye Hospital, Lahore from 1st July, 2016 to 30th Aug., 2017. A total of 80 type two diabetics of both genders fulfilling the inclusion criteria were included and divided in two groups based on absence and presence of diabetic retinopathy. Obtained data were analyzed using IBM SPSS for Windows software (version 22). For comparison of both groups, Independent "t" Test or Mann-Whitney U tests were applied accordingly. For correlation of quantitative variables in each group, Spearman rho correlation and Pearson correlation test were applied depending upon normality of data. Results: Among 80 type-two diabetics, 42 (52.5%) patients had diabetic retinopathy and 38 (47.5%) were without diabetic retinopathy. Overall, females (62.5%) outnumbered males (37.5%). Both study group were age matched (p=0.45). Mean serum albumin in diabetic retinopathy and non-diabetic retinopathy group was 4.20 ±0.56 gm/dL and 4.43 ±0.39 gm/dL respectively (p=0.031). In diabetic retinopathy group, mean glycated albumin was 1.48 (0.63-1.76) gm/dL and median IQR in non-diabetic retinopathy was 0.52 (0.23-1.10) gm/dL (p=0.003). In diabetic retinopathy group, mean glycated albumin (percent) was 30.71±18.63% and in non-diabetic retinopathy group, the median IQR was 11.80 (5.06-27.25) (p= 0.001). The angiopoietin-2 median IQR in diabetic retinopathy group 5.70 (5.47-5.80) was significantly different (p=0.033) from diabetics without diabetic retinopathy groups 5.40 (4.97-5.60). Conclusion: Our study reported raised levels of glycated albumin (percent) and angiopoietin-2 in type-two diabetics, highlighting their possible involvement in disease and its progression.

17.
Crit Rev Eukaryot Gene Expr ; 31(1): 79-92, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33639058

RESUMEN

Diabetic cardiomyopathy is characterized as abnormal function and structure of myocardium associated with diabetes irrespective of other cardiac risk factors like hypertension or coronary artery disease (CAD). The pathogenesis of DCM was not well understood in the past due to its complexity but it has been discovered recently. Various factors are found to be associated with the onset of DCM including impaired calcium handling, remodeling of extracellular matrix (ECM), increased oxidative stress, altered metabolism, mitochondrial dysfunction, and endothelial dysfunction. Micro-RNAs (miRNAs) are also found to be of great importance in the pathogenesis of DCM. Different miRNAs like miR-126, miR-24, miR-1, miR-155, miR-499, and miR-199a are found to be associated with different types of heart diseases like CAD and myocardial infarction. Studies have shown that the miRNA plays a crucial role in the development of DCM and it was found that the expression levels of different miRNAs differ in patients as compared to healthy individuals. This review focuses on the pathogenesis of DCM and various factors involved in the onset of diabetic car-diomyopathy. Moreover, the probable role of miRNA in the pathogenesis of DCM is also discussed.


Asunto(s)
Cardiomiopatías Diabéticas/diagnóstico , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , MicroARNs/fisiología , Animales , Calcio/metabolismo , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Humanos , Mitocondrias/patología , Estrés Oxidativo , Factores de Riesgo , Transducción de Señal
18.
Crit Rev Eukaryot Gene Expr ; 31(5): 67-78, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34591392

RESUMEN

The junk DNA "pseudogenes," known as genomic fossils, are characterized by their ubiquitousness and abundance within the genomic structure. These genomics sets are recognized by the potential activity of meta-regulating the parent genes; these are transcribed into interfering RNA, consequently acting on miRNA concentration, thereby shedding light on the crosstalk of the pseudogenes' miRNA, siRNA, lncRNA/tumor therapy co-relationship. Moreover, an upcoming visualization regarding pseudogenes is under investigation, which describes the potentiality of pseudogenes as a fundamental component of cancerous evolutionary processing tools. Accordingly, here is a systematic review covering pseudobirth, pseudosignatures, and functional properties of pseudogenes, concluding that these pseudogenes are hypothetically predictive tumor therapies.


Asunto(s)
Evolución Biológica , Genómica , Neoplasias/genética , Seudogenes , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Terapia Genética/métodos , Humanos
19.
Microb Pathog ; 152: 104754, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33508415

RESUMEN

Mitochondria is a cellular source of energy, appears to play an essential role in dealing with cellular stress induced by environmental stimuli. The genetic diversity of mitochondrial genes involved in oxidative phosphorylation affecting the production of cellular energy and regional adaptation to various ecological (climatic) pressures affecting amino acid sequences (variants of protein). However, little is known about the combined effect of protein changes on cell-level metabolic alterations in simultaneous exposure to various environmental conditions, including mitochondrial dysfunction and oxidative stress induction. The present study was designed to address this issue by analyzing the mitochondrial proteins in Fasciola species including Cytochrome oxidase (COX1, COX2, COX3, and CYTB) and NADH dehydrogenase (ND1, ND2, ND3, ND4, ND5, and ND6). Mitochondrial proteins were used for detailed computational investigation, using available standard bioinformatics tools to exploit structural and functional relationships. These proteins in Fasciola hepatica, Fasciola gigentica, and Fasciola jacksoni were functionally annotated using public databases. The results showed that the protein of COX1 of F. hepatica, F. gigantica, and F. jacksoni consist of 510, 513, and 517 amino acids, respectively. The alignment of proteins showed that these proteins are conserved in the same regions at ten positions in COX and CYTB proteins while at twelve locations in NADH. Three-dimensional structure of COX, CYTB, and NADH proteins were compared and showed differences in additional conserved and binding sites in COX and CYTB proteins as compared to NADH in three species of Fasciola. These results based on the amino acid diversity pattern were used to identify sites in the enzyme and the variations in mitochondrial proteins among Fasciola species. Our study provides valuable information for future experimental studies, including identification of therapeutic, diagnostic, and immunoprophylactic interests with novel mitochondrial proteins.


Asunto(s)
Fasciola hepatica , Fasciola , Fascioliasis , Animales , Fasciola hepatica/genética , Variación Genética , Proteínas Mitocondriales/genética
20.
BMC Infect Dis ; 21(1): 637, 2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34215203

RESUMEN

BACKGROUND: Cedecea neteri is a gram-negative, oxidase-negative bacillus, a rare pathogen. Few reports are emerging globally about its antimicrobial resistance pattern especially in immunocompromised individuals with comorbidities. CASE PRESENTATION: In this paper, we report the first case of C. neteri causing urinary tract infection in a pregnant woman at a specialty care hospital in the Northern Emirates of Ras al Khaimah, UAE. DISCUSSION AND CONCLUSION: C. neteri is a rare and unusual pathogen, unlike routine gram-negative urinary tract pathogens from the family of Enterobacteriaceae and therefore may be missed or misidentified by routine laboratories using conventional microbiology identification techniques. Hence, Cedecea infections may be under-reported. Physicians and microbiology technicians must be aware of such a rare pathogen, as most of the isolates are multi-drug-resistant and require combined antibiotic treatment with beta-lactamase inhibitors and hence pose a treatment challenge especially in immunocompromised patients with comorbidities. In recent years, it has been reported as an emerging opportunistic pathogen.


Asunto(s)
Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/aislamiento & purificación , Polihidramnios/fisiopatología , Mujeres Embarazadas , Infecciones Urinarias/epidemiología , Adulto , Antibacterianos/uso terapéutico , Enterobacteriaceae/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Embarazo , Pronóstico , Emiratos Árabes Unidos/epidemiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología
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