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1.
Artigo em Inglês | MEDLINE | ID: mdl-38825837

RESUMO

This study investigated the impact of heat stress on growth and carcass traits in four poultry genotypes-Giriraja, Country chicken, Naked Neck and Kadaknath reared in a hot and humid tropical environment. Birds from all genotypes had ad libitum access to feed and water while being challenged with consistently high environmental temperatures in the experimental shed. Daily diurnal meteorological data were recorded inside and outside the shed. The study specifically examined growth variables and carcass characteristics. Significant differences (p < 0.01) were observed in body weight and average daily gain at various intervals. Notably, feed intake showed significant differences (p < 0.01) across weeks, indicating interactions between genotypes and time intervals. The feed conversion ratio (FCR) varied significantly (p < 0.01), with the highest FCR recorded in the Kadaknath breed. Livability percentages were similar across groups, except for Giriraja, which had significantly lower livability (p < 0.01). Carcass traits, including dressing, wings, feathers and giblet percentages, showed significant differences among genotypes (p < 0.01). Hepatic mRNA expression of growth-related genes revealed numerical variations, with Naked Neck displaying the highest (p < 0.05) fold change in IGF-1 expression compared to other genotypes. The study recognized in the Naked Neck genotype to possess higher resilience in maintaining homoeostasis and uncompromised growth under heat stress, providing valuable insights for sustainable poultry farming in challenging environmental conditions.

2.
RSC Adv ; 13(23): 15783-15804, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37235108

RESUMO

Although the sorption of uranyl ions and other heavy metal ions over magnetic nanoparticles is well reported, the parameters governing the sorption process over the magnetic nanoparticles have not been clearly enumerated. However, to increase the efficiency of the sorption over the surface of these magnetic nanoparticles, it is essential to understand the different structural parameters that are involved in the sorption process. The sorption of uranyl ions and other competitive ions in simulated urine samples at different pH was effectively accomplished over magnetic nanoparticles of Fe3O4 (MNPs) and Mn-doped Fe3O4 (Mn-MNPs). The MNPs and Mn-MNPs were synthesized using an easily modified co-precipitation method and were thoroughly characterised using several techniques, such as XRD, HRTEM, SEM, zeta potential, and XPS. The substitutional doping of Mn (1 to 5 at%) in the Fe3O4 lattice (Mn-MNPs) showed better sorption ability as compared to that of MNPs. The sorption properties of these nanoparticles were mainly correlated with the different structural parameters to understand the roles of surface charge and different morphological parameters. The interaction centres over the surface of MNPs with the uranyl ions were designated and the effects of ionic interactions with uranyl ions for these sites were calculated. Extensive XPS, ab initio calculations and zeta potential studies have provided deep insights into the different aspects that play key roles in the sorption process. These materials showed one of the best Kd values (∼3 × 106 cm3) in a neutral medium with very low t1/2 values (∼0.9 min). The fast sorption kinetics (very low t1/2) makes them amongst the best sorption materials for uranyl ions and optimal for the quantification of ultra-low-level uranyl ions in simulated bioassays.

3.
Int J Tuberc Lung Dis ; 26(1): 6-11, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969422

RESUMO

The bidirectional relationship between TB and nutrition is well recognized - primary undernutrition is a risk factor for developing TB disease, while TB results in wasting. Although nutrition support is acknowledged as an important intervention in TB programmes, it is seldom afforded commensurate priority for action. TB incidence and deaths worldwide are falling too slowly to meet WHO End TB Strategy milestones, and the number of undernourished people is increasing, likely to be further exacerbated by the ongoing COVID-19 pandemic. Undernutrition needs to be more urgently and intensively addressed. This is especially true for the WHO South-East Asia Region, where the high rates of undernutrition are a key driver of the TB epidemic. The evidence base has been sufficiently robust for clear and workable programmatic guidance to be formulated on assessment, counselling and interventions for TB patients. Many high-burden countries have developed policies addressing TB and nutrition. Gaps in research to date have frustrated the development of more refined programmatic approaches related to addressing TB and malnutrition. Future research can be shaped to inform targeted, actionable policies and programmes delivering dual benefits in terms of undernutrition and TB. There are clear opportunities for policy-makers to amplify efforts to end TB by addressing undernutrition.


