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1.
Cell ; 187(3): 624-641.e23, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211590

RESUMO

The therapeutic potential for human type 2 innate lymphoid cells (ILC2s) has been underexplored. Although not observed in mouse ILC2s, we found that human ILC2s secrete granzyme B (GZMB) and directly lyse tumor cells by inducing pyroptosis and/or apoptosis, which is governed by a DNAM-1-CD112/CD155 interaction that inactivates the negative regulator FOXO1. Over time, the high surface density expression of CD155 in acute myeloid leukemia cells impairs the expression of DNAM-1 and GZMB, thus allowing for immune evasion. We describe a reliable platform capable of up to 2,000-fold expansion of human ILC2s within 4 weeks, whose molecular and cellular ILC2 profiles were validated by single-cell RNA sequencing. In both leukemia and solid tumor models, exogenously administered expanded human ILC2s show significant antitumor effects in vivo. Collectively, we demonstrate previously unreported properties of human ILC2s and identify this innate immune cell subset as a member of the cytolytic immune effector cell family.


Assuntos
Granzimas , Imunidade Inata , Linfócitos , Neoplasias , Animais , Humanos , Camundongos , Apoptose , Citocinas , Neoplasias/imunologia , Neoplasias/terapia
2.
BMC Public Health ; 23(1): 1693, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658309

RESUMO

BACKGROUND: Routine immunisation coverage in Cameroon is still below the target of the national Expanded Programme on Immunisation (EPI), with only 42% of children fully immunised according to Demographic and Health Survey (DHS) report in 2018. The objective of this study was to evaluate factors associated with full immunisation and zero-dose in Cameroonian children. METHODS: A two-stage cross-sectional cluster survey was conducted in Yaoundé in November 2021, targeting children aged 12-59 months. The clusters were chosen with probability proportionate to population size (PPS), and households selected by restricted sampling technique. Data were collected from the vaccination card of the child or from parents' recall, if the card was not available, using electronic forms with tablets. Using R (version 4.1.0.), the proportion of fully immunised children was calculated. The household wealth index was described using principal component analysis, and factors associated with full immunisation assessed with multiple logistics regression. The threshold of statistical significance was set at 5%. FINDINGS: A total, 273 children aged 12-59 months enrolled; 37% of participants were fully immunised, and 16% had never received any vaccine. Mother's level of education: Primary (OR = 3.59, p = 0.0200), high school (OR = 3.68, p = 0.0400*), and higher education (OR = 8.25, p = 0.0018), and sharing household with biological father (OR = 2.11, p = 0.0305) were significantly associated with full vaccination. Living in a richer (3rd-5th wealth quintiles) household (OR = 0.25, p = 0.0053); mother's education: Primary (OR = 0.07, p = 0.0271) and Higher education (OR = 0.10, p = 0.0419), living with the mother (OR = 0.05, p = < 0.0001) and living with the father (OR = 0.22, p = 0.0253) had significant negative association with zero-dose in children. CONCLUSION: The proportion of fully vaccinated children in Yaounde is lower than the national average. Children from poor homes and those borne by uneducated mother have higher odds of not being vaccinated. Immunisation programmes in Yaounde need to be stepped up to improve coverage. Equally, there is a need to reconsider how the poor can the better reached with immunisation services.


Assuntos
Vacinação , Vacinas , Criança , Humanos , Camarões/epidemiologia , Estudos Transversais , Imunização
3.
J Cell Mol Med ; 25(18): 8701-8714, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34342123

RESUMO

To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. The removal of cytokines revealed a broad developmental potential of the early blood cells, stabilized the hPSC-derived definitive precursors and led to spontaneous activation of inflammatory signalling. Our cytokine-free protocol is simple, efficient, reproducible and applicable for embryonic stem cells (ESCs) and induced PSCs. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying the early human haematopoietic development.


