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1.
Blood ; 142(25): 2198-2215, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-37738561

RESUMEN

ABSTRACT: Regulation of RNA polymerase II (RNAPII) activity is an essential process that governs gene expression; however, its contribution to the fundamental process of erythropoiesis remains unclear. hexamethylene bis-acetamide inducible 1 (HEXIM1) regulates RNAPII activity by controlling the location and activity of positive transcription factor ß. We identified a key role for HEXIM1 in controlling erythroid gene expression and function, with overexpression of HEXIM1 promoting erythroid proliferation and fetal globin expression. HEXIM1 regulated erythroid proliferation by enforcing RNAPII pausing at cell cycle check point genes and increasing RNAPII occupancy at genes that promote cycle progression. Genome-wide profiling of HEXIM1 revealed that it was increased at both repressed and activated genes. Surprisingly, there were also genome-wide changes in the distribution of GATA-binding factor 1 (GATA1) and RNAPII. The most dramatic changes occurred at the ß-globin loci, where there was loss of RNAPII and GATA1 at ß-globin and gain of these factors at γ-globin. This resulted in increased expression of fetal globin, and BGLT3, a long noncoding RNA in the ß-globin locus that regulates fetal globin expression. GATA1 was a key determinant of the ability of HEXIM1 to repress or activate gene expression. Genes that gained both HEXIM1 and GATA1 had increased RNAPII and increased gene expression, whereas genes that gained HEXIM1 but lost GATA1 had an increase in RNAPII pausing and decreased expression. Together, our findings reveal a central role for universal transcription machinery in regulating key aspects of erythropoiesis, including cell cycle progression and fetal gene expression, which could be exploited for therapeutic benefit.


Asunto(s)
Eritropoyesis , Factores de Transcripción , Humanos , Eritropoyesis/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica , Transcripción Genética , Globinas beta/genética , Globinas beta/metabolismo , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Factor de Transcripción GATA1/genética , Factor de Transcripción GATA1/metabolismo , Proteínas de Unión al ARN/genética
2.
Iran J Microbiol ; 12(2): 148-155, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32494349

RESUMEN

BACKGROUND AND OBJECTIVES: Use of antibiotics as growth promoters in animal feeds has been restricted due to the residues in poultry products such as egg and meat, furthermore to the antibiotic resistant of pathogenic bacteria. The prohibition of their use opens the opportunity for the use of non-antibiotic feed additives such as probiotics. The objectives of this study were to investigate the effect of the addition of Lactobacillus casei WB 315 and crude fish oil (CFO) to diets on growth performance, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), low density lipoproteins (LDL), high density lipoprotein (HDL), and cholesterol levesl of broiler chickens. MATERIALS AND METHODS: In this research, one-day old male broiler chicks were used and divided equally into four groups, namely a basal diet without L. casei WB 315 and without CFO (P0), basal diet supplemented with 0.5% L. casei WB 315 of total broiler basal feed (1.2 × 109 cfu/ml) and without CFO (P1), basal diet supplemented without L. casei WB 315 and 1% CFO of total broiler basal feed (P2), and basal diet supplemented with 0.5% L. casei WB 315 of total broiler basal feed (1.2 × 109 cfu/ml) and 1% CFO of total broiler basal feed (P3) for 35 days. RESULTS: The results of addition 0.5% Lactobacillus casei WB 315 (1.2 × 109 cfu/ml) and 1% CFO of total broiler basal feed after 35 days showed significant difference among treatment in feed efficiency (p<0.05), feed conversion ratio (p<0.05), feed consumption (p<0.05), EPA (p<0.05), DHA (p<0.05), increase HDL (p<0.05), reduced the LDL (p<0.05), and reduce cholesterol (p<0.05) in meat broiler chicken. CONCLUSION: It is concluded that the addition of L. casei WB 315 and crude fish oil (CFO) could significant improve the growth performance (feed efficiency, feed conversion ratio, feed consumption) and could significantly improve EPA, DHA and increase HDL and decrease LDL in meat poultry product.

3.
Vet World ; 12(6): 860-867, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31440006

RESUMEN

AIM: This study aimed to determine the use of probiotics Bifidobacterium spp. and Lactobacillus casei as alternative antibiotic growth promoters (AGPs) to improve growth performance and business analysis. MATERIALS AND METHODS: This study used a completely randomized factorial design. The first factor was the time of administration (1, 2, 3, and 4 weeks) and the second was the use of probiotics (control without probiotics; 0.1% AGP and 0.5% Bifidobacterium spp. + 0.25% L. casei). One hundred and eighty laying hens (Lohmann strain), of 30 weeks old, were divided into 12 treatment groups, composed of five replicates, each consisting of three laying hens. RESULTS: The results showed that using 0.5% Bifidobacterium spp. + 0.25% L. casei in weeks 1 and 2 showed the lowest feed intake (FI) (112.11-112.19 g/day), the highest egg weight (60.28 g) in the 1st week, the lowest feed conversion ratio (FCR) (2.21-2.23), and highest feed efficiency (44.75-45.25%) for 3-4 weeks, and the highest hen-day production (86.66-86.90%) for 3-4 weeks and the most profitable business analysis (IDR. 30,353). CONCLUSIONS: Based on the results, it can be concluded that the addition of 0.5% Bifidobacterium spp. + 25% L. casei probiotics can be used as a substitute for AGP; it can reduce the FI and FCR, increasing egg weight, feed efficiency, and hen-day production, as well as illustrating the results of the most profitable business analysis.

4.
J Coll Physicians Surg Pak ; 17(10): 626-8, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17999857

RESUMEN

We present a case of 34 years old male harboring a rare foreign body at an unusual abode with untoward consequences, after a motorbike accident. This resulted in lodging of a broken piece of aluminum alloy clutch lever, in the right submandibular region, with rounded blunt end medially deep in the region, abutting the Wharton's duct. Mechanism of injury, delayed consequences and management are discussed.

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