Assuntos
Desnutrição , Tuberculose , Humanos , Desnutrição/epidemiologia , Desnutrição/prevenção & controle , Estado Nutricional , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
4.
Kathmandu Univ Med J (KUMJ) ; 19(73): 62-68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34812160

RESUMO

Background Recently there has been an increased preference for intranasal delivery of drugs due to highly vascular nasal mucosa, bypassing first pass metabolism and the blood brain barrier (BBB) lead in quick drug absorption to the systemic circulation and direct access to brain from olfactory region. For pediatric patients this route offers significant benefits over injections or oral routes, like increased compliance, easy administration, and minimal side effects. Objective Assessment of prescription pattern of drugs and safety profile of drugs used by intranasal route in paediatric age group. Method Our study was a prospective observational study paediatric age group of patients conducted in the departments of Pharmacology, Paediatrics and Otorhinolaryngology of Burdwan Medical College and Hospital, Burdwan. Data were collected in CRF and frequency distribution of collected data done. Microsoft Excel 2010 was used for analysis. Result Common age group was infants. Males were more in number. Most common indication was epistaxis. Intranasal drugs per prescription were 1.05. Most commonly prescribed intranasal drug was nasal saline. Nasal decongestant was the most common prescribed medication. Nasal drops were the most common dose formulation. Conclusion Intranasal drug prescribing in our study was mainly aimed for treating local problems, very few being for systemic action. Some prescribing indicators like prescribing by generic name and prescribing from national essential drug lists were acceptable with scope for improvement. Average number of drugs per prescription and antibiotic use was high. Adverse events after intranasal drug use were primarily local and nose related.


Assuntos
Pediatria , Preparações Farmacêuticas , Administração Intranasal , Criança , Humanos , Lactente , Masculino , Mucosa Nasal , Centros de Atenção Terciária
5.
Int J Tuberc Lung Dis ; 25(5): 382-387, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977906

RESUMO

In September 2018, all countries made a commitment at the first ever United Nations High-Level Meeting (UNHLM) on TB, to provide TB preventive treatment (TPT) to at least 30 million people at high-risk of TB disease between 2018 and 2022. In the WHO South-East Asia Region (SEA Region), which accounts for 44% of the global TB burden, only 1.2 million high-risk individuals (household contacts and people living with HIV) were provided TPT (11% of the 10.8 million regional UNHLM TPT target) in 2018 and 2019. By 2020, almost all 11 countries of the SEA Region had revised their policies on TPT target groups and criteria to assess TPT eligibility, and had adopted at least one shorter TPT regimen recommended in the latest WHO TPT guidelines. The major challenges for TPT scale-up in the SEA Region are resource shortages, knowledge and service delivery/uptake gaps among providers and service recipients, and the lack of adequate quantities of rifapentine for use in shorter TPT regimens. There are several regional opportunities to address these gaps and countries of the SEA Region must make use of these opportunities to scale up TPT services rapidly to reduce the TB burden in the SEA Region.


Assuntos
Tuberculose , Sudeste Asiático/epidemiologia , Ásia Oriental , Humanos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Nações Unidas , Organização Mundial da Saúde
6.
Science ; 368(6490): 532-534, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32355032

RESUMO

According to conventional wisdom, the extraordinary properties of the cuprate high-temperature superconductors arise from doping a strongly correlated antiferromagnetic insulator. The highly overdoped cuprates-whose doping lies beyond the dome of superconductivity-are considered to be conventional Fermi liquid metals. We report the emergence of itinerant ferromagnetic order below 4 kelvin for doping beyond the superconducting dome in thin films of electron-doped La2- x Ce x CuO4 (LCCO). The existence of this ferromagnetic order is evidenced by negative, anisotropic, and hysteretic magnetoresistance, hysteretic magnetization, and the polar Kerr effect, all of which are standard signatures of itinerant ferromagnetism in metals. This surprising result suggests that the overdoped cuprates are strongly influenced by electron correlations.