Assuntos
Citocinas/metabolismo , Células-Tronco Embrionárias , Hematopoese , Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo
4.
Haematologica ; 106(8): 2191-2202, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732364

RESUMO

MYB is a key regulator of definitive hematopoiesis and it is dispensable for the development of primitive hematopoietic cells in vertebrates. To delineate definitive versus primitive hematopoiesis during differentiation of human embryonic stem cells, we have introduced reporters into the MYB locus and inactivated the gene by bi-allelic targeting. To recapitulate the early developmental events more adequately, the mutant and wild type human embryonic stem cell lines were differentiated in defined culture conditions without the addition of hematopoietic cytokines. The differentiation of the reporter cell lines demonstrated that MYB is specifically expressed throughout emerging hematopoietic cell populations. Here we show that the disruption of the MYB gene leads to severe defects in the development and proliferation of primitive hematopoietic progenitors while the emergence of primitive blood cells is not affected. We also provide evidence that MYB is essential for neutrophil and T cell development and the upregulation of innate immunity genes during hematopoietic differentiation. Our results suggest that the endothelial origin of primitive blood cells is direct and does not include the intermediate step of primitive hematopoietic progenitors.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas , Animais , Células Sanguíneas , Diferenciação Celular , Linhagem Celular , Hematopoese/genética , Humanos
5.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34202945

RESUMO

Trillions of microbes exist in the human body, particularly the gastrointestinal tract, coevolved with the host in a mutually beneficial relationship. The main role of the intestinal microbiome is the fermentation of non-digestible substrates and increased growth of beneficial microbes that produce key antimicrobial metabolites such as short-chain fatty acids, etc., to inhibit the growth of pathogenic microbes besides other functions. Intestinal microbiota can prevent pathogen colonization through the mechanism of colonization resistance. A wide range of resistomes are present in both beneficial and pathogenic microbes. Giving antibiotic exposure to the intestinal microbiome (both beneficial and hostile) can trigger a resistome response, affecting colonization resistance. The following review provides a mechanistic overview of the intestinal microbiome and the impacts of antibiotic therapy on pathogen colonization and diseases. Further, we also discuss the epidemiology of immunocompromised patients who are at high risk for nosocomial infections, colonization and decolonization of multi-drug resistant organisms in the intestine, and the direct and indirect mechanisms that govern colonization resistance to the pathogens.


Assuntos
Antibiose , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/etiologia , Resistência a Múltiplos Medicamentos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Sepse/etiologia
6.
Molecules ; 26(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207000

RESUMO

In this modern era, nanofluids are considered one of the advanced kinds of heat transferring fluids due to their enhanced thermal features. The present study is conducted to investigate that how the suspension of molybdenum-disulfide (MoS2) nanoparticles boosts the thermal performance of a Casson-type fluid. Sodium alginate (NaAlg) based nanofluid is contained inside a vertical channel of width d and it exhibits a flow due to the movement of the left wall. The walls are nested in a permeable medium, and a uniform magnetic field and radiation flux are also involved in determining flow patterns and thermal behavior of the nanofluid. Depending on velocity boundary conditions, the flow phenomenon is examined for three different situations. To evaluate the influence of shape factor, MoS2 nanoparticles of blade, cylinder, platelet, and brick shapes are considered. The mathematical modeling is performed in the form of non-integer order operators, and a double fractional analysis is carried out by separately solving Caputo-Fabrizio and Atangana-Baleanu operators based fractional models. The system of coupled PDEs is converted to ODEs by operating the Laplace transformation, and Zakian's algorithm is applied to approximate the Laplace inversion numerically. The solutions of flow and energy equations are presented in terms of graphical illustrations and tables to discuss important physical aspects of the observed problem. Moreover, a detailed inspection on shear stress and Nusselt number is carried out to get a deep insight into skin friction and heat transfer mechanisms. It is analyzed that the suspension of MoS2 nanoparticles leads to ameliorating the heat transfer rate up to 9.5%. To serve the purpose of achieving maximum heat transfer rate and reduced skin friction, the Atangana-Baleanu operator based fractional model is more effective. Furthermore, it is perceived that velocity and energy functions of the nanofluid exhibit significant variations because of the different shapes of nanoparticles.

7.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806939

RESUMO

Human immunodeficiency virus (HIV) is a life life-threatening and serious infection caused by a virus that attacks CD4+ T-cells, which fight against infections and make a person susceptible to other diseases. It is a global public health problem with no cure; therefore, it is highly important to study and understand the intricate phenomena of HIV. In this article, we focus on the numerical study of the path-tracking damped oscillatory behavior of a model for the HIV infection of CD4+ T-cells. We formulate fractional dynamics of HIV with a source term for the supply of new CD4+ T-cells depending on the viral load via the Caputo-Fabrizio derivative. In the formulation of fractional HIV dynamics, we replaced the constant source term for the supply of new CD4+ T-cells from the thymus with a variable source term depending on the concentration of the viral load, and introduced a term that describes the incidence of the HIV infection of CD4+ T-cells. We present a novel numerical scheme for fractional view analysis of the proposed model to highlight the solution pathway of HIV. We inspect the periodic and chaotic behavior of HIV for the given values of input factors using numerical simulations.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Modelos Imunológicos , Carga Viral , Replicação Viral/fisiologia , Humanos
8.
Vet Anaesth Analg ; 48(5): 671-678, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34364789