7.
Kathmandu Univ Med J (KUMJ) ; 18(69): 42-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33582687

RESUMO

Background Calcium channel blockers are considered the first line drug over renin-angiotensinaldosterone system inhibitor in black population and with renin-angiotensinaldosterone system inhibitor in non-black population with Hypertension. Amlodipine has longer biological half life and lower potential to stimulate SNS. But, is associated with reflex tachycardia and pedal oedema. Cilnidipine has potent inhibitory both on voltage gated L-type and N-type calcium channels with better anti-proteinuric effect and good tolerability. Hence, our study compared the efficacy, safety and compliance of cilnidipine over amlodipine in Stage 1 hypertensive subjects. Objective To find out antihypertensive and renoprotective effect of cilnidipine. Method The study was open-label, single centre, prospective, parallel design, randomized controlled was done in Outdoor Patient Department (OPD) of Medicine and Department of Pharmacology in Burdwan Medical College and Hospital (BMCH). Patients with stage 1 HTN received cilnidipine while the other group received amlodipine. There were 4 follow-up visits for each participant consisting of baseline, 1 week, 6 weeks and after 12 weeks. Clinical parameters including pulse rate, blood pressure and ankle oedema noted also laboratory investigations were done. Safety parameters with adverse events and compliance by traditional pill count method. Result Blood pressure was effectively decreased by both amlodipine and cilnidipine. Cilnidipine significantly decreased Pulse Rate while amlodipine increased it and the difference in Pulse Rate comparing both the groups was statistically significant. None of the ADRs were statistically significant except pedal oedema. Pedal oedema was noted only in amlodipine arm and was statistically significant. Compliance to both the drugs was excellent. Total cost of therapy was higher with cilnidipine. Conclusion Though amlodipine is preferred drug, cilnidipine should be a better alternative when we consider subjects with sympathetic over activity, proteinuria or pedal oedema.


Assuntos
Di-Hidropiridinas , Hipertensão , Anlodipino/efeitos adversos , Pressão Sanguínea , Di-Hidropiridinas/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico , Estudos Prospectivos
8.
Nature ; 576(7787): 423-428, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31853081

RESUMO

Magnetically doped topological insulators enable the quantum anomalous Hall effect (QAHE), which provides quantized edge states for lossless charge-transport applications1-8. The edge states are hosted by a magnetic energy gap at the Dirac point2, but hitherto all attempts to observe this gap directly have been unsuccessful. Observing the gap is considered to be essential to overcoming the limitations of the QAHE, which so far occurs only at temperatures that are one to two orders of magnitude below the ferromagnetic Curie temperature, TC (ref. 8). Here we use low-temperature photoelectron spectroscopy to unambiguously reveal the magnetic gap of Mn-doped Bi2Te3, which displays ferromagnetic out-of-plane spin texture and opens up only below TC. Surprisingly, our analysis reveals large gap sizes at 1 kelvin of up to 90 millielectronvolts, which is five times larger than theoretically predicted9. Using multiscale analysis we show that this enhancement is due to a remarkable structure modification induced by Mn doping: instead of a disordered impurity system, a self-organized alternating sequence of MnBi2Te4 septuple and Bi2Te3 quintuple layers is formed. This enhances the wavefunction overlap and size of the magnetic gap10. Mn-doped Bi2Se3 (ref. 11) and Mn-doped Sb2Te3 form similar heterostructures, but for Bi2Se3 only a nonmagnetic gap is formed and the magnetization is in the surface plane. This is explained by the smaller spin-orbit interaction by comparison with Mn-doped Bi2Te3. Our findings provide insights that will be crucial in pushing lossless transport in topological insulators towards room-temperature applications.

9.
Sci Adv ; 5(5): eaav6753, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31114800

RESUMO

An understanding of the normal state in the high-temperature superconducting cuprates is crucial to the ultimate understanding of the long-standing problem of the origin of the superconductivity itself. This so-called "strange metal" state is thought to be associated with a quantum critical point (QCP) hidden beneath the superconductivity. In electron-doped cuprates-in contrast to hole-doped cuprates-it is possible to access the normal state at very low temperatures and low magnetic fields to study this putative QCP and to probe the T ➔ 0 K state of these materials. We report measurements of the low-temperature normal-state magnetoresistance (MR) of the n-type cuprate system La2-x Ce x CuO4 and find that it is characterized by a linear-in-field behavior, which follows a scaling relation with applied field and temperature, for doping (x) above the putative QCP (x = 0.14). The magnitude of the unconventional linear MR decreases as T c decreases and goes to zero at the end of the superconducting dome (x ~ 0.175) above which a conventional quadratic MR is found. These results show that there is a strong correlation between the quantum critical excitations of the strange metal state and the high-T c superconductivity.

10.
11.
Proc Natl Acad Sci U S A ; 116(13): 5991-5994, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30862739

RESUMO

In the physics of condensed matter, quantum critical phenomena and unconventional superconductivity are two major themes. In electron-doped cuprates, the low critical field (HC2) allows one to study the putative quantum critical point (QCP) at low temperature and to understand its connection to the long-standing problem of the origin of the high-TC superconductivity. Here we present measurements of the low-temperature normal-state thermopower (S) of the electron-doped cuprate superconductor La2-x Ce x CuO4 (LCCO) from x = 0.11-0.19. We observe quantum critical [Formula: see text] versus [Formula: see text] behavior over an unexpectedly wide doping range x = 0.15-0.17 above the QCP (x = 0.14), with a slope that scales monotonically with the superconducting transition temperature (TC with H = 0). The presence of quantum criticality over a wide doping range provides a window on the criticality. The thermopower behavior also suggests that the critical fluctuations are linked with TC Above the superconductivity dome, at x = 0.19, a conventional Fermi-liquid [Formula: see text] behavior is found for [Formula: see text] 40 K.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30588873

RESUMO

The X-ray crystal structures of a decamer sequence d(CGCGTACGCG)2 and a tetradecamer sequence d(CGCGCGTACGCGCG)2 are presented here. Both sequences are alternating pyrimidine-purine repeat sequences and they form disordered, pseudo-continuous left handed Z-type helices. They demonstrate interesting variants of the 'bundles of columns of helices' mode of packing.


Assuntos
Cristalização , DNA/química , Sequência de Bases , Cristalografia por Raios X/métodos , Bases de Dados de Ácidos Nucleicos , Modelos Moleculares , Conformação de Ácido Nucleico , Purinas/química , Pirimidinas/química
13.
Int J Tuberc Lung Dis ; 22(7): 807-812, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29914607

RESUMO

SETTING: Despite overwhelming evidence for the association between tuberculosis (TB) and tobacco use, it remains neglected in the context of policy, planning and practice. There is limited evidence about the extent of integration of TB and tobacco control programmes in South-East Asia Region (SEAR) countries. OBJECTIVE: To assess the level of TB-tobacco integration in 11 SEAR countries. DESIGN: Cross-sectional study using a structured questionnaire addressed to TB and tobacco focal points at the World Health Organization Country Offices. RESULTS: Apart from India, no country in the SEAR has a formal coordination mechanism for national TB and tobacco control programmes or a system of referral for tobacco users among TB patients for treatment of tobacco dependence. There is no joint planning, joint training or joint supervision and monitoring in any country. CONCLUSION: There is poor integration between TB and tobacco control programmes in most SEAR countries. This assessment fed into the development of a regional framework for TB-tobacco integration, which outlines three strategies: 1) integrated patient-centred care and prevention; 2) joint TB tobacco actions covering policy development, planning, training and monitoring; and 3) research and innovation. Every country in the region should adopt the TB-tobacco integration framework to improve programme performance.


Assuntos
Política de Saúde , Tabagismo/prevenção & controle , Uso de Tabaco/prevenção & controle , Tuberculose/prevenção & controle , Sudeste Asiático , Estudos Transversais , Humanos , Assistência Centrada no Paciente/organização & administração , Desenvolvimento de Programas , Inquéritos e Questionários
14.
Biophys Rev ; 10(3): 709-719, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29305702