RESUMO

OBJECTIVE: To elucidate the antinociceptive, physiologic and biochemical effects of electroacupuncture (EA) and xylazine in hybrid goats. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 30 female hybrid goats aged 1-2 years and weighing 25 ± 2.9 kg (mean ± standard deviation). METHODS: The goats were divided into five groups and administered xylazine (0.1 mg kg-1; group XYL.1), xylazine (0.3 mg kg-1; group XYL.3), EA (group EA), EA + xylazine (0.1 mg kg-1; group XYL.1-EA) and 0.9% saline (0.3 mL; control group CON). Nociceptive threshold and serum glucose concentration were measured at time 0 and at 15, 30, 45, 60 minutes and 24 hours after treatment. Nociceptive threshold was measured by passing potassium ions through the skin using potassium iontophoresis. Mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR) and rectal temperature (RT) were recorded at times 0 and at 5, 10, 15, 20, 30, 45, 60 minutes and 24 hours. Repeated-measures analyses were performed for each response variable; p < 0.05 was considered significant for all analyses. RESULTS: Antinociceptive effects in groups XYL.1 and XYL.3 were increased significantly at 15-60 minutes compared with group CON. Antinociceptive effect was higher in group XYL.1-EA than groups XYL.1 or EA at 15-60 minutes (p < 0.05). No significant difference in the nociceptive threshold was recorded in groups XYL.1-EA and XYL.3, except at 30 minutes. HR, MAP, fR, RT values were higher in group XYL.1-EA than in groups XYL.1 or XYL.3. Serum glucose concentration was higher in group XYL.3 at 15-60 minutes than in CON. CONCLUSIONS AND CLINICAL RELEVANCE: The XYL.1 and EA combination was effective for antinociception with minimum physiologic alteration, suggesting that the combination may be a new and effective strategy for pain relief during clinical procedures in goats.


Assuntos
Analgésicos , Eletroacupuntura , Xilazina , Analgésicos/farmacologia , Animais , Eletroacupuntura/veterinária , Feminino , Cabras , Estudos Prospectivos , Xilazina/farmacologia
9.
Biochem Biophys Res Commun ; 529(2): 474-479, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32703454

RESUMO

Currently, there is a growing interest in understanding the cellular and molecular events of immune-cell trafficking and recruitment of hepatic stellate cells (HSCs) in liver diseases. Aberrant activation of HSCs is the key event leading to chronic liver fibrosis. However, the underlying mechanisms of the recruitment of HSCs in a locally injured liver are not clearly understood. Here, we report a new experimental approach for the study of inflammatory responses as well as the recruitment of HSCs into the localized cryolesion. We observed a significant liver damage accompanied by the up-regulation of plasma ALT and AST. In addition, we also found increased levels of MCP-1, IL-6 and IL-10 cytokines. The peak cytokine levels were detected at 8 h after injury, followed by intrahepatic infiltration of neutrophils and monocytes into the injury site (from 8 h to day 3), while the kupffer cells (KCs) and HSCs were mainly detected on day 3 after injury. Interestingly, the depletion of KCs, but not neutrophils, reduced the directional recruitment and accumulation of HSCs at the injury site. Moreover, the combinatorial recruitment of KCs and HSCs resulted in the gradual restoration of fibrotic area to almost typical histological appearance on day 14 post-injury. In conclusion, our data demonstrated a localized infiltration and accumulation of neutrophils and monocytes at a "predefined loci", and further revealed that KCs are critical for the recruitment of HSCs during injury, and thus, may play an important role in tissue repair.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Células Estreladas do Fígado/patologia , Células de Kupffer/patologia , Cirrose Hepática/patologia , Animais , Tetracloreto de Carbono , Movimento Celular , Modelos Animais de Doenças , Feminino , Fígado/patologia , Camundongos Endogâmicos C57BL
10.
Molecules ; 25(4)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075150