RESUMO

Understanding the interaction of ionic liquids with cellular membrane becomes utterly important to comprehend the activities of these liquids in living organisms. Lipid monolayer formed at the air-water interface is employed as a model system to follow this interaction by investigating important thermodynamic parameters. The penetration kinetics of the imidazolium-based ionic liquid 1-decyl-3-methylimidazolium tetrafluoroborate ([DMIM][BF4]) into the zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid layer is found to follow the Boltzmann-like equation that reveals the characteristic time constant which is observed to be the function of initial surface pressure. The enthalpy and entropy calculated from temperature-dependent pressure-area isotherms of the monolayer show that the added ionic liquids bring about a disordering effect in the lipid film. The change in Gibbs free energy indicates that an ionic liquid with longer chain has a far greater disordering effect compared to an ionic liquid with shorter chain. The differential scanning calorimetric measurement on a multilamellar vesicle system shows the main phase transition temperature to shift to a lower value, which, again, indicates the disordering effect of the ionic liquid on lipid membrane. All these studies fundamentally point out that, when ionic liquids interact with lipid molecules, the self-assembled structure of a cellular membrane gets perturbed, which may be the mechanism of these molecules having adverse effects on living organisms.

15.
Soft Matter ; 13(47): 8969-8979, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29152634

RESUMO

Ionic liquids (ILs) are potential candidates for new antimicrobials due to their tunable antibacterial and antifungal properties that are required to keep pace with the growing challenge of bacterial resistance. To a great extent their antimicrobial actions are related to the interactions of ILs with cell membranes. Here, we report the effects of ILs on the nanoscopic dynamics and phase behaviour of a dimyristoylphosphatidylcholine (DMPC) membrane, a model cell membrane, as studied using neutron scattering techniques. Two prototypical imidazolium-based ILs 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM[BF4]) and 1-decyl-3-methylimidazolium tetrafluoroborate (DMIM[BF4]), which differ only in terms of the alkyl chain length of cations, have been used for the present study. Fixed Elastic Window Scan (FEWS) shows that the incorporation of ILs affects the phase behaviour of the phospholipid membrane significantly and the transition from a solid gel to a fluid phase shifts to lower temperature. This is found to be consistent with our differential scanning calorimetry measurements. DMIM[BF4], which has a longer alkyl chain cation, affects the phase behaviour more strongly in comparison to BMIM[BF4]. The pressure-area isotherms of the DMPC monolayer measured at the air-water interface show that in the presence of ILs, isotherms shift towards higher area-per lipid molecule. DMIM[BF4] is found to shift the isotherm to a greater extent compared to BMIM[BF4]. Quasielastic neutron scattering (QENS) data show that both ILs act as a plasticizer, which enhances the fluidity of the membrane. DMIM[BF4] is found to be a stronger plasticizing agent in comparison to BMIM[BF4] that has a cation with a shorter alkyl chain. The incorporation of DMIM[BF4] enhances not only the long range lateral motion but also the localised internal motion of the lipids. On the other hand, BMIM[BF4] acts weakly in comparison to DMIM[BF4] and mainly alters the localised internal motion of the lipids. Any subtle change in the dynamical properties of the membrane can profoundly affect the stability of the cell. Hence, the dominant effect of the IL with the longer chain length on the dynamics of the phospholipid membrane might be correlated with its cytotoxic activity. QENS data analysis has provided a quantitative description of the effects of the two imidazolium-based ILs on the dynamical and phase behaviour of the model cell membrane, which is essential for a detailed understanding of their action mechanism.

17.
Sci Rep ; 7(1): 11731, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28916795

RESUMO

The effect of high pressure (up to 8 GPa) on normal and superconducting state properties of PrFeAsO0.6F0.12, an 1111-type iron based superconductor close to optimal doped region, has been investigated by measuring the temperature dependence of resistivity. Initially, the superconducting transition temperature (T c ) is observed to increase slowly by about 1 K as pressure (P) increases from 0 to 1.3 GPa. With further increase in pressure above 1.3 GPa, T c decreases at the rate of ~1.5 K/GPa. The normal-state resistivity decreases monotonically up to 8 GPa. We have also measured the pressure dependence of magnetization (M) on the same piece of PrFeAsO0.6F0.12 sample up to 1.1 GPa and observed T c as well as the size of the Meissner signal to increase with pressure in this low-pressure region. In contrast, for an over-doped PrFeAsO0.6F0.14 sample, magnetization measurements up to 1.06 GPa show that both T c and the Meissner signal decrease with pressure. The present study clearly reveals two distinct regions in the dome-shaped (T c -P) phase diagram of PrFeAsO0.6F0.12.