RESUMO

In this research article, we investigated a comprehensive analysis of time-dependent free convection electrically and thermally conducted water-based nanofluid flow containing Copper and Titanium oxide (Cu and TiO 2 ) past a moving porous vertical plate. A uniform transverse magnetic field is imposed perpendicular to the flow direction. Thermal radiation and heat sink terms are included in the energy equation. The governing equations of this flow consist of partial differential equations along with some initial and boundary conditions. The solution method of these flow interpreting equations comprised of two parts. Firstly, principal equations of flow are symmetrically transformed to a set of nonlinear coupled dimensionless partial differential equations using convenient dimensionless parameters. Secondly, the Laplace transformation technique is applied to those non-dimensional equations to get the close form exact solutions. The control of momentum and heat profile with respect to different associated parameters is analyzed thoroughly with the help of graphs. Fluid accelerates with increasing Grashof number (Gr) and porosity parameter (K), while increasing values of heat sink parameter (Q) and Prandtl number (Pr) drop the thermal profile. Moreover, velocity and thermal profile comparison for Cu and TiO 2 -based nanofluids is graphed.


Assuntos
Convecção , Hidrodinâmica , Nanoestruturas/química , Água/química , Temperatura Alta , Campos Magnéticos , Modelos Teóricos , Porosidade , Temperatura
11.
Molecules ; 25(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046124

RESUMO

This paper examines the time independent and incompressible flow of magnetohydrodynamic (MHD) nanofluid through a porous rotating disc with velocity slip conditions. The mass and heat transmission with viscous dissipation is scrutinized. The proposed partial differential equations (PDEs) are converted to ordinary differential equation (ODEs) by mean of similarity variables. Analytical and numerical approaches are applied to examine the modeled problem and compared each other, which verify the validation of both approaches. The variation in the nanofluid flow due to physical parameters is revealed through graphs. It is witnessed that the fluid velocities decrease with the escalation in magnetic, velocity slip, and porosity parameters. The fluid temperature escalates with heightening in the Prandtl number, while other parameters have opposite impacts. The fluid concentration augments with the intensification in the thermophoresis parameter. The validity of the proposed model is presented through Tables.


Assuntos
Hidrodinâmica , Movimento (Física) , Nanotecnologia/métodos , Temperatura Alta , Modelos Teóricos , Porosidade , Temperatura , Viscosidade
12.
Entropy (Basel) ; 22(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33286253

RESUMO

Magnetohydrodynamic (MHD) flow with Hall current has numerous applications in industrial areas such as Hall current accelerators, MHD power generators, planetary dynamics, Hall current sensors, etc. In this paper, the analysis of an unsteady MHD Casson fluid with chemical reaction over a rotating cone is presented. The impacts of Hall current, joule heating, thermal radiation, and viscous dissipation are analyzed. Entropy optimization is also considered in the present analysis. The system of coupled equations is tackled with homotopy analysis method (HAM). The convergence of HAM is also shown through figures. Deviations in the flow due to dimensionless parameters are shown graphically. Similarly, the variation in skin friction, Nusselt number, and Sherwood number are deliberated through Tables. A justification of the current consequences is presented.

13.
Entropy (Basel) ; 21(1)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33266768

RESUMO

This article examines the entropy analysis of magnetohydrodynamic (MHD) nanofluid flow of single and multiwall carbon nanotubes between two rotating parallel plates. The nanofluid flow is taken under the existence of Hall current and ion-slip effect. Carbon nanotubes (CNTs) are highly proficient heat transmission agents with bordering entropy generation and, thus, are considered to be a capable cooling medium. Entropy generation and Hall effect are mainly focused upon in this work. Using the appropriate similarity transformation, the central partial differential equations are changed to a system of ordinary differential equations, and an optimal approach is used for solution purposes. The resultant non-dimensional physical parameter appear in the velocity and temperature fields discussed using graphs. Also, the effect of skin fraction coefficient and Nusselt number of enclosed physical parameters are discussed using tables. It is observed that increased values of magnetic and ion-slip parameters reduce the velocity of the nanofluids and increase entropy generation. The results reveal that considering higher magnetic forces results in greater conduction mechanism.

14.
Entropy (Basel) ; 21(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33266855

RESUMO

Chemical reaction in mixed convection magnetohydrodynamic second grade nanoliquid thin film flow through a porous medium containing nanoparticles and gyrotactic microorganisms is considered with entropy generation. The stratification phenomena, heat and mass transfer simultaneously take place within system. Microorganisms are utilized to stabilize the suspended nanoparticles through bioconvection. For the chemical reaction of species, the mass transfer increases. The governing equations of the problem are transformed to nonlinear differential equations through similarity variables, which are solved through a well known scheme called homotopy analysis method. The solution is expressed through graphs and illustrations which show the influences of all the parameters. The residual error graphs elucidate the authentication of the present work.

15.
Entropy (Basel) ; 21(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33267206

RESUMO

The impact of nonlinear thermal radiations rotating with the augmentation of heat transfer flow of time-dependent single-walled carbon nanotubes is investigated. Nanofluid flow is induced by a shrinking sheet within the rotating system. The impact of viscous dissipation is taken into account. Nanofluid flow is assumed to be electrically conducting. Similarity transformations are applied to transform PDEs (partial differential equations) into ODEs (ordinary differential equations). Transformed equations are solved by the homotopy analysis method (HAM). The radiative source term is involved in the energy equation. For entropy generation, the second law of thermodynamics is applied. The Bejan number represents the current investigation of non-dimensional entropy generation due to heat transfer and fluid friction. The results obtained indicate that the thickness of the boundary layer decreases for greater values of the rotation parameter. Moreover, the unsteadiness parameter decreases the temperature profile and increases the velocity field. Skin friction and the Nusselt number are also physically and numerically analyzed.

16.
Entropy (Basel) ; 21(8)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33267461

RESUMO

In this research article, the investigation of the three-dimensional Casson nanofluid flow in two rotating parallel plates has been presented. The nanofluid has been considered in steady state. The rotating plates have been considered porous. The heat equation is considered to study the magnetic field, joule heating, and viscous dissipation impacts. The nonlinear ordinary system of equations has been solved analytically and numerically. For skin friction and Nusslt number, numerical results are tabulated. It is found that velocity declines for higher values of magnetic and porosity parameter while it is heightened through squeezing parameter. Temperature is an enhancing function for Eckert number and nanoparticles volume fraction. Entropy generation is augmented with radiation parameter, Prandtl, and Eckert numbers. The Casson, porosity, magnetic field, and rotation parameters were reduced while the squeezing and suction parameters increased the velocity profile along x-direction. The porosity parameter increased the Bejan number while the Eckert and Prandtl numbers decreased the Bejan number. Skin friction was enhanced with increasing the Casson, porosity, and magnetic parameters while it decreased with enhancing rotation and squeezing parameters. All these impacts have been shown via graphs. The influences by fluid flow parameters over skin friction and Nusselt number are accessible through tables.

17.
Entropy (Basel) ; 21(8)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-33267514

RESUMO

In this research work, a 3D rotating flow of carbon nanotubes (CNTs) over a porous stretchable sheet for heat and mass transfer is investigated. Kerosene oil is considered as a base liquid and two types of CNTs, (Single & Multi) WCNTs are added as the additives to the base liquid. The present analysis further comprises the combined effect of the Hall, ion-slip, and thermal radiation, along with heat generation/absorption. The appropriate ordinary differential system of equations after applying appropriate transformation is calculated. The resulting nonlinear system of equations (conservation of mass, momentum, temperature) is explained by HAM (Homotopy Analysis Method). Solution of velocities and thermal fields are obtained and discussed graphically. Expression of C f and N u are intended for both type of nanoliquids. The influences of prominent physical factors are plotted for velocities and thermal profiles using Methematica. These graphical results are qualitatively in excellent agreement with the previous published results. Also, single wall nanoparticles are found to have higher temperatures than multi wall CNTs nanoparticles.

18.
Entropy (Basel) ; 20(6)2018 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33265502

RESUMO

This research paper investigates entropy generation analysis on two-dimensional nanofluid film flow of Eyring-Powell fluid with heat amd mass transmission over an unsteady porous stretching sheet in the existence of uniform magnetic field (MHD). The flow of liquid films are taken under the impact of thermal radiation. The basic time dependent equations of heat transfer, momentum and mass transfer are modeled and converted to a system of differential equations by employing appropriate similarity transformation with unsteady dimensionless parameters. Entropy analysis is the main focus in this work and the impact of physical parameters on the entropy profile are discussed in detail. The influence of thermophoresis and Brownian motion has been taken in the nanofluids model. An optima approach has been applied to acquire the solution of modeled problem. The convergence of the HAM (Homotopy Analysis Method) has been presented numerically. The disparity of the Nusslet number, Skin friction, Sherwood number and their influence on the velocity, heat and concentration fields has been scrutinized. Moreover, for comprehension, the physical presentation of the embedded parameters are explored analytically for entropy generation and discussed.