18.
Phys Rev Lett ; 119(10): 106602, 2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28949185

RESUMO

Negative longitudinal magnetoresistance (NLMR) is shown to occur in topological materials in the extreme quantum limit, when a magnetic field is applied parallel to the excitation current. We perform pulsed and dc field measurements on Pb_{1-x}Sn_{x}Se epilayers where the topological state can be chemically tuned. The NLMR is observed in the topological state, but is suppressed and becomes positive when the system becomes trivial. In a topological material, the lowest N=0 conduction Landau level disperses down in energy as a function of increasing magnetic field, while the N=0 valence Landau level disperses upwards. This anomalous behavior is shown to be responsible for the observed NLMR. Our work provides an explanation of the outstanding question of NLMR in topological insulators and establishes this effect as a possible hallmark of bulk conduction in topological matter.

19.
Nature ; 546(7657): 280-284, 2017 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-28593963

RESUMO

The discovery of new materials is hampered by the lack of efficient approaches to the exploration of both the large number of possible elemental compositions for such materials, and of the candidate structures at each composition. For example, the discovery of inorganic extended solid structures has relied on knowledge of crystal chemistry coupled with time-consuming materials synthesis with systematically varied elemental ratios. Computational methods have been developed to guide synthesis by predicting structures at specific compositions and predicting compositions for known crystal structures, with notable successes. However, the challenge of finding qualitatively new, experimentally realizable compounds, with crystal structures where the unit cell and the atom positions within it differ from known structures, remains for compositionally complex systems. Many valuable properties arise from substitution into known crystal structures, but materials discovery using this approach alone risks both missing best-in-class performance and attempting design with incomplete knowledge. Here we report the experimental discovery of two structure types by computational identification of the region of a complex inorganic phase field that contains them. This is achieved by computing probe structures that capture the chemical and structural diversity of the system and whose energies can be ranked against combinations of currently known materials. Subsequent experimental exploration of the lowest-energy regions of the computed phase diagram affords two materials with previously unreported crystal structures featuring unusual structural motifs. This approach will accelerate the systematic discovery of new materials in complex compositional spaces by efficiently guiding synthesis and enhancing the predictive power of the computational tools through expansion of the knowledge base underpinning them.

20.
Oncogene ; 36(32): 4619-4628, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28368400

RESUMO

B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells. We proved that during combined treatment, inhibition of constitutive signal transducer and activator of transcription (STAT) 5 activation by IM allowed the specific enhancement of the STAT1 dependent, direct upregulation of BCL6 by IFNγ in CML cells. By using colony-forming assay, we found that IFNγ enhanced the ex vivo colony or cluster-forming capacity of human CML stem cells in the absence or presence of IM, respectively. Furthermore, inhibition of the transcriptional repressor function of BCL6 in the presence of IM and IFNγ almost completely blocked the cluster formation of human CML stem cells. On the other hand, by using small interfering RNA knockdown of BCL6, we demonstrated that in an IM-treated CML line the antiapoptotic effect of IFNγ was independent of BCL6 upregulation. We found that IFNγ also upregulated several antiapoptotic members of the BCL2 and BIRC gene families in CML cells, including the long isoform of MCL1, which proved to be essential for the antiapoptotic effect of IFNγ in an IM-treated CML line. Our results suggest that combination of TKIs with BCL6 and MCL1 inhibitors may potentially lead to the complete eradication of CML stem cells.


Assuntos
Mesilato de Imatinib/uso terapêutico , Interferon gama/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/metabolismo , Antígenos CD34/metabolismo , Linhagem Celular Tumoral , Humanos , Mesilato de Imatinib/farmacologia , Interferon gama/farmacologia , Leucaférese , Leucemia Mieloide de Fase Crônica/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteína Inibidora de Apoptose Neuronal/efeitos dos fármacos , Proteína Inibidora de Apoptose Neuronal/metabolismo , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Proteína de Morte Celular Associada a bcl/efeitos dos fármacos , Proteína de Morte Celular Associada a bcl/metabolismo
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