19.
Toxicol Appl Pharmacol ; 276(2): 121-8, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24582689

RESUMO

BACKGROUND AND PURPOSE: Quinolones cause obvious cartilaginous lesions in juvenile animals by chondrocyte apoptosis, which results in the restriction of their use in pediatric and adolescent patients. Studies showed that chondrocytes can be induced to produce TNFα, and the cisternae of the endoplasmic reticulum in quinolone-treated chondrocytes become dilated. We investigated whether TNF/TNFR1 pathway and endoplasmic reticulum stress (ERs) are involved in ofloxacin (a typical quinolone)-induced apoptosis of juvenile canine chondrocytes. EXPERIMENTAL APPROACH: Canine juvenile chondrocytes were treated with ofloxacin. Cell survival and apoptosis rates were determined with MTT method and flow cytometry, respectively. The gene expression levels of the related signaling molecules (TNFα, TNFR1, TRADD, FADD and caspase-8) in death receptor pathways and main apoptosis-related molecules (calpain, caspase-12, GADD153 and GRP78) in ERs were measured by qRT-PCR. The gene expression of TNFR1 was suppressed with its siRNA. The protein levels of TNFα, TNFR1 and caspase-12 were assayed using Western blotting. KEY RESULTS: The survival rates decreased while apoptosis rates increased after the chondrocytes were treated with ofloxacin. The mRNA levels of the measured apoptosis-related molecules in death receptor pathways and ERs, and the protein levels of TNFα, TNFR1 and caspase-12 increased after the chondrocytes were exposed to ofloxacin. The downregulated mRNA expressions of TNFR1, Caspase-8 and TRADD, and the decreased apoptosis rates of the ofloxacin-treated chondrocytes occurred after TNFR1-siRNA interference. CONCLUSIONS AND IMPLICATIONS: Ofloxacin-induced chondrocyte apoptosis in a time- and concentration-dependent fashion. TNF/TNFR1 pathway and ERs are involved in ofloxacin-induced apoptosis of juvenile canine chondrocytes in the early stage.


Assuntos
Antibacterianos/toxicidade , Apoptose/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Ofloxacino/toxicidade , Receptores Tipo I de Fatores de Necrose Tumoral/fisiologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Envelhecimento , Animais , Caspase 12/análise , Células Cultivadas , Condrócitos/patologia , Cães , Relação Dose-Resposta a Droga , RNA Mensageiro/análise , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/genética
20.
PLoS One ; 19(6): e0304375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38935766

RESUMO

Hepatitis B virus (HBV) infection is a global public health issue. We offer a comprehensive analysis of the dynamics of HBV, which can be successfully controlled with vaccine and treatment. Hepatitis B virus (HBV) causes a significantly more severe and protracted disease compared to hepatitis A. While it initially presents as an acute disease, in approximately 5 to 10% of cases, it can develop into a chronic disease that causes permanent damage to the liver. The hepatitis B virus can remain active outside the body for at least seven days. If the virus penetrates an individual's body without immunization, it may still result in infection. Upon exposure to HBV, the symptoms often last for a duration ranging from 10 days to 6 months. In this study, we developed a new model for Hepatitis B Virus (HBV) that includes asymptomatic carriers, vaccination, and treatment classes to gain a comprehensive knowledge of HBV dynamics. The basic reproduction number [Formula: see text] is calculated to identify future recurrence. The local and global stabilities of the proposed model are evaluated for values of [Formula: see text] that are both below and above 1. The Lyapunov function is employed to ensure the global stability of the HBV model. Further, the existence and uniqueness of the proposed model are demonstrated. To look at the solution of the proposed model graphically, we used a useful numerical strategy, such as the non-standard finite difference method, to obtain more thorough numerical findings for the parameters that have a significant impact on disease elimination. In addition, the study of treatment class in the population, we may assess the effectiveness of alternative medicines to treat infected populations can be determined. Numerical simulations and graphical representations are employed to illustrate the implications of our theoretical conclusions.


Assuntos
Simulação por Computador , Vírus da Hepatite B , Hepatite B , Humanos , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B/fisiologia , Epidemias/prevenção & controle , Vacinas contra Hepatite B/uso terapêutico , Vacinas contra Hepatite B/administração & dosagem , Número Básico de Reprodução , Vacinação
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